Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy.
Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited.
Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups.
Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result.
Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses.
Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration.
Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.
METHODS: Sodium nitrite (50mg/L) was given to angiotensin II-infused hypertensive C57BL/6J (eight to ten weeks old) mice for two weeks in the drinking water. Arterial systolic blood pressure was measured using the tail-cuff method. Vascular responsiveness of isolated aortae and renal arteries was studied in wire myographs. The level of nitrite in the plasma and the cyclic guanosine monophosphate (cGMP) content in the arterial wall were determined using commercially available kits. The production of reactive oxygen species (ROS) and the presence of proteins (nitrotyrosine, NOx-2 and NOx-4) involved in ROS generation were evaluated with dihydroethidium (DHE) fluorescence and by Western blotting, respectively.
RESULTS: Chronic administration of sodium nitrite for two weeks to mice with angiotensin II-induced hypertension decreased systolic arterial blood pressure, reversed endothelial dysfunction, increased plasma nitrite level as well as vascular cGMP content. In addition, sodium nitrite treatment also decreased the elevated nitrotyrosine and NOx-4 protein level in angiotensin II-infused hypertensive mice.
CONCLUSIONS: The present study demonstrates that chronic treatment of hypertensive mice with sodium nitrite improves impaired endothelium function in conduit and resistance vessels in addition to its antihypertensive effect, partly through inhibition of ROS production.
OBJECTIVE: The present review discusses the literature concerning the antidiabetic and antioxidant properties of MC focusing on the complication of diabetes mellitus along with its mode of delivery. We found that among the whole part of MC, its fruit extract has been widely studied, therapeutically. The evidence based analysis of the beneficiary effects of MC on the different organs involved in diabetes complication is also highlighted. This review elucidated an essential understanding of MC based drug delivery system in both clinical and experimental studies and appraised the great potential of the protein based MC extract against diabetes mellitus.
CONCLUSION: The review paper is believed to assist the researchers and medical personnel in treating diabetic associated complications.
MATERIALS AND METHODS: Twenty female athletes (aged 21.3 [2.1] years; body weight [BW] 54.1 [5.7] kg) were randomly assigned into two groups and consumed either 1.5 g/kg BW TH (high honey; HH; n = 10) or 0.75 g/kg BW TH (low honey; LH; n = 10). Blood sample was collected at fasting and at 0.5, 1, 2, and 3 h after TH consumption. Plasma was analyzed for total phenolic content (TPC), antioxidant activity (ferric reducing antioxidant power [FRAP]), and oxidative stress biomarkers (malondialdehyde [MDA] and reactive oxygen species [ROS]).
RESULTS: The 3-h area under the curve (AUC) for MDA was significantly lower in the LH group compared with HH group, suggesting less oxidative stress in the LH group. However, the AUCs for TPC, FRAP, and ROS were not affected by the dosages. The concentrations of TPC and FRAP increased from baseline to 2 and 1 h after TH consumption, respectively, and concentrations returned toward baseline at 3 h in both LH and HH groups. MDA concentration significantly decreased (p
METHODS: To reach this goal, total phenolic content (TPC) of ethanolic (Eth) and aqueous (Aq) extracts were determined and radical scavenging activity was assayed by 2,2-diphenyl-1-picrylhydrazyl. Chemical compositions of each extract were also determined via GC-Mass. Behavioral changes were studied via passive avoidance and Morris water maze in Aβ-induced model of Alzheimer's disease. Catalase (CAT) and superoxide dismutase (SOD) determination were also done on rats' hippocampus.
RESULTS: The results showed that seed Eth extract has a high level of TPC and radical scavenging activity. However, this extract had surprisingly no effect on memory and CAT and SOD activities. In contrast, fruit Aq and Eth extracts (containing furfurals as major compounds) inhibited memory impairment (P
MATERIAL AND METHODS: A single dose of streptozotocin (45mg/kg body weight, iv) was used to induced diabetes in male Sprague Dawley rats which were then divided into two groups: Diabetic control (DC) and HSL-treated diabetic (DR) group. Normal rats were divided into normal control (NC), HSL-treated control (NR). Aqueous calyxes extract of HSL (100mg/kg/day, orally) was given for 28 consecutive days in the treated group. Weight, biochemical and histopathological (light and electron microscopic) parameters were compared in all groups.
RESULTS: Supplementation of HSL significantly lowered the level of fasting blood glucose and increased plasma insulin level in DR group compared to DC group (p<0.05). Alanine aminotransaminases and aspartate aminotransferase enzymes level were found to be significantly reduced in DR compared to DC. Microscopic examination demonstrated destruction of the liver architecture, cytoplasmic vacuolation of the hepatocytes and signs of necrosis in diabetic rats. Moreover, dilatation and congestion of blood vessels with leucocytes adherence were detected. Ultrastructural study using electron microscope showed homogeneous substance accumulation in nuclear chromatin, a decrease of organelles and mitochondrial degeneration in the diabetic rats.
CONCLUSION: Administration of HSL in diabetic rats causes significant decrease in hepatocyte destruction and prevented the changes associated with the diabetic condition. Thus, our findings provide a scientific rationale for the use of HSL as promising agent in preventing liver injury in diabetes.
METHODS: In this article, several studies on stingless bee honey that pointed out the numerous therapeutic profiles of this honey in terms of its antioxidant, antimicrobial, anti-inflammatory, as well as moisturizing properties are reviewed. All of these therapeutic properties are related to wound healing properties.
RESULTS: Antioxidant in stingless bee honey could break the chain of free radicals that cause a detrimental effect to the wounded area. Furthermore, the antimicrobial properties of stingless bee honey could overcome the bacterial contamination and thus improve the healing rate. Moreover, the anti-inflammatory attribute in this honey could protect the tissue from highly toxic inflammatory mediators. The moisturizing properties of the honey could improve wound healing by promoting angiogenesis and oxygen circulation.
CONCLUSION: The application of honey to the wound has been widely used since ancient times. As a result, it is essential to understand the pharmacological mechanism of the honey towards the physiology of the wounded skin in order to optimize the healing rate in the future.
METHODS AND ANALYSIS: In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons.
ETHICS AND DISSEMINATION: This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.
TRIAL REGISTRATION NUMBER: NCT02058420; results.
STUDY DESIGN: In total, 282 patients with oral submucous fibrosis were treated with topical corticosteroid and oral antioxidant and the ice-cream stick exercise regimen. Patients in subgroups A1, A2, and A3 were additionally given a new MED. Patients in subgroups A1 and B1 patients with interincisal distance (IID) of 20 to 35 mm were managed without any additional therapy; patients in subgroups A2 and B2 with IID of 20 to 35 mm were additionally managed with intralesional injections; and those in subgroups A3 and B3 with IID less than 20 mm were managed surgically. Subjective evaluation of decrease in the oral mucosal burning was measured on a visual analogue scale (VAS). Analysis of variance and Tukey's multiple post hoc analysis were carried out to present the results.
RESULTS: Patients using the MED, that is, subgroups A1, A2, and A3, showed reduction in burning sensation in the range of 64.8% to 71.1% and 27.8% to 30.9%, whereas in subgroups B1, B2, and B3, reduction in burning sensation ranged from 64.7% to 69.9% and from 29.3% to 38.6% after 6 months. The wo-way analysis of variance indicated statistically significant results in changes in initial VAS scores to 6-monthly VAS scores between MED users and non-MED users.
CONCLUSIONS: The MED helps to enhance the rate of reduction of mucosal burning sensation, in addition to the conventional ice-cream stick regimen, as an adjunct to local and surgical treatment.
MATERIALS AND METHODS: A total of 231 OSMF patients were selected and treated with basic regime including topical corticosteroids, oral antioxidants and the icecream-stick exercise regime and allotted randomly to two equal groups A and B. Group-A patients were additionally given MED. Subgroups A1 and B1 patients with an inter-incisal distance (IID) 20-35mm were not given any additional therapy; subgroup A2 and B2 patients (IID 20-35mm) were treated additionally with intra-lesional injections. Subgroups A3 and B3 with IID<20mm were managed surgically. IID was measured at baseline and at 6 months recall. The change in IID measurements was calculated and statistically analyzed using 2-way ANOVA and Tukeys multiple post hoc analysis.
RESULTS: Average improvement in IID after six months of recall visits was observed to be 8.4 mm in subgroup-A1 (n-53) compared to 5.5 mm in B1(n-50) (p<0.01). The IID improvement in subgroup-A2 was found to be 9.3mm (n-46) compared to 5.1 mm in B2 (n-48) (p<0.01). In the surgery group, mouth opening improvement was observed to be 9.6 mm in subgroup A3 (n-18) compared to 4.8 mm for B3 (n-16) (p<0.01).
CONCLUSIONS: Use of the MED appears to be effective for increasing oral opening in OMSF patients in conjunction with local, injection and/or surgical treatment.