In vivo tissue uptake of intravenously injected water soluble all-trans β-carotene used as a food colorant

Water soluble β-carotene (WS-BC) is a carotenoid form that has been developed as a food colorant. WS-BC is known to contain 10% of all-trans β-carotene (AT-BC). The aim of the present study was to investigate in vivo tissue uptake of AT-BC after the administration of WS-BC into rats. Seven-week-old male rats were administered 20 mg of WS-BC dissolved in saline by intravenous injection into the tail vein. At 0, 6, 24, 72, 120 and 168 hours (n = 7/time), blood was drawn and liver, lungs, adrenal glands, kidneys and testes were dissected. The levels of AT-BC in the plasma and dissected tissues were quantified with HPLC. After intravenous administration, AT-BC level in plasma first increased up to 6 h and returned to normal at 72 h. In the testes, the AT-BC level first increased up to 24 h and then did not decrease but was retained up to 168 h. In the other tissues, the level first increased up to 6 h and then decreased from 6 to 120 or 168 h but did not return to normal. The accumulation of WS-BC in testes but not in the other 5 tissues examined may suggest that AT-BC was excreted or metabolized in these tissues but not in testes. Although WS-BC is commonly used as a food colorant, its effects on body tissues are still not clarified. Results of the present study suggest that further investigations are required to elucidate effects of WS-BC on various body tissues

Inhibition of Transglutaminase 2 activity increases cisplatin cytotoxicity in a model of human hepatocarcinoma chemotherapy

Transglutaminase 2 (TG2) is a ubiquitous multifunctional enzyme whose expression has been found to be altered in numerous studies of apoptosis and cell survival; its activity has been found to be increased in many types of cancer, where it is often over-expressed. Cisplatin has long been used as an effective therapeutic drug to treat numerous cancers. Although its activity is based on cross-linking of DNA, cisplatin may also operate via other mechanisms that involve modification and alteration in the activity of protein and RNA modulators of the cell cycle and apoptotic processes; these mechanisms are less well characterised. In this study, we investigated the effects of cisplatin-induced apoptosis on TG2 expression and activity in the human hepatocarcinoma (HepG2) cell line. Through a combination of Western blotting, enzymatic activity assays, flow cytometry and fluorescence microscopy we provide evidence that TG2 is inhibited during initiation of apoptosis by cisplatin, an observation that was reversed by increasing the expression of TG2, by treating cells with retinoic acid. We also report, for the first time, that cisplatin can directly inhibit transglutaminase activity in vitro. Collectively, these studies increase our understanding of the mechanism(s) of action of cisplatin, as cisplatin–mediated reduction in TG2 activity appears to act as an early activator of apoptosis during chemotherapeutic treatment of hepatocarcinoma cells. This observation suggests an explanation as to how increased levels of TG2 activity in cancer cells could contribute to chemotherapeutic resistance to cisplatin, and so has implications for novel approaches to cisplatin therap

Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis

BACKGROUND: The potential of ascorbic acid and two botanical decoctions, green tea and cat's claw, to limit cell death in response to oxidants were evaluated in vitro. METHODS: Cultured human gastric epithelial cells (AGS) or murine small intestinal epithelial cells (IEC-18) were exposed to oxidants – DPPH (3 μM), H(2)O(2) (50 μM), peroxynitrite (300 μM) – followed by incubation for 24 hours, with antioxidants (10 μg/ml) administered as a 1 hour pretreatment. Cell number (MTT assay) and death via apoptosis or necrosis (ELISA, LDH release) was determined. The direct interactions between antioxidants and DPPH (100 μM) or H(2)O(2) (50 μM) were evaluated by spectroscopy. RESULTS: The decoctions did not interact with H(2)O(2), but quenched DPPH although less effectively than vitamin C. In contrast, vitamin C was significantly less effective in protecting human gastric epithelial cells (AGS) from apoptosis induced by DPPH, peroxynitrite and H(2)O(2) (P < 0.001). Green tea and cat's claw were equally protective against peroxynitrite and H(2)O(2), but green tea was more effective than cat's claw in reducing DPPH-induced apoptosis (P < 0.01). Necrotic cell death was marginally evident at these low concentrations of peroxynitrite and H(2)O(2), and was attenuated both by cat's claw and green tea (P < 0.01). In IEC-18 cells, all antioxidants were equally effective as anti-apoptotic agents. CONCLUSIONS: These results indicate that dietary antioxidants can limit epithelial cell death in response to oxidant stress. In the case of green tea and cat's claw, the cytoprotective response exceed their inherent ability to interact with the injurious oxidant, suggestive of actions on intracellular pathways regulating cell death

Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

<p>Abstract</p> <p>Background</p> <p>Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies.</p> <p>Methods</p> <p>In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking.</p> <p>Results</p> <p>Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed.</p> <p>Conclusion</p> <p>We conclude that VE might prevent lung tumor induced by smoking in Swiss mice.</p

The NTI-tss device for the therapy of bruxism, temporomandibular disorders, and headache – Where do we stand? A qualitative systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The NTI-tss device is an anterior bite stop, which, according to the manufacturer, is indicated for the prevention and treatment of bruxism, temporomandibular disorders (TMDs), tension-type headaches, and migraine. The aim of this systematic review was to appraise the currently available evidence regarding the efficacy and safety of the NTI-tss splint.</p> <p>Methods</p> <p>We performed a systematic search in nine electronic databases and in NTI-tss-associated websites (last update: December 31, 2007). The reference lists of all relevant articles were perused. Five levels of scientific quality were distinguished. Reporting quality of articles about randomized controlled trials (RCTs) was evaluated using the Jadad score. To identify adverse events, we searched in the identified publications and in the MAUDE database.</p> <p>Results</p> <p>Nine of 68 relevant publications reported about the results of five different RCTs. Two RCTs concentrated on electromyographic (EMG) investigations in patients with TMDs and concomitant bruxism (Baad-Hansen et al 2007, Jadad score: 4) or with bruxism alone (Kavaklı 2006, Jadad score: 2); in both studies, compared to an occlusal stabilization splint the NTI-tss device showed significant reduction of EMG activity. Two RCTs focused exclusively on TMD patients; in one trial (Magnusson et al 2004, Jadad score: 3), a stabilization appliance led to greater improvement than an NTI-tss device, while in the other study (Jokstad et al 2005, Jadad score: 5) no difference was found. In one RCT (Shankland 2002, Jadad score: 1), patients with tension-type headache or migraine responded more favorably to the NTI-tss splint than to a bleaching tray. NTI-tss-induced complications related predominantly to single teeth or to the occlusion.</p> <p>Conclusion</p> <p>Evidence from RCTs suggests that the NTI-tss device may be successfully used for the management of bruxism and TMDs. However, to avoid potential unwanted effects, it should be chosen only if certain a patient will be compliant with follow-up appointments. The NTI-tss bite splint may be justified when a reduction of jaw closer muscle activity (e.g., jaw clenching or tooth grinding) is desired, or as an emergency device in patients with acute temporomandibular pain and, possibly, restricted jaw opening.</p

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

<p>Abstract</p> <p>Background</p> <p>Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk.</p> <p>Methods</p> <p>We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers.</p> <p>Results</p> <p>The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ²₁(heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ²₁₆(heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ²₉(heterogeneity) = 149.68, p < 0.001).</p> <p>Conclusions</p> <p>Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk.</p

Use of vitamin supplements and risk of total cancer and cardiovascular disease among the Japanese general population: A population-based survey

<p>Abstract</p> <p>Background</p> <p>Despite the popular use of vitamin supplements and several prospective cohort studies investigating their effect on cancer incidence and cardiovascular disease (CVD), scientific data supporting their benefits remain controversial. Inconsistent results may be partly explained by the fact that use of supplements is an inconsistent behavior in individuals. We examined whether vitamin supplement use patterns affect cancer and CVD risk in a population-based cohort study in Japan.</p> <p>Methods</p> <p>A total of 28,903 men and 33,726 women in the Japan Public Health Center-based Prospective Study cohort, who answered questions about vitamin supplement use in the first survey from 1990-1994 and the second survey from 1995-1998, were categorized into four groups (never use, past use, recent use, and consistent use) and followed to the end of 2006 for cancer and 2005 for CVD. Sex-specific hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to describe the relative risks of cancer and CVD associated with vitamin supplement use.</p> <p>Results</p> <p>During follow-up, 4501 cancer and 1858 CVD cases were identified. Multivariate adjusted analysis revealed no association of any pattern of vitamin supplement use with the risk of cancer and CVD in men. In women, consistent use was associated with lower risk of CVD (HR 0.60, 95% CI 0.41-0.89), whereas past (HR 1.17, 95% CI 1.02-1.33) and recent use (HR 1.24, 95% CI 1.01-1.52) were associated with higher risk of cancer.</p> <p>Conclusions</p> <p>To our knowledge, this is the first prospective cohort study to examine simultaneously the associations between vitamin supplement use patterns and risk of cancer and CVD. This prospective cohort study demonstrated that vitamin supplement use has little effect on the risk of cancer or CVD in men. In women, however, consistent vitamin supplement use might reduce the risk of CVD. Elevated risk of cancer associated with past and recent use of vitamin supplements in women may be partly explained by preexisting diseases or unhealthy background, but we could not totally control for this in our study.</p

The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: A review based on controversial evidence

PURPOSE: A review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD). METHODS: Medline and Embase search. RESULTS: Recent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking. CONCLUSION: An intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities