Katherine T. Gottschall-Pass

Zinc and the eye.

Zinc, a trace element that influences cell metabolism through a variety of mechanisms, appears to play an integral role in maintaining normal ocular function. This element is present in high concentrations in ocular tissue, particularly in retina and choroid. Zinc deficiency has been shown in a number of species to result in a variety of gross, ultrastructural and electrophysiologic ocular manifestations. The physiological functions for zinc have been studied predominantly in retina and retinal pigment epithelium where zinc is believed to interact with taurine and vitamin A, modify photoreceptor plasma membranes, regulate the light-rhodopsin reaction, modulate synaptic transmission and serve as an antioxidant. Suboptimal zinc status in North America may influence the development and progression of several chronic eye diseases. Zinc supplementation trials and epidemiological studies have produced conflicting results concerning the role of zinc in age-related macular degeneration. Additional well-controlled supplementation trials are indicated to clarify the role of zinc in this disease. Future investigations must also expand our understanding of the mechanisms by which zinc regulates ocular morphology and function.

Feeding Rats Diets Enriched in Lowbush Blueberries for Six Weeks Decreases Ischemia-induced Brain Damage

Abstract Oxidative stress is an important element in the etiology of ischemic stroke. Lowbush blueberries (Vaccinium angustifolium Aiton) have a high antioxidant capacity and thus we determined whether consumption of lowbush blueberries would protect neurons from stroke-induced damage. Rats were fed AIN-93G diets containing 0 or 14.3% blueberries (g fresh weight/100 g feed) for 6 weeks. Stroke was then simulated by ligation of the left common carotid artery (ischemia), followed by hypoxia. One week later, plasma and urine were collected, and neuronal damage in the hippocampus was determined histologically. In control rats, hypoxia-ischemia resulted in 40±2% loss of neurons in the hippocampus of the left cerebral hemisphere, as compared to the right hemisphere. Rats on blueberry-supplemented diets lost only 17±2% of neurons in the ischemic hippocampus. Neuroprotection was observed in the CA1 and CA2 regions, but not CA3 region, of the hippocampus. The blueberry diet had no detectable effects on the plasma or urine oxygen radical absorbance capacity (ORAC) or plasma lipids. We conclude that consumption of lowbush blueberries by rats confers protection to the brain against damage from ischemia, suggesting that inclusion of blueberries in the diet may improve ischemic stroke outcomes.

Diets containing blueberry extract lower blood pressure in spontaneously hypertensive stroke-prone rats.

Oxidative stress in the vasculature and kidneys contributes to hypertension, a major risk factor for cardiovascular disease. Blueberries (BB) are rich in antioxidants, and so we hypothesized that feeding diets enriched with BB would slow the development of hypertension in spontaneously hypertensive stroke-prone rats (SHRSP). Eight-week-old normotensive rats and SHRSP were fed either a control diet (Con) or a diet enriched with 3% freeze-dried BB for 8 weeks. Systolic blood pressure (SBP) was measured at weeks 2, 4, 6, 7, and 8 by the tail cuff method, and urine was collected at weeks 4 and 8. The SBP was elevated in SHRSP relative to normotensive rats over the entire 8-week feeding period. In SHRSP consuming BB, SBP was 19% lower at week 4 and 30% lower at week 6, relative to SHRSP on Con. Maximum SBP was 216 +/- 11 mm Hg in SHRSP consuming Con vs 178 +/- 15 mm Hg in the BB-fed group (P = .036). Spontaneously hypertensive stroke-prone rats had elevated levels of urine F2-isoprostanes/creatinine relative to normotensive rats, indicating systemic oxidative stress in this strain. Blueberry feeding had no effect on urinary excretion of F2-isoprostanes; therefore, it is unlikely that a systemic antioxidant effect of BB is responsible for the antihypertensive effects at weeks 4 and 6. Blueberry-fed rats had reduced markers of renal oxidative stress, such as proteinuria and kidney nitrites. Thus, a 3% BB diet may be capable of protecting the kidneys from oxidative damage in SHRSP, thereby reducing the magnitude of hypertension.

Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways.

Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individuals diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti‐cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP‐2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI‐3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF‐κB p65 protein to the nucleus. Cranberry PACs increased c‐jun and decreased c‐fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI‐3 kinase, NF‐κB and AP‐1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti‐cancer agents. J. Cell. Biochem. 111: 742–754, 2010.

Fruit and vegetable consumption: benefits and barriers.

Few people on Prince Edward Island meet the goal of consuming five or more servings of vegetables and fruit a day. The main objective of this qualitative study was to explore the perceptions of the nutritional benefits and barriers to vegetable and fruit intake among adult women in Prince Edward Island. Participants were 40 women aged 20-49, with or without children at home, who were or were not currently meeting the objective of eating five or more fruit and vegetable servings a day. In-home, one-on-one interviews were used for data collection. Thematic analysis was conducted on the transcribed interviews. Data were examined for trustworthiness in the context of credibility, transferability, and dependability. Most participants identified one or more benefits of eating fruit and vegetables; however, comments tended to be non-specific. The main barriers that participants identified were effort, lack of knowledge, sociopsychological and socioenvironmental factors, and availability. Internal influences, lif...

North American Cranberry (Vaccinium Macrocarpon) Stimulates Apoptotic Pathways in DU145 Human Prostate Cancer Cells In Vitro

Diets rich in fruits and vegetables have been shown to improve patient prognosis in a variety of cancers, a benefit partly derived from phytochemicals, many of which target cell death pathways in tumor cells. Cranberries (Vaccinium macrocarpon) are a phytochemical-rich fruit containing a variety of polyphenolic compounds. As flavonoids have been shown to induce apoptosis in human tumor cells, this study investigated the hypothesis that cranberry-mediated cytotoxicity in DU145 human prostate adenocarcinoma cells involves apoptosis. The results showed that induction of apoptosis in these cells occurred in response to treatment with whole cranberry extract and occurred through caspase-8 mediated cleavage of Bid protein to truncated Bid resulting in cytochrome-C release from the mitochondria. Subsequent activation of caspase-9 ultimately resulted in cell death as characterized by DNA fragmentation. Increased Par-4 protein expression was observed, and this is suggested to be at least partly responsible for caspase-8 activation. Proanthocyanidin-enriched and flavonol-enriched fractions of cranberry also increased caspase-8 and caspase-9 activity, suggesting that these compounds play a possible role in apoptosis induction. These findings indicate that cranberry phytochemicals can induce apoptosis in prostate cancer cells in vitro, and these findings further establish the potential value of cranberry phytochemicals as possible agents against prostate cancer.

Cranberries and wild blueberries treated with gastrointestinal enzymes positively modify glutathione mechanisms in Caco-2 cells in vitro.

Beneficial health effects of cranberries (CBs) and wild blueberries (BBs), such as reduced levels of oxidative stress, have been demonstrated in feeding studies. These Vaccinium berries contain high levels of flavonoids; however, the bioavailability of flavonoids is generally low. We investigated the in vitro effects of these berries on intestinal cells, focusing on mitigating oxidative stress and associated reactive oxygen species (ROS). First, we simulated the passage of CB and BB through the gastrointestinal (GI) tract by treating berry homogenates to a battery of digestive enzymes. Then, Caco-2 cells, a model of small intestine epithelial uptake, were exposed to these homogenates for 60 min. Using a cell-free assay, we found that the antioxidant activity in CB homogenates was not affected by these enzymes, but that BB homogenates treated with gut enzymes had 43% lower free-radical quenching activity (P < 0.05). However, both of the enzyme-treated homogenates were still able to counteract the ROS-generating ability of H2O2 added exogenously to Caco-2 cells. Berry homogenates also increased mitochondrial metabolic rates at 60 min posttreatment, as measured by MTT assays. Enzyme-treated CB (but not BB) homogenates increased the levels of reduced glutathione (GSH) relative to oxidized glutathione (GSSG), a critical indicator of the cellular redox state (P < 0.05). Our data suggest that CBs do not lose their antioxidant ability when passing through the GI tract, and specifically, digested CB may serve to enhance cytoprotective effects in intestinal cells by reducing potential damage caused by free radicals and ROS derived from other food sources.

Postnatal deficiencies of zinc and taurine alter electroretinograms, oscillatory potentials and morphology of the rat retina

The study objective was to evaluate the retinal response to deficiencies of zinc and taurine present throughout the period of postnatal retinal development. At parturition, Sprague-Dawley dams were assigned to one of four treatments in a 2 × 2 factorial design with two levels of zinc (4.5 and 50 μg/g) and two levels of taurine (0 and 2 μmol/g). Guanidinoethyl sulfonate, a taurine transport inhibitor, was added to the drinking water of the rats receiving 0 μmol/g taurine. Male pups (n = 10) were weaned on to their respective diets at postnatal day 22. Dark adapted electroretinograms and oscillatory potentials (OP) were recorded in the pups at 48-57 days of age. At maximal light intensity, the amplitudes of the a- and b-waves were depressed by deficiency of either nutrient, but the influence of combining these treatments was less than additive; the same pattern was evident for Vmax, the maximum amplitude obtained when the b-wave was plotted as a function of light intensity. This type of interaction was also evident for the amplitudes of OP1, OP3 and OP4. Zinc deficiency independently decreased the amplitude and increased the latency of OP5, and increased the latencies of OP3 and OP4. Light and transmitting electron microscopic examination revealed the most pronounced retinal degeneration in the rats deficient in both zinc and taurine. Tibia zinc and liver taurine concentrations provide evidence that these nutrients also interact in other tissues. The findings of this study demonstrate retinal damage with deficiencies of zinc and taurine during postnatal life. These nutrients interact in at least some of their functions in the retina through an as yet unidentified mechanism.

Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production

Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8) of male spontaneously hypertensive rats were fed one of four AIN ‘93G-based diets for 8 weeks: Control (CON); 3% freeze-dried wild blueberry (BB); 1% probiotic bacteria (PRO); or 3% BB + 1% PRO (BB+PRO). Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2-isoprostanes), nitric oxide synthesis (nitrites), and polyphenol metabolism (hippuric acid). Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046), with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035). Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220), again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185). Diet had a significant main effect on hippuric acid excretion (p<0.0001), with 2- and ~1.5-fold higher levels at weeks 4 and 8, respectively, in the BB and BB+PRO vs. PRO and CON groups. Diet did not have a significant main effect on F2-isoprostane (p = 0.159) or nitrite excretion (p = 0.670). Our findings show that adding probiotics to a blueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric acid.

What Do Adults in Prince Edward Island: Know About Nutrition?

Purpose: To assess adults’ knowledge of dietary recommendations, food sources of key nutrients, food choices, and diet-disease relationships. Methods: A previously validated survey, designed to assess nutrition knowledge, was adapted for use in Prince Edward Island and mailed to a random sample of 3,500 adults (aged 18 to 74). Dillmans Total Design Method was followed and a response rate of 26.4% achieved. Mean scores and 95% confidence intervals (CIs) were calculated for the overall survey and for each section. Demographic variations were assessed by univariate analysis. Results: Of an overall possible score of 110 points, the mean score with 95% CI was 71.0 (70.1, 71.9). Respondents scored higher on the sections on dietary recommendations, food sources, and food choices than diet-disease relationships. Demographic differences existed in gender, age, education, and income. Findings suggest that adults have good general knowledge of dietary recommendations, but lack knowledge about how to make healthier ...Purpose: To assess adults’ knowledge of dietary recommendations, food sources of key nutrients, food choices, and diet-disease relationships. Methods: A previously validated survey, designed to assess nutrition knowledge, was adapted for use in Prince Edward Island and mailed to a random sample of 3,500 adults (aged 18 to 74). Dillmans Total Design Method was followed and a response rate of 26.4% achieved. Mean scores and 95% confidence intervals (CIs) were calculated for the overall survey and for each section. Demographic variations were assessed by univariate analysis. Results: Of an overall possible score of 110 points, the mean score with 95% CI was 71.0 (70.1, 71.9). Respondents scored higher on the sections on dietary recommendations, food sources, and food choices than diet-disease relationships. Demographic differences existed in gender, age, education, and income. Findings suggest that adults have good general knowledge of dietary recommendations, but lack knowledge about how to make healthier ...