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Pharmacokinetics of Caffeine in the Lens Capsule/Epithelium After Peroral Intake: A Pilot Randomized Controlled Study.
Kronschläger, M, Stimpfl, T, Ruiß, M, Hirnschall, N, Leisser, C, Findl, O
Investigative ophthalmology & visual science. 2018;(5):1855-1860
Abstract
PURPOSE To determine the pharmacokinetics of perorally administered caffeine, a widely consumed and potent dietary antioxidant, in the anterior lens capsule and lens epithelial cells, a crucial cell monolayer for cataract development. METHODS Bilateral cataract patients were scheduled for cataract surgery with a caffeine abstinence of 1 week before surgery of each eye. At the day of surgery of the second eye patients were administered no drink (0-mg group) or coffee with 60-, 120-, or 180-mg caffeine. After capsulorhexis the lens capsule including lens epithelial cells was transferred to a test tube for analysis of caffeine concentration by gas chromatography-mass spectrometry (GC-MS/MS). RESULTS Coffee consumption significantly (P < 0.05) increased caffeine levels of the lens capsule/epithelium in the 60-, 120-, and 180-mg group. Caffeine concentrations (caffeine ng/lens capsule/epithelium) measured as difference between 1st and 2nd eye were -0.52 ± 1.16 (0-mg group, n = 7), 1.88 ± 2.02 (60-mg group, n = 8), 2.09 ± 0.67 (120-mg group, n = 9), and 3.68 ± 1.86 (180-mg group, n = 9). The increase constant of caffeine in a linear regression model was estimated as a 95% CI 0.02 ± 0.0046 (degrees of freedom; 25; r = 0.85). CONCLUSIONS Peroral intake of coffee significantly increased caffeine concentrations in the lens capsule and lens epithelial cells in a dose-dependent manner. This information is important for further investigations on preventing cataract.
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Effects of a Mediterranean Diet Intervention on Anti- and Pro-Inflammatory Eicosanoids, Epithelial Proliferation, and Nuclear Morphology in Biopsies of Normal Colon Tissue.
Djuric, Z, Turgeon, DK, Ren, J, Neilson, A, Plegue, M, Waters, IG, Chan, A, Askew, LM, Ruffin, MT, Sen, A, et al
Nutrition and cancer. 2015;(5):721-9
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Abstract
This randomized trial evaluated the effects of intervention with either a Healthy Eating or a Mediterranean diet on colon biomarkers in 120 healthy individuals at increased colon cancer risk. The hypothesis was that eicosanoids and markers of proliferation would be favorably affected by the Mediterranean diet. Colon epithelial biopsy tissues and blood samples were obtained at baseline and after 6 mo of intervention. Colonic eicosanoid concentrations were evaluated by HPLC-MS-MS, and measures of epithelial proliferation and nuclear morphology were evaluated by image analysis of biopsy sections. There was little change in proinflammatory eicosanoids and in plasma cytokine concentrations with either dietary intervention. There was, however, a 50% increase in colonic prostaglandin E3 (PGE3), which is formed from eicosapentanoic acid, in the Mediterranean arm. Unlike PGE2, PGE3, was not significantly affected by regular use of non-steroidal anti-inflammatory drugs at baseline, and normal weight subjects had significantly higher colon PGE3 than overweight or obese subjects. Increased proliferation in the colon at baseline, by Ki67 labeling, was associated with morphological features that defined smaller nuclei in the epithelial cells, lower colon leukotriene concentrations and higher plasma cytokine concentrations. Dietary intervention had little effect on measures of epithelial proliferation or of nuclear morphology. The increase in PGE3 with a Mediterranean diet indicates that in normal colon, diet might affect protective pathways to a greater extent than proinflammatory and proliferative pathways. Hence, biomarkers from cancer models might not be relevant in a true prevention setting.
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Expression of p53 and caspase-8 in lens epithelial cells of diabetic cataract.
Lim, SA, Joo, CK, Kim, MS, Chung, SK
Journal of cataract and refractive surgery. 2014;(7):1102-8
Abstract
PURPOSE To determine expression of apoptotic factors p53 and caspase-8 in human lens epithelial cells (LECs) of cataract patients with or without diabetic retinopathy (DR), the duration of diabetes mellitus (DM), and the level of glycated hemoglobin (hemoglobin A1c [HbA1c]). SETTING St. Mary's Hospital, Catholic University of Korea, Seoul, South Korea. DESIGN Randomized prospective study. METHODS The LECs were isolated during cataract surgery. The isolated samples were classified into 4 groups as follows: patients without DM (Group 1), patients with DM but not DR (Group 2), diabetic patients with nonproliferative DR (Group 3), and diabetic patients with proliferative DR (Group 4). To explore the mechanism of apoptosis, the expressions of p53 and caspase-8 were measured by immunohistochemical staining and compared with the data according to the duration of DM, HbA1c levels, and severity of DR. RESULTS All groups comprised 15 eyes. The expressions of P53 and caspase-8 were higher in Groups 2, 3, and 4 than in Group 1 (P<.001). The expressions were statistically significantly increased with a longer duration of DM, higher HbA1c levels, and advanced DR. CONCLUSIONS The expressions of P53 and caspase-8 were strong in patients with DM and advanced DR. Knowledge of these relationships may lead to a better understanding of the development of diabetic cataract. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.
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Changes in apoptosis factors in lens epithelial cells of cataract patients with diabetes mellitus.
Kim, B, Kim, SY, Chung, SK
Journal of cataract and refractive surgery. 2012;(8):1376-81
Abstract
PURPOSE To determine and compare the expression of apoptotic factors Bax and Bcl-2 in lens epithelial cells (LECs) of cataract patients with and without diabetic retinopathy (DR), the duration of diabetes mellitus (DM), and the glycated hemoglobin (HbA1c) level. SETTING St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. DESIGN Randomized prospective study. METHODS Patients were classified into 3 groups as follows: patients without DM (Group 1), patients with DM but without DR (Group 2), and diabetic patients with DR (Group 3). Data on the duration of DM and the HbA1c levels were recorded. The anterior capsule was obtained from the patients after cataract surgery, and immunohistochemical stains of Bax and Bcl-2 were performed. The stained anterior capsules were analyzed by reactivity scoring. RESULTS Each group comprised 20 eyes. There was a statistically significant increase in Bax expression in all groups (P<.001). The Bcl-2 expression increased more in Group 2 and Group 3 than in Group 1, although the difference was not significant (P=.615). With a longer duration of DM and higher HbA1c level, Bax expression significantly increased but Bcl-2 was weakly expressed. CONCLUSIONS The apoptosis in LECs increased in cataract patients with DM and with or without DR. Using this knowledge on the regulation of apoptosis will permit better identification of the factors involved in the etiology of diabetes and may result in new therapies for diabetic cataract. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.
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Dietary fiber decreases colonic epithelial cell proliferation and protein synthetic rates in human subjects.
Weerasooriya, V, Rennie, MJ, Anant, S, Alpers, DH, Patterson, BW, Klein, S
American journal of physiology. Endocrinology and metabolism. 2006;(6):E1104-8
Abstract
Although it has been proposed that high fiber consumption can prevent proliferative diseases of the colon, the clinical data to support this hypothesis have been inconsistent. To provide a more robust measure of the effects of fiber on colonic mucosal growth than previous studies, we evaluated both cell proliferation and colonic mucosal protein synthesis in nine healthy volunteers after they consumed a typical Western diet (<20 g fiber/day) or a Western diet supplemented with wheat bran (24 g/day) in a randomized crossover design. Biopsies taken from the sigmoid colon were used to assess mucosal proliferation by determining proliferating cell nuclear antigen (PCNA) in crypt cells and to assess mucosal protein synthetic rate using stable isotopically labeled leucine infusion. Fiber supplementation produced a 12% decrease in labeling index (%crypt cells stained with PCNA) (P < 0.001) and an 11% decrease in mucosal protein fractional synthetic rate (FSR; P < 0.05). Moreover, mucosal protein FSR correlated directly with labeling index (r2= 0.22, P < 0.05). These data demonstrate that increased wheat bran consumption decreases colonic mucosal proliferation and support the potential importance of dietary fiber in preventing proliferative diseases of the colon.
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Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D.
Holt, PR, Arber, N, Halmos, B, Forde, K, Kissileff, H, McGlynn, KA, Moss, SF, Kurihara, N, Fan, K, Yang, K, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002;(1):113-9
Abstract
Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25-hydroxyvitamin D (25-OH D(3)). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)(2) D(3)], which interacts with nuclear vitamin D receptors in several organs. Until recently, the metabolism of 25-OH D(3) to 1,25-(OH)(2) D(3) was believed to occur only in the kidney, but more recent studies have shown that 25-OH D(3) conversion to 1,25-(OH)(2) D(3) can occur in other tissues. We examined the association between fasting levels of 25-OH D(3), 1,25-(OH)(2) D(3), and BsmI polymorphism of the vitamin D receptor (VDR) gene with indices of colonic epithelial cell proliferation and differentiation in a chemoprevention study, after giving vitamin D or calcium and taking rectal biopsies that were incubated with bromodeoxyuridine. Vitamin D receptor polymorphism was determined by genotyping of the 3' BsmI polymorphism in intron eight of the VDR gene. No significant changes in cell proliferation or in differentiation were found in subjects between study start and end. However, fasting serum levels of 25-OH D(3) showed a highly significant decrease with whole crypt labeling index and the size of the proliferative compartment (phi h). There was no correlation between serum levels of 1,25-(OH)(2) D(3) and the proliferative parameters. Calcium supplementation induced a significant effect upon the relationship between serum 25-OH D(3) and rectal epithelial cell labeling index and phi h when studied by covariance analysis without a relationship with 1,25-(OH)(2) D(3) levels. VDR genotype did not influence the effects of serum 25-OH D(3) or serum 1,25-(OH)(2) D(3) levels upon proliferation. These data suggest that there might be a local effect of 25-OH D(3) on colonic epithelial cells through conversion of 25-OH D(3) to 1,25-(OH)(2) D(3). Subsequent studies have demonstrated the presence of 1alpha-hydroxylase mRNA in normal colorectal epithelium and in colorectal cancer. Thus, vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation and may explain some of the discrepancies found previously in studies that examine the direct role of calcium on the colorectal epithelium.
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Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients.
Rozen, P, Lubin, F, Papo, N, Knaani, J, Farbstein, H, Farbstein, M, Zajicek, G
Cancer. 2001;(4):833-40
Abstract
BACKGROUND Calcium supplements to the western-style diet may reduce the risk for colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as a biomarker of response to intervention, the authors evaluated the effects of 1-year calcium supplementation in adenoma patients and its possible interactions with the patients' dietary and lifestyle habits. METHODS Consenting adenoma patients, without a family history of colorectal neoplasia, were randomly selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no treatment. All had their long-term dietary and lifestyle habits assessed and their REP labeling index (LI) evaluated before and at end of follow-up. The change in LI was compared between groups, and statistical associations were examined between mean nutrient consumption and treatment effect and between lifestyle and treatment effect. RESULTS Fifty-two adenoma patients (33 treated and 19 untreated) completed intervention and follow-up. There were no significant differences between study groups in age, weight, cigarette smoking, or medication use. The LI decreased in 58% of calcium-intervened patients and in only 26% of nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58 to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate, fiber, or fluid intake each interacted with the calcium supplementation to decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS Long-term calcium supplements significantly suppressed REP in adenoma patients, and long-term dietary habits contributed to this effect. Patient diet should be assessed when researchers use REP as a biomarker in calcium chemoprevention studies. Study results indicated that relevant dietary counseling may be useful in addition to calcium supplements in persons at increased risk for colorectal neoplasia.