Angiogenesis and Inflammation Signaling Are Targets of Beer Polyphenols on Vascular Cells

Emerging evidence indicates that chronic inflammation and oxidative stress cluster together with angiogenic imbalance in a wide range of pathologies. In general, natural polyphenols present health‐protective properties, which are likely attributed to their effect on oxidative stress and inflammation. Hops used in beer production are a source of polyphenols such as xanthohumol (XN), and its metabolites isoxanthohumol (IXN) and phytoestrogen 8‐prenylnaringenin (8PN). Our study aimed to evaluate XN, IXN, and 8PN effects on angiogenesis and inflammation processes. Opposite in vitro effects were observed between 8PN, stimulating endothelial and smooth muscle cell (SMC) growth, motility, invasion and capillary‐like structures formation, and XN and IXN, which inhibited them. Mouse matrigel plug and rat skin wound‐healing assays confirmed that XN and IXN treatments reduced vessel number as well as serum macrophage enzymatic activity, whereas 8PN increased blood vessels formation in both assays and enzyme activity in the wound‐healing assay. A similar profile was found for serum inflammatory interleukin‐1β quantification, in the wound‐healing assay. Our data indicate that whereas 8PN stimulates angiogenesis, XN and IXN manifested anti‐angiogenic and anti‐inflammatory effects in identical conditions. These findings suggest that the effects observed for individual compounds on vascular wall cells must be carefully taken into account, as these polyphenols are metabolized after in vivo administration. The modulation of SMC proliferation and migration is also of special relevance, given the role of these cells in many pathological conditions. Furthermore, these results may provide clues for developing useful therapeutic agents against inflammation‐ and angiogenesis‐associated pathologies. J. Cell. Biochem. 111: 1270–1279, 2010. © 2010 Wiley‐Liss, Inc.     

Replacing sweetened caloric beverages with drinking water is associated with lower energy intake

Objective: Reduced intake of sweetened caloric beverages (SCBs) is recommended to lower total energy intake. Replacing SCBs with non‐caloric diet beverages does not automatically lower energy intake, however. Compensatory increases in other food or beverages reportedly negate benefits of diet beverages. The purpose of this study was to evaluate drinking water as an alternative to SCBs. Research Methods and Procedures: Secondary analysis of data from the Stanford A TO Z intervention evaluated change in beverage pattern and total energy intake in 118 overweight women (25 to 50 years) who regularly consumed SCBs (>12 ounces/d) at baseline. At baseline and 2, 6, and 12 months, mean daily beverage intake (SCBs, drinking water, non‐caloric diet beverages, and nutritious caloric beverages), food composition (macronutrient, water, and fiber content), and total energy intake were estimated using three 24‐hour diet recalls. Beverage intake was expressed in relative terms (percentage of beverages). Results: In fixed effects models that controlled for total beverage intake, non‐caloric and nutritious caloric beverage intake (percentage of beverages), food composition, and energy expenditure [metabolic equivalent (MET)], replacing SCBs with drinking water was associated with significant decreases in total energy intake that were sustained over time. The caloric deficit attributable to replacing SCBs with water was not negated by compensatory increases in other food or beverages. Replacing all SCBs with drinking water was associated with a predicted mean decrease in total energy of 200 kcal/d over 12 months. Discussion: The results suggest that replacing SCBs with drinking water can help lower total energy intake in overweight consumers of SCBs motivated to diet.     

Effect of xanthohumol and isoxanthohumol on 3T3-L1 cell apoptosis and adipogenesis

Xanthohumol (XN), the chalcone from beer hops has several biological activities. XN has been shown to induce apoptosis in cancer cells and also has been reported to be involved in lipid metabolism. Based on these studies and our previous work with natural compounds, we hypothesized that XN and its isomeric flavanone, isoxanthohumol (IXN), would induce apoptosis in adipocytes through the mitochondrial pathway and would inhibit maturation of preadipocytes. Adipocytes were treated with various concentrations of XN or IXN. In mature adipocytes both XN and IXN decreased viability, increased apoptosis and increased ROS production, XN being more effective. Furthermore, the antioxidants ascorbic acid and 2-mercaptoethanol prevented XN and IXN-induced ROS generation and apoptosis. Immunoblotting analysis showed an increase in the levels of cytoplasmic cytochrome c and cleaved poly (ADP-ribose) polymerase (PARP) by XN and IXN. Concomitantly, we observed activation of the effectors caspase-3/7. In maturing preadipocytes both XN and IXN were effective in reducing lipid content, XN being more potent. Moreover, the major adipocyte marker proteins such as PPARγ, C/EBPα, and aP2 decreased after treatment with XN during the maturation period and that of DGAT1 decreased after treatment with XN and IXN. Taken together, our data indicate that both XN and IXN inhibit differentiation of preadipocytes, and induce apoptosis in mature adipocytes, but XN is more potent. Drs. Baile and Della-Fera are shareholders and serve on the Board of Directors of AptoTec, Inc.     

Xanthohumol inhibits inflammatory factor production and angiogenesis in breast cancer xenografts

Xanthohumol (XN), a natural polyphenol present in beer, is known to exert anti-cancer effects. However, its precise mechanisms are not yet clearly defined. The aim of this study was to investigate the effect of oral administration of XN in breast cancer xenografts in nude mice. Proliferation and apoptosis were first examined in MCF7 cell cultures after incubation with XN by trypan blue exclusion assay, [3H]-thymidine incorporation, KI67 immunostaining and TUNEL. Morphological and histological characteristics of tumours from XN-treated or control (vehicle-treated) mice were compared. Immunohistochemistry for proliferative, inflammatory and endothelial cell markers was performed and activation of nuclear factor kappa B (NFkappaB) pathway was assessed by ELISA. In vitro MCF7 cell proliferation decreased in a dose-dependent manner. Oral administration of XN to nude mice inoculated with MCF7 cells resulted in central necrosis within tumours, reduced inflammatory cell number, focal proliferation areas, increased percentage of apoptotic cells and decreased microvessel density. Anti-angiogenic effects of XN were further confirmed by immunoblotting for factor VIII expression in XN-treated tumours as compared to controls. Decreased immunostaining for NFkappaB, phosphorylated-inhibitor of kappa B and interleukin-1beta were also observed as well as a significant decrease in NFkappaB activity to 60% of control values. These novel findings indicate that XN is able to target both breast cancer and host cells, namely inflammatory and endothelial cells, suggesting its potential use as a double-edge anti-cancer agent.     

Alcohol Consumption and Metabolic Syndrome: Does the Type of Beverage Matter?

Objective: To examine the association between total and beverage‐specific alcohol consumption and the prevalence odds of metabolic syndrome (MS). Research Methods and Procedures: Using a cross‐sectional design, we studied 4510 white participants of the National Heart, Lung, and Blood Institute Family Heart Study. We used generalized estimating equations adjusting for age, education, risk group, smoking, physical activity, diabetes mellitus, coronary heart disease, energy intake, energy from fat, fruits, and vegetables, dietary cholesterol, dietary fiber, and use of multivitamins to estimate the prevalence odds of MS by alcohol intake. Results: Compared with never‐drinkers, multivariate odds ratios (95% confidence interval) for MS were 1.12 (0.85 to 1.49), 0.68 (0.36 to 1.28), 0.72 (0.50 to 1.03), 0.66 (0.44 to 0.99), and 0.80 (0.55 to 1.16) among men who were former drinkers and who were current drinkers of 0.1 to 2.5, 2.6 to 12.0, 12.1 to 24.0, and >24.0 g/d of alcohol, respectively (p for linear trend 0.018). Corresponding values for women were 0.86 (0.69 to 1.09), 0.80 (0.43 to 1.34), 0.47 (0.33 to 0.66), 0.47 (0.30 to 0.74), and 0.39 (0.21 to 0.74), respectively (p for trend < 0.0001). The reduced prevalence odds of MS was observed across all beverage types: compared with never‐drinkers, multivariate adjusted odds ratios (95% confidence interval) of MS were 0.32 (0.14 to 0.73), 0.42 (0.23 to 0.77), 0.57 (0.30 to 1.09), and 0.56 (0.36 to 0.88) for subjects who consumed >7 drinks/wk of wine only, beer only, spirits only, and more than one type of beverage, respectively. Discussion: Our data indicate that alcohol consumption is associated with a lower prevalence of MS irrespective of the type of beverage consumed. Prospective studies are needed to confirm these findings and to assess the influence of drinking patterns on the alcohol‐MS association.     

Beer increases plasma antioxidant capacity in humans

The positive association of a moderate intake of alcoholic beverages with a low risk for cardiovascular disease, in addition to ethanol itself, may be linked to their polyphenol content. This article describes the effect of acute ingestion of beer, dealcoholized beer, and ethanol (4.5% v/v) on the total plasma antioxidant status of subjects, and the change in the high performance liquid chromatography profile of some selected phenolic acids (caffeic, sinapic, syringic, and vanillic acids) in 14 healthy humans. Plasma was collected at various times: before (T0), 1 hour after (T1), and 2 hours after (T2) drinking. The study is part of a larger research planned to identify both the impact of brewing on minor components potentially present in beer and their metabolic fate in humans. Beer was able to induce a significant (P < 0.05) increase in plasma antioxidant capacity at T1 (mean +/- SD: T0 1,353 +/- 320 microM; T1 1,578 +/- 282 microM), returning close to basal values at T2. All phenolic acids measured in plasma tended to increase after beer intake (20% at T1, 40% at T2). Syringic and sinapic acid reached statistical significance (P < 0.05 by one-way analysis of variance-Fisher's test) at T1 and T2, respectively. Plasma metabolic parameters (glucose, total cholesterol, triglycerides, and uric acid) and plasma antioxidants (alpha-tocopherol and glutathione) remained unchanged. Ethanol removal impaired the absorption of phenolic acids, which did not change over the time of the experiment, accounting for the low (and not statistically significant) increase in plasma antioxidant capacity after dealcoholized beer drinking. Ethanol alone did not affect plasma antioxidant capacity or any of the antioxidant and metabolic parameters measured.     

Role of PPARgamma, a nuclear hormone receptor in neuroprotection

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. PPAR-alpha is involved in wound healing, stimulation of lipid and folic acid catabolism, inflammation control, inhibition of ureagenesis and peroxisome proliferation. The PPARgamma/delta is involved wound healing, cell proliferation, embryo implantation, adipocyte differentiation, myelination alteration and apoptosis. The PPARgamma is involved in fat, lipid and calorie utilization, sugar control, inflammation control and macrophage (MQ) matutation. Homocysteine (Hcy) binds to nuclear peroxisome proliferator activated receptor. Increase in PPAR expression decreases the level of nitrotyrosine and increases endothelial nitric oxide concentration, decreases metalloproteinase activity and expression as well as elastinolysis and reverses Hcy-mediated vascular dysfunction. The PPARgamma initially recognized as a regulator of adipocyte development has become a potential therapeutic target for the treatment of diverse disorders. In addition, the activation of PPARgamma receptor ameliorates neurodegenerative disease. This review focuses on the recent knowledge of PPARgamma in neuroprotection and deals with the mechanism of neuroprotection of central nervous system disorder by PPARgamma.     

Self-reported sugar-sweetened beverage intake among college students

Objective: To characterize sugar‐sweetened beverage intake of college students. Research Methods and Procedures: Undergraduates in an urban southern community campus were surveyed anonymously about sugared beverage consumption (soda, fruit drinks, energy drinks, sports drinks, sweet ice tea) in the past month. Results: Two hundred sixty‐five undergraduates responded (66% women, 46% minority, 100% of volunteers solicited). Most students (95%) reported sugared beverage intake in the past month, and 65% reported daily intake. Men were more likely than women to report daily intake (74% vs. 61%, p = 0.035). Soda was the most common sugar‐sweetened beverage. Black undergraduates reported higher sugared beverage intake than whites (p = 0.02), with 91% of blacks reporting sugar‐sweetened fruit drink intake in the past month and 50% reporting daily consumption. Mean estimated caloric intake from combined types of sugar‐sweetened beverages was significantly higher among black students than whites, 796 ± 941 vs. 397 ± 396 kcal/d (p = 0.0003); the primary source of sugar‐sweetened beverage calories among blacks was sugared fruit drinks (556 ± 918 kcal/d). Younger undergraduates reported significantly higher intake than older students (p = 0.025). Discussion: Self‐reported sugar‐sweetened beverage consumption among undergraduates is substantial and likely contributes considerable non‐nutritive calories, which may contribute to weight gain. Black undergraduates may be particularly vulnerable due to higher sugared beverage intake. Obesity prevention interventions targeting reductions in sugar‐sweetened beverages in this population merit consideration.     

Drinking water is associated with weight loss in overweight dieting women independent of diet and activity

Background: Data from short‐term experiments suggest that drinking water may promote weight loss by lowering total energy intake and/or altering metabolism. The long‐term effects of drinking water on change in body weight and composition are unknown, however. Objective: This study tested for associations between absolute and relative increases in drinking water and weight loss over 12 months. Methods and Procedures: Secondary analyses were conducted on data from the Stanford A TO Z weight loss intervention on 173 premenopausal overweight women (aged 25–50 years) who reported <1 l/day drinking water at baseline. Diet, physical activity, body weight, percent body fat (dual‐energy X‐ray absorptiometry), and waist circumference were assessed at baseline, 2, 6, and 12 months. At each time point, mean daily intakes of drinking water, noncaloric, unsweetened caloric (e.g., 100% fruit juice, milk) and sweetened caloric beverages, and food energy and nutrients were estimated using three unannounced 24‐h diet recalls. Beverage intake was expressed in absolute (g) and relative terms (% of beverages). Mixed models were used to test for effects of absolute and relative increases in drinking water on changes in weight and body composition, controlling for baseline status, diet group, and changes in other beverage intake, the amount and composition of foods consumed and physical activity. Results: Absolute and relative increases in drinking water were associated with significant loss of body weight and fat over time, independent of covariates. Discussion: The results suggest that drinking water may promote weight loss in overweight dieting women.     

Effects of recovery beverages on glycogen restoration and endurance exercise performance

The restorative capacities of a high carbohydrate-protein (CHO-PRO) beverage containing electrolytes and a traditional 6% carbohydrate-electrolyte sports beverage (SB) were assessed after glycogen-depleting exercise. Postexercise ingestion of the CHO-PRO beverage, in comparison with the SB, resulted in a 55% greater time to exhaustion during a subsequent exercise bout at 85% maximum oxygen consumption (VO(2)max). The greater recovery after the intake of the CHO-PRO beverage could be because of a greater rate of muscle glycogen storage. Therefore, a second study was designed to investigate the effects of after exercise CHO-PRO and SB supplements on muscle glycogen restoration. Eight endurance-trained cyclists (VO(2)max = 62.1 +/- 2.2 ml.kg(-1) body wt.min(-1)) performed 2 trials consisting of a 2-hour glycogen-depletion ride at 65-75% VO(2)max. Carbohydrate-protein (355 ml; approximately 0.8 g carbohydrate (CHO).kg(-1) body wt and approximately 0.2 g protein.kg(-1) body wt) or SB (355 ml; approximately 0.3 g CHO.kg(-1) body wt) was provided immediately and 2 hours after exercise. Trials were randomized and separated by 7-15 days. Ingestion of the CHO-PRO beverage resulted in a 17% greater plasma glucose response, a 92% greater insulin response, and a 128% greater storage of muscle glycogen (159 +/- 18 and 69 +/- 32 micromol.g(-1) dry weight for CHO-PRO and SB, respectively) compared with the SB (p < 0.05). These findings indicate that the rate of recovery is coupled with the rate of muscle glycogen replenishment and suggest that recovery supplements should be consumed to optimize muscle glycogen synthesis as well as fluid replacement.     

Delayed cutaneous wound closure in HO‐2 deficient mice despite normal HO‐1 expression

Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO‐1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal wound healing in HO‐2 deficient mice is impaired with exorbitant inflammation and absence of HO‐1 expression. This study addresses the role of HO‐2 in cutaneous excisional wound healing using HO‐2 knockout (KO) mice. Here, we show that HO‐2 deficiency also delays cutaneous wound closure compared to WT controls. In addition, we detected reduced collagen deposition and vessel density in the wounds of HO‐2 KO mice compared to WT controls. Surprisingly, wound closure in HO‐2 KO mice was accompanied by an inflammatory response comparable to WT mice. HO‐1 induction in HO‐2 deficient skin was also similar to WT controls and may explain this protection against exaggerated cutaneous inflammation but not the delayed wound closure. Proliferation and myofibroblast differentiation were similar in both two genotypes. Next, we screened for candidate genes to explain the observed delayed wound closure, and detected delayed gene and protein expression profiles of the chemokine (C‐X‐C) ligand‐11 (CXCL‐11) in wounds of HO‐2 KO mice. Abnormal regulation of CXCL‐11 has been linked to delayed wound healing and disturbed angiogenesis. However, whether aberrant CXCL‐11 expression in HO‐2 KO mice is caused by or is causing delayed wound healing needs to be further investigated.     

Proteome analysis reveals antiangiogenic environments in chronic wounds of diabetes mellitus type 2 patients

In contrast to normal healing wounds, chronic wounds commonly show disturbances in proteins regulating wound healing processes, particularly those involved in cell proliferation and protein degradation. Multidimensional protein identification technology MS/MS was conducted to investigate and compare the protein composition of chronic diabetic foot exudates to exudates from split‐skin donor sites of burn victims otherwise healthy. Spectral counting revealed 188 proteins differentially expressed (more than twofold and p‐value <0.05) in chronic wounds. Most were involved in biological processes including inflammation, angiogenesis, and cell mortality. Increased expression of the inflammatory response stimulating S100 proteins, predominantly S100A8 and S100A9 (almost tenfold), was identified. Matrix metalloproteinases (MMPs) MMP1, MMP2, and MMP8 were identified to be elevated in chronic wounds with significant impact on collagen degradation and tissue destruction. Further, proteins with antiangiogenic properties were found at higher expression levels in chronic wounds. Reduced angiogenesis leads to drastic shortage in nutrition supply and causes increased cell death, demonstrated by Annexin A5 exclusively found in chronic wound exudates. However, excessive nucleic and cytosolic material infers cell death occurring not only by apoptosis but also by necrosis. In conclusion, mass spectrometric investigation of exudates from chronic wounds demonstrated dramatic impairment in wound repair with excessive inflammation, antiangiogenic environment, and accelerated cell death.     

Scratch wound closure of C2C12 mouse myoblasts is enhanced by human platelet lysate

The effect of a platelet lysate (PL) on muscle wound healing, based on in vitro scratch wound of C2C12 mouse myoblasts, has been investigated. Cell viability assays show that PL induced an increase in cell proliferation at concentrations of 1-20%, but was slightly cytotoxic at 100%. PL promoted wound closure after scratch wounding of cell monolayers. The p38 inhibitor SB203580 and the PI3K inhibitor, wortmannin, decreased the PL effect, whereas the ERK inhibitor, PD98059, did not. Transwell migration of cells was also increased by PL, and although SB203580 abrogated this effect, wortmannin reduced it, whereas PD98059 was ineffective. Western blot analyses of scratch wounded cells showed activation of AKT and p38, while in the presence of PL there was a faster and sustained activation of AKT and p38 (up to 6 h), and a transient activation of ERK1/2. Taken together, the data show that PL promotes C2C12 wound healing by enhancing cell proliferation and motility.     

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study

BackgroundThere is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders.MethodsTwenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type.ResultsWe observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10–19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12–15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90).ConclusionsWhether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.     

Nitric oxide and wound repair: role of cytokines?

Wound healing involves platelets, inflammatory cells, fibroblasts, and epithelial cells. All of these cell types are capable of producing nitric oxide (NO), either constitutively or in response to inflammatory cytokines, through the activity of nitric oxide synthases (NOSs): eNOS (NOS3; endothelial NOS) and iNOS (NOS2; inducible NOS), respectively. Indeed, pharmacological inhibition or gene deletion of these enzymes impairs wound healing. The wound healing mechanisms that are triggered by NO appear to be diverse, involving inflammation, angiogenesis, and cell proliferation. All of these processes are controlled by defined cytokine cascades; in many cases, NO appears to modulate these cytokines. In this review, we summarize the history and present state of research on the role of NO in wound healing within the framework of modulation of cytokines.     

Inhibitory effects of beer on heterocyclic amine-induced mutagenesis and PhIP-induced aberrant crypt foci in rat colon

Anti-mutagenic and anti-carcinogenic effects of beer on heterocyclic amine (HCA)-induced carcinogenesis were studied in vitro and in vivo. Four commercial beers (two pilsner-type, black, and stout) showed inhibitory effects against five HCAs, 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), in the Ames assay using Salmonella typhimurium TA98 in the presence of rat S9 mix. The inhibitory effects of dark-colored beers (stout and black beer) were greater than those of pilsner-type beers. Dark-colored beers suppressed CYP1A2 activity in a dose-dependent manner, suggesting that inhibition of HCA activation is partly responsible for their strong anti-mutagenic effects. Anti-mutagenic effects were also observed when the pooled human S9 mix or activated IQ was used in the assay. The micronucleus test using Chinese hamster lung CHL/IU cells showed that the addition of freeze-dried samples of pilsner-type and stout beer to the culture medium significantly reduced the number of cells with micronuclei induced with PhIP or Trp-P-2. Single-cell gel electrophoresis assay (comet assay) revealed that oral ingestion of pilsner-type and stout beers for 1 week significantly inhibited DNA damage in the liver cells of male ICR mice exposed to MeIQx (13 mg/kg, i.p.). A decrease in the formation of DNA adducts was also observed using a 32P-postlabeling method. Male Fischer 344 rats orally received PhIP (75 mg/kg, five times a week for 2 weeks) and aberrant crypt foci (ACF) formation in the colon was analyzed after 5 weeks. The number of ACF was significantly reduced in rats fed a diet containing freeze-dried beer. These results suggest that beer inhibits the genotoxic effects of HCAs and may reduce the risk of carcinogenesis caused by food borne carcinogens.     

In vitro glucuronidation of xanthohumol, a flavonoid in hop and beer, by rat and human liver microsomes

Xanthohumol (XN) is the major prenylated flavonoid of hop plants and has been detected in beer. Previous studies suggest a variety of potential cancer chemopreventive effects for XN, but there is no information on its metabolism. The aim of this study was to investigate in vitro glucuronidation of XN by rat and human liver microsomes. Using high-performance liquid chromatography, two major glucuronides of XN were found with either rat or human liver microsomes. Release of the aglycone by enzymatic hydrolysis with beta-glucuronidase followed by liquid chromatography/mass spectrometry and nuclear magnetic resonance analysis revealed that these were C-4' and C-4 monoglucuronides of XN.     

Blood values of adult captive cheetahs (Acinonyx jubatus) fed either supplemented beef or whole rabbit carcasses

This study evaluated nutrient intake and relevant blood parameters of 14 captive cheetahs, randomly assigned to a meat‐only diet (supplemented beef, SB) or a whole prey diet (whole rabbit, WR) for 4 weeks each. Despite a higher food intake, daily metabolizable energy intake was lower when fed WR (308 kJ BW^?1) compared with SB (347 kJ BW^?1) (P = 0.002). The ratio of protein to fat was markedly lower for WR (2.3:1) compared with SB (8.8:1), which was reflected in higher serum urea levels when fed SB (P = 0.033), and a tendency for elevated cholesterol levels when fed WR (P = 0.055). Taurine intake of cheetahs fed WR was low (0.06% on DM basis); however, analytical error during taurine analysis cannot be ruled out. Feeding WR resulted in a well‐balanced mineral intake, in contrast to SB. The latter provided a low calcium:phosphorus ratio (1:2.3), thereby increasing the risk of metabolic bone disease. The high zinc content of SB (200 mg/kg DM), compared with WR (94 mg/kg DM), was reflected in higher serum zinc concentrations (P = 0.011). Feeding WR resulted in an increase in serum vitamin A (P = 0.011). Therefore, the risk of hypervitaminosis A in captive cheetahs when fed WR exclusively on a long‐term basis should be evaluated. Our findings suggest that neither diet is likely to provide appropriate nutrition to captive cheetahs when fed exclusively. Zoo Biol 31:629‐641, 2012. © 2011 Wiley Periodicals, Inc.     

The role of nuclear hormone receptors in cutaneous wound repair

The cutaneous wound repair process involves balancing a dynamic series of events ranging from inflammation, oxidative stress, cell migration, proliferation, survival and differentiation. A complex series of secreted trophic factors, cytokines, surface and intracellular proteins are expressed in a temporospatial manner to restore skin integrity after wounding. Impaired initiation, maintenance or termination of the tissue repair processes can lead to perturbed healing, necrosis, fibrosis or even cancer. Nuclear hormone receptors (NHRs) in the cutaneous environment regulate tissue repair processes such as fibroplasia and angiogenesis. Defects in functional NHRs and their ligands are associated with the clinical phenotypes of chronic non‐healing wounds and skin endocrine disorders. The functional relationship between NHRs and skin niche cells such as epidermal keratinocytes and dermal fibroblasts is pivotal for successful wound closure and permanent repair. The aim of this review is to delineate the cutaneous effects and cross‐talk of various nuclear receptors upon injury towards functional tissue restoration. Copyright © 2014 John Wiley & Sons, Ltd.