Short communication: A decrease in diameter of milk fat globules accompanies milk fat depression induced by conjugated linoleic acid supplementation in lactating dairy cows.

Milk fat is secreted from the mammary gland in the form of milk fat globules (MFG). Although milk fat depression has been studied since the beginning of the last century, the extent to which this phenomenon alters MFG synthesis is not fully understood. The aim of this study was to evaluate the effect of conjugated linoleic acid (CLA) on the size and distribution of MFG during milk fat depression in dairy cows. Twelve Holstein cows in mid lactation (145 ± 31 d in milk, 583 ± 34.6 kg of body weight, and 27.2 ± 2.4 kg of milk/d) were randomly assigned to a control diet or control plus Ca-protected CLA at 15 g/kg of dry matter for a 6-d period. The average diameter and particle size distribution of MFG were measured using a Mastersizer 3000 laser particle size analyzer (Malvern Instruments Ltd., Malvern, UK). Feeding CLA did not affect dry matter intake (16.2 ± 0.4 kg/d), milk production (28.4 ± 0.4 kg/d), milk protein, or lactose, but it decreased milk fat content (3.46 vs. 2.52%). In addition, surface area-related mean diameter of fat globules in cows fed CLA was lower compared with controls (3.02 vs. 3.45 µm). The percentage of large fat globules decreased and that of small fat globules increased in response to CLA. Overall, the data suggest that the milk fat depression induced by CLA is accompanied by a decrease in average diameter of MFG.

[Efficacy of Weitan Waifu patch on the postsurgical gastroparesis syndrome of gastrointestinal cancer: a multi-center trial].

Objective: To investigate the safety and efficacy of the Weitan Waifu patch on the postsurgical gastroparesis syndrome (PGS) of gastrointestinal cancer. Methods: The multi-center, double-blind, randomized controlled trial was conducted with superiority design. Patients with PGS of gastrointestinal cancer diagnosed in 4 AAA hospitals and the abdominal symptom manifested as cold syndrome by Chinese local syndrome differentiation were recruited. These patients were randomly divided into two groups according to 1∶1 proportion. Placebo or Weitan Waifu patch was applied in control group or intervention group, respectively, based on the basic treatments, including nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine.Two acupuncture points (Zhongwan and Shenque) were stuck with placebo in control group or patch in treatment group. The intervention course was 14 days or reached the effective standard. Results: From July 15, 2013 to Jun 3, 2015, 128 participants were recruited and 120 eligible cases were included in the full analysis set (FAS), and 60 cases in each group. 88 cases were included in the per-protocol set (PPS), including 45 cases in the treatment group and 43 cases in the control group. In the FAS, the clinical effective rate in the treatment group was 68.3%, significantly superior than 41.7% of the control group (P=0.003). The medium time of effective therapy in the treatment group was 8 days, significantly shorter than 10 days in the control group (P=0.017). In the FAS, 3 adverse events occurred in the treatment group, including mild to moderate decrustation, pruritus and nausea. The incidence rate of adverse events was 5.0% (3/60) and these symptoms were spontaneously remitted after drug withdrawal. No severe adverse events were observed in the control group. There was no significant difference between these two groups (P=0.244). Conclusion: Weitan Waifu patch is a safely and effectively therapeutic method for patients with PGS (cold syndrome) of gastroenterological cancer. Trial registration: International Standard Randomized Controlled Trial Number Register, ISRCTN18291857.

Diabetes Mellitus, Cognitive Impairment, and Traditional Chinese Medicine.

Diabetes mellitus (DM) is a metabolic disorder affecting a large number of people worldwide. Numerous studies have demonstrated that DM can cause damage to multiple systems, leading to complications such as heart disease, cancer, and cerebrovascular disorders. Numerous epidemiological studies have shown that DM is closely associated with dementia and cognition dysfunction, with recent research focusing on the role of DM-mediated cerebrovascular damage in dementia. Despite the therapeutic benefits of antidiabetic agents for the treatment of DM-mediated cognitive dysfunction, most of these pharmaceutical agents are associated with various undesirable side-effects and their long-term benefits are therefore in doubt. Early evidence exists to support the use of traditional Chinese medicine (TCM) interventions, which tend to have minimal toxicity and side-effects. More importantly, these TCM interventions appear to offer significant effects in reducing DM-related complications beyond blood glucose control. However, more research is needed to further validate these claims and to explore their relevant mechanisms of action. The aims of this paper are (1) to provide an updated overview on the association between DM and cognitive dysfunction and (2) to review the scientific evidence underpinning the use of TCM interventions for the treatment and prevention of DM-induced cognitive dysfunction and dementia.

Acupoint herbal patching for allergic rhinitis: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Acupoint herbal patching (AHP) is extensively used in treatment of allergic rhinitis in China. However, existing systematic review is insufficient. OBJECTIVE OF REVIEW: To evaluate the effectiveness and safety of AHP in treating allergic rhinitis. SEARCH STRATEGY: We searched seven electronic databases for randomised controlled trials (RCTs) from inception until August 2014. EVALUATION METHOD: Two authors selected studies, extracted data and evaluated risk of bias independently. The Cochrane risk of bias tool was applied to assess the methodological quality of the included trials, and RevMan 5.2 software was utilised to perform data analysis. RESULTS: Twenty RCTs involving 2438 participants were included. Most of them were evaluated as high risk of bias. Acupoint herbal patching significantly decreased the recurrence rate at 6 months compared with Western medicine (RR 0.52; 95% CI 0.42-0.64), and similar effect was found for AHP plus Western medicine versus Western medicine (RR 0.53; 95% CI 0.44-0.65). Acupoint herbal patching appeared to be more effective than placebo in improving total clinical symptoms and signs after treatment and at 6 months, and in improving quality of life at <3 months and over 3 months. No severe adverse effects were found in the AHP groups. CONCLUSIONS: Acupoint herbal patching alone or combined with Western medicine appears to be more effective than placebo or Western medicine, respectively. Acupoint herbal patching seems to be a safe treatment. However, the findings should be interpreted with caution. Further large-scale, rigorously designed trials are warranted to confirm the findings.

Conjugated linoleic acid-induced milk fat reduction associated with depressed expression of lipogenic genes in lactating Holstein mammary glands.

The efficacy of conjugated linoleic acid (CLA) in diet supplements for milk fat reduction is well documented in several species. However, the mechanisms by which fatty acids regulate mammary lipogenesis remain largely unknown, especially with regard to gene expression of enzyme and regulators. In this study, 8 Holstein dairy cows in their mid-lactation period were randomly divided into 2 groups. Control cows received a Ca salt of palm oil fatty acid dietary supplement, and those in the CLA group were fed Ca salts of CLA (Ca-CLA), all in a dose of approximately 200 g∙cow(-1)∙day(-1) for 14 days. The milk yield was recorded daily, and protein, lactose, and fat in the milk were quantified every 3 days for 2 weeks. Fatty acids in the milk were analyzed with gas-liquid chromatography. Measurement of messenger RNA levels of the main lipogenic genes of lipoprotein lipase, acetyl-coenzyme A (CoA) carboxylase, fatty acid synthase, stearoyl-CoA desaturase, and transcription factors such as sterol response element binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor γ was performed in biopsy samples of mammary tissue on the last day. The results indicated that dietary Ca-CLA caused a continuous reduction of milk fat (P < 0.01) with no effect on milk yield, milk protein, and lactose. The fatty acid profile in the milk from the CLA group differed from that from controls, and the yield of milk fatty acid decreased (P < 0.01) with Ca-CLA supplementation. The depressed expression of lipogenic genes (lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase) demonstrated inhibition of fatty acid de novo synthesis and uptake in the mammary gland of the CLA group. Furthermore, the gene expression of transcription factor SREBP1 was also downregulated (P < 0.01), but peroxisome proliferator-activated receptor γ was unchanged, suggesting that SREBP1 may play a key role in the regulation of lipogenic gene expression in the lactating mammary gland.

[Effect of bushen huoxue decoction on in vitro fertilization and early embryonic development in mice].

OBJECTIVE: To explore the effect of Bushen Huoxue decoction (BSHX) on female reproduction and elucidate its therapeutic mechanism to infertility. METHODS: The BSHX medicated serum of rabbit, as a supplement, was co-cultured with the sperm and ovum of non-copulated mice, and the 2-cell embryos of copulated female mice separately, to observe the changes of in vitro fertilization rate (IVF) and early embryogenesis rate. RESULTS: By co-cultured with BSHX medicated serum, IVF rate was increased obviously (P < 0.01), and the follow-up early embryogenesis rate at various period was promoted, particularly that of the 4-cell and 8-cell embryos (P < 0.05). No influence on developmental rate of in vitro 4-cell embryos obtained from the in vivo 2-cell embryos. But the development of the 8-cell embryos, morula, blastula and hatching were promoted significantly. CONCLUSION: BSHX could raise the fertilization rate and promote the early embryonic development.

Effect of black and green tea polyphenols on c-jun phosphorylation and H(2)O(2) production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction.

The biological activities of theaflavin (TF), theaflavin gallate (TFG) and theaflavin digallate (TFdiG) from black tea and (-)-epigallocatechin 3-gallate (EGCG) and (-)-epigallocatechin (EGC) from green tea were investigated using SV40-immortalized (33BES) and Ha-ras gene transformed (21BES) human bronchial epithelial cell lines. Growth inhibition and cell viability were measured by trypan blue dye exclusion assay following 24 h treatment with the tea polyphenols. TFdiG, EGC and EGCG displayed comparable inhibitory effects on the growth of 21BES cells, with estimated IC(50) values of 22-24 microM. TFG exhibited a lower inhibitory activity (IC(50) 37 microM) and TF was even less effective (IC(50) 47 microM) in this cell line. A similar effect was also observed in 33BES cells. These results suggest that the gallate structure of theaflavins is important for growth inhibition. Exposure of 21BES cells to 25 microM TFdiG, EGC and EGCG for 24 h led to induction of cell apoptosis/death as determined by the Annexin V apoptosis assay. With TFdiG treatment cell death occurred early, and quickly peaked at 8-12 h. Morphological observations showed that TFdiG-treated cells appeared irregular in shape, with cytoplasmic granules, suggesting a cytotoxic effect. On the other hand, EGC and EGCG showed a lag phase before a rapid increase in apoptosis between 16 and 24 h, without any marked morphological changes, which was similar to that induced by H(2)O(2). TFdiG, EGC and EGCG induced similar amounts of H(2)O(2) formation in 21BES cells. Exogenously added catalase significantly prevented EGC- and EGCG-induced cell apoptosis, but did not prevent TFdiG-induced cell death, suggesting that H(2)O(2) is involved in the apoptosis induced by EGCG and EGC, but not in TFdiG-induced cell death. EGCG and TFdiG were shown to decrease c-jun protein phosphorylation in 21BES cells. Such inhibition is expected to result in lowered AP-1 activity, which may contribute to the growth inhibitory activity of tea polyphenols.

Plasma and tissue levels of tea catechins in rats and mice during chronic consumption of green tea polyphenols.

To understand the relationship between tea consumption and its biological effects, plasma and tissue levels of (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC) were measured after rats and mice were given a 0.6% green tea polyphenol preparation as the drinking fluid for different periods of time. EGC and EC levels in rat plasma increased over time and reached peak values (3 times the Day 1 values) on Day 14. Then the plasma levels of tea catechins decreased, to Day 1 values on Day 28. The plasma concentrations of EGCG were much lower than those of EGC or EC. High levels of EGC and EC were found in urine, whereas high levels of EGCG were found in feces. The changes in the urinary and fecal excretions of tea catechins could not account for the above-described changes in the plasma levels. The amounts of catechins in different tissues reflected the ingestion, absorption, and excretion pattern. When the green tea polyphenol preparation was given to mice, the "increase-and-then-decrease" pattern of catechin levels was also observed in the plasma, lung, and liver; the EGCG levels were much higher than in the rats. The results suggest that consumption of tea by rodents could induce adaptive responses affecting blood and tissue levels of tea catechins with time and that investigation of a similar phenomenon in humans is warranted.

Effects of vitamin E and selenium supplementation on esophageal adenocarcinogenesis in a surgical model with rats.

Two well-known antioxidative nutrients, vitamin E and selenium, were used in this study to investigate possible inhibitory action against the formation of esophageal adenocarcinoma (EAC) in rats. In this model, carcinogenesis is believed to be driven by oxidative stress. Male Sprague-Dawley rats (8 weeks old) were divided into four groups and received esophagoduodenal anastomosis (EDA) surgery plus iron supplementation (12 mg/kg/week). Vitamin E and selenium were supplemented in the diet in the forms of alpha-tocopheryl acetate (750 IU/kg) and sodium selenate (1.7 mg Se/kg), which were 10 times the regular amounts in the basic AIN93M diet. At 40 weeks after surgery, all the EDA groups had lower body weights than the non-operated control group. Iron nutrition (hemoglobin, total serum iron and transferrin saturation) was normal as a result of iron supplementation after EDA. Vitamin E supplementation maintained the normal plasma level of alpha-tocopherol in EDA rats, but not those of gamma-tocopherol and retinol. Selenium supplementation increased the serum and liver selenium contents of the EDA rats. Histopathological analysis showed that selenium supplementation increased the incidence of EAC and the tumor volume. The selenium level in the tumor is higher than that in the duodenum of the same animal. Vitamin E supplementation, however, inhibited carcinogenesis, especially in the selenium-supplemented group. We believe that vitamin E exerts its effect through its antioxidative properties, and a high dose of inorganic selenium may promote carcinogenesis by enhancing oxidative stress.

Oxidative damage in an esophageal adenocarcinoma model with rats.

Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. Recently a rat esophageal adenocarcinoma (EAC) model was established in our laboratory by using esophagoduodenal anastomosis (EDA) plus iron supplementation. Our previous study suggested that iron supplementation enhanced inflammation and the production of reactive nitrogen species in the esophageal epithelium, which could contribute to esophageal adenocarcinogenesis. Here we further characterized oxidative damage in this model. We were particularly interested in how excess iron was deposited in the esophagus, and which cells were targeted by oxidative damage. Male Sprague-Dawley rats received iron supplementation (50 mg Fe/kg/month, i.p.) starting 4 weeks after EDA. The animals were killed at 11, 30 or 35 weeks after surgery. EAC appeared as early as week 11 after surgery, and increased over time, up to 60% at 35 weeks after surgery. All EACs were well-differentiated mucinous adenocarcinoma at the squamocolumnar junction. Iron deposition was found at the squamocolumnar junction and in the area with esophagitis. Esophageal iron overload could result from transient increase of blood iron after i.p. injection, and the overexpression of transferrin receptor in the premalignant columnar-lined esophagus (CLE) cells. Oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine), protein (carbonyl content) and lipid (thiobarbituric acid reactive substance) in the esophagus was significantly higher than that of the non-operated control. CLE cells were believed to be the target cells of oxidative damage because they overexpressed heme oxygenase 1 and metallothionein, both known to be responsive to oxidative damage. We propose that oxidative damage plays an important role in the formation of EAC in the EDA model, and a similar situation may occur in humans with gastroesophageal reflux and iron over-nutrition.

Mechanisms of inhibition of carcinogenesis by tea.

Tea (Camellia sinensis) preparations have been shown to inhibit tumorigenesis at the initiation, promotion, and progression stages in different animal models. The anti-proliferative effects of tea polyphenols may be a key mechanism, especially in the NNK-induced lung tumorigenesis model with mice. Studies with cell lines have demonstrated that tea polyphenols inhibit cell proliferation and induce apoptosis. The effective concentrations used in these studies (20-100 microM) are usually higher than those observed in blood and tissues of humans and animals, which are in the low micromolar range. Glucuronide and sulfate conjugated and methylated catechins as well as ring fission products (due to intestinal microflora) have been observed in human plasma and urine. Purified green and black tea polyphenols inhibited the H-ras induced milogen-activated protein kinases, AP-1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among the catechins, both the galloyl structure on the B ring and the gallate moiety are important for the inhibition. Both (-)-epigallocatechin-3-gallate and theaflavin-3,3'-digallate inhibited the phosphorylation of c-jun and p44/42 (ERK 1/2). More mechanistic and human studies in these areas will help us to understand the possible inhibitory action of tea against carcinogenesis in humans.

An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload.

The aim of this study is to establish a good animal model for esophageal adenocarcinoma (EAC) and to test the hypothesis that iron over-nutrition enhances EAC formation. With rats, esophagogastroduodenal anastomosis (EGDA) was accomplished by anastomosing the duodenum to the gastroesophageal junction. Iron supplementation was given by i.p. injection of iron dextran (4 mg Fe/kg/week). This model mimics the development of human EAC by introducing mixed reflux of gastric and duodenal contents. At 40 weeks after surgery, the body weight, food intake, hemoglobin, total serum iron, transferrin saturation, serum albumin, and plasma levels of alpha-tocopherol, gamma-tocopherol and retinol of the EGDA rats were not significantly different from those of the non-operated controls. The animals generally had only mild esophagitis, except that the area surrounding the anastomosis opening had more severe esophagitis. Columnar-lined esophagus (CLE), CLE with dysplasia, and EAC were diagnosed in 53.5, 34.9 and 25.6%, respectively, of the 43 rats. Intraperitoneal iron supplementation significantly enhanced esophageal lesions with CLE, CLE with dysplasia, and EAC to 78.0, 53. 7 and 53.7%, respectively, of the 41 rats. All the tumors were well-differentiated mucinous adenocarcinomas at the squamocolumnar junction area, where most iron deposition was observed. EGDA avoids nutritional problems seen in other animal models for EAC. We believe that direct anastomosis of squamous epithelium to columnar epithelium and mixed reflux of gastric and duodenal contents lead to the formation of CLE and EAC. With this model, we demonstrated that iron supplementation significantly enhanced EAC formation, suggesting that iron over-nutrition could also be a risk factor for human EAC.

Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma.

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.

Tea and tea polyphenols inhibit cell hyperproliferation, lung tumorigenesis, and tumor progression.

Both green and black tea have been shown to inhibit lung tumorigenesis in laboratory animal experiments. Green tea inhibited N-nitrosodiethylamine-induced lung tumor incidence and multiplicity in female A/J mice when tea was given either during the carcinogen treatment period or during the post-carcinogen treatment period. In a separate tumorigenesis model, both decaffeinated black tea and decaffeinated green tea inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor formation. Studies in which tea was administered during different time periods in relation to the NNK suggest that tea can inhibit lung tumorigenesis at both the initiation and promotion stages. The antiproliferative effects of tea may be responsible for these anti-carcinogenic actions. Black tea polyphenol preparations decreased NNK-induced hyperproliferation. Black tea also inhibited the progression of pulmonary adenomas to adenocarcinomas and the formation of spontaneous lung tumors in A/J mice. Growth inhibition by various tea polyphenols has been demonstrated in human lung H661 and H1299 cells. Although inhibition of cell growth and signal transduction pathways by tea components have been demonstrated, the concentrations required to produce the effect are higher than achievable in tissues in vivo. More research is necessary to translate these laboratory results to applications in human chemoprevention.

Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols.

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis by dietary olive oil and squalene.

Epidemiological studies have suggested that frequent olive oil consumption may be a protective factor against lung cancer formation. Squalene, a characteristic compound in olive oil, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and has been proposed to inhibit the farnesylation of ras oncoproteins. The present study investigated the effect of dietary olive oil and squalene in a mouse lung tumorigenesis model. Female A/J mice were fed AIN-76A diets containing 5% corn oil (control), 19.6% olive oil, or 2% squalene starting at 3 weeks before a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (103 mg/kg, i.p.). Animals were maintained on their respective diets throughout the study. At 16 weeks after NNK administration, 100% of the mice in the control group had lung tumors with a tumor multiplicity of 16 tumors per mouse. The olive oil and squalene diets significantly (P < 0.05) decreased the lung tumor multiplicity by 46 and 58%, respectively. The squalene diet significantly (P < 0.05) decreased lung hyperplasia by 70%. In mice fed a diet containing 2% squalene for 3 weeks, the activation of NNK was increased by 1.4- and 2.0-fold in lung and liver microsomes, respectively, but its relationship to the inhibition of carcinogenesis is not clear. These results demonstrate that dietary olive oil and squalene can effectively inhibit NNK-induced lung tumorigenesis.

Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice by black and green tea.

We investigated the effects of black tea (BT) and green tea (GT) infusion on the spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice. Female A/J mice, 6 weeks of age, were allocated into five groups (50 per group) and were given the following as the sole source of drinking fluid: (i) deionized water (control group), (ii) 0.5% BT, (iii) 1% BT, (iv) 2% BT and (v) 1% GT. After 60 weeks, the mice were killed by decapitation. Lung tumor incidence, multiplicity and volume were significantly lower in the 2% BT group as compared with the controls (27 versus 52%, 0.33 versus 0.72 tumors/mouse and 4.27 versus 38.3 mm3, respectively). The 1% GT group had significantly lower lung tumor multiplicity (0.41/mouse), while the 1% BT group had significantly decreased tumor volume (7.17 mm3). Rhabdomyosarcomas were found in 34% of the mice in the control group, and both the 1 and 2% BT groups had significantly lower incidences at 13 and 14%, respectively. The mice in the 2% BT group weighed 16% less than those in the control group, although they consumed more food than the control group. The other tea-consuming groups also weighed less than the control group (7.8-11%) while consuming more food and fluid. In a separate experiment, similar carcinogenesis inhibition was also observed in female A/J mice that were given 0.6% and then 0.3% instant black tea for 52 weeks. These results demonstrate the inhibitory activity of BT against the spontaneous formation of lung tumors and rhabdomyosarcomas in mice.

Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen.

In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperproliferation, but not EAC. Additional treatment with a carcinogen has been shown to be necessary for the development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We found that the surgically treated animals developed anemia due possibly to reduced iron absorption. When the operated animals were supplemented with iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment with carcinogen, however, induced SCC in the group of rats killed after 22 weeks. The results suggest that iron overload, which is known to cause oxidative damage, is an enhancing factor for adenocarcinogenesis. The pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group resembles human esophageal adenocarcinogenesis in many features. All the BE was the specialized type with goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin) as well as an incompletely developed brush border. Almost all of the BE was located at the bottom of the esophagus and was continuous with the duodenal mucosa; dysplasia became more frequent at later time points. All of the cancers were well-differentiated mucinous EAC, and most of the EAC had an adjacent area of BE with dysplasia. The results are consistent with the proposed human sequence for pathogenic events of BE progression to 'BE with dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment in rats produces a high rate of BE and EAC which are morphologically similar to human BE and EAC; this may be a useful animal model to study the development and prevention of EAC in humans.