HIV enteropathy: HAART reduces HIV-induced stem cell hyperproliferation and crypt hypertrophy to normal in jejunal mucosa.

PubMed

Batman, Philip A; Kapembwa, Moses S; Belmonte, Liliana; Tudor, Gregory; Kotler, Donald P; Potten, Christopher S; Booth, Catherine; Cahn, Pedro; Griffin, George E

2014-01-01

To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

Characterization and comparison of proteins in the sperm storage tubules of female chickens to bovine epididymal fluid

USDA-ARS?s Scientific Manuscript database

Female birds are able to store sperm in crypts called sperm storage tubules (SSTs) in their reproductive tracts for between two and six weeks. Comparatively, sperm in a cow’s reproductive tract remain viable for between 18 and 24 hours. The objective of this experiment was to try to identify and co...

Colonic aberrant crypts may originate from impaired fissioning: relevance to increased risk of neoplasia.

PubMed

Kristt, D; Bryan, K; Gal, R

1999-12-01

Colonic aberrant crypt foci (ACF) can be identified on the unembedded mucosal surface as clusters of abnormal crypts with enlarged, surface opening. Because dysplasia is frequent, and may be a precursor of carcinoma, epithelial changes have been well studied. However, the basis for the distinctive changes in crypt architecture remain unclear. We hypothesized that some of the architectural alterations of aberrant crypts may reflect impaired fissioning during normal crypt duplication cycles. Fissioning begins at the crypt base. Using morphometric and immunocytochemical approaches, we examined 55 human ACF, both dysplastic and nondysplastic, for their architectural features. Non-ACF mucosa was compared. Microscopically, all lesions contained crypts that were attached, paired, dilated, and angulated. In 3 dimensions, these features related to multiple, individual complexes of connected crypts, referred to as connected crypt structures (CCSs). CCSs terminated in enlarged surface openings (2 to 5 x normal) which are morphometrically equivalent to the macroscopic aberrant crypts (P > .1). These openings trap marker dye. Support for an origin of CCSs in impaired basal fissioning is 3-fold. Crypt profiles in ACF are twice as frequent in basal mucosa as superficially (P < .001); in normal mucosa, the ratio is 1. In a CCS with vertically connected, co-planar crypts, the upper parent crypt diameter was the sum of diameters of inferiorly attached daughter crypts (P > .1). Proliferating cell marker, Ki-67, is not expressed at attachment points. In non-ACF mucosa, isolated CCSs consistently occur at foci of mechanical crypt distortion such as mucosal folds. We conclude that a CCS is a fundamental component of ACF of all histotypes. Impairment of normal crypt fissioning is probably a major factor in the histogenesis of CCSs, which often occurs in settings of mechanical distortion of the mucosa. The pathological significance of this process may be in the formation of enlarged crypt openings. The latter could trap dietary carcinogens as they trap dye, and thereby predispose the CCS to dysplasia.

Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress.

PubMed

Zaborin, Alexander; Krezalek, Monika; Hyoju, Sanjiv; Defazio, Jennifer R; Setia, Namrata; Belogortseva, Natalia; Bindokas, Vytautas P; Guo, Qiti; Zaborina, Olga; Alverdy, John C

2017-02-01

Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts' microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery. This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts. Copyright © 2017 the American Physiological Society.

Calcium-activated potassium channels in basolateral membranes of colon epithelial cells; reconstitution and functional properties.

PubMed

Wiener, H; Turnheim, K

1990-10-26

Using differential sedimentation, isopycnic and Ficoll-400 barrier centrifugation, basolateral membrane vesicles of surface and crypt cells of the rabbit distal colon were enriched 34- and 9-fold, respectively. 86Rb(+)-uptake into these vesicles, driven by an electrical potential difference, was stimulated by submicromolar Ca2+ activities and inhibited by Ba2+. These findings indicate the presence of Ca2(+)-activated K+ channels. The K+ channels in surface and crypt cell membranes differed with respect to inhibition by the bee venom apamin, the scorpion venom charybdotoxin and tetraethylammonium and exhibited a different pH dependence. Fusion of basolateral membrane vesicles with planar phospholipid bilayers revealed the presence of high-conductance Ba2(+)-sensitive K+ channels which were activated by micromolar Ca2+ and inhibited by crude scorpion venom and trifluoperazine. These K+ channels may be involved in the coupling of apical and basolateral membrane conductances during Na+ absorption and Cl- secretion, but they may also play a role in cell volume regulation.

Post-irradiation somatic mutation and clonal stabilisation time in the human colon.

PubMed Central

Campbell, F; Williams, G T; Appleton, M A; Dixon, M F; Harris, M; Williams, E D

1996-01-01

BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems. PMID:8944567

Activated Notch signaling cascade is correlated with stem cell differentiation toward absorptive progenitors after massive small bowel resection in a rat.

PubMed

Sukhotnik, Igor; Coran, Arnold G; Pollak, Yulia; Kuhnreich, Eviatar; Berkowitz, Drora; Saxena, Amulya K

2017-09-01

Notch signaling is thought to act to drive cell versification in the lining of the small intestine. The purpose of the present study was to evaluate the role of the Notch signaling pathway in stem cell differentiation in the late stages of intestinal adaptation after massive small bowel resection in a rat. Male Sprague-Dawley rats were randomly assigned to one of two experimental groups of eight rats each: Sham rats underwent bowel transection and reanastomosis, while SBS rats underwent 75% small bowel resection. Rats were euthanized on day 14 Illumina's Digital Gene Expression (DGE) analysis was used to determine Notch signaling gene expression profiling. Notch-related gene and protein expression was determined using real-time PCR, Western blot analysis, and immunohistochemistry. From seven investigated Notch-related (by DGE analysis) genes, six genes were upregulated in SBS vs. control animals with a relative change in gene expression level of 20% or more. A significant upregulation of Notch signaling-related genes in resected animals was accompanied by a significant increase in Notch-1 protein levels (Western blot analysis) and a significant increase in the number of Notch1 and Hes1 (target gene)-positive cells (immunohistochemistry) compared with sham animals. Evaluation of cell differentiation has shown a strong increase in total number of absorptive cells (unchanged secretory cells) compared with control rats. In conclusion, 2 wk after bowel resection in rats, stimulated Notch signaling directs the crypt cell population toward absorptive progenitors. NEW & NOTEWORTHY This study provides novel insight into the mechanisms of cell proliferation following massive small bowel resection. We show that 2 wk after bowel resection in rats, enhanced stem cell activity was associated with stimulated Notch signaling pathway. We demonstrate that activated Notch signaling cascade directs the crypt cell population toward absorptive progenitors. Copyright © 2017 the American Physiological Society.

HIV enteropathy: crypt stem and transit cell hyperproliferation induces villous atrophy in HIV/Microsporidia-infected jejunal mucosa.

PubMed

Batman, Philip A; Kotler, Donald P; Kapembwa, Moses S; Booth, Dawn; Potten, Christopher S; Orenstein, Jan M; Scally, Andrew J; Griffin, George E

2007-02-19

The study aim was to analyse the kinetics of stem and transit cells in the crypts of jejunal mucosa infected with HIV and Microsporidia. The size of villi, depth of crypts and proliferative activity of transit and stem cells in jejunal mucosa were measured using morphometric techniques. The surface area/volume ratio (S/V) of jejunal biopsies was estimated under light microscopy using a Weibel graticule. Crypt length was measured by counting enterocytes along the crypt side from the base to the villus junction, and the mean crypt length was calculated. The S/V and crypt lengths of the jejunal mucosa of 21 HIV and Microsporidia-infected test cases were compared with 14 control cases. The labelling index in relation to the crypt cell position of 10 of the test cases was analysed compared with 13 control cases. Differences were found in the S/V and crypt length, and there was a negative correlation between S/V and crypt length in test and control cases combined. Cell labelling indices fell into low and high proliferation groups. There were significant differences in labelling indices between low proliferation test cases and controls, between high proliferation test cases and controls, and between high and low proliferation test cases. Villous atrophy induced by HIV and Microsporidia is attributed to crypt cell hyperplasia and the encroachment of crypt cells onto villi. These infections induce crypt hypertrophy by stimulating cell mitosis predominantly in transit cells but also in stem cells. Increased stem cell proliferation occurs only in high proliferation cases.

Topical methotrexate alters solute and water transport in the rat jejunum in vivo and rabbit ileum in vitro.

PubMed Central

Pinkerton, C R; Booth, I W; Milla, P J

1985-01-01

The topical effect of methotrexate (MTX) on small intestinal hexose and ion transport has been studied using an in vivo steady state jejunal perfusion technique in the rat, and short circuited rabbit terminal ileum in Ussing chambers in vitro. In rat jejunum, perfusion with MTX (1 mumol/l) caused significant reductions in water, sodium, and glucose absorption within 110 minutes of exposure. Fructose absorption was, however, unimpaired. The same concentration of MTX, when added to the mucosal side of distal rabbit ileum caused significant increases in transmucosal potential difference, short circuit current and the unidirectional flux of chloride from serosa to mucosa. In the presence of a subphysiological magnesium concentration (0.3 mmol/l), MTX resulted in the abolition of net sodium absorption and the conversion of net chloride absorption to secretion. We conclude that MTX has a topical effect on small intestinal transport which is independent of its effect on crypt cell kinetics. PMID:4018634

Multi-scale modeling of APC and [Formula: see text]-catenin regulation in the human colonic crypt.

PubMed

Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

2018-06-01

Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas. We formulate a PDE model describing cell movement and reproduction in a static crypt domain. We consider a single cell population whose proliferative capabilities are determined by stemness, a quantity defined by intracellular levels of adenomatous polyposis coli (APC) scaffold protein and [Formula: see text]-catenin. We fit APC regulation parameters to biological data that describe normal protein gradients in the crypt. We also fit cell movement and protein flux parameters to normal crypt characteristics such as renewal time, total cell count, and proportion of proliferating cells. The model is used to investigate abnormal crypt dynamics when subjected to a diminished APC gradient, a scenario synonymous to mutations in the APC gene. We find that a 25% decrease in APC synthesis leads to a fraction of 0.88 proliferative, which is reflective of normal-appearing FAP crypts. A 50% drop in APC activity yields a fully proliferative crypt showing a doubling of the level of stemness, which characterizes the initial stages of colorectal cancer development. A sensitivity analysis of APC regulation parameters shows the perturbation of factors that is required to restore crypt dynamics to normal in the case of APC mutations.

The influence of dibutyryl adenosine cyclic monophosphate on cell proliferation in the epithelium of the jejunal crypts, the colonic crypts and in colonic carcinomata of rat.

PubMed

Tutton, P J; Barkla, D H

1980-01-01

1. Cell proliferation in the jejunal crypts, the colonic crypts and in dimethylhydrazine (DMH)-induced adenocarcinomata of rat colon was measured using a stathmokinetic technique. 2. Dibutryl cyclic adneosine monophosphate (dibutyryl cAMP) was found to inhibit cell proliferation in colonic crypts and in colonic adenocarcinomata. 3. Dibutryl cAMP at very high doses was found to inhibit jejunal crypt cell proliferation but at lower doses was found to accelerate jejunal crypt cell proliferation. 4. Neither bilateral adrenalectomy nor chemical sympathectomy was found to abolish the ability of dibutryl cAMP to stimulate jejunal crypt cell proliferation. 5. The present results are difficult to interpret in terms of known hormonal influences on cell proliferation in the tissues examined and of established actions, of these hormones on cyclic nucleotide metabolism in other tissues.

Neural control of colonic cell proliferation.

PubMed

Tutton, P J; Barkla, D H

1980-03-15

The mitotic rate in rat colonic crypts and in dimethylhydrazine-induced colonic carcinomas was measured using a stathmokinetic technique. In sympathectomized animals cell proliferation was retarded in the crypts but not in the tumors, whereas in animals treated with Metaraminol, a drug which releases norepinephrine from nerve terminals, crypt cell but not tumor cell proliferation was accelerated. Blockade of alpha-adrenoceptors also inhibited crypt cell proliferation. However, stimulation of beta-adrenoceptors inhibited and blockade of beta-adrenoceptors accelerated tumor cell proliferation without influencing crypt cell proliferation. Injection of either serotonin or histamine stimulated tumor but not crypt cell proliferation and blockade or serotonin receptors or histamine H2-receptors inhibited tumor cell proliferation. It is postulated that cell proliferation in the colonic crypts, like that in the jejunal crypts, is under both endocrine and autonomic neural control whereas colonic tumor cell division is subject to endocrine regulation alone.

Sperm storage in the human cervix: a quantitative study.

PubMed

Insler, V; Glezerman, M; Zeidel, L; Bernstein, D; Misgav, N

1980-03-01

Twenty-five women scheduled for hysterectomy for nonmalignant disease participated in the study. Sperm storage in endocervical crypts was examined in three groups of patients: nine women pretreated with estrogen and inseminated with normal semen, nine women pretreated with gestagen and inseminated with normal semen, and seven women pretreated with estrogen and inseminated with abnormal semen. The number of crypts containing spermatozoa (colonized crypts) and the sperm density per crypt were examined in serially sectioned cervices. In estrogen-pretreated cervices both the percentage of colonized crypts and the sperm density were significantly higher than in gestagen-pretreated cervices. Large and giant crypts proved to be the main storage facility for spermatozoa. The localization of crypts along the endocervical canal did not influence sperm storage. The quality of semen appeared to be of critical importance to sperm storage. The percentage of colonized crypts and sperm density were severly reduced in patients inseminated with abnormal semen.

Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

PubMed Central

Liskay, R.Michael

2014-01-01

Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

Short bowel syndrome: highlights of patient management, quality of life, and survival.

PubMed

Kelly, Darlene G; Tappenden, Kelly A; Winkler, Marion F

2014-05-01

Short bowel syndrome (SBS) occurs as a result of intestinal resection, and in many patients is associated with complications, such as diarrhea, dehydration, weight loss, and nutrition deficiencies. Many individuals with SBS develop intestinal failure and require parenteral nutrition (PN) and/or intravenous (IV) fluids (PN/IV). Although PN is essential for survival, some patients with SBS who require long-term PN experience significant complications that contribute to morbidity and mortality. Consequently, therapies that decrease reliance on PN are of considerable importance. Intestinal adaptation, which results in morphologic and functional changes that increase performance of the remnant bowel, occurs spontaneously after intestinal resection. These effects can be enhanced with nutrition and pharmaceutical approaches. For example, oral or tube-fed nutrients stimulate growth and adaptation of intestinal tissues. In addition, prebiotics support growth of beneficial intestinal microbiota that produce short-chain fatty acids, which have been shown in preclinical studies to enhance intestinal structure and function. Finally, glucagon-like peptide 2 (GLP-2) is an endogenous peptide that promotes intestinal rehabilitation and improves intestinal absorption. Teduglutide, a recombinant human GLP-2 analog, has recently been approved in the United States for the treatment of adults with SBS who are dependent on PN. In pharmacodynamic and clinical studies, teduglutide has been shown to promote changes in intestinal structure, such as increases in villus height and crypt depth, and to improve intestinal absorption, as indicated by reduced PN/IV dependence. This article presents a brief overview of SBS, including effects on survival and quality of life and current treatment options.

Protein source and nutrient density in the diets of male broilers from 8 to 21 d of age: Effects on small intestine morphology.

PubMed

Wang, X; Peebles, E D; Morgan, T W; Harkess, R L; Zhai, W

2015-01-01

In a companion study, high amino acid (AA) or apparent metabolizable energy (AME) densities in the diets of broilers from 8 to 21 d of age were found to improve feed conversion. A total of 1,120 male Ross×Ross 708 chicks were randomly allocated to 80 pens (8 treatments, 10 replications per treatment, 14 chicks per pen). A 2×2×2 factorial arrangement of treatments was used to investigate the interaction among the protein source (high distillers dried grains with solubles diet [hDDGS] or high meat and bone meal diet [hMBM]), AA density (moderate or high), and AME density (2,998 or 3,100 kcal/kg) of diets on small intestine morphology. Duodenum, jejunum, and ileum samples from 2 chicks per pen were collected and measured individually at 21 d. Jejunum sections were processed for histological analysis. Chicks fed hDDGS diets exhibited longer small intestines than did chicks fed hMBM diets. Particularly, when chicks were fed high AA density diets, jejuna were longer in groups fed hDDGS diets than groups fed hMBM diets. Dietary treatments did not affect jejunum villus height, width, area, crypt depth, villus to crypt ratio, goblet cell size, or cell density. In birds fed diets containing a moderate AA and a high AME density, jejunum muscle layers of chicks fed hDDGS diets were thicker than those fed hMBM diets. Chicks exhibited a lower feed conversion ratio (FCR) and a higher BW gain when their crypts were shorter. In conclusion, an hDDGS diet may facilitate small intestine longitudinal growth in broilers, which may subsequently improve dietary nutrient absorption. In addition, broiler chicks with shallow intestinal crypts exhibited better growth performance. © 2014 Poultry Science Association Inc.

Crypt dysplasia in Barrett's oesophagus shows clonal identity between crypt and surface cells.

PubMed

Khan, Shabuddin; McDonald, Stuart A C; Wright, Nicholas A; Graham, Trevor A; Odze, Robert D; Rodriguez-Justo, Manuel; Zeki, Sebastian

2013-09-01

Epithelial dysplasia is an important histological diagnosis signifying the presence of pre-invasive disease, usually needing intervention. However, the specific genetic changes responsible for the induction of this phenotypic change are unknown. Moreover, recent reports indicate that the dysplastic phenotype may not be immutable: in basal crypt dysplasia (CD), unequivocal dysplastic changes are seen in the crypts in Barrett's oesophagus and other pre-invasive lesions in the gastrointestinal tract, but the upper crypts and surface epithelium associated with these dysplastic crypts show the definitive morphology of a differentiated epithelium. The genotypic relationship between CD and the differentiated surface epithelium is presently unclear. We obtained 17 examples of CD: the lower and upper crypts and surface epithelium were differentially laser-microdissected from formalin-fixed, paraffin-embedded sections and mutations were sought in tumour suppressor genes frequently associated with progression in Barrett's oesophagus. We found two patients who both showed a c. C238T mutation in the CDKN2A (CDKN2AInk4A) gene and where the precise microanatomical relationships could be discerned: this mutation was present in both the CD at the crypt base and in the upper crypt and surface epithelium. We conclude that, in CD, the dysplastic basal crypt epithelium and the upper crypt and surface epithelium show clonal CDKN2A mutations, thus showing definitively that the surface epithelium is derived from the dysplastic crypt epithelium: the dysplastic phenotype is therefore not fixed and can be reversed. The mechanism of this change is unclear but may be related to the possibility that dysplastic cells can, probably early in their progression, respond to differentiation signals. However, it is also clear that a heavy mutational burden can be borne by crypts in the gastrointestinal tract without the development of phenotypic dysplasia. We are evidently some way from understanding the plasticity and the genotypic correlates of the dysplastic phenotype. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer.

PubMed

Konstantakos, A K; Siu, I M; Pretlow, T G; Stellato, T A; Pretlow, T P

1996-09-01

Aberrant crypt foci are putative preneoplastic lesions found in the colons of carcinogen-treated rodents and at an increased frequency in humans at increased risk for colon cancer. There is a strong association between aberrant crypt foci and colon cancer, including many shared phenotypic and genetic alterations. The aim of this study is to present further evidence of a relationship between aberrant crypt foci and colon cancer in humans. Multiple aberrant crypt foci from a single patient were identified in unembedded colonic mucosa. Histological sections of the aberrant crypt foci and adjacent mucosa were evaluated for dysplasia, proliferative activity, and pigment-laden macrophages that were characterized with histochemical techniques. The first patient with sporadic colon cancer identified with aberrant crypt foci with carcinoma in situ is described. It is interesting that this 99-year-old patient had multiple carcinomas in situ, pseudomelanosis coli, and two metachronous colon cancers. These data lend support to the hypothesis that aberrant crypt foci are precursors of some colon cancers.

Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs

PubMed Central

Liu, Hong; Wang, Jun; Mou, Daolin; Che, Lianqiang; Fang, Zhengfeng; Feng, Bin; Lin, Yan; Xu, Shengyu; Li, Jian; Wu, De

2017-01-01

This study was conducted to explore whether exposure to bisphenol A (BPA) during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET) could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON); control diet supplemented with BPA (50 mg/kg); control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 μg/kg vitamin B12, and 15 mg/kg folic acid); and control diet with BPA and MET supplementation (BPA + MET). Intestine samples were collected from pigs’ offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1) and DNA methyl transferase 3a (DNMT3a), and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT), DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR), and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05). Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring’s intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation. PMID:28445388

HCO3− secretion and CaCO3 precipitation play major roles in intestinal water absorption in marine teleost fish in vivo

PubMed Central

Cooper, Christopher A.; Wilson, Rod W.

2010-01-01

The intestine of marine teleosts must effectively absorb fluid from ingested seawater to avoid dehydration. This fluid transport has been almost exclusively characterized as driven by NaCl absorption. However, an additional feature of the osmoregulatory role of the intestine is substantial net HCO3− secretion. This is suggested to drive additional fluid absorption directly (via Cl−/HCO3− exchange) and indirectly by precipitating ingested Ca2+ as CaCO3, thus creating the osmotic gradient for additional fluid absorption. The present study tested this hypothesis by perfusing the intestine of the European flounder in vivo with varying [Ca2+]: 10 (control), 40, and 90 mM. Fractional fluid absorption increased from 47% (control) to 73% (90 mM Ca2+), where almost all secreted HCO3− was excreted as CaCO3. This additional fluid absorption could not be explained by NaCl cotransport. Instead, a significant positive relationship between Na+-independent fluid absorption and total HCO3− secretion was consistent with the predicted roles for anion exchange and CaCO3 precipitation. Further analysis suggested that Na+-independent fluid absorption could be accounted for by net Cl− and H+ absorption (from Cl−/HCO3− exchange and CO2 hydration, respectively). There was no evidence to suggest that CaCO3 alone was responsible for driving fluid absorption. However, by preventing the accumulation of luminal Ca2+ it played a vital role by dynamically maintaining a favorable osmotic gradient all along the intestine, which permits substantially higher rates of solute-linked fluid absorption. To overcome the resulting hyperosmotic and highly acidic absorbate, it is proposed that plasma HCO3− buffers the absorbed H+ (from HCO3− production), and consequently reduces the osmolarity of the absorbed fluid entering the body. PMID:20130226

Effects of Saccharomyces cerevisiae fermentation products on dairy calves: Ruminal fermentation, gastrointestinal morphology, and microbial community.

PubMed

Xiao, J X; Alugongo, G M; Chung, R; Dong, S Z; Li, S L; Yoon, I; Wu, Z H; Cao, Z J

2016-07-01

The aim of this study was to evaluate the effects of Saccharomyces cerevisiae fermentation products (SCFP) in the calf starter and milk on ruminal fermentation, gastrointestinal morphology, and microbial community in the first 56 d of life. Thirty Holstein bull calves were randomly assigned to 1 of 3 groups: a texturized calf starter containing 0 (CON), 0.5, or 1% SCFP (XPC, Diamond V, Cedar Rapids, IA) of dry matter from d 4 to 56. In addition, the XPC-supplemented calves were fed with 1 g/d SCFP (SmartCare, Diamond V, Cedar Rapids, IA) in milk from d 2 to 30. All calves were fed 4 L of colostrum within 1 h of birth and were subsequently fed milk twice daily until weaned on d 56. Rumen fluid was collected by an esophageal tube 4 h after the morning feeding on d 28 and 56 to determine ruminal pH, ammonia-N, and volatile fatty acids concentrations. On d 56, 15 (5 per treatment) calves were harvested and slaughter weight, gastrointestinal morphology parameters, and bacteria community were recorded. Papilla length, width, and surface area were measured from 5 locations within the rumen. Villus height, width, surface area, crypt depth, and villus height-to-crypt depth ratio were measured in the duodenum, jejunum, and ileum. Next-generation sequencing technology was used to test the microbial community of the rumen and duodenum samples on d 28 and 56. Data were analyzed by MIXED procedure in SAS (SAS Institute Inc., Cary, NC) with contrast statements to declare CON versus all SCFP and 0.5 versus 1% SCFP in starter grains. Ruminal pH, ammonia-N, and total volatile fatty acids were not altered by SCFP. However, the supplemented groups exhibited higher ruminal butyrate concentrations coinciding with higher Butyrivibrio and lower Prevotella richness than CON group. Supplementation of SCFP increased papilla length in the rumen. In the small intestine, SCFP reduced crypt depth of jejunum, and increased villus height-to-crypt depth ratio in all segments of the small intestine, especially when supplemented at a higher dosage in the starter. In conclusion, Saccharomyces cerevisiae fermentation products improved gastrointestinal morphology, possibly due to increased Butyrivibrio and decreased Prevotella richness of the rumen fluid, which resulted in an increase in butyrate production, and the effect was slightly greater with the higher dosage of SCFP in the starter. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Spectrophotometric Determination of the Characteristics of Stromal and Parenchymal Components of Colon Tumors

NASA Astrophysics Data System (ADS)

Motevich, I. G.; Strekal, N. D.; Shulha, A. V.; Maskevich, S. A.

2016-05-01

We consider the dependence of the spectral properties of eosin and hematoxylin (dyes routinely used in histology as contrast agents) on their localization in biological tissues with different levels of pathology: benign and malignant neoplasms and sigmoid colonic crypts. We have analyzed the fluorescent images and fluorescence spectra of the parenchyma and stromal elements. We have established that on going from physiologically normal cells to tumor cells, the contribution to the absorption cross section of histologic sections due to hematoxylin increases. In pathologically altered cells in a colonic crypt, we observe a hypsochromic effect in the fluorescence spectra of the samples with appreciable quenching of the fluorescence, while in the model systems the reverse effect occurs: a shift of the fluorescence maximum toward the red region. We discuss the influence on the indicated effects from local pH and the polarity of the dye environment in the model systems and histologic sections. As the systems modeling the polarity and acidity of the biological media, we use aqueous solutions of the dyes with different pH values and synthetic polyelectrolytes.

Optimality in the Development of Intestinal Crypts

PubMed Central

Itzkovitz, Shalev; Blat, Irene C.; Jacks, Tyler; Clevers, Hans; van Oudenaarden, Alexander

2012-01-01

SUMMARY Intestinal crypts in mammals are comprised of long-lived stem cells and shorter-lived progenies. These two populations are maintained in specific proportions during adult life. Here, we investigate the design principles governing the dynamics of these proportions during crypt morphogenesis. Using optimal control theory, we show that a proliferation strategy known as a “bang-bang” control minimizes the time to obtain a mature crypt. This strategy consists of a surge of symmetric stem cell divisions, establishing the entire stem cell pool first, followed by a sharp transition to strictly asymmetric stem cell divisions, producing nonstem cells with a delay. We validate these predictions using lineage tracing and single-molecule fluorescence in situ hybridization of intestinal crypts in infant mice, uncovering small crypts that are entirely composed of Lgr5-labeled stem cells, which become a minority as crypts continue to grow. Our approach can be used to uncover similar design principles in other developmental systems. PMID:22304925

Optimality in the Development of Intestinal Crypts

NASA Astrophysics Data System (ADS)

van Oudenaarden, Alexander

2012-02-01

Intestinal crypts in mammals are comprised of long-lived stem cells and shorter-lived progenies, maintained under tight proportions during adult life. Here we ask what are the design principles that govern the dynamics of these proportions during crypt morphogenesis. We use optimal control theory to show that a stem cell proliferation strategy known as a `bang-bang' control minimizes the time to obtain a mature crypt. This strategy consists of a surge of symmetric stem cell divisions, establishing the entire stem cell pool first, followed by a sharp transition to strictly asymmetric stem cell divisions, producing non-stem cells with a delay. We validate these predictions using lineage tracing and single molecule fluorescent in-situ hybridization of intestinal crypts in newborn mice and find that small crypts are entirely composed of Lgr5 stem cells, which become a minority as crypts further grow. Our approach can be used to uncover similar design principles in other developmental systems.

Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance.

PubMed

Zhou, Xin; Ma, Xiaofei; Wang, Zhenhua; Sun, Chao; Wang, Yupei; He, Yang; Zhang, Hong

2015-12-15

Radiation-induced hyperproliferation of intestinal crypts is well documented, but its potential tumorigenic effects remain elusive. Here we aim to determine the genomic surveillance process during crypt hyperproliferation, and its consequential outcome after ionizing radiation. Crypt regeneration in the intestine was induced by a single dose of 12Gy abdominal irradiation. γ-H2AX, 53BP1 and DNA-PKcs were used as DNA repair surrogates to investigate the inherent ability of intestinal crypt cells to recognize and repair double-strand breaks. Ki67 staining and the 5-bromo-2'-deoxyuridine incorporation assay were used to study patterns of cell proliferation in regenerating crypts. Staining for ATM, p53, Chk1 and Chk2 was performed to study checkpoint activation and release. Apoptosis was evaluated through H&E staining and terminal deoxynucleotidyl transferase (dUTP) nick-end labeling. The ATM-p53 pathway was immediately activated after irradiation. A second wave of DSBs in crypt cells was observed in regenerating crypts, accompanied with significantly increased chromosomal bridges. The p53-related genomic surveillance pathway was not active during the regeneration phase despite DSBs and chromosomal bridges in the cells of regenerating crypts. Non-homologous end joining (NHEJ) DSBs repair was involved in the DSBs repair process, as indicated by p-DNA-PKcs staining. Intestinal crypt cells retained hyperproliferation with inactive p53-related genomic surveillance system. NHEJ was involved in the resultant genomic instability during hyperproliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation of computer-aided colonic crypt pattern analysis

NASA Astrophysics Data System (ADS)

Qi, Xin; Pan, Yinsheng; Sivak, Michael V., Jr.; Olowe, Kayode; Rollins, Andrew M.

2007-02-01

Colorectal cancer is the second leading cause of cancer-related death in the United States. Approximately 50% of these deaths could be prevented by earlier detection through screening. Magnification chromoendoscopy is a technique which utilizes tissue stains applied to the gastrointestinal mucosa and high-magnification endoscopy to better visualize and characterize lesions. Prior studies have shown that shapes of colonic crypts change with disease and show characteristic patterns. Current methods for assessing colonic crypt patterns are somewhat subjective and not standardized. Computerized algorithms could be used to standardize colonic crypt pattern assessment. We have imaged resected colonic mucosa in vitro (N = 70) using methylene blue dye and a surgical microscope to approximately simulate in vivo imaging with magnification chromoendoscopy. We have developed a method of computerized processing to analyze the crypt patterns in the images. The quantitative image analysis consists of three steps. First, the crypts within the region of interest of colonic tissue are semi-automatically segmented using watershed morphological processing. Second, crypt size and shape parameters are extracted from the segmented crypts. Third, each sample is assigned to a category according to the Kudo criteria. The computerized classification is validated by comparison with human classification using the Kudo classification criteria. The computerized colonic crypt pattern analysis algorithm will enable a study of in vivo magnification chromoendoscopy of colonic crypt pattern correlated with risk of colorectal cancer. This study will assess the feasibility of screening and surveillance of the colon using magnification chromoendoscopy.

An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

PubMed Central

Boman, Bruce M.; Fields, Jeremy Z.

2013-01-01

APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

Effects of Ginger Supplementation on Cell Cycle Biomarkers in the Normal-Appearing Colonic Mucosa of Patients at Increased Risk for Colorectal Cancer: Results from a Pilot, Randomized, Controlled Trial

PubMed Central

Citronberg, Jessica; Bostick, Roberd; Ahearn, Thomas; Turgeon, D. Kim; Ruffin, Mack T.; Djuric, Zora; Sen, Ananda; Brenner, Dean E.; Zick, Suzanna M.

2013-01-01

To estimate the effects of ginger on apoptosis, proliferation, and differentiation in the normal-appearing colonic mucosa, we randomized 20 people at increased risk for colorectal cancer to 2.0 g of ginger or placebo daily for 28 days in a pilot trial. Overall expression and distributions of Bax, Bcl-2, p21, hTERT and MIB-1 (Ki-67) in colorectal crypts in rectal mucosa biopsies were measured using automated immunohistochemistry and quantitative image analysis. Relative to placebo, Bax expression in the ginger group decreased 15.6% (p = 0.78) in the whole crypts, 6.6% (p = 0.95) in the upper 40% (differentiation zone) of crypts, and 21.7% (p = 0.67) in the lower 60% (proliferative zone) of crypts; however, there was a 19% increase (p = 0.14) in Bax expression in the upper 40% relative to the whole crypt. While p21 and Bcl-2 expression remained relatively unchanged, hTERT expression in the whole crypts decreased by 41.2% (p = 0.05); the estimated treatment effect on hTERT expression was larger in the upper 40% of crypts (−47.9%; p = 0.04). In the ginger group, MIB-1 expression decreased in the whole crypts, upper 40% of crypts, and lower 60% of crypts by 16.9% (p = 0.39), 46.8% (p = 0.39), and 15.3% (p = 0.41), respectively. These pilot study results suggest that ginger may reduce proliferation in the normal-appearing colorectal epithelium and increase apoptosis and differentiation relative to proliferation—especially in the differentiation zone of the crypts, and support a larger study to further investigate these results. PMID:23303903

Use of the cryptogein gene to stimulate the accumulation of Bacopa saponins in transgenic Bacopa monnieri plants.

PubMed

Majumdar, Sukanya; Garai, Saraswati; Jha, Sumita

2012-10-01

Genetic transformation of the Indian medicinal plant, Bacopa monnieri, using a gene encoding cryptogein, a proteinaceous elicitor, via Ri and Ti plasmids, were established and induced bioproduction of bacopa saponins in crypt-transgenic plants were obtained. Transformed roots obtained with A. rhizogenes strain LBA 9402 crypt on selection medium containing kanamycin (100 mg l(-1)) dedifferentiated forming callus and redifferentiated to roots which, spontaneously showed shoot bud induction. Ri crypt-transformed plants thus obtained showed integration and expression of rol genes as well as crypt gene. Ti crypt-transformed B. monnieri plants were established following transformation with disarmed A. tumefaciens strain harboring crypt. Transgenic plants showed significant enhancement in growth and bacopa saponin content. Bacopasaponin D (1.4-1.69 %) was maximally enhanced in transgenic plants containing crypt. In comparison to Ri-transformed plants, Ri crypt-transformed plants showed significantly (p ≤ 0.05) enhanced accumulation of bacoside A(3), bacopasaponin D, bacopaside II, bacopaside III and bacopaside V. Produced transgenic lines can be used for further research on elicitation in crypt-transgenic plants as well as for large scale production of saponins. Key message The cryptogein gene, which encodes a proteinaceous elicitor is associated with increase in secondary metabolite accumulation-either alone or in addition to the increases associated with transformation by A. rhizogenes.

Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome

PubMed Central

Takemura, Naoki; Kawasaki, Takumi; Kunisawa, Jun; Sato, Shintaro; Lamichhane, Aayam; Kobiyama, Kouji; Aoshi, Taiki; Ito, Junichi; Mizuguchi, Kenji; Karuppuchamy, Thangaraj; Matsunaga, Kouta; Miyatake, Shoichiro; Mori, Nobuko; Tsujimura, Tohru; Satoh, Takashi; Kumagai, Yutaro; Kawai, Taro; Standley, Daron M.; Ishii, Ken J.; Kiyono, Hiroshi; Akira, Shizuo; Uematsu, Satoshi

2014-01-01

High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. Tlr3−/− mice show substantial resistance to GIS owing to significantly reduced radiation-induced crypt cell death. Despite showing reduced crypt cell death, p53-dependent crypt cell death is not impaired in Tlr3−/− mice. p53-dependent crypt cell death causes leakage of cellular RNA, which induces extensive cell death via TLR3. An inhibitor of TLR3–RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS. PMID:24637670

Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

PubMed Central

Baker, Ann-Marie; Cereser, Biancastella; Melton, Samuel; Fletcher, Alexander G.; Rodriguez-Justo, Manuel; Tadrous, Paul J.; Humphries, Adam; Elia, George; McDonald, Stuart A.C.; Wright, Nicholas A.; Simons, Benjamin D.; Jansen, Marnix; Graham, Trevor A.

2014-01-01

Summary Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+). Furthermore, we show that, in adenomatous crypts (APC−/−), there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics. PMID:25127143

Modelling Spatially Regulated β-Catenin Dynamics and Invasion in Intestinal Crypts

PubMed Central

Murray, Philip J.; Kang, Jun-Won; Mirams, Gary R.; Shin, Sung-Young; Byrne, Helen M.; Maini, Philip K.; Cho, Kwang-Hyun

2010-01-01

Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from mouse and rat to human) and throughout the different regions of the small and large intestines. In this article, we construct a partial differential equation model of a single colonic crypt that describes the spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of our continuum model is that it is based upon assumptions that can be directly related to processes at the cellular and subcellular scales. We use the model to predict how the distributions of Wnt pathway proteins are affected by mutations. The model is then extended to investigate how mutant cell populations can invade neighboring crypts. The model simulations suggest that cell crowding caused by increased proliferation and decreased cell loss may be sufficient for a mutant cell population to colonize a neighboring healthy crypt. PMID:20682248

Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horita, Nobukatsu; Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp; Hayashi, Ryohei

Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualisedmore » in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.« less

Human colonic crypts in culture: segregation of immunochemical markers in normal versus adenoma-derived.

PubMed

Dame, Michael K; Jiang, Yan; Appelman, Henry D; Copley, Kelly D; McClintock, Shannon D; Aslam, Muhammad Nadeem; Attili, Durga; Elmunzer, B Joseph; Brenner, Dean E; Varani, James; Turgeon, D Kim

2014-02-01

In order to advance a culture model of human colonic neoplasia, we developed methods for the isolation and in vitro maintenance of intact colonic crypts from normal human colon tissue and adenomas. Crypts were maintained in three-dimensional Matrigel culture with a simple, serum-free, low Ca(2+) (0.15 mM) medium. Intact colonic crypts from normal human mucosa were viably maintained for 3-5 days with preservation of the in situ crypt-like architecture, presenting a distinct base and apex. Abnormal structures from adenoma tissue could be maintained through multiple passages (up to months), with expanding buds/tubules. Immunohistochemical markers for intestinal stem cells (Lgr5), growth (Ki67), differentiation (E-cadherin, cytokeratin 20 (CK20) and mucin 2 (MUC2)) and epithelial turnover (Bax, cleaved Caspase-3), paralleled the changes in function. The epithelial cells in normal crypts followed the physiological sequence of progression from proliferation to differentiation to dissolution in a spatially and temporally appropriate manner. Lgr5 expression was seen in a few basal cells of freshly isolated crypts, but was not detected after 1-3 days in culture. After 24 h in culture, crypts from normal colonic tissue continued to show strong Ki67 and MUC2 expression at the crypt base, with a gradual decrease over time such that by days 3-4 Ki67 was not expressed. The differentiation marker CK20 increased over the same period, eventually becoming intense throughout the whole crypt. In adenoma-derived structures, expression of markers for all stages of progression persisted for the entire time in culture. Lgr5 showed expression in a few select cells after months in culture. Ki67 and MUC2 were largely associated with the proliferative budding regions while CK20 was localized to the parent structure. This ex vivo culture model of normal and adenomatous crypts provides a readily accessible tool to help understand the growth and differentiation process in human colonic epithelium.

The Development of M Cells in Peyer’s Patches Is Restricted to Specialized Dome-Associated Crypts

PubMed Central

Gebert, Andreas; Fassbender, Susanne; Werner, Kerstin; Weissferdt, Annikka

1999-01-01

It is controversial whether the membranous (M) cells of the Peyer’s patches represent a separate cell line or develop from enterocytes under the influence of lymphocytes on the domes. To answer this question, the crypts that produce the dome epithelial cells were studied and the distribution of M cells over the domes was determined in mice. The Ulex europaeus agglutinin was used to detect M cells in mouse Peyer’s patches. Confocal microscopy with lectin-gold labeling on ultrathin sections, scanning electron microscopy, and laminin immuno-histochemistry were combined to characterize the cellular composition and the structure of the dome-associated crypts and the dome epithelium. In addition, the sites of lymphocyte invasion into the dome epithelium were studied after removal of the epithelium using scanning electron microscopy. The domes of Peyer’s patches were supplied with epithelial cells that derived from two types of crypt: specialized dome-associated crypts and ordinary crypts differing not only in shape, size, and cellular composition but also in the presence of M cell precursors. When epithelial cells derived from ordinary crypts entered the domes, they formed converging radial strips devoid of M cells. In contrast to the M cells, the sites where lymphocytes invaded the dome epithelium were not arranged in radial strips, but randomly distributed over the domes. M cell development is restricted to specialized dome-associated crypts. Only dome epithelial cells that derive from these specialized crypts differentiate into M cells. It is concluded that M cells represent a separate cell line that is induced in the dome-associated crypts by still unknown, probably diffusible lymphoid factors. PMID:10329609

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

Using crypts as iris minutiae

NASA Astrophysics Data System (ADS)

Shen, Feng; Flynn, Patrick J.

2013-05-01

Iris recognition is one of the most reliable biometric technologies for identity recognition and verification, but it has not been used in a forensic context because the representation and matching of iris features are not straightforward for traditional iris recognition techniques. In this paper we concentrate on the iris crypt as a visible feature used to represent the characteristics of irises in a similar way to fingerprint minutiae. The matching of crypts is based on their appearances and locations. The number of matching crypt pairs found between two irises can be used for identity verification and the convenience of manual inspection makes iris crypts a potential candidate for forensic applications.

Modelling spatially regulated beta-catenin dynamics and invasion in intestinal crypts.

PubMed

Murray, Philip J; Kang, Jun-Won; Mirams, Gary R; Shin, Sung-Young; Byrne, Helen M; Maini, Philip K; Cho, Kwang-Hyun

2010-08-04

Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from mouse and rat to human) and throughout the different regions of the small and large intestines. In this article, we construct a partial differential equation model of a single colonic crypt that describes the spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of our continuum model is that it is based upon assumptions that can be directly related to processes at the cellular and subcellular scales. We use the model to predict how the distributions of Wnt pathway proteins are affected by mutations. The model is then extended to investigate how mutant cell populations can invade neighboring crypts. The model simulations suggest that cell crowding caused by increased proliferation and decreased cell loss may be sufficient for a mutant cell population to colonize a neighboring healthy crypt. 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

c-Myb is required for progenitor cell homeostasis in colonic crypts

PubMed Central

Malaterre, Jordane; Carpinelli, Marina; Ernst, Matthias; Alexander, Warren; Cooke, Michael; Sutton, Susan; Dworkin, Sebastian; Heath, Joan K.; Frampton, Jon; McArthur, Grant; Clevers, Hans; Hilton, Douglas; Mantamadiotis, Theo; Ramsay, Robert G.

2007-01-01

The colonic crypt is the functional unit of the colon mucosa with a central role in ion and water reabsorption. Under steady-state conditions, the distal colonic crypt harbors a single stem cell at its base that gives rise to highly proliferative progenitor cells that differentiate into columnar, goblet, and endocrine cells. The role of c-Myb in crypt homeostasis has not been elucidated. Here we have studied three genetically distinct hypomorphic c-myb mutant mouse strains, all of which show reduced colonic crypt size. The mutations target the key domains of the transcription factor: the DNA binding, transactivation, and negative regulatory domains. In vivo proliferation and cell cycle marker studies suggest that these mice have a progenitor cell proliferation defect mediated in part by reduced Cyclin E1 expression. To independently assess the extent to which c-myb is required for colonic crypt homeostasis we also generated a novel tissue-specific mouse model to allow the deletion of c-myb in adult colon, and using these mice we show that c-Myb is required for crypt integrity, normal differentiation, and steady-state proliferation. PMID:17360438

Intestinal fluid absorption in spontaneously hypertensive rats.

PubMed Central

Dorey, P G; King, J; Munday, K A; Parsons, B J; Poat, J A

1983-01-01

A comparison has been made of intestinal fluid absorption between male Okamoto spontaneously hypertensive rats (s.h.r.) and normotensive male Wistar controls. S.h.r. show enhanced fluid absorption both in hypertensive adults and in young s.h.r. before hypertension has developed. Several potential causes for increased fluid transport in s.h.r. were tested using pharmacological antagonists. It is unlikely that enhanced fluid absorption is due to high sympathetic nervous activity, the renin-angiotensin system or is secondary to hypertension. Intestine from s.h.r. have a high short-circuit current indicating a change in ion pump activity. These results are discussed in relation to the possible causes of increased fluid (ion) transport by the intestine of s.h.r. PMID:6361232

Regulation of intramembranous absorption and amniotic fluid volume by constituents in fetal sheep urine

PubMed Central

Jonker, Sonnet S.; Louey, Samantha; Cheung, Cecilia Y.; Brace, Robert A.

2013-01-01

Our objective was to test the hypothesis that fetal urine contains a substance(s) that regulates amniotic fluid volume by altering the rate of intramembranous absorption of amniotic fluid. In late gestation ovine fetuses, amniotic fluid volumes, urine, and lung liquid production rates, swallowed volumes and intramembranous volume and solute absorption rates were measured over 2-day periods under control conditions and when urine was removed and continuously replaced at an equal rate with exogenous fluid. Intramembranous volume absorption rate decreased by 40% when urine was replaced with lactated Ringer solution or lactated Ringer solution diluted 50% with water. Amniotic fluid volume doubled under both conditions. Analysis of the intramembranous sodium and chloride fluxes suggests that the active but not passive component of intramembranous volume absorption was altered by urine replacement, whereas both active and passive components of solute fluxes were altered. We conclude that fetal urine contains an unidentified substance(s) that stimulates active intramembranous transport of amniotic fluid across the amnion into the underlying fetal vasculature and thereby functions as a regulator of amniotic fluid volume. PMID:23824958

A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments.

PubMed

Bravo, Rafael; Axelrod, David E

2013-11-18

Normal colon crypts consist of stem cells, proliferating cells, and differentiated cells. Abnormal rates of proliferation and differentiation can initiate colon cancer. We have measured the variation in the number of each of these cell types in multiple crypts in normal human biopsy specimens. This has provided the opportunity to produce a calibrated computational model that simulates cell dynamics in normal human crypts, and by changing model parameter values, to simulate the initiation and treatment of colon cancer. An agent-based model of stochastic cell dynamics in human colon crypts was developed in the multi-platform open-source application NetLogo. It was assumed that each cell's probability of proliferation and probability of death is determined by its position in two gradients along the crypt axis, a divide gradient and in a die gradient. A cell's type is not intrinsic, but rather is determined by its position in the divide gradient. Cell types are dynamic, plastic, and inter-convertible. Parameter values were determined for the shape of each of the gradients, and for a cell's response to the gradients. This was done by parameter sweeps that indicated the values that reproduced the measured number and variation of each cell type, and produced quasi-stationary stochastic dynamics. The behavior of the model was verified by its ability to reproduce the experimentally observed monocolonal conversion by neutral drift, the formation of adenomas resulting from mutations either at the top or bottom of the crypt, and by the robust ability of crypts to recover from perturbation by cytotoxic agents. One use of the virtual crypt model was demonstrated by evaluating different cancer chemotherapy and radiation scheduling protocols. A virtual crypt has been developed that simulates the quasi-stationary stochastic cell dynamics of normal human colon crypts. It is unique in that it has been calibrated with measurements of human biopsy specimens, and it can simulate the variation of cell types in addition to the average number of each cell type. The utility of the model was demonstrated with in silico experiments that evaluated cancer therapy protocols. The model is available for others to conduct additional experiments.

Advances in Evaluation of Chronic Diarrhea in Infants.

PubMed

Thiagarajah, Jay R; Kamin, Daniel S; Acra, Sari; Goldsmith, Jeffrey D; Roland, Joseph T; Lencer, Wayne I; Muise, Aleixo M; Goldenring, James R; Avitzur, Yaron; Martín, Martín G

2018-06-01

Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Absorption fluids data survey

NASA Astrophysics Data System (ADS)

Macriss, R. A.; Zawacki, T. S.

Development of improved data for the thermodynamic, transport and physical properties of absorption fluids were studied. A specific objective of this phase of the study is to compile, catalog and coarse screen the available US data of known absorption fluid systems and publish it as a first edition document to be distributed to manufacturers, researchers and others active in absorption heat pump activities. The methodology and findings of the compilation, cataloguing and coarse screening of the available US data on absorption fluid properties and presents current status and future work on this project are summarized. Both in house file and literature searches were undertaken to obtain available US publications with pertinent physical, thermodynamic and transport properties data for absorption fluids. Cross checks of literature searches were also made, using available published bibliographies and literature review articles, to eliminate secondary sources for the data and include only original sources and manuscripts. The properties of these fluids relate to the liquid and/or vapor state, as encountered in normal operation of absorption equipment employing such fluids, and to the crystallization boundary of the liquid phase, where applicable. The actual data were systematically classified according to the type of fluid and property, as well as temperature, pressure and concentration ranges over which data were available. Data were sought for 14 different properties: Vapor-Liquid Equilibria, Crystallization Temperature, Corrosion Characteristics, Heat of Mixing, Liquid-Phase-Densities, Vapor-Liquid-Phase Enthalpies, Specific Heat, Stability, Viscosity, Mass Transfer Rate, Heat Transfer Rate, Thermal Conductivity, Flammability, and Toxicity.

Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.

PubMed

Tang, Lieqi; Fang, Xiefan; Winesett, Steven P; Cheng, Catherine Y; Binder, Henry J; Rivkees, Scott A; Cheng, Sam X

2017-01-01

Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 μM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.

Computational Models Reveal a Passive Mechanism for Cell Migration in the Crypt

PubMed Central

Dunn, Sara-Jane; Näthke, Inke S.; Osborne, James M.

2013-01-01

Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt. PMID:24260407

Lack of evidence in vivo for a remote effect of Escherichia coli heat stable enterotoxin on jejunal fluid absorption.

PubMed

Lucas, M L; Duncan, N W; o'reilly, N F; McIlvenny, T J; Nelson, Y B

2008-05-01

On contact with the mucosa, heat stable (STa) enterotoxin from Escherichia coli reduces fluid absorption in vivo in the perfused jejunum of the anaesthetized rat. The question of whether it also has a vagally mediated remote action on jejunal absorption, when instilled into the ileum, was re-examined, given contradictory findings in the literature. A standard perfused loop preparation was used to measure luminal uptake of fluid in vivo by means of volume recovery. STa in the ileum was found to have no effect on jejunal absorption, regardless of cervical or sub-diaphragmatic vagotomy and also regardless of the nature of the perfusate anion. The batches of toxin were shown in parallel experiments to reduce fluid absorption directly in the jejunum and also in the ileum. Similarly, vagal nerves prior to section had demonstrable in vivo physiological function. There was therefore no evidence for an indirect, vagally mediated ileal effect of STa on proximal fluid absorption.

Duodenal crypt health following exposure to Cr(VI): Micronucleus scoring, γ-H2AX immunostaining, and synchrotron X-ray fluorescence microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Chad M.; Wolf, Jeffrey C.; Elbekai, Reem H.

2015-08-01

Lifetime exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal damage and an increase in duodenal tumors in B6C3F1 mice. To assess whether these tumors could be the result of a direct mutagenic or genotoxic mode of action, we conducted a GLP-compliant 7-day drinking water study to assess crypt health along the entire length of the duodenum. Mice were exposed to water (vehicle control), 1.4, 21, or 180 ppm Cr(VI) via drinking water for 7 consecutive days. Crypt enterocytes in Swiss roll sections were scored as normal, mitotic, apoptotic, karyorrhectic, or as having micronuclei. Amore » single oral gavage of 50 mg/kg cyclophosphamide served as a positive control for micronucleus induction. Exposure to 21 and 180 ppm Cr(VI) significantly increased the number of crypt enterocytes. Micronuclei and γ-H2AX immunostaining were not elevated in the crypts of Cr(VI)-treated mice. In contrast, treatment with cyclophosphamide significantly increased numbers of crypt micronuclei and qualitatively increased γ-H2AX immunostaining. Synchrotron-based X-ray fluorescence (XRF) microscopy revealed the presence of strong Cr fluorescence in duodenal villi, but negligible Cr fluorescence in the crypt compartment. Together, these data indicate that Cr(VI) does not adversely effect the crypt compartment where intestinal stem cells reside, and provide additional evidence that the mode of action for Cr(VI)-induced intestinal cancer in B6C3F1 mice involves chronic villous wounding resulting in compensatory crypt enterocyte hyperplasia.« less

In vitro and in vivo percutaneous absorption of retinol from cosmetic formulations: Significance of the skin reservoir and prediction of systemic absorption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yourick, Jeffrey J.; Jung, Connie T.; Bronaugh, Robert L.

2008-08-15

The percutaneous absorption of retinol (Vitamin A) from cosmetic formulations was studied to predict systemic absorption and to understand the significance of the skin reservoir in in vitro absorption studies. Viable skin from fuzzy rat or human subjects was assembled in flow-through diffusion cells for in vitro absorption studies. In vivo absorption studies using fuzzy rats were performed in glass metabolism cages for collection of urine, feces, and body content. Retinol (0.3%) formulations (hydroalcoholic gel and oil-in-water emulsion) containing {sup 3}H-retinol were applied and absorption was measured at 24 or 72 h. All percentages reported are % of applied dose.more » In vitro studies using human skin and the gel and emulsion vehicles found 0.3 and 1.3% retinol, respectively, in receptor fluid at 24 h. Levels of absorption in the receptor fluid increased over 72 h with the gel and emulsion vehicles. Using the gel vehicle, in vitro rat skin studies found 23% in skin and 6% in receptor fluid at 24 h, while 72-h studies found 18% in skin and 13% in receptor fluid. Thus, significant amounts of retinol remained in rat skin at 24 h and decreased over 72 h, with proportional increases in receptor fluid. In vivo rat studies with the gel found 4% systemic absorption of retinol after 24 h and systemic absorption did not increase at 72 h. Retinol remaining in rat skin after in vivo application was 18% and 13% of the applied dermal dose after 24 and 72 h, respectively. Similar observations were made with the oil-in water emulsion vehicle in the rat. Retinol formed a reservoir in rat skin both in vivo and in vitro. Little additional retinol was bioavailable after 24 h. Comparison of these in vitro and in vivo results for absorption through rat skin indicates that the 24-h in vitro receptor fluid value accurately estimated 24-h in vivo systemic absorption. Therefore, the best single estimate of retinol systemic absorption from in vitro human skin studies is the 24-h receptor fluid value. However, the receptor fluid value from the 72-h extended study may be used in a worst-case exposure estimate. In conclusion, in vivo skin absorption studies can be useful in determining whether to include material in the in vitro skin reservoir as absorbable material in estimates of systemic absorption.« less

Architecture for Absorption Based Heaters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moghaddam, Saeed; Chugh, Devesh

An absorption based heater is constructed on a fluid barrier heat exchanging plate such that it requires little space in a structure. The absorption based heater has a desorber, heat exchanger, and absorber sequentially placed on the fluid barrier heat exchanging plate. The vapor exchange faces of the desorber and the absorber are covered by a vapor permeable membrane that is permeable to a refrigerant vapor but impermeable to an absorbent. A process fluid flows on the side of the fluid barrier heat exchanging plate opposite the vapor exchange face through the absorber and subsequently through the heat exchanger. Themore » absorption based heater can include a second plate with a condenser situated parallel to the fluid barrier heat exchanging plate and opposing the desorber for condensation of the refrigerant for additional heating of the process fluid.« less

Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut

PubMed Central

Huang, Ching‐Ying; Kuo, Wei‐Ting; Huang, Chung‐Yen; Lee, Tsung‐Chun; Chen, Chin‐Tin; Peng, Wei‐Hao; Lu, Kuo‐Shyan; Yang, Chung‐Yi

2016-01-01

Key points Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria‐derived septic complications.Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive.A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes.Pyruvate suppressed epithelial cell death in an ATP‐independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut.Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti‐necroptotic role of glycolytic pyruvate under ischaemic stress. Abstract Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor‐interacting protein kinase (RIP)‐dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium‐glucose transporter 1 ameliorated ischaemia/reperfusion‐induced epithelial injury, partly via anti‐apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1‐dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell‐permeable pyruvate suppressed epithelial cell death in an ATP‐independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal‐to‐serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP. PMID:27121603

Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance.

PubMed

Naito, Tomoaki; Mulet, Céline; De Castro, Cristina; Molinaro, Antonio; Saffarian, Azadeh; Nigro, Giulia; Bérard, Marion; Clerc, Mélanie; Pedersen, Amy B; Sansonetti, Philippe J; Pédron, Thierry

2017-10-17

We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter , Delftia , and Stenotrophomonas ). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS), through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4)-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage. IMPORTANCE The LPS from crypt-specific core microbiota controls intestinal epithelium proliferation through necroptosis of stem cells and enhances cell differentiation, mainly the goblet cell lineage. Copyright © 2017 Naito et al.

Extracellular pH regulation in microdomains of colonic crypts: effects of short-chain fatty acids.

PubMed Central

Chu, S; Montrose, M H

1995-01-01

It has been suggested that transepithelial gradients of short-chain fatty acids (SCFAs; the major anions in the colonic lumen) generate pH gradients across the colonic epithelium. Quantitative confocal microscopy was used to study extracellular pH in mouse distal colon with intact epithelial architecture, by superfusing tissue with carboxy SNARF-1 (a pH-sensitive fluorescent dye). Results demonstrate extracellular pH regulation in two separate microdomains surrounding colonic crypts: the crypt lumen and the subepithelial tissue adjacent to crypt colonocytes. Apical superfusion with (i) a poorly metabolized SCFA (isobutyrate), (ii) an avidly metabolized SCFA (n-butyrate), or (iii) a physiologic mixture of acetate/propionate/n-butyrate produced similar results: alkalinization of the crypt lumen and acidification of subepithelial tissue. Effects were (i) dependent on the presence and orientation of a transepithelial SCFA gradient, (ii) not observed with gluconate substitution, and (iii) required activation of sustained vectorial acid/base transport by SCFAs. Results suggest that the crypt lumen functions as a pH microdomain due to slow mixing with bulk superfusates and that crypts contribute significant buffering capacity to the lumen. In conclusion, physiologic SCFA gradients cause polarized extracellular pH regulation because epithelial architecture and vectorial transport synergize to establish regulated microenvironments. Images Fig. 1 Fig. 3 PMID:7724557

Smad3 contributes to positioning of proliferating cells in colonic crypts by inducing EphB receptor protein expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furukawa, Kiyoshi; Sato, Toru; Katsuno, Tatsuro, E-mail: katsuno@faculty.chiba-u.jp

2011-02-25

Research highlights: {yields} Smad3{sup -/-} mice showed an increased number of proliferating epithelial cells in colonic crypts. {yields} Proliferating epithelial cells showed activated Wnt/{beta}-catenin pathway. {yields} Smad3{sup -/-} mice also showed intermingling of proliferating cells with differentiated cells. {yields} Loss of EphB receptor expression was observed in the colonic crypts of Smad3{sup -/-} mice. {yields} Loss of EphB receptor expression is likely responsible for cell intermingling. -- Abstract: Deficiency of Smad3, an intracellular mediator of TGF-{beta}, was shown to significantly accelerate re-epithelialization of the colonic mucosa. This study was performed to investigate the molecular mechanisms by which Smad3 controls colonicmore » epithelial cell proliferation and crypt formation. Smad3{sup ex8/ex8} C57BL/6 mice were used in this study and wild-type littermates served as controls. The number of proliferating cells in the isolated colonic epithelium of Smad3{sup -/-} mice was significantly increased compared to that in wild-type littermates. Protein levels of the cell cycle inhibitors p21 and p27 were significantly decreased, while that of c-Myc was increased in the isolated colonic epithelium from Smad3{sup -/-} mice. In the colonic tissue of wild-type mice, cell proliferation was restricted to the bottom of the crypts in accordance with nuclear {beta}-catenin staining, whereas proliferating cells were located throughout the crypts in Smad3{sup -/-} mice in accordance with nuclear {beta}-catenin staining, suggesting that Smad3 is essential for locating proliferating cells at the bottom of the colonic crypts. Notably, in Smad3{sup -/-} mice, there was loss of EphB2 and EphB3 receptor protein expression, critical regulators of proliferating cell positioning, while EphB receptor protein expression was confirmed at the bottom of the colonic crypts in wild-type mice. These observations indicated that disturbance of the EphB/ephrin B system brings about mispositioning of proliferating cells in the colonic crypts of Smad3{sup -/-} mice. In conclusion, Smad3 is essential for controlling number and positioning of proliferating cells in the colonic crypts and contributes to formation of a 'proliferative zone' at the bottom of colonic crypts in the normal colon.« less

Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle.

PubMed

Lyons, John D; Klingensmith, Nathan J; Otani, Shunsuke; Mittal, Rohit; Liang, Zhe; Ford, Mandy L; Coopersmith, Craig M

2017-12-01

Cell production and death are tightly regulated in the rapidly renewing gut epithelium, with proliferation confined to crypts and apoptosis occurring in villi and crypts. This study sought to determine how stress alters these compartmentalized processes. Wild-type mice made septic via cecal ligation and puncture had decreased crypt proliferation and increased crypt and villus apoptosis. Fabpi -TAg mice expressing large T-antigen solely in villi had ectopic enterocyte proliferation with increased villus apoptosis in unmanipulated animals. Septic fabpi -TAg mice had an unexpected increase in villus proliferation compared with unmanipulated littermates, whereas crypt proliferation was decreased. Cell cycle regulators cyclin D1 and cyclin D2 were decreased in jejunal tissue in septic transgenic mice. In contrast, villus and crypt apoptosis were increased in septic fabpi -TAg mice. To examine the relationship between apoptosis and proliferation in a compartment-specific manner, fabpi -TAg mice were crossed with fabpl -Bcl-2 mice, resulting in expression of both genes in the villus but Bcl-2 alone in the crypt. Septic bi-transgenic animals had decreased crypt apoptosis but had a paradoxical increase in villus apoptosis compared with septic fabpi -TAg mice, associated with decreased proliferation in both compartments. Thus, sepsis unmasks compartment-specific proliferative and apoptotic regulation that is not present under homeostatic conditions.-Lyons, J. D., Klingensmith, N. J., Otani, S., Mittal, R., Liang, Z., Ford, M. L., Coopersmith, C. M. Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle. © FASEB.

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

PubMed

Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p < 0.001). This one patient had "Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance

PubMed Central

Naito, Tomoaki; Mulet, Céline; De Castro, Cristina; Molinaro, Antonio; Saffarian, Azadeh; Nigro, Giulia; Bérard, Marion; Clerc, Mélanie; Pedersen, Amy B.; Pédron, Thierry

2017-01-01

ABSTRACT We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS), through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4)-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage. PMID:29042502

Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation

PubMed Central

Yuan, Jia; Cha, Jeeyeon; Deng, Wenbo; Bartos, Amanda; Sun, Xiaofei; Ho, Hsin-Yi Henry; Borg, Jean-Paul; Yamaguchi, Terry P.; Yang, Yingzi; Dey, Sudhansu K.

2016-01-01

Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo–uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudinal axis within specialized implantation chambers (crypts) that originate within the evaginations directed from the primary lumen toward the AM domain. The morphological orientation of crypts in rodent uteri was recognized more than a century ago, but the mechanism remained unknown. Here we provide evidence that planar cell polarity (PCP) signaling orchestrates directed epithelial evaginations to form crypts for implantation in mice. Uterine deletion of Vang-like protein 2, but not Vang-like protein 1, conferred aberrant PCP signaling, misdirected epithelial evaginations, defective crypt formation, and blastocyst attachment, leading to severely compromised pregnancy outcomes. The study reveals a previously unrecognized role for PCP in executing spatial cues for crypt formation and implantation. Because PCP is an evolutionarily conserved phenomenon, our study is likely to inspire implantation studies of this signaling pathway in humans and other species. PMID:27911818

Tales from the crypt: a parasitoid manipulates the behaviour of its parasite host

PubMed Central

Liu, Sean M.; Forbes, Andrew A.; Egan, Scott P.

2017-01-01

There are many examples of apparent manipulation of host phenotype by parasites, yet few examples of hypermanipulation—where a phenotype-manipulating parasite is itself manipulated by a parasite. Moreover, few studies confirm manipulation is occurring by quantifying whether the host's changed phenotype increases parasite fitness. Here we describe a novel case of hypermanipulation, in which the crypt gall wasp Bassettia pallida (a phenotypic manipulator of its tree host) is manipulated by the parasitoid crypt-keeper wasp Euderus set, and show that the host's changed behaviour increases parasitoid fitness. Bassettia pallida parasitizes sand live oaks and induces the formation of a ‘crypt’ within developing stems. When parasitized by E. set, B. pallida adults excavate an emergence hole in the crypt wall, plug the hole with their head and die. We show experimentally that this phenomenon benefits E. set, as E. set that need to excavate an emergence hole themselves are about three times more likely to die trapped in the crypt. In addition, we discuss museum and field data to explore the distribution of the crypt-keeping phenomena. PMID:28123089

Foci of aberrant crypts in the colons of mice and rats exposed to carcinogens associated with foods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tudek, B.; Bird, R.P.; Bruce, W.R.

1989-03-01

Aberrant crypt foci can be identified in the colons of rodents treated 3 wk earlier with azoxymethane, a known colon carcinogen. These crypts can easily be visualized in the unsectioned methylene blue-stained colons under light microscopy, where they are distinguished by their increased size, more prominent epithelial cells, and pericryptal space. They occur as single aberrant crypts or as two, three, or four aberrant crypts in a cluster. We compared the reported ability of carcinogens associated with the human diet to induce colon cancer with the measured rate of induction of aberrant crypts in female CF1 mice and Sprague-Dawley rats.more » The carcinogens used were 1,2-dimethylhydrazine, methyl nitrosourea, N-nitrosodimethylamine, benzo(a)pyrene, aflatoxin B1, 2-amino-6-methyldipyrido(1,2-alpha:3',2'-d)imidazole, 2-amino-3-methylimidazo(4,5-P)quinoline, 2-amino-3,4-dimethylimidazo(4,5-P)quinoline, and 3-amino-1-methyl-5H-pyrido(4,3-b)indole. Graded doses of these compounds were given to the animals by gavage twice with a 4-day interval, and the animals were terminated 3 wk later. All colon carcinogens induced aberrant crypts in a dose-related fashion. N-Nitrosodimethylamine and 3-amino-1-methyl-5H-pyrido(4,3-b)indole, carcinogenic compounds that do not induce colon cancer, did not induce them. The ability of the studied compounds to induce aberrant crypts was species specific; e.g., aflatoxin B1 and 2-amino-3,4-dimethylimidazo(4,5-P)quinoline induce about 20 times more in rats than mice. This relationship was consistent with their reported ability to induce colon cancer in these species. Results of the present study support the use of the aberrant crypt assays to screen colon-specific carcinogens and to study the process of colon carcinogenesis.« less

WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeilstra, Jurrit; Joosten, Sander P.J.; Wensveen, Felix M.

Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causesmore » constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the stem cell compartment can be counterbalanced by an increased propensity to undergo cell death.« less

Evaluation of fluid absorption during holmium laser enucleation of prostate by breath ethanol technique.

PubMed

Shah, Hemendra N; Kausik, Vikram; Hegde, Sunil; Shah, Jignesh N; Bansal, Manish B

2006-02-01

In a prospective manner we studied various factors affecting fluid absorption during HoLEP. We also simultaneously evaluated changes in serum electrolytes and hemoglobin decrease during HoLEP. This prospective study comprised of 53 patients who underwent HoLEP at our institute. Irrigation fluid was normal saline tagged with ethanol (1% w/v). Intraoperatively a standard breath analyzer was used to monitor expired breath ethanol levels during the procedure at 10-minute intervals. Patients who absorbed irrigating fluid as indicated by positive intraoperative breath tests were considered absorbers. Serum electrolyte and hemoglobin estimations were done before and after surgery. Total irrigation time, amount of irrigation fluid used, weight of resected tissue and presence of capsular perforation were recorded. Statistical analysis was performed to observe the effects of various factors on the amount of intraoperative fluid absorption. Of 53 patients studied 14 (26.41%) demonstrated fluid absorption in the range of 213 to 930 ml (mean 459). Preoperative prostate weight, total irrigation time, amount of irrigation fluid used and resected tissue weight were all significantly greater in absorbers. Similarly, absorbers had a statistically significant decrease in hemoglobin level postoperatively. There was no statistically significant change in serum electrolytes between absorbers and nonabsorbers. Preoperative weight of prostate, total irrigation time, amount of irrigation fluid used and weight of resected tissue all directly influence the amount of fluid absorption during HoLEP. There is no significant change in serum electrolytes and no risk of the transurethral resection syndrome.

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed Central

Kennedy, M. F.; Tutton, P. J.; Barkla, D. H.

1985-01-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour. PMID:4041364

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.

Cryptosporidial infection in a captive European hedgehog (Erinaceus europaeus).

PubMed

Meredith, Anna Louise; Milne, Elspeth Mary

2009-12-01

An adult female hedgehog (Erinaceus europaeus) developed hemorrhagic diarrhea and was euthanized after failure to respond to treatment. At postmortem examination, the gastrointestinal tract was distended with clear fluid. Histopathologic examination of the jejunum and ileum revealed numerous small, round, pale basophilic organisms typical of cryptosporidia on the luminal surface of the enterocytes and free in the crypts. In addition, there was severe villus atrophy in the ileum. It was thought that an underlying chronic systemic disease had predisposed the hedgehog to cryptosporidiosis by immunosuppression. This report appears to be the first detailed description of cryptosporidiosis in this species.

Synchrotron-based imaging of chromium and  γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Chad M.; Seiter, Jennifer; Chappell, Mark A.

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodenamore » from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by ~2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. Lastly, these findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia.« less

Synchrotron-Based Imaging of Chromium and γ-H2AX Immunostaining in the Duodenum Following Repeated Exposure to Cr(VI) in Drinking Water

PubMed Central

Thompson, Chad M.; Seiter, Jennifer; Chappell, Mark A.; Tappero, Ryan V.; Proctor, Deborah M.; Suh, Mina; Wolf, Jeffrey C.; Haws, Laurie C.; Vitale, Rock; Mittal, Liz; Kirman, Christopher R.; Hays, Sean M.; Harris, Mark A.

2015-01-01

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by ∼2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia. PMID:25352572

Synchrotron-based imaging of chromium and  γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water

DOE PAGES

Thompson, Chad M.; Seiter, Jennifer; Chappell, Mark A.; ...

2014-10-28

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodenamore » from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by ~2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. Lastly, these findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia.« less

Culturing and Characterization of Gut Symbiont Burkholderia spp. from the Southern Chinch Bug, Blissus insularis (Hemiptera: Blissidae)

PubMed Central

Buss, Eileen A.; Boucias, Drion G.

2016-01-01

ABSTRACT The phloem-feeding Southern chinch bug, Blissus insularis, harbors a high density of the exocellular bacterial symbiont Burkholderia in the lumen of specialized midgut crypts. Here we developed an organ culture method that initially involved incubating the B. insularis crypts in osmotically balanced insect cell culture medium. This approach enabled the crypt-inhabiting Burkholderia spp. to make a transition to an in vitro environment and to be subsequently cultured in standard bacteriological media. Examinations using ribotyping and BOX-PCR fingerprinting techniques demonstrated that most in vitro-produced bacterial cultures were identical to their crypt-inhabiting Burkholderia counterparts. Genomic and physiological analyses of gut-symbiotic Burkholderia spp. that were isolated individually from two separate B. insularis laboratory colonies revealed that the majority of individual insects harbored a single Burkholderia ribotype in their midgut crypts, resulting in a diverse Burkholderia community within each colony. The diversity was also exhibited by the phenotypic and genotypic characteristics of these Burkholderia cultures. Access to cultures of crypt-inhabiting bacteria provides an opportunity to investigate the interaction between symbiotic Burkholderia spp. and the B. insularis host. Furthermore, the culturing method provides an alternative strategy for establishing in vitro cultures of other fastidious insect-associated bacterial symbionts. IMPORTANCE An organ culture method was developed to establish in vitro cultures of a fastidious Burkholderia symbiont associated with the midgut crypts of the Southern chinch bug, Blissus insularis. The identities of the resulting cultures were confirmed using the genomic and physiological features of Burkholderia cultures isolated from B. insularis crypts, showing that host insects maintained the diversity of Burkholderia spp. over multiple generations. The availability of characterized gut-symbiotic Burkholderia cultures provides a resource for genetic manipulation of these bacteria and for examination of the mechanisms underlying insect-bacterium symbiosis. PMID:27016568

Effects of calcium and vitamin D supplementation on crypt morphology in normal colon mucosa: A randomized clinical trial.

PubMed

Shen, Huafeng; Ahearn, Thomas U; Bostick, Roberd M

2015-03-01

Calcium and vitamin D modify the molecular phenotypic profiles of colon crypts in the normal colorectal mucosa of colorectal adenoma patients, but their effects on crypt morphology (length, perimeter, and area) are unknown. We analyzed data from a previously conducted pilot, randomized, double-blind, placebo-controlled 2 × 2 factorial chemoprevention clinical trial of supplemental calcium 2000 mg/d and vitamin D3 800 IU/d, alone and in combination, versus placebo over 6 mo. Colorectal crypt length, perimeter, and area in the normal-appearing rectal mucosa were quantified by image analysis. The mean crypt length increased by 1% (P=0.92) in the calcium group, and decreased by 2% (P=0.69) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. The mean crypt perimeter decreased by 2% (P=0.70) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group, but did not change appreciably in the calcium group. The mean crypt area decreased by 2% (P=0.74), 5% (P=0.41) and 7% (P=0.30) in the calcium, vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. Calcium and/or vitamin D3 supplementation do not appear to appreciably change crypt morphology in the normal colorectal mucosa of sporadic adenoma patients. These results, taken together with previous findings, support the use of molecular phenotypic over morphologic pre-neoplastic biomarkers of risk for colorectal neoplasms. © 2013 Wiley Periodicals, Inc.

Histopathological studies on the cystic formation of the human urothelium.

PubMed

Noda, S; Eto, K

1990-01-01

Histopathological examination of pyeloureteritis cystica and cystitis cystica revealed the mechanisms for the cystic formation of the urothelium. Chronic stimulation with inflammation or physical stimulation with crystals or calculi causes the urothelium to form an inflammatory crypt. The crypt is isolated as a result of an adhesive occlusion of the urothelium at the orifice of the crypt. This crypt is an immature cyst that cannot be clinically detected. A von Brunn's cell nest represents a cut surface of the immature cyst. The inflammatory cyst isolated from the urinary tract, i.e., the immature cyst, gradually grows into a complete cyst, i.e., a clinically visible mature cyst, because of a hydrodynamic flow between the surrounding tissue and neogenetic capillaries, and inflammation. These findings indicate that von Brunn's cell nest, and glandular and cystic formation, occur during development from an inflammatory crypt to an immature cyst and then, a mature cyst.

Effect of seven different additives on the properties of MR fluids

NASA Astrophysics Data System (ADS)

Zhang, J. Q.; Zhang, J.; Jing, Q.

2009-02-01

Magnetorheological (MR) fluids have been developed for application in semi-active magnetorheological fluid dampers and other magnetorheological fluid devices. In order to prepare special MR fluids to satisfy the demands of tracked vehicle, two different carrier fluids were chose to prepare MR fluids. Preparation of MR fluids, which are based on carriers such as special shock absorption fluid and 45# transformer oil, was finished. And characteristics of these samples were tested and analyzed. Results indicate, Tween-80 and Span-80 can improve sedimentary stability. Using 45# transformer oil instead of special shock absorption fluid as a carrier, the shear yield stress remains nearly invariable but the viscosity and the sedimentary stability are reduced. MR fluids with diameter of 2.73μm show better sedimentary stability than that of the MR fluids with diameter of 2.3μm, or 4.02μm. Stearic acid obviously improves sedimentary stability and off-state viscosity, but don't perform an obvious function on shear yield stress. In magnetic field of 237KA/m, the shear yield stress of MR fluid based on special shock absorption fluid and 45# transformer oil is 18.34KPa, 14.26KPa, respectively.

Effect of an inhibitor of noradrenaline uptake, desipramine, on cell proliferation in the intestinal crypt epithelium.

PubMed

Tutton, P J; Barkla, D H

1989-01-01

The intestinal mucosa receives an adrenergic innervation for which there is no commonly accepted function. However, in recent years, cell kinetic studies have raised the possibility that this innervation may be an important regulator of crypt cell proliferation. The effects of noradrenaline released from adrenergic nerves is terminated principally by re-uptake of the amine into the nerve and this process can be inhibited by the antidepressant drug, desipramine. In this report desipramine is shown to accelerate crypt cell proliferation in intact, but not in chemically sympathectomized rats, thus adding support to the notion that regulation of crypt cell division is an important function of the sympathetic nervous system.

Transepithelial SCFA fluxes link intracellular and extracellular pH regulation of mouse colonocytes.

PubMed

Chu, S; Montrose, M H

1997-10-01

We have studied pH regulation in both intracellular and extracellular compartments of mouse colonic crypts, using distal colonic mucosa with intact epithelial architecture. In this work, we question how transepithelial SCFA gradients affect intracellular pH (pHi) and examine interactions between extracellular pH (pHo) and pHi regulation in crypts of distal colonic epithelium from mouse. We studied pH regulation in three adjacent compartments of distal colonic epithelium (crypt lumen, crypt epithelial cell cytosol, and lamina propria) with SNARF-1 (a pH sensitive fluorescent dye), digital imaging microscopy (for pHi), and confocal microscopy (for pHo). Combining results from the three compartments allows us to find how pHi and pHo are regulated and related under the influence of physiological transepithelial SCFA gradients, and develop a better understanding of pH regulation mechanisms in colonic crypts. Results suggest a complex interdependency between SCFA fluxes and pHo values, which can directly affect how strongly SCFAs acidify colonocytes.

Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice: increased small intestinal crypt survival, crypt lengths and prolongation of average time to death.

PubMed

Ohara, M; Lu, H; Shiraki, K; Ishimura, Y; Uesaka, T; Katoh, O; Watanabe, H

2001-12-01

The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60Co-gamma-ray irradiation at a dose rate of 2Gy min(-1). Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1), the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects.

Synchrotron-based imaging of chromium and γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water.

PubMed

Thompson, Chad M; Seiter, Jennifer; Chappell, Mark A; Tappero, Ryan V; Proctor, Deborah M; Suh, Mina; Wolf, Jeffrey C; Haws, Laurie C; Vitale, Rock; Mittal, Liz; Kirman, Christopher R; Hays, Sean M; Harris, Mark A

2015-01-01

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum--the latter evidenced by lengthening of the crypt compartment by ∼2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology.

Culturing and Characterization of Gut Symbiont Burkholderia spp. from the Southern Chinch Bug, Blissus insularis (Hemiptera: Blissidae).

PubMed

Xu, Yao; Buss, Eileen A; Boucias, Drion G

2016-06-01

The phloem-feeding Southern chinch bug, Blissus insularis, harbors a high density of the exocellular bacterial symbiont Burkholderia in the lumen of specialized midgut crypts. Here we developed an organ culture method that initially involved incubating the B. insularis crypts in osmotically balanced insect cell culture medium. This approach enabled the crypt-inhabiting Burkholderia spp. to make a transition to an in vitro environment and to be subsequently cultured in standard bacteriological media. Examinations using ribotyping and BOX-PCR fingerprinting techniques demonstrated that most in vitro-produced bacterial cultures were identical to their crypt-inhabiting Burkholderia counterparts. Genomic and physiological analyses of gut-symbiotic Burkholderia spp. that were isolated individually from two separate B. insularis laboratory colonies revealed that the majority of individual insects harbored a single Burkholderia ribotype in their midgut crypts, resulting in a diverse Burkholderia community within each colony. The diversity was also exhibited by the phenotypic and genotypic characteristics of these Burkholderia cultures. Access to cultures of crypt-inhabiting bacteria provides an opportunity to investigate the interaction between symbiotic Burkholderia spp. and the B. insularis host. Furthermore, the culturing method provides an alternative strategy for establishing in vitro cultures of other fastidious insect-associated bacterial symbionts. An organ culture method was developed to establish in vitro cultures of a fastidious Burkholderia symbiont associated with the midgut crypts of the Southern chinch bug, Blissus insularis The identities of the resulting cultures were confirmed using the genomic and physiological features of Burkholderia cultures isolated from B. insularis crypts, showing that host insects maintained the diversity of Burkholderia spp. over multiple generations. The availability of characterized gut-symbiotic Burkholderia cultures provides a resource for genetic manipulation of these bacteria and for examination of the mechanisms underlying insect-bacterium symbiosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Insights into embryo defenses of the invasive apple snail Pomacea canaliculata: egg mass ingestion affects rat intestine morphology and growth.

PubMed

Dreon, Marcos S; Fernández, Patricia E; Gimeno, Eduardo J; Heras, Horacio

2014-06-01

The spread of the invasive snail Pomacea canaliculata is expanding the rat lungworm disease beyond its native range. Their toxic eggs have virtually no predators and unusual defenses including a neurotoxic lectin and a proteinase inhibitor, presumably advertised by a warning coloration. We explored the effect of egg perivitellin fluid (PVF) ingestion on the rat small intestine morphology and physiology. Through a combination of biochemical, histochemical, histopathological, scanning electron microscopy, cell culture and feeding experiments, we analyzed intestinal morphology, growth rate, hemaglutinating activity, cytotoxicity and cell proliferation after oral administration of PVF to rats. PVF adversely affects small intestine metabolism and morphology and consequently the standard growth rate, presumably by lectin-like proteins, as suggested by PVF hemaglutinating activity and its cytotoxic effect on Caco-2 cell culture. Short-term effects of ingested PVF were studied in growing rats. PVF-supplemented diet induced the appearance of shorter and wider villi as well as fused villi. This was associated with changes in glycoconjugate expression, increased cell proliferation at crypt base, and hypertrophic mucosal growth. This resulted in a decreased absorptive surface after 3 days of treatment and a diminished rat growth rate that reverted to normal after the fourth day of treatment. Longer exposure to PVF induced a time-dependent lengthening of the small intestine while switching to a control diet restored intestine length and morphology after 4 days. Ingestion of PVF rapidly limits the ability of potential predators to absorb nutrients by inducing large, reversible changes in intestinal morphology and growth rate. The occurrence of toxins that affect intestinal morphology and absorption is a strategy against predation not recognized among animals before. Remarkably, this defense is rather similar to the toxic effect of plant antipredator strategies. This defense mechanism may explain the near absence of predators of apple snail eggs.

Corrosion inhibitor for aqueous ammonia absorption system

DOEpatents

Phillips, Benjamin A.; Whitlow, Eugene P.

1998-09-22

A method of inhibiting corrosion and the formation of hydrogen and thus improving absorption in an ammonia/water absorption refrigeration, air conditioning or heat pump system by maintaining the hydroxyl ion concentration of the aqueous ammonia working fluid within a selected range under anaerobic conditions at temperatures up to 425.degree. F. This hydroxyl ion concentration is maintained by introducing to the aqueous ammonia working fluid an inhibitor in an amount effective to produce a hydroxyl ion concentration corresponding to a normality of the inhibitor relative to the water content ranging from about 0.015 N to about 0.2 N at 25.degree. C. Also, working fluids for inhibiting the corrosion of carbon steel and resulting hydrogen formation and improving absorption in an ammonia/water absorption system under anaerobic conditions at up to 425.degree. F. The working fluids may be aqueous solutions of ammonia and a strong base or aqueous solutions of ammonia, a strong base, and a specified buffer.

Corrosion inhibitor for aqueous ammonia absorption system

DOEpatents

Phillips, B.A.; Whitlow, E.P.

1998-09-22

A method is described for inhibiting corrosion and the formation of hydrogen and thus improving absorption in an ammonia/water absorption refrigeration, air conditioning or heat pump system by maintaining the hydroxyl ion concentration of the aqueous ammonia working fluid within a selected range under anaerobic conditions at temperatures up to 425 F. This hydroxyl ion concentration is maintained by introducing to the aqueous ammonia working fluid an inhibitor in an amount effective to produce a hydroxyl ion concentration corresponding to a normality of the inhibitor relative to the water content ranging from about 0.015 N to about 0.2 N at 25 C. Also, working fluids for inhibiting the corrosion of carbon steel and resulting hydrogen formation and improving absorption in an ammonia/water absorption system under anaerobic conditions at up to 425 F. The working fluids may be aqueous solutions of ammonia and a strong base or aqueous solutions of ammonia, a strong base, and a specified buffer. 5 figs.

Removing sulphur oxides from a fluid stream

DOEpatents

Katz, Torsten; Riemann, Christian; Bartling, Karsten; Rigby, Sean Taylor; Coleman, Luke James Ivor; Lail, Marty Alan

2014-04-08

A process for removing sulphur oxides from a fluid stream, such as flue gas, comprising: providing a non-aqueous absorption liquid containing at least one hydrophobic amine, the liquid being incompletely miscible with water; treating the fluid stream in an absorption zone with the non-aqueous absorption liquid to transfer at least part of the sulphur oxides into the non-aqueous absorption liquid and to form a sulphur oxide-hydrophobic amine-complex; causing the non-aqueous absorption liquid to be in liquid-liquid contact with an aqueous liquid whereby at least part of the sulphur oxide-hydrophobic amine-complex is hydrolyzed to release the hydrophobic amine and sulphurous hydrolysis products, and at least part of the sulphurous hydrolysis products is transferred into the aqueous liquid; separating the aqueous liquid from the non-aqueous absorption liquid. The process mitigates absorbent degradation problems caused by sulphur dioxide and oxygen in flue gas.

THE EFFECTS OF A HIGH ANIMAL FAT DIET ON THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO TRIHALOMETHANES IN THE DRINKING WATER

EPA Science Inventory

The Effects of a High Animal Fat Diet on the Induction of Aberrant Crypt Foci in the Colons of Male F344/N Rats Exposed to Trihalomethanes in the Drinking Water

Abstract

Aberrant crypt foci (ACF), identified as the putative precursor lesion in the development of co...

The effect of hyperthermia on the radiation response of crypt cells in mouse jejunum

NASA Technical Reports Server (NTRS)

Wilson, J. D.

1978-01-01

The effect of hyperthermia and/or gamma-radiation on the survival of intestinal crypt cells was studied in BDF sub 1 mice using a microcolony assay. Hyperthermia treatments, which in themselves caused no detectable cell lethality, inhibited the capacity of crypt cells to repair sublethal radiation damage. In addition, heat applied either before or after single radiation exposures potentiated lethal damage to crypt cells; the degree of enhancement was dependent on the time interval between treatments. At the levels of heating employed, DNA synthesis in the intestinal epithelium was significantly reduced immediately following exposure, but returned rapidly to normal levels. No further disturbances in cellular kinetics were observed for up to 10 days after heating.

Mast cell regulation of Na-glutamine co-transporters B0AT1 in villus and SN2 in crypt cells during chronic intestinal inflammation.

PubMed

Singh, Soudamani; Arthur, Subha; Talukder, Jamilur; Palaniappan, Balasubramanian; Coon, Steven; Sundaram, Uma

2015-04-15

In the chronically inflamed rabbit small intestine, brush border membrane (BBM) Na-glutamine co-transport is inhibited in villus cells (mediated by B0AT1), while it is stimulated in crypt cells (mediated by SN2/SNAT5). How mast cells, known to be enhanced in the chronically inflamed intestine, may regulate B0AT1 in villus and SN2/SNAT5 in crypt cell is unknown. Thus, the aim of the present study is to determine the regulation of B0AT1 and SN2/SNAT5 by mast cells during chronic enteritis. Chronic intestinal inflammation was induced in male rabbits with intra-gastric inoculation of Eimeria magna oocytes. Rabbits with chronic inflammation were treated with ketotifen (10 mg/day) or saline (Placebo) for 2 days. Villus and crypts cells were isolated from the rabbit intestine using the Ca++ chelation technique. Na/K-ATPase activity was measured as Pi from cellular homogenate. BBM vesicles (BBMV) were prepared from villus and crypt cells and uptake studies were performed using rapid filtration technique with (3)H-Glutamine. Western blot analyses were done using B0AT1 and SN2 specific antibodies. In villus cells, Na-glutamine co-transport inhibition observed during inflammation was completely reversed by ketotifen, a mast cell stabilizer. In contrast, in crypt cells, Na-glutamine co-transport stimulation was reversed to normal levels by ketotifen. Kinetic studies demonstrated that ketotifen reversed the inhibition of B0AT1 in villus cells by restoring co-transporter numbers in the BBM, whereas the stimulation of SN2/SNAT5 in crypts cells was reversed secondary to restoration of affinity of the co-transporter. Western blot analysis showed that ketotifen restored immune-reactive levels of B0AT1 in villus cells, while SN2/SNAT5 levels from crypts cell remained unchanged. In the present study we demonstrate that mast cells likely function as a common upstream immune pathway regulator of the Na-dependent glutamine co-transporters, B0AT1 in villus cells and SN2 in crypts cells that are uniquely altered in the chronically inflamed small intestine.

The coupled effect of fiber volume fraction and void fraction on hydraulic fluid absorption of quartz/BMI laminates

NASA Astrophysics Data System (ADS)

Hurdelbrink, Keith R.; Anderson, Jacob P.; Siddique, Zahed; Altan, M. Cengiz

2016-03-01

Bismaleimide (BMI) resin with quartz (AQ581) fiber reinforcement is a composite material frequently used in aerospace applications, such as engine cowlings and radomes. Various composite components used in aircrafts are exposed to different types of hydraulic fluids, which may lead to anomalous absorption behavior over the service life of the composite. Accurate predictive models for absorption of liquid penetrants are particularly important as the composite components are often exposed to long-term degradation due to absorbed moisture, hydraulic fluids, or similar liquid penetrants. Microstructural features such as fiber volume fraction and void fraction can have a significant effect on the absorption behavior of fiber-reinforced composites. In this paper, hydraulic fluid absorption characteristics of quartz/BMI laminates fabricated from prepregs preconditioned at different relative humidity and subsequently cured at different pressures are presented. The composite samples are immersed into hydraulic fluid at room temperature, and were not subjected to any prior degradation. To generate process-induced microvoids, prepregs were conditioned in an environmental chamber at 2% or 99% relative humidity at room temperature for a period of 24 hours prior to laminate fabrication. To alter the fiber volume fraction, the laminates were fabricated at cure pressures of 68.9 kPa (10 psi) or 482.6 kPa (70 psi) via a hot-press. The laminates are shown to have different levels of microvoids and fiber volume fractions, which were observed to affect the absorption dynamics considerably and exhibited clear non-Fickian behavior. A one-dimensional hindered diffusion model (HDM) was shown to be successful in predicting the hydraulic fluid absorption. Model prediction indicates that as the fabrication pressure increased from 68.9 kPa to 482.6 kPa, the maximum fluid content (M∞) decreased from 8.0% wt. to 1.0% wt. The degree of non-Fickian behavior, measured by hindrance coefficient (μ), was shown to increase with the increased void fraction.

DNA-based watermarks using the DNA-Crypt algorithm.

PubMed

Heider, Dominik; Barnekow, Angelika

2007-05-29

The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

Association of iris crypts with acute primary angle closure.

PubMed

Koh, Victor; Chua, Jacqueline; Shi, Yuan; Thakku, Sri Gowtham; Lee, Ryan; Nongpiur, Monisha E; Baskaran, Mani; Kumar, Rajesh S; Perera, Shamira; Aung, Tin; Cheng, Ching-Yu

2017-10-01

To determine the relationship between iris surface features and acute primary angle closure (APAC) in eyes with angle closure. Case-control study involving Asian patients diagnosed with previous APAC, primary angle closure suspect (PACS), primary angle closure (PAC) and primary angle closure glaucoma (PACG) at an eye centre in Singapore between August 2012 and January 2015. Participants underwent ophthalmic examination and digital slit-lamp iris photography. Iris surface features were graded based on crypts, furrows and colour. Fellow eyes of APAC were compared with PACS and PAC/PACG eyes with regard to their iris surface features. Occurrence of APAC. A total of 309 patients (71 APAC, 139 PACS, 47 PAC and 52 PACG) were included (mean age: 67.7±7.2 years and 36.6% male). Compared with PACS, higher crypt grade was significantly associated with lower odds of APAC (OR=0.58 for one grade higher in crypt grade; p=0.027, adjusted for age, gender, ethnicity and pupil diameter). The results remained similar when compared with PAC/PACG group (OR=0.58 for one grade higher in crypt grade; p=0.043). We did not observe any significant associations between iris furrows or colour with presence of APAC. Our study comprising Asian eyes with angle closure suggests that the presence of a higher crypt grading may be protective for APAC. As such, assessing iris surface architecture for crypts could be a new measure for risk stratification of developing APAC in eyes with angle closure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

DNA-based watermarks using the DNA-Crypt algorithm

PubMed Central

Heider, Dominik; Barnekow, Angelika

2007-01-01

Background The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. Results The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. Conclusion The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms. PMID:17535434

Association of iris surface features with iris parameters assessed by swept-source optical coherence tomography in Asian eyes.

PubMed

Tun, Tin A; Chua, Jacqueline; Shi, Yuan; Sidhartha, Elizabeth; Thakku, Sri Gowtham; Shei, William; Tan, Marcus Chiang Lee; Quah, Joanne Hui Min; Aung, Tin; Cheng, Ching-Yu

2016-12-01

To characterise the association of iris surface features (crypts, furrows and colour) with iris volume and curvature assessed by swept-source optical coherence tomography (SSOCT) in Asian eyes. Iris crypts (by number and size) and furrows (by number and circumferential extent) were graded from iris photographs. Iris colour was measured by a customised algorithm written on MATLAB (MathWorks, Natick, Massachusetts, USA). The iris was imaged by SSOCT (SS-1000, CASIA, Tomey, Nagoya, Japan). The associations of surface features with iris parameters were analysed using a generalised estimating equation. A total of 1704 subjects (3297 eyes) were included in the analysis. The majority was Chinese (86.4%), and 63.2% were females, and their mean age (±SD) was 61.4±6.6 years. After adjusting for age, sex, ethnicity, pupil size and corneal arcus, higher iris crypt grade was independently associated with smaller iris volume (β=-0.54, p<0.001), whereas darker irides and higher iris furrow grade were associated with larger iris volume (β=-0.041, p<0.001) and (β=0.233, p<0.001), respectively. Lighter coloured irides with more crypts and/or more furrows were also associated with less convexity (crypts: β=-0.003, p=0.03; furrows: β=-0.004, p=0.007; and colour: β=-0.001, p=0.005). Iris surface features were highly correlated with iris volume and curvature. Irides with more crypts have a smaller volume; and darker irides with more furrows have a larger volume. Lighter irides with more crypts and/or furrows have less convexity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

PubMed Central

Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

2015-01-01

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

Toll-like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis*

PubMed Central

Afrazi, Amin; Branca, Maria F.; Sodhi, Chhinder P.; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E.; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D.; Ozolek, John A.; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K.; Billiar, Timothy R.; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J.

2014-01-01

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4ΔIEC-OVER mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4ΔIEC mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development. PMID:24519940

Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis.

PubMed

Afrazi, Amin; Branca, Maria F; Sodhi, Chhinder P; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D; Ozolek, John A; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K; Billiar, Timothy R; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J

2014-04-04

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4(ΔIEC-OVER) mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4(ΔIEC) mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development.

Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

NASA Astrophysics Data System (ADS)

Welge, Weston A.; Barton, Jennifer K.

2016-03-01

Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

The influence of arachidonic acid metabolites on cell division in the intestinal epithelium and in colonic tumors.

PubMed

Petry, F M; Tutton, P J; Barkla, D H

1984-09-01

Various metabolites of arachidonic acid are now known to influence cell division. In this paper the effects on cell proliferation of arachidonic acid, some inhibitors of arachidonic acid metabolism and some analogs of arachidonic acid metabolites is described. The epithelial cell proliferation rate in the jejunum, in the descending colon and in dimethylhydrazine-induced tumors of rat colon was measured using a stathmokinetic technique. Administration of arachidonic acid resulted in retardation of cell proliferation in each of the tissues examined. A cyclooxygenase inhibitor (Flurbiprofen) prevented this effect of arachidonic acid in the jejunal crypts and in colonic tumors, but not in colonic crypts. In contrast, inhibitors of both cyclooxygenase and lipoxygenase (Benoxaprofen and BW755c) prevented the effect of arachidonic acid in the colonic crypts and reduced its effect on colonic tumours but did not alter its effect on the jejunum. An inhibitor of thromoboxane A2 synthetase (U51,605) was also able to prevent the inhibitory effect of arachidonic acid on colonic tumors. Treatment with 16,16-dimethyl PGE2 inhibited cell proliferation in jejunal crypts and in colonic tumors, as did a thromboxane A2 mimicking agent, U46619. Nafazatrom, an agent that stimulates prostacyclin synthesis and inhibits lypoxygenase, promoted cell proliferation in the jejunal crypts and colonic crypts, but inhibited cell proliferation in colonic tumours.

Method of and apparatus for determining the similarity of a biological analyte from a model constructed from known biological fluids

DOEpatents

Robinson, Mark R.; Ward, Kenneth J.; Eaton, Robert P.; Haaland, David M.

1990-01-01

The characteristics of a biological fluid sample having an analyte are determined from a model constructed from plural known biological fluid samples. The model is a function of the concentration of materials in the known fluid samples as a function of absorption of wideband infrared energy. The wideband infrared energy is coupled to the analyte containing sample so there is differential absorption of the infrared energy as a function of the wavelength of the wideband infrared energy incident on the analyte containing sample. The differential absorption causes intensity variations of the infrared energy incident on the analyte containing sample as a function of sample wavelength of the energy, and concentration of the unknown analyte is determined from the thus-derived intensity variations of the infrared energy as a function of wavelength from the model absorption versus wavelength function.

SNOM Imaging of a Crypt-Like Feature in Adenocarcinoma Associated with Barrett's Oesophagus

DOE PAGES

Craig, Timothy; Smith, Andrew D.; Holder, Gareth M.; ...

2018-01-05

The development of more accurate and sensitive diagnostic techniques is a key factor in efforts to improve cancer survival rates. The technique of infrared aperture fibre scanning near-field optical microscopy (IR-SNOM),together with radiation from the infrared free-electron laser (IR-FEL) on ALICEat Daresbury Laboratory (UK), has been used to obtain IR images of a crypt-like feature and the surrounding tissue; the tissue was taken from a patient with oesophageal adenocarcinoma and with a history of Barrett’s oesophagus. We have shown that the DNA signal is enhanced relative to other contributions in the region of the crypt, and the glycoprotein signal showsmore » a less pronounced increase in the region of the crypt. The Amide II signal is found to be anti-correlated with the DNA and glycoprotein profiles. The absorbance of the Amide II signal is found to differ for three different types of cancer tissue. In conclusion, high-resolution IR images of the crypt reveal additional structure that would not be resolved in diffraction-limited techniques.« less

Effects of dietary inclusion of silymarin on performance, intestinal morphology and ileal bacterial count in aflatoxin-challenged broiler chicks.

PubMed

Jahanian, E; Mahdavi, A H; Asgary, S; Jahanian, R

2017-10-01

This study was conducted to investigate the effect of dietary supplementation of silymarin on performance, jejunal morphology and ileal bacterial population in broiler chicks intoxicated with a mix of aflatoxins. A total of three hundred thirty six 7-day-old Ross broiler chicks were randomly distributed between seven experimental groups with four replicates of 12 birds each. Experimental treatments consisted of a control group (unchallenged), and a 2 × 3 factorial arrangement, including two aflatoxin levels (0.5 and 2 ppm) and three levels of silymarin (0, 500 and 1000 ppm). Birds were challenged with a mix of aflatoxins from 7 to 28 days of age. Results showed that increasing aflatoxin level resulted in decreased average daily feed intake (ADFI) and weight gain (ADWG), consequently impaired feed conversion ratio (FCR) throughout the trial period. Dietary supplementation of silymarin resulted in the marked increases in ADFI and ADWG, and improved FCR values in aflatoxin-challenged chicks. Ileal bacterial populations at days 28 and 42 of age were increased by incremental levels of aflatoxins. On the other hand, dietary silymarin supplementation suppressed ileal populations of Escherichia coli, Salmonella, Klebsiella and total negative bacteria in aflatoxicated birds. Increase in dietary aflatoxin level resulted in the decreased villi height, villi height-to-crypt depth ratio (VH:CD), villi surface area and apparent villi absorptive area, while it increased crypt depth, goblet cell count and lymphoid follicular diameter. Feeding silymarin at the level of 1000 ppm increased villi height and VH:CD in aflatoxicated birds. Present results indicate that dietary inclusion of silymarin could improve performance by suppressing ileal bacteria and enhancing absorptive surface area in aflatoxin-challenged broiler chicks. Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.

Enteral exposure to crude red kidney bean lectin induces maturation of the gut in suckling pigs.

PubMed

Rådberg, K; Biernat, M; Linderoth, A; Zabielski, R; Pierzynowski, S G; Weström, B R

2001-10-01

The present investigation characterized the effect of red kidney bean lectin exposure on gut maturation and function in young piglets. Eleven suckling pigs were given by stomach tube a crude red kidney bean lectin preparation (containing about 25% lectin, 400 mg/kg BW) (lectin-treated pigs) at 10, 11, and 12 d of life, and an additional 16 pigs (control pigs) were given saline instead. On the next day, the intestinal absorptive capacity was determined in vivo, and on the 14th d of life the piglets were killed and organs and small intestine samples were collected for analyses and in vitro permeability experiments. The lectin-treated pigs showed an increase in stomach weights and mucosa thickness, whereas no weight effect was found for the small intestine, spleen, liver, or adrenals. Morphometric analyses of the small intestine in lectin-treated pigs showed a decrease in villus heights, an increase in crypt depths and crypt cell mitotic indices, and fewer vacuolated enterocytes per villus and reduced vacuole size. Lectin treatment also resulted in a decrease in the absorption of different-sized marker molecules after gavage feeding, a decrease in intestinal marker permeability, and a change in small intestinal disaccharidase activities, with increased maltase and sucrase activities. The size of the pancreatic acini was also greater in the lectin-treated pigs, but no increases in enzyme content or pancreatic weight could be determined. In addition, the blood plasma levels of cholecystokinin were higher in the lectin-treated than in the control pigs. The results indicate that exposure to crude red kidney bean lectin induces structural and functional maturation of the gut and pancreatic growth in young suckling piglets. This possibility of inducing gut maturation may lead to an improvement in the piglets' ability to adapt to weaning and to an increase in the growth and health of these animals.

Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus

PubMed Central

Leedham, S J; Preston, S L; McDonald, S A C; Elia, G; Bhandari, P; Poller, D; Harrison, R; Novelli, M R; Jankowski, J A; Wright, N A

2008-01-01

Objectives: Current models of clonal expansion in human Barrett’s oesophagus are based upon heterogenous, flow-purified biopsy analysis taken at multiple segment levels. Detection of identical mutation fingerprints from these biopsy samples led to the proposal that a mutated clone with a selective advantage can clonally expand to fill an entire Barrett’s segment at the expense of competing clones (selective sweep to fixation model). We aimed to assess clonality at a much higher resolution by microdissecting and genetically analysing individual crypts. The histogenesis of Barrett’s metaplasia and neo-squamous islands has never been demonstrated. We investigated the oesophageal gland squamous ducts as the source of both epithelial sub-types. Methods: Individual crypts across Barrett’s biopsy and oesophagectomy blocks were dissected. Determination of tumour suppressor gene loss of heterozygosity patterns, p16 and p53 point mutations were carried out on a crypt-by-crypt basis. Cases of contiguous neo-squamous islands and columnar metaplasia with oesophageal squamous ducts were identified. Tissues were isolated by laser capture microdissection and genetically analysed. Results: Individual crypt dissection revealed mutation patterns that were masked in whole biopsy analysis. Dissection across oesophagectomy specimens demonstrated marked clonal heterogeneity, with multiple independent clones present. We identified a p16 point mutation arising in the squamous epithelium of the oesophageal gland duct, which was also present in a contiguous metaplastic crypt, whereas neo-squamous islands arising from squamous ducts were wild-type with respect to surrounding Barrett’s dysplasia. Conclusions: By studying clonality at the crypt level we demonstrate that Barrett’s heterogeneity arises from multiple independent clones, in contrast to the selective sweep to fixation model of clonal expansion previously described. We suggest that the squamous gland ducts situated throughout the oesophagus are the source of a progenitor cell that may be susceptible to gene mutation resulting in conversion to Barrett’s metaplastic epithelium. Additionally, these data suggest that wild-type ducts may be the source of neo-squamous islands. PMID:18305067

Abnormal passive chloride absorption in cystic fibrosis jejunum functionally opposes the classic chloride secretory defect

PubMed Central

Russo, Michael A.; Högenauer, Christoph; Coates, Stephen W.; Santa Ana, Carol A.; Porter, Jack L.; Rosenblatt, Randall L.; Emmett, Michael; Fordtran, John S.

2003-01-01

Due to genetic defects in apical membrane chloride channels, the cystic fibrosis (CF) intestine does not secrete chloride normally. Depressed chloride secretion leaves CF intestinal absorptive processes unopposed, which results in net fluid hyperabsorption, dehydration of intestinal contents, and a propensity to inspissated intestinal obstruction. This theory is based primarily on in vitro studies of jejunal mucosa. To determine if CF patients actually hyperabsorb fluid in vivo, we measured electrolyte and water absorption during steady-state perfusion of the jejunum. As expected, chloride secretion was abnormally low in CF, but surprisingly, there was no net hyperabsorption of sodium or water during perfusion of a balanced electrolyte solution. This suggested that fluid absorption processes are reduced in CF jejunum, and further studies revealed that this was due to a marked depression of passive chloride absorption. Although Na+-glucose cotransport was normal in the CF jejunum, absence of passive chloride absorption completely blocked glucose-stimulated net sodium absorption and reduced glucose-stimulated water absorption 66%. This chloride absorptive abnormality acts in physiological opposition to the classic chloride secretory defect in the CF intestine. By increasing the fluidity of intraluminal contents, absence of passive chloride absorption may reduce the incidence and severity of intestinal disease in patients with CF. PMID:12840066

Calibration method and apparatus for measuring the concentration of components in a fluid

DOEpatents

Durham, M.D.; Sagan, F.J.; Burkhardt, M.R.

1993-12-21

A calibration method and apparatus for use in measuring the concentrations of components of a fluid is provided. The measurements are determined from the intensity of radiation over a selected range of radiation wavelengths using peak-to-trough calculations. The peak-to-trough calculations are simplified by compensating for radiation absorption by the apparatus. The invention also allows absorption characteristics of an interfering fluid component to be accurately determined and negated thereby facilitating analysis of the fluid. 7 figures.

Calibration method and apparatus for measuring the concentration of components in a fluid

DOEpatents

Durham, Michael D.; Sagan, Francis J.; Burkhardt, Mark R.

1993-01-01

A calibration method and apparatus for use in measuring the concentrations of components of a fluid is provided. The measurements are determined from the intensity of radiation over a selected range of radiation wavelengths using peak-to-trough calculations. The peak-to-trough calculations are simplified by compensating for radiation absorption by the apparatus. The invention also allows absorption characteristics of an interfering fluid component to be accurately determined and negated thereby facilitating analysis of the fluid.

Evaluation of Fluid Absorbency of Retraction Cords after Immersing in Two Retraction Medicaments - An In-vitro Study.

PubMed

Vishnubhotla, Gautam; Basapogu, Sreeramulu; Karnati, Rajeev Kumar Reddy; Dasari, Pradeep Prabhu; Thommandru, Mani Victor; Bethu, Mohana Bindu

2016-11-01

Dry retraction cords help to displace the gingiva and also to absorb the gingival crevicular fluid and saliva to maintain a dry field. When used along with medicaments whether these medicaments help to improve the absorption of fluid or affect the fluid absorption by decreasing the efficiency of the retraction cord is unknown. The aim of the study was to know the effect of various medicaments on the fluid absorbency of the retraction cords and also, to know whether the thickness of the retraction cords influences it's fluid absorbency. A total of 90 samples of 5cm length retraction cords were taken. Cords were divided into 30 samples for each cord thickness of 0, 1 and 2. Of these 30 samples, 10 samples were used to measure dry weight (Group I), 10 samples were immersed in 15.5% ferric sulfate (Group II) and remaining 10 samples were immersed in 10% aluminium chloride (Group III) for a period of 20 minutes. The excess medicament was removed by blotting paper. Initial weight was recorded. Following this, five cords from each group were immersed in plasma solution and remaining in artificial saliva for 10 minutes. Then these were taken out and measured. The amount of the fluid absorbed was determined by subtracting the weight before fluid immersion (weight after immersion in test medicament) from the weight after fluid immersion (weight after immersion in plasma or artificial saliva). The study was analyzed through one-way ANOVA and Bonferroni post-hoc comparisons for pair wise differences. When immersed in medicaments, there is a significant difference in absorption of fluids (artificial saliva and plasma) between the untreated dry cord and cord treated with 15.5% ferric sulfate (p<0.05). But, there was no significant difference in fluid absorption between the dry untreated cord and cord treated with 10% aluminum chloride and between cords treated with 15.5% ferric sulfate and 10% aluminum chloride. Ferric sulfate (15.5%) is a better medicament for absorption of fluid.

Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

PubMed Central

Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

1998-01-01

Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. 
Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. 
Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine. 

 Keywords: urokinase; intestinal epithelium; colon; epithelial proliferation PMID:9824347

Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer.

PubMed

Nguyen, Huy; Loustaunau, Cristy; Facista, Alexander; Ramsey, Lois; Hassounah, Nadia; Taylor, Hilary; Krouse, Robert; Payne, Claire M; Tsikitis, V Liana; Goldschmid, Steve; Banerjee, Bhaskar; Perini, Rafael F; Bernstein, Carol

2010-07-28

In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia. Using immunohistochemistry, entire crypts within 10 cm on each side of colonic adenocarcinomas or advanced colonic neoplasias were found to be frequently reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1. Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide excision repair. The reduced or absent expression of both ERCC1 and Pms2 would create cells with both increased ability to survive (apoptosis resistance) and increased level of mutability. The reduced or absent expression of both ERCC1 and Pms2 is likely an early step in progression to colon cancer. DNA repair gene Ku86 (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I (involved in apoptosis) had each been reported to be decreased in expression in mucosal areas close to colon cancers. However, immunohistochemical evaluation of their levels of expression showed only low to modest frequencies of crypts to be deficient in their expression in a field defect surrounding colon cancer or surrounding advanced colonic neoplasia. We show, here, our method of evaluation of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20 cm long areas surrounding a colonic neoplasia, while frequency of crypts deficient in Ku86 has a median value of 2% and frequency of crypts deficient in CcOI has a median value of 16% in these areas. The entire colon is 150 cm long (about 5 feet) and has about 10 million crypts in its mucosal layer. The defect in Pms2 and ERCC1 surrounding a colon cancer thus may include 1 million crypts. It is from a defective crypt that colon cancer arises.

A kinetic approach to the study of absorption of solutes by isolated perfused small intestine

PubMed Central

Fisher, R. B.; Gardner, M. L. G.

1974-01-01

1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine. 2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen-carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid. 3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions. 4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume. 5. In the steady state the concentration of glucose in the tissue fluid is 71 mM when the luminal concentration is 28 mM, and is 45 mM when the luminal concentration is 8·3 mM. 6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50-60 min. 7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15-20 min. 8. The Km for glucose absorption (14-19 mM) is much lower than is found with unsegmented flow perfusion. 9. These findings emphasize problems in interpreting results from other types of intestinal preparation. 10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions. ImagesPlate 1 PMID:4422346

Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface.

PubMed

Tanaka, Akiko; Furubayashi, Tomoyuki; Enomura, Yuki; Hori, Tomoki; Shimomura, Rina; Maeda, Chiaki; Kimura, Shunsuke; Inoue, Daisuke; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

2017-01-01

The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin-Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.

Evidence of functional cross talk between the Notch and NF-κB pathways in nonneoplastic hyperproliferating colonic epithelium.

PubMed

Ahmed, Ishfaq; Roy, Badal; Chandrakesan, Parthasarathy; Venugopal, Anand; Xia, Lijun; Jensen, Roy; Anant, Shrikant; Umar, Shahid

2013-02-15

The Notch and NF-κB signaling pathways regulate stem cell function and inflammation in the gut, respectively. We investigate whether a functional cross talk exists between the two pathways during transmissible murine colonic hyperplasia (TMCH) caused by Citrobacter rodentium (CR). During TMCH, NF-κB activity and subunit phosphorylation in colonic crypts of NIH Swiss mice at days 6 and 12 were associated with increases in downstream target CXC chemokine ligand (CXCL)-1/keratinocyte-derived chemokine (KC) expression. Blocking Notch signaling acutely for 5 days with the Notch blocker dibenzazepine (DBZ) failed to inhibit crypt NF-κB activity or CXCL-1/KC expression. Chronic DBZ administration for 10 days, however, blocked Notch and NF-κB signaling in the crypts and abrogated hyperplasia. Intriguingly, chronic Notch inhibition was associated with significant increases in IL-1α, granulocyte colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and KC in the crypt-denuded lamina propria or whole distal colon, with concomitant increases in myeloperoxidase activity. In core-3(-/-) mice, which are defective in intestinal mucin, DBZ administration replicated the results of NIH Swiss mice; in Apc(Min/+) mice, which are associated with CR-induced elevation of NF-κB-p65(276) expression, DBZ reversed the increase in NF-κB-p65(276), which may have blocked rapid proliferation of the mutated crypts. DBZ further blocked reporter activities involving the NF-κB-luciferase reporter plasmid or the Toll-like receptor 4/NF-κB/SEAPorter HEK-293 reporter cell line, while ectopic expression of Notch-N(ICD) reversed the inhibitory effect. Dietary bael (Aegle marmelos) extract (4%) and curcumin (4%) restored Notch and NF-κB cross talk in NIH Swiss mice, inhibited CR/DBZ-induced apoptosis in the crypts, and promoted crypt regeneration. Thus functional cross talk between the Notch and NF-κB pathways during TMCH regulates hyperplasia and/or inflammation in response to CR infection.

Surface tension mediated conversion of light to work

DOEpatents

Okawa, David; Pastine, Stefan J; Zettl, Alexander K; Frechet, Jean M. J

2014-12-02

Disclosed are a method and apparatus for converting light energy to mechanical energy by modification of surface tension on a supporting fluid. The apparatus comprises an object which may be formed as a composite object comprising a support matrix and a highly light absorptive material. The support matrix may comprise a silicon polymer. The highly light absorptive material may comprise vertically aligned carbon nanotubes (VANTs) embedded in the support matrix. The composite object is supported on a fluid. By exposing the highly light absorptive material to light, heat is generated, which changes the surface tension of the composite object, causing it to move physically within the fluid.

Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi-differentiated Cell Populations in Dysplastic Colonic Crypts.

PubMed

Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio

2018-02-01

Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.

Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine.

PubMed

McFarlane, Matthew R; Liang, Guosheng; Engelking, Luke J

2014-01-24

Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes.

Insig Proteins Mediate Feedback Inhibition of Cholesterol Synthesis in the Intestine*

PubMed Central

McFarlane, Matthew R.; Liang, Guosheng; Engelking, Luke J.

2014-01-01

Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes. PMID:24337570

The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa.

PubMed

Linardi, R L; Stokes, A M; Andrews, F M

2013-02-01

Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability for 120 min, and the flux of methadone across the jejunal membrane (mucosal to submucosal direction) was calculated based on the relative drug concentration measured by ELISA. The flux of methadone was significantly higher only in the presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane of the jejunal epithelial cells (enterocytes), mainly located in the tip of the villi compared to cells of the crypts. P-glycoprotein is present in the equine jejunum and may possibly mediate the intestinal transport of methadone. This study suggests that P-glycoprotein may play a role in the poor intestinal absorption of methadone in vivo. © 2012 Blackwell Publishing Ltd.

Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

PubMed

Finch, Anthony J; Benson, Jamie M; Donnelly, Patrick E; Torzilli, Peter A

2017-06-01

Objective Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers. Materials UV-visible spectroscopy was performed on each major component of cartilage in solution, on bovine synovial fluid, and on four photosensitizers, riboflavin, Irgacure 2959, quinine, and riboflavin-5'-phosphate. Molar extinction and absorption coefficients were calculated at wavelengths of maximum absorbance and 365 nm. Intact articular cartilage was also examined. Results The individual major biochemical components of cartilage, Irgacure 2959, and quinine did not exhibit a significant absorption at 365 nm. Riboflavin and riboflavin-5'-phosphate were more effectual light absorbers at 365 nm, compared with the individual native species. Intact cartilage absorbed a significantly greater amount of UV light in comparison with the native species. Conclusion Our results indicate that none of the individual native species in cartilage will interfere with the absorption of UV light at 365 nm by these commonly used photoinitiators. Intact cartilage slices exhibited significant light absorption at 365 nm, while also having distinct absorbance peaks at wavelengths less than 300 nm. Determining the UV absorptive properties of the biomolecules native to articular cartilage and synovial fluid will aid in optimizing scaffolding procedures to ensure sufficient scaffold polymerization at a minimum UV intensity.

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium.

PubMed

Wang, Yuli; Gunasekara, Dulan B; Reed, Mark I; DiSalvo, Matthew; Bultman, Scott J; Sims, Christopher E; Magness, Scott T; Allbritton, Nancy L

2017-06-01

The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution

PubMed Central

Humphries, Adam; Cereser, Biancastella; Gay, Laura J.; Miller, Daniel S. J.; Das, Bibek; Gutteridge, Alice; Elia, George; Nye, Emma; Jeffery, Rosemary; Poulsom, Richard; Novelli, Marco R.; Rodriguez-Justo, Manuel; McDonald, Stuart A. C.; Wright, Nicholas A.; Graham, Trevor A.

2013-01-01

The genetic and morphological development of colorectal cancer is a paradigm for tumorigenesis. However, the dynamics of clonal evolution underpinning carcinogenesis remain poorly understood. Here we identify multipotential stem cells within human colorectal adenomas and use methylation patterns of nonexpressed genes to characterize clonal evolution. Numerous individual crypts from six colonic adenomas and a hyperplastic polyp were microdissected and characterized for genetic lesions. Clones deficient in cytochrome c oxidase (CCO−) were identified by histochemical staining followed by mtDNA sequencing. Topographical maps of clone locations were constructed using a combination of these data. Multilineage differentiation within clones was demonstrated by immunofluorescence. Methylation patterns of adenomatous crypts were determined by clonal bisulphite sequencing; methylation pattern diversity was compared with a mathematical model to infer to clonal dynamics. Individual adenomatous crypts were clonal for mtDNA mutations and contained both mucin-secreting and neuroendocrine cells, demonstrating that the crypt contained a multipotent stem cell. The intracrypt methylation pattern was consistent with the crypts containing multiple competing stem cells. Adenomas were epigenetically diverse populations, suggesting that they were relatively mitotically old populations. Intratumor clones typically showed less diversity in methylation pattern than the tumor as a whole. Mathematical modeling suggested that recent clonal sweeps encompassing the whole adenoma had not occurred. Adenomatous crypts within human tumors contain actively dividing stem cells. Adenomas appeared to be relatively mitotically old populations, pocketed with occasional newly generated subclones that were the result of recent rapid clonal expansion. Relative stasis and occasional rapid subclone growth may characterize colorectal tumorigenesis. PMID:23766371

Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution.

PubMed

Humphries, Adam; Cereser, Biancastella; Gay, Laura J; Miller, Daniel S J; Das, Bibek; Gutteridge, Alice; Elia, George; Nye, Emma; Jeffery, Rosemary; Poulsom, Richard; Novelli, Marco R; Rodriguez-Justo, Manuel; McDonald, Stuart A C; Wright, Nicholas A; Graham, Trevor A

2013-07-02

The genetic and morphological development of colorectal cancer is a paradigm for tumorigenesis. However, the dynamics of clonal evolution underpinning carcinogenesis remain poorly understood. Here we identify multipotential stem cells within human colorectal adenomas and use methylation patterns of nonexpressed genes to characterize clonal evolution. Numerous individual crypts from six colonic adenomas and a hyperplastic polyp were microdissected and characterized for genetic lesions. Clones deficient in cytochrome c oxidase (CCO(-)) were identified by histochemical staining followed by mtDNA sequencing. Topographical maps of clone locations were constructed using a combination of these data. Multilineage differentiation within clones was demonstrated by immunofluorescence. Methylation patterns of adenomatous crypts were determined by clonal bisulphite sequencing; methylation pattern diversity was compared with a mathematical model to infer to clonal dynamics. Individual adenomatous crypts were clonal for mtDNA mutations and contained both mucin-secreting and neuroendocrine cells, demonstrating that the crypt contained a multipotent stem cell. The intracrypt methylation pattern was consistent with the crypts containing multiple competing stem cells. Adenomas were epigenetically diverse populations, suggesting that they were relatively mitotically old populations. Intratumor clones typically showed less diversity in methylation pattern than the tumor as a whole. Mathematical modeling suggested that recent clonal sweeps encompassing the whole adenoma had not occurred. Adenomatous crypts within human tumors contain actively dividing stem cells. Adenomas appeared to be relatively mitotically old populations, pocketed with occasional newly generated subclones that were the result of recent rapid clonal expansion. Relative stasis and occasional rapid subclone growth may characterize colorectal tumorigenesis.

Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis.

PubMed

Rigby, Rachael J; Carr, Jacquelyn; Orgel, Kelly; King, Stephanie L; Lund, P Kay; Dekaney, Christopher M

2016-09-02

Doxorubicin (DOXO) induces significant, but transient, increases in apoptosis in the stem cell zone of the jejunum, followed by mucosal damage involving a decrease in crypt proliferation, crypt number, and villus height. The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated a symbiotic relationship between intestinal bacteria and intestinal epithelial cells (IEC) in maintaining homeostatic functions of the intestine. However, whether enteric bacteria play a role in DOXO-induced damage is not well understood. We hypothesized that enteric bacteria are necessary for induction of apoptosis and damage associated with DOXO treatment. Conventionally raised (CONV) and germ free (GF) mice were given a single injection of DOXO, and intestinal tissue was collected at 6, 72, and 120 h after treatment and from no treatment (0 h) controls. Histology and morphometric analyses quantified apoptosis, mitosis, crypt depth, villus height, and crypt density. Immunostaining for muc2 and lysozyme evaluated Paneth cells, goblet cells or dual stained intermediate cells. DOXO administration induced significant increases in apoptosis in jejunal epithelium regardless of the presence of enteric bacteria; however, the resulting injury, as demonstrated by statistically significant changes in crypt depth, crypt number, and proliferative cell number, was dependent upon the presence of enteric bacteria. Furthermore, we observed expansion of Paneth and goblet cells and presence of intermediate cells only in CONV and not GF mice. These findings provide evidence that manipulation and/or depletion of the enteric microbiota may have clinical significance in limiting chemotherapy-induced mucositis.

Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

PubMed

Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

2017-02-01

We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21 CIP/WAF1 )-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21 CIP/WAF1 )-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21 CIP/WAF1 )-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21 CIP/WAF1 )-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

Convective fluid flow through the paracellular system of Necturus gall-bladder epithelium as revealed by dextran probes.

PubMed Central

Shachar-Hill, B; Hill, A E

1993-01-01

1. Bidirectional paracellular fluxes using radioactive dextrans as inert molecular probes have been measured across Necturus gall-bladder epithelium during conditions of normal fluid absorption. There is a net flux at all radii analysed (0.4-2.2 nm) in the direction of fluid absorption. 2. The net flux is substantial at all radii within the range. The data extraplate to 2 x 10(-6) cm s-1 at zero probe radius, which is very close to the rate of epithelial fluid absorption. 3. The unstirred layers at the epithelial faces during transport have been determined; their contribution to the net fluxes is negligible. 4. Two possible mechanisms for the net flow of probes are considered: (i) that the probes diffuse across the junctions and are then entrained in a local osmotic flow along the interspaces and subepithelium; (ii) that the probes are entrained in volume flow across the junctions and the emergent solution subsequently passes through the interspaces and subepithelium. Model calculations clearly rule out mechanism (i) in which the maximum net flow obtainable is less than 10% of that observed. In addition the presence of leak paths shunting the junctions is not compatible with the observed fluxes. With mechanism (ii) the net flows are correctly predicted with all the fluid flow being transjunctional. The fluid absorption is therefore entirely paracellular. 5. The slope of the net flow curve shows no apparent change in magnitude over the range of the probe radii, indicating that effectively only one population of convective channels is present with parallel walls separated by about 7.7 nm. This agrees with the width previously determined by electron microscopy. 6. If the fluid absorption is junctional then the cellular route offers little if any relative contribution. The hydraulic conductivity of the junctions is not high enough, or the osmotic permeability of the membranes low enough, to accommodate this by osmosis and therefore the junctional fluid absorption must be non-osmotic. Images Fig. 1 Fig. 4 PMID:7504731

Small intestine histomorphometry of beef cattle with divergent feed efficiency

PubMed Central

2013-01-01

Background The provision of feed is a major cost in beef production. Therefore, the improvement of feed efficiency is warranted. The direct assessment of feed efficiency has limitations and alternatives are needed. Small intestine micro-architecture is associated with function and may be related to feed efficiency. The objective was to verify the potential histomorphological differences in the small intestine of animals with divergent feed efficiency. Methods From a population of 45 feedlot steers, 12 were selected with low-RFI (superior feed efficiency) and 12 with high-RFI (inferior feed efficiency) at the end of the finishing period. The animals were processed at 13.79 ± 1.21 months of age. Within 1.5 h of slaughter the gastrointestinal tract was collected and segments from duodenum and ileum were harvested. Tissue fragments were processed, sectioned and stained with hematoxylin and eosin. Photomicroscopy images were taken under 1000x magnification. For each animal 100 intestinal crypts were imaged, in a cross section view, from each of the two intestinal segments. Images were analyzed using the software ImageJ®. The measurements taken were: crypt area, crypt perimeter, crypt lumen area, nuclei number and the cell size was indirectly calculated. Data were analyzed using general linear model and correlation procedures of SAS®. Results Efficient beef steers (low-RFI) have a greater cellularity (indicated by nuclei number) in the small intestinal crypts, both in duodenum and ileum, than less efficient beef steers (high-RFI) (P < 0.05). The mean values for the nuclei number of the low-RFI and high-RFI groups were 33.16 and 30.30 in the duodenum and 37.21 and 33.65 in the ileum, respectively. The average size of the cells did not differ between feed efficiency groups in both segments (P ≥ 0.10). A trend was observed (P ≤ 0.10) for greater crypt area and crypt perimeter in the ileum for cattle with improved feed efficiency. Conclusion Improved feed efficiency is associated with greater cellularity and no differences on average cell size in the crypts of the small intestine in the bovine. These observations are likely to lead to an increase in the energy demand by the small intestine regardless of the more desirable feed efficiency. PMID:23379622

Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula.

PubMed

Yang, Chengbo; Yang, Xiaojian; Lackeyram, Dale; Rideout, Todd C; Wang, Zirong; Stoll, Barbara; Yin, Yulong; Burrin, Douglas G; Fan, Ming Z

2016-06-01

Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA co-transporter (B(0)AT1, encoded by the SLC6A19 gene) plays a dominant role for apical uptake of large neutral AA including L-Gln, we hypothesized that high apical Na(+)-Gln co-transport activity, and B(0)AT1 (SLC6A19) in co-expression with angiotensin-converting enzyme 2 (ACE2) were expressed along the entire small intestinal crypt-villus axis in young animals via unique control mechanisms. Kinetics of Na(+)-Gln co-transport activity in the apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from liquid formula-fed young pigs, were measured with the membrane potential being clamped to zero using thiocyanate. Apical maximal Na(+)-Gln co-transport activity was much higher (p < 0.05) in the upper villus cells than in the middle villus (by 29 %) and the crypt (by 30 %) cells, whereas Na(+)-Gln co-transport affinity was lower (p < 0.05) in the upper villus cells than in the middle villus and the crypt cells. The B(0)AT1 (SLC6A19) mRNA abundance was lower (p < 0.05) in the crypt (by 40-47 %) than in the villus cells. There were no significant differences in B(0)AT1 and ACE2 protein abundances on the apical membrane among the upper villus, the middle villus and the crypt cells. Our study suggests that piglet fast growth is associated with very high intestinal apical Na(+)-neutral AA uptake activities via abundantly co-expressing B(0)AT1 and ACE2 proteins in the apical membrane and by transcribing the B(0)AT1 (SLC6A19) gene in the epithelia along the entire crypt-villus axis.

Colon cancer cells adopt an invasive phenotype without mesenchymal transition in 3-D but not 2-D culture upon combined stimulation with EGF and crypt growth factors.

PubMed

Ludwig, Kirsten; Tse, Edison S; Wang, Jean Yj

2013-05-02

The intestinal crypt homeostasis is maintained by a combination of growth factors including Wnt, R-Spondin1, Noggin and the epidermal growth factor (EGF). In human colorectal cancer, the Wnt pathway is constitutively activated through genetic and epigenetic alterations in as many as 11 genes encoding components of this crypt stem-cell maintenance mechanism. Although the proliferation of colon cancer cells does not require Wnt, it is possible that colon cancer cells can still respond to the crypt growth factors in the colonic microenvironment. A number of studies have shown that epithelial cells behave differently in 3-D versus 2-D cultures. Because the 3-D conditions more closely mimic the in vivo environment, we examined the effects of Wnt and other crypt growth factors on colon cancer cell growth in 3-D culture. Colon cancer cells were grown in 3-D matrigel supplemented with different combinations of crypt growth factors and colonies were examined for morphology and pathways. When colon cancer cells were cultured in 3-D with EGF, they grew as round spheroid colonies. However, colon cancer cells also grew as flat, disc-like colonies when cultured with EGF plus Wnt, R-Spondin1 and Noggin. Disc colonies were found to have comparable levels of E-cadherin as the spheroid colonies, but showed decreased E-cadherin at the cell-matrix contact sites. Disc colonies also elaborated F-actin rich protrusions (FRP) at the cell-matrix edge, reminiscent of an invasive phenotype but without the expression of vimentin. These E-cadherin and F-actin alterations were not induced by the four growth factors in 2-D culture. Formation of the disc colonies was inhibited by the knockdown of β-catenin and by protein kinase inhibitors such as gefitinib, imatinib and MK-2206. Furthermore, withdrawal of the crypt growth factors was able to revert the disc colonies to spheroid growth, showing that the invasive phenotype was reversible dependent on the availability of growth factors. These findings show that colon cancer cells remain responsive to the growth factors in the crypt microenvironment and can be induced to undergo morphological transformation in the more physiologically relevant 3-D culture.

Combined changes in Wnt signaling response and contact inhibition induce altered proliferation in radiation-treated intestinal crypts

PubMed Central

Dunn, S.-J.; Osborne, J. M.; Appleton, P. L.; Näthke, I.

2016-01-01

Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis. PMID:27053661

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Lerner, Aaron; Coran, Arnold G; Lurie, Michael; Miselevich, Iness; Shiloni, Eitan

2005-06-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Shamir, Raanan; Shehadeh, Naim; Bejar, Jacob; Hirsh, Mark; Coran, Arnold G

2005-03-01

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

A comparison of mode of attachment and histopathogenicity of four tapeworm species representing two orders infecting the spiral intestine of the nurse shark, Ginglymostoma cirratum.

PubMed

Borucinska, J; Caira, J N

1993-04-01

This study was undertaken to compare 2 species of Tetraphyllidea and 2 species of Trypanorhyncha with regard to the relationship between attachment structure morphology, mode of attachment, and tapeworm size, to damage at the sites of attachment in the Atlantic nurse shark, Ginglymostoma cirratum. Regions of the spiral intestine with worms attached were removed from 8 nurse sharks and sectioned according to conventional techniques. Sections of 5-50 specimens of each tapeworm species were examined. Regions of the spiral intestine devoid of worms were processed for characterization of the normal mucosa. The normal mucosa was found to consist of a folded surface covered with round-to-oval primary mucosal crypts. In the first 7 or 8 chambers of the spiral intestine the mucosal surface was thrown into secondary folds, forming ridges and secondary crypts. The primary mucosal crypts were lined with a single layer of columnar epithelium resting on a basement membrane. A highly cellular lamina propria and submucosa were found between the crypts and the muscularis mucosa. The small tetraphyllidean Pedibothrium brevispine was found with its scolex lying within the primary mucosal crypts with its hooks embedded in the basement membrane. Epithelial denudation was evident. The large tetraphyllidean Pedibothrium globicephalum was found with its bothridia engulfing large portions of the mucosa and its hooks embedded into the lamina propria. It was associated with moderate to severe mucosal necrosis. The small trypanorhynch Prochristianella tenuispine was found lying between the mucosal ridges in the secondary crypts with its tentacles either penetrating the epithelium, or occasionally, the lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

PubMed

Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

2015-01-01

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Se-Chul; Park, Jeong-Mi; Jang, Hong-Seok

Captopril, an inhibitor of angiotensin I converting enzyme, has been shown to modify radiation damage and prevent radiation injury of normal tissue in rats and pigs. The present study was carried out to determine whether captopril would reduce radiation changes in the proximal small bowel in mice. Mice were subjected to whole body irradiation with 9 Gy or 15 Gy. Captopril was administered in drinking water at a regimen of 62.5 mg/kg/day (captopril group I) and 125 mg/kg/day (captopril group II), continuously from 7 days before irradiation to the end of each designed experiment. The jejunal damage was evaluated microscopicallymore » by crypt count per circumference and by histologic damage grading. Crypt number in the sham-irradiated control was 133 {plus_minus} 6.8/circumference. In both captopril group I and II, crypt numbers and histologic scores were not significantly different from those in the normal group. The 9 Gy and 15 Gy radiation alone groups showed significantly lower crypt counts and histologic scores compared with the sham-irradiated control group (p<0.05). The groups exposed to 9 Gy radiation plus captopril I and II showed significantly higher crypt counts and lower histologic damage scores on the third day, and lower histologic damage scores on the fifth day compared with the 9 Gy radiation alone group (p<0.05). The 15 Gy radiation plus captopril I and II groups had significantly higher crypt counts and lower histologic damage scores on the third day than those of the 15 Gy radiation alone group (p<0.05). All mice of the 15 Gy radiation group succumbed to intestinal radiation death. Our results suggest that captopril provides protection from acute radiation damage to the jejunal mucosa in mice. 28 refs., 5 figs., 4 tabs.« less

A kinetic model to study the regulation of β-catenin, APC, and Axin in the human colonic crypt.

PubMed

Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

2017-11-01

The Wnt/[Formula: see text]-catenin pathway plays a crucial role in stem cell renewal and differentiation in the normal human colonic crypt. The balance between [Formula: see text]-catenin and APC along the crypt axis determines its normal functionality. The mechanism that deregulates this balance may give insight into the initiation of colorectal cancer. This is significant because the spatial dysregulation of [Formula: see text]-catenin by the mutated tumor suppressor gene/protein APC in human colonic crypts is responsible for the initiation and growth of colorectal cancer. We consider a regulatory function that promotes APC synthesis within the cell and its effect on the accumulation of the Wnt target protein, [Formula: see text]-catenin. It is evident that an APC gradient exists along the crypt axis; however, the mechanism by which APC expression is regulated within the cell is not well known. We investigate the dynamics of an APC regulatory mechanism with an increased level of Axin at the subcellular level. Model output shows an increase of APC for a diminished Wnt signal, which explains the APC gradient along the crypt. We find that the dynamic interplay between [Formula: see text]-catenin, APC, and Axin produces oscillatory behavior, which is controlled by the Wnt stimulus. In the presence of reduced functional APC, the oscillations are amplified, which suggests that the cell remains in a more proliferative state for longer periods of time. Increased Axin levels (typical of mammalian cells) reduce oscillatory behavior and minimize the levels of [Formula: see text]-catenin within the cell while raising the levels of APC.

Unique regulation of Na-glutamine cotransporter SN2/SNAT5 in rabbit intestinal crypt cells during chronic enteritis.

PubMed

Singh, Soudamani; Arthur, Subha; Sundaram, Uma

2018-03-01

The only Na-nutrient cotransporter described in mammalian small intestinal crypt cells is SN2/SNAT5, which facilitates glutamine uptake. In a rabbit model of chronic intestinal inflammation, SN2 stimulation is secondary to an increase in affinity of the cotransporter for glutamine. However, the immune regulation of SN2 in the crypt cells during chronic intestinal inflammation is unknown. We sought to determine the mechanism of regulation of Na-nutrient cotransporter SN2 by arachidonic acid metabolites in crypt cells. The small intestines of New Zealand white male rabbits were inflamed via inoculation with Eimeria magna oocytes. After 2-week incubation, control and inflamed rabbits were subjected to intramuscular injections of arachidonyl trifluoromethyl ketone (ATK), piroxicam and MK886 for 48 hrs. After injections, the rabbits were euthanized and crypt cells from small intestines were harvested and used. Treatment of rabbits with ATK prevented the release of AA and reversed stimulation of SN2. Inhibition of cyclooxygenase (COX) with piroxicam did not affect stimulation of SN2. However, inhibition of lipoxygenase (LOX) with MK886, thus reducing leukotriene formation during chronic enteritis, reversed the stimulation of SN2. Kinetic studies showed that the mechanism of restoration of SN2 by ATK or MK886 was secondary to the restoration of the affinity of the cotransporter for glutamine. For all treatment conditions, Western blot analysis revealed no change in SN2 protein levels. COX inhibition proved ineffective at reversing the stimulation of SN2. Thus, this study provides evidence that SN2 stimulation in crypt cells is mediated by the leukotriene pathway during chronic intestinal inflammation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Crypt dynamics and colorectal cancer: advances in mathematical modelling.

PubMed

van Leeuwen, I M M; Byrne, H M; Jensen, O E; King, J R

2006-06-01

Mathematical modelling forms a key component of systems biology, offering insights that complement and stimulate experimental studies. In this review, we illustrate the role of theoretical models in elucidating the mechanisms involved in normal intestinal crypt dynamics and colorectal cancer. We discuss a range of modelling approaches, including models that describe cell proliferation, migration, differentiation, crypt fission, genetic instability, APC inactivation and tumour heterogeneity. We focus on the model assumptions, limitations and applications, rather than on the technical details. We also present a new stochastic model for stem-cell dynamics, which predicts that, on average, APC inactivation occurs more quickly in the stem-cell pool in the absence of symmetric cell division. This suggests that natural niche succession may protect stem cells against malignant transformation in the gut. Finally, we explain how we aim to gain further understanding of the crypt system and of colorectal carcinogenesis with the aid of multiscale models that cover all levels of organization from the molecular to the whole organ.

Autoradiographic study on healing process of cysteamine-induced duodenal ulcer in rat. Possible importance of Brunner's glands in ulcer healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuse, Y.; Tsuchihashi, Y.; Sugihara, H.

1988-09-01

The healing process of cysteamine-induced duodenal ulcer was studied by (/sup 3/H)thymidine autoradiography. After the development of ulcer in the duodenum, cell proliferation was markedly activated not only in the crypts but also in the Brunner's glands near the ulcer. In the initial stages of ulcer healing, they both contributed to form the surface covering regenerating epithelium. Granulation tissue also proliferated at the base of the ulcer. In later stages of ulcer healing, new crypts were formed in the floor of the ulcer. New villi regenerated from these crypts and Brunner's glands regenerated by proliferation in situ. The ulcer basemore » then was completely covered with new villi and granulation tissue was replaced by dense fibrous connective tissue. The present study suggested that the Brunner's glands, together with the crypts of Lieberkuehn, play an important role in the healing process of cysteamine-induced duodenal ulcer.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craig, Timothy; Smith, Andrew D.; Holder, Gareth M.

The development of more accurate and sensitive diagnostic techniques is a key factor in efforts to improve cancer survival rates. The technique of infrared aperture fibre scanning near-field optical microscopy (IR-SNOM),together with radiation from the infrared free-electron laser (IR-FEL) on ALICEat Daresbury Laboratory (UK), has been used to obtain IR images of a crypt-like feature and the surrounding tissue; the tissue was taken from a patient with oesophageal adenocarcinoma and with a history of Barrett’s oesophagus. We have shown that the DNA signal is enhanced relative to other contributions in the region of the crypt, and the glycoprotein signal showsmore » a less pronounced increase in the region of the crypt. The Amide II signal is found to be anti-correlated with the DNA and glycoprotein profiles. The absorbance of the Amide II signal is found to differ for three different types of cancer tissue. In conclusion, high-resolution IR images of the crypt reveal additional structure that would not be resolved in diffraction-limited techniques.« less

Understanding and controlling plasmon-induced convection

NASA Astrophysics Data System (ADS)

Roxworthy, Brian J.; Bhuiya, Abdul M.; Vanka, Surya P.; Toussaint, Kimani C.

2014-01-01

The heat generation and fluid convection induced by plasmonic nanostructures is attractive for optofluidic applications. However, previously published theoretical studies predict only nanometre per second fluid velocities that are inadequate for microscale mass transport. Here we show both theoretically and experimentally that an array of plasmonic nanoantennas coupled to an optically absorptive indium-tin-oxide (ITO) substrate can generate >micrometre per second fluid convection. Crucially, the ITO distributes thermal energy created by the nanoantennas generating an order of magnitude increase in convection velocities compared with nanoantennas on a SiO2 base layer. In addition, the plasmonic array alters absorption in the ITO, causing a deviation from Beer-Lambert absorption that results in an optimum ITO thickness for a given system. This work elucidates the role of convection in plasmonic optical trapping and particle assembly, and opens up new avenues for controlling fluid and mass transport on the micro- and nanoscale.

Assessment of K-Ras mutant frequency and micronucleus incidence in the mouse duodenum following 90-days of exposure to Cr(VI) in drinking water.

PubMed

O'Brien, Travis J; Ding, Hao; Suh, Mina; Thompson, Chad M; Parsons, Barbara L; Harris, Mark A; Winkelman, William A; Wolf, Jeffrey C; Hixon, J Gregory; Schwartz, Arnold M; Myers, Meagan B; Haws, Laurie C; Proctor, Deborah M

2013-06-14

Chronic exposure to high concentrations of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) in drinking water induces duodenal tumors in mice, but the mode of action (MOA) for these tumors has been a subject of scientific debate. To evaluate the tumor-site-specific genotoxicity and cytotoxicity of SDD in the mouse small intestine, tissue pathology and cytogenetic damage were evaluated in duodenal crypt and villus enterocytes from B6C3F1 mice exposed to 0.3-520mg/L SDD in drinking water for 7 and 90 days. Allele-competitive blocker PCR (ACB-PCR) was used to investigate the induction of a sensitive, tumor-relevant mutation, specifically in vivo K-Ras codon 12 GAT mutation, in scraped duodenal epithelium following 90 days of drinking water exposure. Cytotoxicity was evident in the villus as disruption of cellular arrangement, desquamation, nuclear atypia and blunting. Following 90 days of treatment, aberrant nuclei, occurring primarily at villi tips, were significantly increased at ≥60mg/L SDD. However, in the crypt compartment, there were no dose-related effects on mitotic and apoptotic indices or the formation of aberrant nuclei indicating that Cr(VI)-induced cytotoxicity was limited to the villi. Cr(VI) caused a dose-dependent proliferative response in the duodenal crypt as evidenced by an increase in crypt area and increased number of crypt enterocytes. Spontaneous K-Ras codon 12 GAT mutations in untreated mice were higher than expected, in the range of 10(-2) to 10(-3); however no treatment-related trend in the K-Ras codon 12 GAT mutation was observed. The high spontaneous background K-Ras mutant frequency and Cr(VI) dose-related increases in crypt enterocyte proliferation, without dose-related increase in K-Ras mutant frequency, micronuclei formation, or change in mitotic or apoptotic indices, are consistent with a lack of genotoxicity in the crypt compartment, and a MOA involving accumulation of mutations late in carcinogenesis as a consequence of sustained regenerative proliferation. Published by Elsevier B.V.

An alternative explanation for the occurrence of short circuit current increases in the small intestine following challenge by bacterial enterotoxins.

PubMed

Lucas, M L

2013-10-01

Secretory diarrhoeal disease due to enterotoxins is thought to arise from the enhancement to pathologically high rates of normally occurring chloride ion and therefore fluid secretion from enterocytes. In support of this concept, many enterotoxins increase intestinal short-circuit current, regarded now as faithfully reflecting the increased chloride ion secretion. Contradicting this assumption, STa reduces absorption but does not cause secretion in vivo although short-circuit current is increased in vitro. There is therefore a mismatch between an assumed enterocyte mediated secretory event that should but does not cause net fluid secretion and an undoubtedly increased short-circuit current. It is proposed here that short-circuit current increases are not themselves secretory events but result from interrupted fluid absorption. A noteworthy feature of compounds that inhibit the increase in short-circuit current is that the majority are vasoactive, neuroactive or both. In general, vasodilator substances increase current. An alternative hypothesis for the origin of short-circuit current increases is that these result from reflex induction of electrogenic fluid absorption. This reflex enhances a compensatory response that is also present at a cellular level. An intestinal reflex is therefore proposed by which decreases in interstitial and intravascular volume or pressure within the intestine initiate an electrogenic fluid absorption mechanism that compensates for the loss of electrically neutral fluid absorption. This hypothesis would explain the apparently complex pharmacology of short-circuit current increases since many depressor substances have receptors in common with enterocytes and enteric nerves. The proposed alternative view of the origin of short-circuit current increases assumes that these do not represent chloride secretion from the enterocytes. This view may therefore aid the successful development of anti-diarrhoeal drugs to overcome a major cause of infant mortality worldwide, if short-circuit current data are being persistently misinterpreted. The putative but testable link between interstitial volume or pressure and fluid absorption also provides support for the alternative view of secretion; namely, that enhanced capillary and epithelial cell tight junctional permeability together with increased intracapillary pressure may cause secretion and not chloride exit from the enterocytes. Copyright © 2013. Published by Elsevier Ltd.

Further studies on the effect of adenosine cyclic monophosphate derivatives on cell proliferation in the jejunal crypts of rat.

PubMed

Tutton, P J; Barkla, D H

1982-01-01

1. Cell proliferation in the jejunal crypt epithelium of rat was measured using a stathmokinetic technique. 2. Sodium butyrate was found to promote jejunal crypt cell proliferation. 3. N6, O2'-Dibutyryl cyclic adenosine monophosphate (cAMP), N6-monobutyryl-cAMP and N6-monobutyryl-8-bromo-cAMP were found to inhibit cell proliferation when compared to sodium butyrate treated tissues. 4. 8-Chlorophenylthio-cAMP was found to inhibit cell division when compared to untreated animals. 5. O2'-Monobutyryl cAMP and 8-bromo-cAMP were not found to inhibit cell proliferation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burgess, Antony W., E-mail: burgess@ludwig.edu.au; Faux, Maree C.; Layton, Meredith J.

In this brief overview we discuss the association between Wnt signaling and colon cell biology and tumorigenesis. Our current understanding of the role of Apc in the {beta}-catenin destruction complex is compared with potential roles for Apc in cell adhesion and migration. The requirement for phosphorylation in the proteasomal-mediated degradation of {beta}-catenin is contrasted with roles for phospho-{beta}-catenin in the activation of transcription, cell adhesion and migration. The synergy between Myb and {beta}-catenin regulation of transcription in crypt stem cells during Wnt signaling is discussed. Finally, potential effects of growth factor regulatory systems, Apc or truncated-Apc on crypt morphogenesis, stemmore » cell localization and crypt fission are considered.« less

Optical detection of tracer species in strongly scattering media.

PubMed

Brauser, Eric M; Rose, Peter E; McLennan, John D; Bartl, Michael H

2015-03-01

A combination of optical absorption and scattering is used to detect tracer species in a strongly scattering medium. An optical setup was developed, consisting of a dual-beam scattering detection scheme in which sample scattering beam overlaps with the characteristic absorption feature of quantum dot tracer species, while the reference scattering beam is outside any absorption features of the tracer. This scheme was successfully tested in engineered breakthrough tests typical of wastewater and subsurface fluid analysis, as well as in batch analysis of oil and gas reservoir fluids and biological samples. Tracers were detected even under highly scattering conditions, conditions in which conventional absorption or fluorescence methods failed.

Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time.

PubMed

Yu, Alex; Jackson, Trachette; Tsume, Yasuhiro; Koenigsknecht, Mark; Wysocki, Jeffrey; Marciani, Luca; Amidon, Gordon L; Frances, Ann; Baker, Jason R; Hasler, William; Wen, Bo; Pai, Amit; Sun, Duxin

2017-11-01

Gastrointestinal (GI) fluid volume and its dynamic change are integral to study drug disintegration, dissolution, transit, and absorption. However, key questions regarding the local volume and its absorption, secretion, and transit remain unanswered. The dynamic fluid compartment absorption and transit (DFCAT) model is proposed to estimate in vivo GI volume and GI fluid transport based on magnetic resonance imaging (MRI) quantified fluid volume. The model was validated using GI local concentration of phenol red in human GI tract, which was directly measured by human GI intubation study after oral dosing of non-absorbable phenol red. The measured local GI concentration of phenol red ranged from 0.05 to 168 μg/mL (stomach), to 563 μg/mL (duodenum), to 202 μg/mL (proximal jejunum), and to 478 μg/mL (distal jejunum). The DFCAT model characterized observed MRI fluid volume and its dynamic changes from 275 to 46.5 mL in stomach (from 0 to 30 min) with mucus layer volume of 40 mL. The volumes of the 30 small intestine compartments were characterized by a max of 14.98 mL to a min of 0.26 mL (0-120 min) and a mucus layer volume of 5 mL per compartment. Regional fluid volumes over 0 to 120 min ranged from 5.6 to 20.38 mL in the proximal small intestine, 36.4 to 44.08 mL in distal small intestine, and from 42 to 64.46 mL in total small intestine. The DFCAT model can be applied to predict drug dissolution and absorption in the human GI tract with future improvements.

Direct Electrothermal Atomic Absorption Determination of Trace Elements in Body Fluids (Review)

NASA Astrophysics Data System (ADS)

Zacharia, A. N.; Arabadji, M. V.; Chebotarev, A. N.

2017-03-01

This review is focused on the state and development of tendencies of electrothermal atomic absorption spectroscopy over the last 25 years (from 1990 to 2016) in the direct determination of Cu, Zn, Pb, Cd, Mn, Se, As, Cr, Co, Ni, Al, and Hg in body fluids such as blood, urine, saliva, and breast milk.

Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture.

PubMed

Levis, Hannah J; Massie, Isobel; Dziasko, Marc A; Kaasi, Andreas; Daniels, Julie T

2013-11-01

Limbal epithelial stem cells are responsible for the maintenance of the human corneal epithelium and these cells reside in a specialised stem cell niche. They are located at the base of limbal crypts, in a physically protected microenvironment in close proximity to a variety of neighbouring niche cells. Design and recreation of elements of various stem cell niches have allowed researchers to simplify aspects of these complex microenvironments for further study in vitro. We have developed a method to rapidly and reproducibly create bioengineered limbal crypts (BLCs) in a collagen construct using a simple one-step method. Liquid is removed from collagen hydrogels using hydrophilic porous absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting topography on the surface of the thin collagen constructs resembles the dimensions of the stromal crypts of the human limbus. Human limbal epithelial cells seeded onto the surface of the constructs populate these BLCs and form numerous layers with a high proportion of the cells lining the crypts expressing putative stem cell marker, p63α. The HPAs are produced using a moulding process that is flexible and can be adapted depending on the requirements of the end user. Creation of defined topographical features using this process could be applicable to numerous tissue-engineering applications where varied 3-dimensional niche architectures are required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells

PubMed Central

Moorefield, Emily C.; Andres, Sarah F.; Blue, R. Eric; Van Landeghem, Laurianne; Mah, Amanda T.; Santoro, M. Agostina; Ding, Shengli

2017-01-01

Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFPLow), activatable reserve IESC and enteroendocrine cells (Sox9-EGFPHigh), Sox9-EGFPSublow progenitors, and Sox9-EGFPNegative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFPLow IESC and Sox9-EGFPHigh cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging. PMID:28854151

Experiment K-6-17. Structural changes and cell turnover in the rats small intestine induced by spaceflight

NASA Technical Reports Server (NTRS)

Phillips, R. W.; Sawyer, H. R.; Smirnov, K. V.

1990-01-01

The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity associated with microgravity conditions of space flight as evidenced by negative nitrogen balance and muscle atrophy (Nicogossian and Parker, 1982; Oganov, 1981), as well as inhibited lymphocyte proliferation (Bechler and Cogoli, 1986), would be evident in cells characterized by a rapid rate of turnover. As a model, researchers chose to study the turnover of mucosal cells lining the jejunum of the small intestine, since these cells are among the most rapidly proliferating in the body. Under normal conditions, epithelial cells that line the small intestine are continually produced in the crypts of Lieberkuhn. These cells migrate out of the crypts onto intestinal villi, are progressively pushed up the villus as new crypt cells are formed, and ultimately reach the tip of villi where they are then descquamated. In rats, the entire process, from initial proliferation in crypts to desquamation, takes approximately 2 days (Cairnie et al., 1965; Lipkin, 1973). In this study, researchers determined the mitotic index for mucosal cells lining the proximal, middle, and distal regions of the jejunum in rats from three treatment groups (synchronous control, vivarium control and flight), and measured the depth of the crypts of Lieberkuhn and the length of villi present in each of the three jejunal regions sampled.

Restoration of the photoreceptor layer and improvement of visual acuity in successfully treated optic disc pit maculopathy: a long follow-up study by optical coherence tomography.

PubMed

Theodossiadis, George P; Grigoropoulos, Vlassis G; Liarakos, Vasilis S; Rouvas, Alexandros; Emfietzoglou, Ioannis; Theodossiadis, Panagiotis G

2012-07-01

To investigate by optical coherence tomography (OCT) the evolution of the photoreceptor layer and its association with best-corrected visual acuity (BCVA) in optic disc pit (ODP) maculopathy after successful surgical treatment. Fourteen eyes of 14 patients were included in this study, and followed up from 36 to 95 months (mean 57.36 ± 18.32 months). The follow-up period started at the time of complete subretinal fluid absorption. Examination was performed by time-domain OCT before and after treatment. Spectral-domain OCT was used after treatment. Parameters assessed were type of elevation, central foveal thickness, time elapsed from onset to treatment, type of treatment, BCVA, and inner segment outer segment (IS/OS) junction line. The IS/OS junction was characterized after treatment as intact, interrupted, or absent (not distinguishable). Significant restoration of the IS/OS junction line was first noticed between 6 and 12 months after fluid absorption (p = 0.02; Wilcoxon signed rank test). Restoration was continuous up to the 24th month of postoperative examination after fluid absorption (p = 0.14; Wilcoxon signed rank test). BCVA was 0.99 ± 0.38 logMar before treatment, 0.81 ± 0.26 logMar (p = 0.011; paired t-test) immediately after fluid absorption and 0.61 ± 0.33 logMar (p = 0.026; one-way ANOVA) 24 months after fluid resolution. BCVA was significantly positively correlated with the integrity of the IS/OS junction line during follow-up (Pearson r = 0.775; p < 0.001). The IS/OS junction restoration cannot be detected immediately after fluid resolution in the majority of cases. It became evident 6-12 months later and was completed 24 months after fluid absorption. Improvement in BCVA was noticed only during the first 2 years of follow-up. No significant changes were noticed in BCVA or the IS/OS line after 2 years. Among the studied variables, the final photoreceptor layer condition and BCVA immediately after fluid absorption are the main factors predicting final BCVA after successful surgical treatment of ODP maculopathy.

Transport suction apparatus and absorption materials evaluation

NASA Technical Reports Server (NTRS)

Krupa, Debra T.; Gosbee, John

1991-01-01

The specific objectives were as follows. The effectiveness and function was evaluated of the hand held, manually powered v-vac for suction during microgravity. The function was evaluated of the battery powered laerdal suction unit in microgravity. The two units in control of various types of simulated bodily fluids were compared. Various types of tubing and attachments were evaluated which are required to control the collection of bodily fluids during transport. Various materials were evaluated for absorption of simulated bodily fluids. And potential problems were identified for waste management and containment of secretions and fluids during transport. Test procedures, results, and conclusions are briefly discussed.

Generator-absorber-heat exchange heat transfer apparatus and method and use thereof in a heat pump

DOEpatents

Phillips, B.A.; Zawacki, T.S.

1998-07-21

Numerous embodiments and related methods for generator-absorber heat exchange (GAX) are disclosed, particularly for absorption heat pump systems. Such embodiments and related methods use, as the heat transfer medium, the working fluid of the absorption system taken from the generator at a location where the working fluid has a rich liquor concentration. 5 figs.

Generator-absorber-heat exchange heat transfer apparatus and method and use thereof in a heat pump

DOEpatents

Phillips, Benjamin A.; Zawacki, Thomas S.

1998-07-21

Numerous embodiments and related methods for generator-absorber heat exchange (GAX) are disclosed, particularly for absorption heat pump systems. Such embodiments and related methods use, as the heat transfer medium, the working fluid of the absorption system taken from the generator at a location where the working fluid has a rich liquor concentration.

Differential effects of oestrogenic hormones on cell proliferation in the colonic crypt epithelium and in colonic carcinomata of rats.

PubMed

Tutton, P J; Barkla, D H

1982-01-01

A number of hormones, including some steroids, have previously been shown to influence the rate of cell division in the colonic crypt epithelium and in colonic tumours. In this report the effect of oophorectomy and of treatment with ovarian hormones on cell proliferation in these tissues is compared. Colonic tumours cell proliferation was retarded following oophorectomy and this retardation was reversed by the administration of oestradiol, but not by the administration of progesterone. Oophorectomy did not retard cell proliferation in the colonic crypts. The possible significance of these findings in relation to age-dependent variations in the sex ratio for human bowel cancer is discussed.

Absorption from a mixture of seventeen free amino acids by the isolated small intestine of the rat.

PubMed Central

Gardner, M L

1976-01-01

Absorption and secretion from a mixture of seventeen free amino acids has been measured in isolated perfused rat small intestine. 2. The absorption rate of an amino acid from this mixture is proportional to its concentration in the perfusate and independent of its chemical constitution. The constant of proportionality is the same as that previously observed when the perfusate contained peptides as well as amino acids. 3. Amino acids are concentrated, on average, sixfold during passage across the mucosa, and the free amino acid composition of the secretion into the tissue fluid is very similar to that of the luminal perfusate. 4. Peptides do not appear to be added to the tissue fluid during absorption of free amino acids. 5. It is concluded that the mechanisms for absorption of free amino acids are in general independent of those for absorption of peptides. PMID:1255532

Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

DTIC Science & Technology

2014-11-01

separated by infiltrates of inflammatory cells and the presence of crypt abscess (lower left panel). With progression to dysplasia, the crypts are...Rajabi, H, et al., MUC1-C oncoprotein induces TCF7L2 activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem, 2012

Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

PubMed Central

Tutton, P. J.; Barkla, D. H.

1981-01-01

Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2. PMID:6268136

Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

PubMed

Tutton, P J; Barkla, D H

1981-08-01

Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2.

Influence of a highly purified senna extract on colonic epithelium.

PubMed

van Gorkom, B A; Karrenbeld, A; van Der Sluis, T; Koudstaal, J; de Vries, E G; Kleibeuker, J H

2000-01-01

Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls. To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression. Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2'-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically. Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased. Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use. Copyright 2000 S. Karger AG, Basel

Regional Differences in Stem and Transit Cell Proliferation and Apoptosis in the Terminal Ileum and Colon of Mice After 12 Gy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gandara, Ricardo M.C.; Mahida, Yashwant R., E-mail: yash.mahida@nottingham.ac.uk; Potten, Christopher S.

2012-03-01

Purpose: The intestinal epithelium has a high rate of cell turnover, which is regulated by stem cells located near the base of crypts. We aimed to investigate stem cell-dependent characteristics of cell proliferation, apoptosis, and crypt size in terminal ileum and different regions of the colon. Methods and Materials: Mice were studied under steady-state conditions and after radiation-induced stem cell apoptosis. Percentage of proliferating or apoptotic cells at a particular cell position (cp) along the crypt axis was expressed as labeling or apoptotic index. Results: Under steady-state conditions: crypt size was smallest in the ascending colon. In contrast to othermore » regions of the colon, the distribution profile of proliferating cells in ascending colon showed some similarity to that in the terminal ileum. Postirradiation: apoptotic cells were prominent at the bottom of the crypt of mid- and descending colon but in the ascending colon, they were seen with similar frequency from cp 1 to 4. During regeneration, a constant proliferative capacity was seen above Paneth cells in the terminal ileum. In the ascending (but not mid- or descending) colon, the profile of proliferating cells over the first 4 days after irradiation showed a similarity to that in the terminal ileum. Conclusions: Profiles of proliferating epithelial cells (under steady-state conditions and postirradiation) and apoptotic cells (postirradiation) suggest similarities in the location of stem cells in the ascending colon and terminal ileum.« less

Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells.

PubMed

Moorefield, Emily C; Andres, Sarah F; Blue, R Eric; Van Landeghem, Laurianne; Mah, Amanda T; Santoro, M Agostina; Ding, Shengli

2017-08-29

Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP Low ), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP High ), Sox9-EGFP Sublow progenitors, and Sox9-EGFP Negative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFP Low IESC and Sox9-EGFP High cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging.

Colon Stem Cell and Crypt Dynamics Exposed by Cell Lineage Reconstruction

PubMed Central

Itzkovitz, Shalev; Elbaz, Judith; Maruvka, Yosef E.; Segev, Elad; Shlush, Liran I.; Dekel, Nava; Shapiro, Ehud

2011-01-01

Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems. PMID:21829376

Leptin, cell proliferation and crypt fission in the gastrointestinal tract of intravenously fed rats.

PubMed

FitzGerald, A J; Mandir, N; Goodlad, R A

2005-02-01

Many peptides, hormones and growth factors have been implicated in the control of cell renewal in the gastrointestinal epithelium. Leptin is present in the stomach and salivary glands and leptin receptors are seen throughout the gut. Leptin can stimulate mitogen-activated protein kinase activity in vitro and short-term infusion has been reported to have a proliferative action on the colon in vivo, suggesting a biological link between obesity, physical activity and colon cancer. Food intake is one of the most important determinants of intestinal mucosal cell renewal, thus any direct effects of leptin on the gut may be hidden. This problem has been avoided experimentally by maintaining animals on total parenteral nutrition (TPN). Male Wistar rats were anaesthetized and cannulae were inserted into the jugular vein to deliver the TPN diet to which had been added 0, 0.5, 2.5, or 10 mg/kg of recombinant murine leptin. Orally fed rats were also studied. After 6 days of treatment, all animals were injected with vincristine and killed 2 h later. Tissue weight was recorded and crypt cell proliferation (arrested metaphases) and crypt fission were scored in 'microdissected' crypts. Leptin infusion led to a small decrease in body weight and in the weight of the caecum. Intestinal cell proliferation was significantly reduced by TPN when compared to the orally fed rats, but the addition of leptin had no effect on the small intestine or colon. Crypt fission was also significantly lowered in the TPN group. Fission was slightly but significantly increased in the proximal and mid-colon of the leptin-treated rats, but was decreased in the distal colon. Although leptin did not significantly alter cell proliferation, it had significant effects on the process of crypt fission in the colon, which varied according to the exact locality.

Identification of flat dysplastic aberrant crypt foci in the colon of azoxymethane-treated A/J mice.

PubMed

Paulsen, Jan Erik; Knutsen, Helle; Ølstørn, Hege Benedikte; Løberg, Else Marit; Alexander, Jan

2006-02-01

The role of aberrant crypt foci (ACF) as preneoplastic lesions in colon carcinogenesis is not clear. In Min/+ mice and their wild-type littermates treated with azoxymethane (AOM), we previously identified a subgroup of flat ACF that seem more immediate precursors of tumors than the classical elevated ACF. In the present study, we identified a similar subgroup of flat ACF in AOM-treated A/J mice and compared them with nascent tumors and classical elevated ACF. At week 1 and 2 after birth, A/J mice were injected subcutaneously with AOM (10 mg/kg bw/injection). At weeks 7-14, we examined the luminal surface of unsectioned colon preparations stained with methylene blue in the inverse light microscope. The lesions were also examined by histopathology and immunohistochemistry. Surface examination revealed flat ACF, classical elevated ACF and nascent tumors. Since flat ACF were not observed as elevated structures, their bright blue appearance and compressed pit pattern of crypt openings seen with transillumination were used as criteria for their identification. Flat ACF and nascent tumors displayed a uniform picture of severe dysplasia, compressed pit pattern, overexpression of cytoplasmic/nuclear beta-catenin and nuclear overexpression of cyclin D1. Apparently, flat ACF and tumors represented the same type of dysplastic lesions at different stages of crypt multiplication. In contrast, classical elevated ACF did not seem to be as clearly related to tumorigenesis. They infrequently (1/20) possessed severe dysplasia, overexpression of cytoplasmic/nuclear beta-catenin, or nuclear overexpression of cyclin D1, and they did not have compressed crypt openings. Furthermore, flat ACF grew significantly faster than classical elevated ACF. In conclusion, our data indicate a development from flat ACF to adenoma characterized by aberrant activation of the Wnt signaling pathway and fast crypt multiplication. Classical elevated ACF do not seem to be as closely related to tumorigenesis. Copyright 2005 Wiley-Liss, Inc.

The Effects of Fluid Absorption on the Mechanical Properties of Joint Prostheses Components

NASA Astrophysics Data System (ADS)

Yarbrough, David; Viano, Ann

2010-02-01

Ultra-high-molecular-weight polyethylene (UHMWPE) is the material playing the role of cartilage in human prosthetic joints. Wear debris from UHMWPE is a common reason for joint arthroplasty failure, and the exact mechanism responsible for wear remains an area of investigation. In this study, the microstructure of UHMWPE was examined as a function of fluid absorption. Samples with varying exposure to e-beam radiation (as part of the manufacturing process) were soaked for forty days in saline or artificial synovial fluid, under zero or 100 lbs load. Samples were then tensile-tested according to ASTM D-3895. The post-stressed material was then examined by transmission electron microscopy to evaluate the molecular response to stress, which correlates with macroscopic mechanical properties. Three parameters of the crystalline lamellae were measured: thickness, stacking ratio, and alignment to stress direction. Results indicate that fluid absorption does affect the mechanical properties of UHMWPE at both the microscopic and microscopic levels. )

Fluid Absorption and Release of Nonwovens and their Response to Compression

NASA Astrophysics Data System (ADS)

Bateny, Fatemeh

Fluid handling is a key property in one of the major nonwoven applications in absorbent product such as wipes, hygiene products, and baby diapers. These products are subjected to various levels of compression in real-use. The aim of this study was to investigate the liquid absorption and release properties of nonwovens to establish the absorption structure-property relationship at various compression levels. A comprehensive methodology, considering various flow directions, was employed to establish the relationship by decoupling the effect of structural parameters and material properties in two phases of this study respectively. In the first phase, the mechanism of absorption by pore structure was investigated through considering various fiber cross-sectional size and shape, as well as heterogeneous layered structures having a pore size reduction and expansion. In the second phase, the mechanism of absorption by fiber and consequent swelling was evaluated in view of fluid diffusion into the rayon fibers in samples having different percentages of PET fiber (non-absorbent) and rayon fiber (absorbent). The analysis of absorption and release properties through the entire dissertation was based on the pore characteristics of the nonwovens by measuring the average pore sizes, pore size distribution, and solidity. The investigation revealed that the absorption and release properties of nonwovens are governed by their pore characteristics. In homogeneous non-layered nonwoven fabrics, maximum absorption is mainly governed by the available pore volume. Absorbency rate is determined according to pore size and the maximum rate of absorption is achieved at a specific range of pore sizes. This indicates that an in-depth understanding of the absorption and release properties brings about valuable information for the absorbent product engineering.

Iris Crypts Influence Dynamic Changes of Iris Volume.

PubMed

Chua, Jacqueline; Thakku, Sri Gowtham; Tun, Tin A; Nongpiur, Monisha E; Tan, Marcus Chiang Lee; Girard, Michael J A; Wong, Tien Yin; Quah, Joanne Hui Min; Aung, Tin; Cheng, Ching-Yu

2016-10-01

To determine the association of iris surface features with iris volume change after physiologic pupil dilation in adults. Cross-sectional observational study. Chinese adults aged ≥ 50 years without ocular diseases. Digital iris photographs were taken from eyes of each participant and graded for crypts (by number and size) and furrows (by number and circumferential extent) following a standardized grading scheme. Iris color was measured objectively, using the Commission Internationale de l'Eclairage (CIE) L* color parameter (higher value denoting lighter iris). The anterior segment was imaged by swept-source optical coherence tomography (SS-OCT) (Casia; Tomey, Nagoya, Japan) under bright light and dark room conditions. Iris volumes in light and dark conditions were measured with custom semiautomated software, and the change in iris volume was quantified. Associations of the change in iris volume after pupil dilation with underlying iris surface features in right eyes were assessed using linear regression analysis. Iris volume change after physiologic pupil dilation from light to dark condition. A total of 65 Chinese participants (mean age, 59.8±5.7 years) had gradable data for iris surface features. In light condition, higher iris crypt grade was associated independently with smaller iris volume (β [change in iris volume in millimeters per crypt grade increment] = -1.43, 95% confidence interval [CI], -2.26 to -0.59; P = 0.001) and greater reduction of iris volume on pupil dilation (β [change in iris volume in millimeters per crypt grade increment] = 0.23, 95% CI, 0.06-0.40; P = 0.010), adjusting for age, gender, presence of corneal arcus, and change in pupil size. Iris furrows and iris color were not associated with iris volume in light condition or change in iris volume (all P > 0.05). Although few Chinese persons have multiple crypts on their irides, irides with more crypts were significantly thinner and lost more volume on pupil dilation. In view that the latter feature is known to be protective for acute angle-closure attack, it is likely that the macroscopic and microscopic composition of the iris is a contributing feature to angle-closure disease. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Role of serotonin in the intestinal mucosal epithelium barrier in weaning mice undergoing stress-induced diarrhea.

PubMed

Dong, Yulan; Wang, Zixu; Qin, Zhuoming; Cao, Jing; Chen, Yaoxing

2018-02-01

Stress-induced diarrhea is a frequent and challenging threat to humans and domestic animals. Serotonin (5-HT) has been shown to be involved in the pathological process of stress-induced diarrhea. However, the role of 5-HT in stress-induced diarrhea remains unclear. A stress-induced diarrhea model was established in 21-day-old ICR weaning mice through an intragastric administration of 0.25 mL of 0.4 g/mL folium sennae and restraint of the hind legs with adhesive tape for 4 h to determine whether 5-HT regulates the mucosal barrier to cause diarrhea. Mice with decreased levels of 5-HT were pretreated with an intraperitoneal injection of 300 mg/kg p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. After 5 days of treatment, the stress level, body weight and intestinal mucosal morphology indexes were measured. Compared to the controls, the mice with stress-induced diarrhea displayed a stress reaction, with increased corticosterone levels, as well as increased 5-HT-positive cells. However, the mice with stress-induced diarrhea exhibited decreased body weights, villus height to crypt depth ratios (V/C), and Occludin and Claudin1 expression. The PCPA injection reversed these effects in mice with different degrees of stress-induced diarrhea. Based on these findings, inhibition of 5-HT synthesis relieved the stress response and improved the health of the intestinal tract, including both the intestinal absorption capacity, as determined by the villus height and crypt depth, and the mucosal barrier function, as determined by the tight junction proteins of epithelial cell.

The influence of serotonin on the mitotic rate in the colonic crypt epithelium and in colonic adenocarcinoma in rats.

PubMed

Tutton, P J; Barkla, D H

1978-01-01

1. The mitotic rate in the crypts of Lieberkühn of the descending colon and in dimethylhydrazine-induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique. 2. Intraperitoneal injection of a small dose (10 microgram/kg) of serotonin resulted in an increase in the tumour cell mitotic rate. 3. Blockade of serotonin receptors by 2-bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL-6-fluorotryptophan both result in a decrease in the tumour cell mitotic rate. 4. Treatment with serotonin, 2-bromolysergic acid diethylamide and DL-6-fluorotryptophan were all without effect on the colonic crypt cell mitotic rate.

Fluid absorption solar energy receiver

NASA Technical Reports Server (NTRS)

Bair, Edward J.

1993-01-01

A conventional solar dynamic system transmits solar energy to the flowing fluid of a thermodynamic cycle through structures which contain the gas and thermal energy storage material. Such a heat transfer mechanism dictates that the structure operate at a higher temperature than the fluid. This investigation reports on a fluid absorption receiver where only a part of the solar energy is transmitted to the structure. The other part is absorbed directly by the fluid. By proportioning these two heat transfer paths the energy to the structure can preheat the fluid, while the energy absorbed directly by the fluid raises the fluid to its final working temperature. The surface temperatures need not exceed the output temperature of the fluid. This makes the output temperature of the gas the maximum temperature in the system. The gas can have local maximum temperatures higher than the output working temperature. However local high temperatures are quickly equilibrated, and since the gas does not emit radiation, local high temperatures do not result in a radiative heat loss. Thermal radiation, thermal conductivity, and heat exchange with the gas all help equilibrate the surface temperature.

Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system

NASA Astrophysics Data System (ADS)

Cromer, W. E.; Zawieja, D. C.

2018-05-01

Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.

Dependence of intestinal glucose absorption on sodium, studied with a new arterial infusion technique

PubMed Central

Fisher, R. B.; Gardner, M. L. G.

1974-01-01

1. A new preparation of isolated rat jejunum plus ileum (ca. 100 cm) is described in which a saline infusate is pumped into the superior mesenteric artery, the superior mesenteric vein having been ligated. 2. The arterial infusate washes out the tissue spaces: the lumen is perfused in a single pass with a segmented flow as by Fisher & Gardner (1974). 3. At an arterial infusion rate of 3 ml./min, steady states are set up in the tissue fluid within 10-15 min: the compositions of the fluids bathing both sides of the mucosa can therefore be controlled. 4. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium is replaced by choline abruptly while the tissue fluid sodium is maintained at 144 m-equiv/l. by arterial infusion. 5. The rate of glucose absorption from the lumen is unaffected by replacement of sodium in the arterial infusate by choline. 6. Ouabain (10-4 M) in an arterial infusate containing sodium 144 m-equiv/l. causes inhibition of glucose and water absorption from the lumen. There is no effect of ouabain when the arterial infusate contains sodium, 0 or 72 m-equiv/l. 7. Arterial ouabain does not reverse the effects of depletion of luminal sodium. Simultaneous removal of luminal sodium and application of arterial ouabain causes faster inhibition of glucose absorption than does either treatment alone. 8. Glucose absorption is more likely to depend on rate of efflux of sodium from mucosal cell to tissue fluid than on a sodium gradient at the brush border or on intracellular sodium concentration. PMID:4422318

Epimorphin Regulates the Intestinal Stem Cell Niche via Effects on the Stromal Microenvironment.

PubMed

Vishy, Courtney E; Swietlicki, Elzbieta A; Gazit, Vered; Amara, Suneetha; Heslop, Gabriela; Lu, Jianyun; Levin, Marc S; Rubin, Deborah C

2018-04-06

Stem cell therapy is a potential therapeutic approach for disorders characterized by intestinal injury or loss of functional surface area. Stem cell function and proliferation are mediated by the stem cell niche. Stromal cells such as intestinal subepithelial myofibroblasts (ISEMFs) are important but poorly studied components of the stem cell niche. To examine the role of ISEMFs, we have previously generated mice with deletion of epimorphin (Epim), an ISEMF protein and member of the syntaxin family of intracellular vesicle docking proteins that regulate cell secretion. Herein we explore the mechanisms for previous observations that Epim deletion increases gut crypt cell proliferation, crypt fission and small bowel length in vivo. Stem cell derived crypt culture techniques were used to explore the interaction between enteroids and myofibroblasts from Epim -/- and WT mice. Enteroids co-cultured with ISEMFS had increased growth and crypt-like budding compared to enteroids cultured without stromal support. Epim deletion in ISEMFs resulted in increased enteroid budding and surface area compared to co-cultures with WT ISEMFs. In primary crypt cultures, Epim -/- enteroids had significantly increased surface area and budding compared WTs. However stem cell assays comparing the number of Epim -/- vs WT colony forming units after first passage showed no differences in the absence of ISEMF support. Epim -/- vs. WT ISEMFs had increased Wnt4 expression and addition of Wnt4 to WT co-cultures enhanced budding. We conclude that ISEMFs play an important role in the stem cell niche. Epim regulates stem cell proliferation and differentiation via stromal contributions to the niche microenvironment.

Comparative genomic analysis of Acinetobacter strains isolated from murine colonic crypts.

PubMed

Saffarian, Azadeh; Touchon, Marie; Mulet, Céline; Tournebize, Régis; Passet, Virginie; Brisse, Sylvain; Rocha, Eduardo P C; Sansonetti, Philippe J; Pédron, Thierry

2017-07-11

A restricted set of aerobic bacteria dominated by the Acinetobacter genus was identified in murine intestinal colonic crypts. The vicinity of such bacteria with intestinal stem cells could indicate that they protect the crypt against cytotoxic and genotoxic signals. Genome analyses of these bacteria were performed to better appreciate their biodegradative capacities. Two taxonomically different clusters of Acinetobacter were isolated from murine proximal colonic crypts, one was identified as A. modestus and the other as A. radioresistens. Their identification was performed through biochemical parameters and housekeeping gene sequencing. After selection of one strain of each cluster (A. modestus CM11G and A. radioresistens CM38.2), comparative genomic analysis was performed on whole-genome sequencing data. The antibiotic resistance pattern of these two strains is different, in line with the many genes involved in resistance to heavy metals identified in both genomes. Moreover whereas the operon benABCDE involved in benzoate metabolism is encoded by the two genomes, the operon antABC encoding the anthranilate dioxygenase, and the phenol hydroxylase gene cluster are absent in the A. modestus genomic sequence, indicating that the two strains have different capacities to metabolize xenobiotics. A common feature of the two strains is the presence of a type IV pili system, and the presence of genes encoding proteins pertaining to secretion systems such as Type I and Type II secretion systems. Our comparative genomic analysis revealed that different Acinetobacter isolated from the same biological niche, even if they share a large majority of genes, possess unique features that could play a specific role in the protection of the intestinal crypt.

Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

PubMed

Yang, K; Lamprecht, S A; Liu, Y; Shinozaki, H; Fan, K; Leung, D; Newmark, H; Steele, V E; Kelloff, G J; Lipkin, M

2000-09-01

In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

Female-Specific Specialization of a Posterior End Region of the Midgut Symbiotic Organ in Plautia splendens and Allied Stinkbugs

PubMed Central

Hayashi, Toshinari; Hosokawa, Takahiro; Meng, Xian-Ying; Koga, Ryuichi

2015-01-01

Many stinkbugs (Insecta: Hemiptera: Heteroptera) are associated with bacterial symbionts in a posterior region of the midgut. In these stinkbugs, adult females excrete symbiont-containing materials from the anus for transmission of the beneficial symbionts to their offspring. For ensuring the vertical symbiont transmission, a variety of female-specific elaborate traits at the cellular, morphological, developmental, and behavioral levels have been reported from diverse stinkbugs of the families Plataspidae, Urostylididae, Parastrachiidae, etc. Meanwhile, such elaborate female-specific traits for vertical symbiont transmission have been poorly characterized for the largest and economically important stinkbug family Pentatomidae. Here, we investigated the midgut symbiotic system of a pentatomid stinkbug, Plautia splendens. A specific gammaproteobacterial symbiont was consistently present extracellularly in the cavity of numerous crypts arranged in four rows on the midgut fourth section. The symbiont was smeared on the egg surface upon oviposition by adult females, orally acquired by newborn nymphs, and thereby transmitted vertically to the next generation and important for growth and survival of the host insects. We found that, specifically in adult females, several rows of crypts at the posterior end region of the symbiotic midgut were morphologically differentiated and conspicuously enlarged, often discharging the symbiotic bacteria from the crypt cavity to the main tract of the symbiotic midgut. The female-specific enlarged end crypts were also found in other pentatomid stinkbugs Plautia stali and Carbula crassiventris. These results suggest that the enlarged end crypts represent a female-specific specialized morphological trait for vertical symbiont transmission commonly found among stinkbugs of the family Pentatomidae. PMID:25636847

The influence of nutrients, biliary-pancreatic secretions, and systemic trophic hormones on intestinal adaptation in a Roux-en-Y bypass model.

PubMed

Taqi, Esmaeel; Wallace, Laurie E; de Heuvel, Elaine; Chelikani, Prasanth K; Zheng, Huiyuan; Berthoud, Hans-Rudolph; Holst, Jens J; Sigalet, David L

2010-05-01

The signals that govern the upregulation of nutrient absorption (adaptation) after intestinal resection are not well understood. A Gastric Roux-en-Y bypass (GRYB) model was used to isolate the relative contributions of direct mucosal stimulation by nutrients, biliary-pancreatic secretions, and systemic enteric hormones on intestinal adaptation in short bowel syndrome. Male rats (350-400 g; n = 8/group) underwent sham or GRYB with pair feeding and were observed for 14 days. Weight and serum hormonal levels (glucagon-like peptide-2 [GLP-2], PYY) were quantified. Adaptation was assessed by intestinal morphology and crypt cell kinetics in each intestinal limb of the bypass and the equivalent points in the sham intestine. Mucosal growth factors and expression of transporter proteins were measured in each limb of the model. The GRYB animals lost weight compared to controls and exhibited significant adaptive changes with increased bowel width, villus height, crypt depth, and proliferation indices in the alimentary and common intestinal limbs. Although the biliary limb did not adapt at the mucosa, it did show an increased bowel width and crypt cell proliferation rate. The bypass animals had elevated levels of systemic PYY and GLP-2. At the mucosal level, insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) increased in all limbs of the bypass animals, whereas keratinocyte growth factor (KGF) and epidermal growth factor (EGF) had variable responses. The expression of the passive transporter of glucose, GLUT-2, expression was increased, whereas GLUT-5 was unchanged in all limbs of the bypass groups. Expression of the active mucosal transporter of glucose, SGLT-1 was decreased in the alimentary limb. Adaptation occurred maximally in intestinal segments stimulated by nutrients. Partial adaptation in the biliary limb may reflect the effects of systemic hormones. Mucosal content of IGF-1, bFGF, and EGF appear to be stimulated by systemic hormones, potentially GLP-2, whereas KGF may be locally regulated. Further studies to examine the relationships between the factors controlling nutrient-induced adaptation are suggested. Direct contact with nutrients appears to be the most potent factor in inducing mucosal adaptation. Copyright (c) 2010 Elsevier Inc. All rights reserved.

THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO THIHALOMETHANE MIXTURES IN THE DRINKING WATER

EPA Science Inventory

THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N
RATS EXPOSED TO TRIHALOMETHANE MIXTURES IN THE DRINKING WATER

The trihalomethanes (THM), bromoform (TBM) and bromodichloromethane (BDCM), administered by corn oil gavage were found to increase large...

Apical Na(+)-D-glucose cotransporter 1 (SGLT1) activity and protein abundance are expressed along the jejunal crypt-villus axis in the neonatal pig

USDA-ARS?s Scientific Manuscript database

Gut apical Na(+)-glucose cotransporter 1 (SGLT1) activity is high at the birth and during suckling, thus contributing substantially to neonatal glucose homeostasis. We hypothesize that neonates possess high SGLT1 maximal activity by expressing apical SGLT1 protein along the intestinal crypt-villus a...

TRIBROMOMETHANE EXPOSURE AND DIETARY FOLATE DEFICIENCY IN THE FORMATION OF ABERRANT CRYPT FOCI IN THE COLONS OF F344/N RATS

EPA Science Inventory

TRIBROMOMETHANE EXPOSURE AND DIETARY FOLATE DEFICIENCY IN THE FORMATION OF ABERRANT CRYPT FOCI IN THE COLONS OF F344/N RATS

David R. Geter', Tanya M. Moore', Michael H. George', Steve R. Kilburn', Gloria Huggins-Clark', James W. Allen', and Anthony B. DeAngelo' 'National H...

Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Background: The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat western diet, but the mechanism underlying this relationship remains to be determined. Objective: We tested the hypothesis that a high-fat diet promotes aberrant crypt (AC) format...

Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

PubMed

Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

2009-12-01

The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation.

Determination of absorption coefficient of nanofluids with unknown refractive index from reflection and transmission spectra

NASA Astrophysics Data System (ADS)

Kim, Joong Bae; Lee, Seungyoon; Lee, Kyungeun; Lee, Ikjin; Lee, Bong Jae

2018-07-01

It has been shown that the absorption coefficient of a nanofluid can be actively tuned by changing material, size, shape, and concentration of the nanoparticle suspension. In applications of engineered nanofluids for the direct absorption of solar radiation, it is important to experimentally characterize the absorption coefficient of nanofluids in the solar spectrum. If the refractive index of the base fluid (i.e., the solution without nanoparticles) is known a priori, the absorption coefficient of nanofluids can be easily determined from the transmission spectrum. However, if the refractive index of the base fluid is not known, it is not straightforward to extract the absorption coefficient solely from the transmission spectrum. The present work aims to develop an analytical method of determining the absorption coefficient of nanofluids with unknown refractive index by measuring both reflection and transmission spectra. The proposed method will be validated with deionized water, and the effect of measurement uncertainty will be carefully examined. Finally, the general applicability of the proposed method will also be demonstrated for Therminol VP-1 as well as the Therminol VP-1 - graphite nanofluid.

The effects of consuming carbohydrate-electrolyte beverages on gastric emptying and fluid absorption during and following exercise.

PubMed

Murray, R

1987-01-01

A variety of beverages formulated to provide fluid, carbohydrates, and electrolytes during and following exercise are commercially available. Such 'sport drinks' commonly contain 4 to 8% carbohydrate (as glucose, fructose, sucrose or maltodextrins) and small amounts of electrolytes (most often sodium, potassium, and chloride). The efficacy of consuming such beverages has been questioned primarily because of concern that beverage carbohydrate content may inhibit gastric emptying rate and fluid absorption during exercise, thereby jeopardizing physiological homeostasis and impairing exercise performance. Gastric motor activity, and consequently gastric emptying rate, is governed by neural and humoral feedback provided by receptors found in the gastric musculature and proximal small intestine. Gastric emptying rate may be influenced by a variety of factors including, but not limited to, the caloric content, volume, osmolality, temperature, and pH of the ingested fluid, diurnal and interindividual variation, metabolic state (rest/exercise), and the ambient temperature. The caloric content of the ingested fluid appears to be the most important variable governing gastric emptying rate, providing a mean caloric efflux from the stomach of 2.0 to 2.5 kcal/min for ingested fluid volumes less than 400 ml. At rest, gastric emptying is inhibited by solutions containing calories in a manner independent of the nutrient source (i.e. carbohydrate, fat or protein). Consequently, plain water is known to empty from the stomachs of resting subjects at rates faster than solutions containing calories. Gastric emptying is increasingly inhibited as the caloric content of the ingested fluid increases. During moderate exercise (less than 75% VO2max), gastric emptying occurs at a rate similar to that during rest; more intense exercise appears to inhibit gastric emptying. When fluids are consumed at regular intervals throughout prolonged exercise (greater than 2 hours), postexercise aspiration of stomach contents reveals that solutions containing up to 10% carbohydrate empty at rates similar to plain water. There is ample physiological justification for the addition of glucose, fructose, sodium, potassium and chloride to fluid replacement beverages. Fluid absorption in the small intestine is stimulated by glucose and sodium (and to a lesser extent by fructose and other electrolytes). Glucose and sodium are absorbed via a common membrane carrier in the mucosal epithelium of the proximal small intestine. The potentiation of sodium uptake by glucose establishes an osmotic gradient for fluid absorption.(ABSTRACT TRUNCATED AT 400 WORDS)

Moderately nonlinear ultrasound propagation in blood-mimicking fluid.

PubMed

Kharin, Nikolay A; Vince, D Geoffrey

2004-04-01

In medical diagnostic ultrasound (US), higher than-in-water nonlinearity of body fluids and tissue usually does not produce strong nonlinearly distorted waves because of the high absorption. The relative influence of absorption and nonlinearity can be characterized by the Gol'dberg number Gamma. There are two limiting cases in nonlinear acoustics: weak waves (Gamma < 1) or strong waves (Gamma > 1). However, at diagnostic frequencies in tissue and body fluids, the nonlinear effects and effects of absorption more likely are comparable (Gol'dberg number Gamma approximately 1). The aim of this work was to study the nonlinear propagation of a moderately nonlinear US second harmonic signal in a blood-mimicking fluid. Quasilinear solutions to the KZK equation are presented, assuming radiation from a flat and geometrically focused circular Gaussian source. The solutions are expressed in a new simplified closed form and are in very good agreement with those of previous studies measuring and modeling Gaussian beams. The solutions also show good agreement with the measurements of the beams produced by commercially available transducers, even without special Gaussian shading.

Mitogenic action of tumour necrosis factor-alpha and interleukin-8 on explants of human duodenal mucosa.

PubMed

Zachrisson, K; Neopikhanov, V; Wretlind, B; Uribe, A

2001-08-07

Our aim is to examine whether tumour necrosis factor-alpha (TNF-alpha) and interleukin affect the mitotic activity in explants of human duodenal mucosa and to estimate the release of cytokines from explants incubated with TNF-alpha. Biopsy specimens of normal duodenal mucosa were taken from 19 subjects that underwent upper endoscopy for investigation of dyspeptic symptoms or chronic gastrointestinal bleeding. The specimens were processed following guidelines for organ culture technique. Paired biopsy specimens from 12 subjects were cultured for 23 h to achieve steady state and thereafter the explants were incubated 25 h with 10(-13)-10(-9) M of TNF-alpha or IL-8. Mitoses were arrested in the metaphase by adding vincristine sulphate for the last three hours. The explants were then fixed and processed for microdissection. Fifteen crypts were microdissected and the total number of metaphases was determined using the whole crypt as reference volume. The number of metaphases per crypt was also estimated in explants incubated with 10(-10) M TNF-alpha in the presence of anti-IL-8 antibodies. Additional duodenal explants from seven subjects were incubated with 10(-10) M TNF-alpha for 25 h. Thereafter the release of IL-1-beta, IL-6, IL-8 and interferon gamma (IFN-gamma) into the culture medium was measured by enzyme immunoassay and expressed as pg/mg protein. TNF-alpha and IL-8 significantly increased the number of metaphases/crypts (P<0.0001). The addition of anti-IL-8 slightly reduced the number of metaphases/crypt compared to the values observed in the explants incubated with 10(-10) M TNF-alpha alone (P<0.0001). The number of metaphases/crypt in the explants incubated with 10(-10) M TNF-alpha in the presence of anti-IL-8 antibodies was, however, markedly and significantly higher than that of the controls (P<0.000). TNF-alpha induced the release of IL-8 (P<0.01) and IL-6 (P<0.05) from the duodenal explants. TNF-alpha and IL-8 are potent mitogens to human small intestinal crypts. The mitogenic action of TNF-alpha is primarily a direct effect of the cytokine and only to a minor extent mediated by a secondary production of IL-8 in the duodenal explant. Our findings indicate that TNF-alpha and IL-8 may participate in the regulation of cell proliferation in the human small intestinal epithelium. Copyright 2001 Academic Press.

Hydrothermal diamond-anvil cell: Application to studies of geologic fluids

USGS Publications Warehouse

Chou, I.-Ming

2003-01-01

The hydrothermal diamond-anvil cell (HDAC) was designed to simulate the geologic conditions of crustal processes in the presence of water or other fluids. The HDAC has been used to apply external pressure to both synthetic and natural fluid inclusions in quartz to minimize problems caused by stretching or decrepitation of inclusions during microthermometric analysis. When the HDAC is loaded with a fluid sample, it can be considered as a large synthetic fluid inclusion and therefore, can be used to study the PVTX properties as well as phase relations of the sample fluid. Because the HDAC has a wide measurement pressure-temperature range and also allows in-situ optical observations, it has been used to study critical phenomena of various chemical systems, such as the geologically important hydrous silicate melts. It is possible, when the HDAC is combined with synchrotron X-ray sources, to obtain basic information on speciation and structure of metal including rare-earth elements (REE) complexes in hydrothermal solutions as revealed by X-ray absorption fine structure (XAFS) spectra. Recent modifications of the HDAC minimize the loss of intensity of X-rays due to scattering and absorption by the diamonds. These modifications are especially important for studying elements with absorption edges below 10 keV and therefore particularly valuable for our understanding of transport and deposition of first-row transition elements and REE in hydrothermal environments.

Duck plague in free-flying waterfowl observed during the Lake Andes epizootic

USGS Publications Warehouse

Proctor, S.J.; Pearson, G.L.; Leibovitz, Louis

1975-01-01

The first major epizootic of duck plague in free-flying waterfowl occurred at Lake Andes, South Dakota, in January and February, 1973. Duck plague was diagnosed in black ducks, mallards, pintail-mallard hybrids, redheads, common mergansers, common golden eyes, canvasbacks, American widgeon, wood ducks, and Canada geese, indicating the general susceptibility of ducks to duck plague. Clinical signs observed in mallards were droopiness, polydipsia, lethargy, reduced wariness, weakness, reluctance to fly, swimming in circles, bloody diarrhea, bloody fluid draining from the nares and bill, and terminal convulsions.Because the mallard was the most numerous and heavily infected species during the Lake Andes epizootic, gross and microscopic lesions of the gastrointestinal tract, liver, spleen, thymus, bursa of Fabricius, heart, lung, bone marrow, pancreas, and ovaries were described. Lesions of the esophagus and cloaca were in the stratified submucosal glands. In the small and large intestine, lesions were located in lymphocytic aggregates, lamina propria, and crypt epithelium. Hemorrhages and necrosis of hepatocytes and bile duct epithelium were noted in the liver. Diffuse necrosis of lymphocytic and reticuloendothelial tissue were evident in the spleen, bursa of Fabricius, and thymus. Hemorrhages in other tissues such as the lung and heart were often associated with lymphoid nodules, while those in organs such as the pancreas were associated with acinar necrosis. Intranuclear inclusion bodies were seen in stratified squamous epithelium of the esophagus and cloaca, crypt epithelium of the intestine, hepatocytes, bile duct epithelium, cells of Hassel's corpuscles, splenic periarteriolar reticular cells, and epithelial cells in the bursa of Fabricius.

VEHICLE AND MODE OF ADMINISTRATION EFFECTS ON THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO BROMODICHLOROMETHANE

EPA Science Inventory

Vehicle and Mode of Administration Effects on the Induction of Aberrant Crypt Foci in the Colons of Male F344/N Rats Exposed to Bromodichloromethane.

David R. Geter, Michael H. George, Tanya M. Moore, Steve Kilburn, Gloria Huggins-Clark, and Anthony B. DeAngelo. Submited ...

Aberrant crypt formation accompanies an increase of opportunistic pathogens/bacteria in the inflammatory gut of C57BL/6 mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Obesity and high fat diet are risk factors for colon cancer, but the mechanism of this relationship remains to be determined. We tested the hypothesis that a high fat diet promotes the formation of aberrant crypt foci (ACF, preneoplastic lesions) in a manner associated with changes in hindgut bacter...

Responsiveness of intestinal epithelial cell turnover to TGF-alpha after bowel resection in a rat is correlated with EGF receptor expression along the villus-crypt axis.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Shaoul, Ron; Karry, Rahel; Lieber, Michael; Suss-Toby, Edith; Ure, Benno M; Coran, Arnold G

2008-01-01

Recent evidence suggests that transforming growth factor alpha (TGF-alpha) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-alpha on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-alpha rats underwent bowel resection and were treated with TGF-alpha (75 microg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-alpha resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 +/- 0.013 vs 0.010 +/- 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 +/- 8 vs 138 +/- 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-alpha administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 +/- 0.002 vs 0.029 +/- 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 +/- 0.001 vs 0.028 +/- 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-alpha (group C). In a rat model of SBS, TGF-alpha increased enterocyte proliferation and stimulated intestinal adaptation. The effect of TGF-alpha on enterocyte turnover is correlated with EGF receptor expression along the villus-crypt axis.

Pathophysiology of avian intestinal ion transport.

PubMed

Nighot, Meghali; Nighot, Prashant

2018-06-01

The gut has great importance for the commercial success of poultry production. Numerous ion transporters, exchangers, and channels are present on both the apical and the basolateral membrane of intestinal epithelial cells, and their differential expression along the crypt-villus axis within the various intestinal segments ensures efficient intestinal absorption and effective barrier function. Recent studies have shown that intensive production systems, microbial exposure, and nutritional management significantly affect intestinal physiology and intestinal ion transport. Dysregulation of normal intestinal ion transport is manifested as diarrhoea, malabsorption, and intestinal inflammation resulting into poor production efficiency. This review discusses the basic mechanisms involved in avian intestinal ion transport and the impact of development during growth, nutritional and environmental alterations, and intestinal microbial infections on it. The effect of intestinal microbial infections on avian intestinal ion transport depends on factors such as host immunity, pathogen virulence, and the mucosal organisation of the particular intestinal segment.

Nutrient-induced intestinal adaption and its effect in obesity.

PubMed

Dailey, Megan J

2014-09-01

Obese and lean individuals respond differently to nutrients with changes in digestion, absorption and hormone release. This may be a result of differences in intestinal epithelial morphology and function driven by the hyperphagia or the type of diet associated with obesity. It is well known that the maintenance and growth of the intestine is driven by the amount of luminal nutrients, with high nutrient content resulting in increases in cell number, villi length and crypt depth. In addition, the type of nutrient appears to contribute to alterations in the morphology and function of the epithelial cells. This intestinal adaptation may be what is driving the differences in nutrient processing in lean versus obese individuals. This review describes how nutrients may be able to induce changes in intestinal epithelial cell proliferation, differentiation and function and the link between intestinal adaptation and obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

An investigation of multi-rate sound decay under strongly non-diffuse conditions: The crypt of the Cathedral of Cadiz

NASA Astrophysics Data System (ADS)

Martellotta, Francesco; Álvarez-Morales, Lidia; Girón, Sara; Zamarreño, Teófilo

2018-05-01

Multi-rate sound decays are often found and studied in complex systems of coupled volumes where diffuse field conditions generally apply, although the openings connecting different sub-spaces are by themselves potential causes of non-diffuse behaviour. However, in presence of spaces in which curved surfaces clearly prevent diffuse field behaviour from being established, things become more complex and require more sophisticated tools (or, better, combinations of them) to be fully understood. As an example of such complexity, the crypt of the Cathedral of Cadiz is a relatively small space characterised by a central vaulted rotunda, with five radial galleries with flat and low ceiling. In addition, the crypt is connected to the main cathedral volume by means of several small openings. Acoustic measurements carried out in the crypt pointed out the existence of at least two decay processes combined, in some points, with flutter echoes. Application of conventional methods of analysis pointed out the existence of significant differences between early decay time and reverberation time, but was inconclusive in explaining the origin of the observed phenomena. The use of more robust Bayesian analysis permitted the conclusion that the late decay appearing in the crypt had a different rate than that observed in the cathedral, thus excluding the explanation based on acoustic coupling of different volumes. Finally, processing impulse responses collected by means of a B-format microphone to obtain directional intensity maps demonstrated that the late decay was originated from the rotunda where a repetitive reflection pattern appeared between the floor and the dome causing both flutter echoes and a longer reverberation time.

Advanced three-dimensional culture of equine intestinal epithelial stem cells.

PubMed

Stewart, A Stieler; Freund, J M; Gonzalez, L M

2018-03-01

Intestinal epithelial stem cells are critical to epithelial repair following gastrointestinal injury. The culture of intestinal stem cells has quickly become a cornerstone of a vast number of new research endeavours that range from determining tissue viability to testing drug efficacy for humans. This study aims to describe the methods of equine stem cell culture and highlights the future benefits of these techniques for the advancement of equine medicine. To describe the isolation and culture of small intestinal stem cells into three-dimensional (3D) enteroids in horses without clinical gastrointestinal abnormalities. Descriptive study. Intestinal samples were collected by sharp dissection immediately after euthanasia. Intestinal crypts containing intestinal stem cells were dissociated from the underlying tissue layers, plated in a 3D matrix and supplemented with growth factors. After several days, resultant 3D enteroids were prepared for immunofluorescent imaging and polymerase chain reaction (PCR) analysis to detect and characterise specific cell types present. Intestinal crypts were cryopreserved immediately following collection and viability assessed. Intestinal crypts were successfully cultured and matured into 3D enteroids containing a lumen and budding structures. Immunofluorescence and PCR were used to confirm the existence of stem cells and all post mitotic, mature cell types, described to exist in the horse intestinal epithelium. Previously frozen crypts were successfully cultured following a freeze-thaw cycle. Tissues were all derived from normal horses. Application of this technique for the study of specific disease was not performed at this time. The successful culture of equine intestinal crypts into 3D "mini-guts" allows for in vitro studies of the equine intestine. Additionally, these results have relevance to future development of novel therapies that harness the regenerative potential of equine intestine in horses with gastrointestinal disease (colic). © 2017 EVJ Ltd.

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

PubMed Central

Schuller, Bradley W.; Binns, Peter J.; Riley, Kent J.; Ma, Ling; Hawthorne, M. Frederick; Coderre, Jeffrey A.

2006-01-01

The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min−1. An additional dose was selectively targeted to endothelial cells from the short-ranged (5–9 μm) particles released from neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70–90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g 10B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min−1, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome. PMID:16505359

Novel Regenerative Peptide TP508 Mitigates Radiation-Induced Gastrointestinal Damage By Activating Stem Cells and Preserving Crypt Integrity

PubMed Central

Kantara, Carla; Moya, Stephanie M.; Houchen, Courtney W.; Umar, Shahid; Ullrich, Robert L.; Singh, Pomila; Carney, Darrell H.

2015-01-01

In recent years, increasing threats of radiation exposure and nuclear disasters have become a significant concern for the United States and countries worldwide. Exposure to high doses of radiation triggers a number of potentially lethal effects. Among the most severe is the gastrointestinal (GI) toxicity syndrome caused by the destruction of the intestinal barrier, resulting in bacterial translocation, systemic bacteremia, sepsis and death. The lack of effective radioprotective agents capable of mitigating radiation-induced damage has prompted a search for novel countermeasures that can mitigate the effects of radiation post-exposure, accelerate tissue repair in radiation-exposed individuals, and prevent mortality. We report that a single injection of regenerative peptide TP508 (rusalatide acetate, Chrysalin®) 24h after lethal radiation exposure (9Gy, LD100/15) appears to significantly increase survival and delay mortality by mitigating radiation-induced intestinal and colonic toxicity. TP508 treatment post-exposure prevents the disintegration of gastrointestinal crypts, stimulates the expression of adherens junction protein E-cadherin, activates crypt cell proliferation, and decreases apoptosis. TP508 post-exposure treatment also up-regulates the expression of DCLK1 and LGR5 markers of stem cells that have been shown to be responsible for maintaining and regenerating intestinal crypts. Thus, TP508 appears to mitigate the effects of GI toxicity by activating radioresistant stem cells and increasing the stemness potential of crypts to maintain and restore intestinal integrity. These results suggest that TP508 may be an effective emergency nuclear countermeasure that could be delivered within 24h post-exposure to increase survival and delay mortality, giving victims time to reach clinical sites for advanced medical treatment. PMID:26280221

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

NASA Astrophysics Data System (ADS)

Schuller, Bradley W.; Binns, Peter J.; Riley, Kent J.; Ma, Ling; Hawthorne, M. Frederick; Coderre, Jeffrey A.

2006-03-01

The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min-1. An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 μm) particles released from neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70-90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g 10B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min-1, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome. gastrointestinal syndrome | boron | liposomes | neutron capture

Inhibition of airway surface fluid absorption by cholinergic stimulation

PubMed Central

Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

2016-01-01

In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

Bovine colostrum to children with short bowel syndrome: a randomized, double-blind, crossover pilot study.

PubMed

Aunsholt, Lise; Jeppesen, Palle Bekker; Lund, Pernille; Sangild, Per Torp; Ifaoui, Inge Bøtker Rasmussen; Qvist, Niels; Husby, Steffen

2014-01-01

Management of short bowel syndrome (SBS) aims to achieve intestinal autonomy to prevent fluid, electrolyte, and nutrient deficiencies and maintain adequate development. Remnant intestinal adaptation is required to obtain autonomy. In the newborn pig, colostrum has been shown to support intestinal development and hence adaptive processes. The efficacy of bovine colostrum to improve intestinal function in children with SBS was evaluated by metabolic balance studies. Nine children with SBS were included in a randomized, double-blind, crossover study. Twenty percent of enteral fluid intake was replaced with bovine colostrum or a mixed milk diet for 4 weeks, separated by a 4-week washout period. Intestinal absorption of energy and wet weight was used to assess intestinal function and the efficacy of colostrum. Colostrum did not improve energy or wet weight absorption compared with the mixed milk diet (P = 1.00 and P = .93, respectively). Growth as measured by weight and knemometry did not differ between diets (P = .93 and P = .28). In these patients, <150% enteral energy absorption of basal metabolic rate and 50% enteral fluid absorption of basal fluid requirement suggested intestinal failure and a need for parenteral nutrition (PN). Inclusion of bovine colostrum to the diet did not improve intestinal function. Metabolic nutrient and wet weight balance studies successfully assessed intestinal function, and this method may distinguish between intestinal insufficiency (non-PN-dependent) and intestinal failure (PN-dependent) patients.

Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

PubMed

Pretlow, T P; O'Riordan, M A; Spancake, K M; Pretlow, T G

1993-06-01

Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues.

Neutral dynamics and cell renewal of colonic crypts in homeostatic regime

NASA Astrophysics Data System (ADS)

Fendrik, A. J.; Romanelli, L.; Rotondo, E.

2018-05-01

The self renewal process in colonic crypts is the object of several studies. We present here a new compartment model with the following characteristics: (a) we distinguish different classes of cells: stem cells, six generations of transit amplifying cells and the differentiated cells; (b) in order to take into account the monoclonal character of crypts in homeostatic regimes we include symmetric divisions of the stem cells. We first consider the dynamic differential equations that describe the evolution of the mean values of the populations, but the small observed value of the total number of cells involved plus the huge dispersion of experimental data found in the literature leads us to study the stochastic discrete process. This analysis allows us to study fluctuations, the neutral drift that leads to monoclonality, and the effects of the fixation of mutant clones.

Synthesis and isolation of [Fe@Ge(10)](3-): a pentagonal prismatic Zintl ion cage encapsulating an interstitial iron atom.

PubMed

Zhou, Binbin; Denning, Mark S; Kays, Deborah L; Goicoechea, Jose M

2009-03-04

Reaction of an ethylenediamine (en) solution of the Zintl phase precursor K(4)Ge(9) with FeAr(2) (Ar = 2,6-Mes(2)C(6)H(3)) in the presence of 2,2,2-crypt (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) yielded the endohedral Zintl ion [Fe@Ge(10)](3-) (1) which was crystallographically characterized as a [K(2,2,2-crypt)](+) salt in [K(2,2,2-crypt)](3)[Fe@Ge(10)]*2en. This unprecedented Zintl ion exhibits a pentagonal prismatic 10-atom germanium cage with an interstitial iron atom in the central cavity. Confirmation of the existence of the cluster anion in solution was corroborated by positive and negative ion mode electrospray mass spectrometry.

Solubility and stability of dalcetrapib in vehicles and biological media.

PubMed

Gross, Günter; Tardio, Joseph; Kuhlmann, Olaf

2012-11-01

Dalcetrapib solubility was determined in aqueous and in non-aqueous vehicles and in biorelevant media. In a pure aqueous environment the solubility was low but could be increased by addition of surfactants or complexing agents. This was also reflected in the solubility seen in simulated gastrointestinal (GI) fluids, with almost no solubility in simulated gastric fluid, but reasonable solubilisation in simulated intestinal fluids containing lecithin and bile salt. Additionally, the stability of dalcetrapib was determined in simulated GI fluids with and without pancreatic lipase. In solutions without lipase, dalcetrapib was slowly hydrolysed, but in the presence of lipase the hydrolysis rate was significantly faster depending on pH and enzyme activity. In biological fluids, dissolved dalcetrapib appeared to behave similarly being rapidly hydrolysed in human intestinal fluids with a half-life below 20s with no degradation observed in human gastric fluids at low pH. The results provide supportive evidence that absorption is higher under fed conditions and indicate lipase inhibitors might interfere with oral absorption of dalcetrapib. Copyright © 2012 Elsevier B.V. All rights reserved.

Crypt cells are involved in kin recognition in larval zebrafish

PubMed Central

Biechl, Daniela; Tietje, Kristin; Gerlach, Gabriele; Wullimann, Mario F.

2016-01-01

Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells, and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal. PMID:27087508

Crypt cells are involved in kin recognition in larval zebrafish.

PubMed

Biechl, Daniela; Tietje, Kristin; Gerlach, Gabriele; Wullimann, Mario F

2016-04-18

Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells, and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal.

Induction of the tumor-suppressor p16(INK4a) within regenerative epithelial crypts in ulcerative colitis.

PubMed

Furth, Emma E; Gustafson, Karen S; Dai, Charlotte Y; Gibson, Steven L; Menard-Katcher, Paul; Chen, Tina; Koh, Jim; Enders, Greg H

2006-06-01

p16(INK4a) is a major tumor-suppressor protein, but its regulation and settings of fuction remain poorly understood. To explore the notion that p16 is induced in vivo in response to replicative stress, we examined p16 expression in tissues from human ulcerative colitis (UC; n = 25) and normal controls (n = 20). p16 was expressed strongly in UC-associated neoplasms (n = 17), as seen previously in sporadic colonic neoplasms. In non-neoplastic UC epithelium, p16 was expressed in 33% of crypts (the proliferative compartment) compared to < 1% of normal controls. p16 expression did not correlate with degree of inflammation but did correlate with the degree of crypt architecture distortion (P = .002)-a reflection of epithelial regeneration. In coimmunofluorescence studies with Ki67, p16 expression was associated with cell cycle arrest (P < .001). Both UC and normal crypts displayed evidence for the activation of the DNA damage checkpoint pathway, and p16 was induced in primary cultures of normal epithelial cells by ionizing irradiation (IR). However, induction by IR displayed delayed kinetics, implying that p16 is not an immediate target of the checkpoint pathway. These findings support a model in which p16 is induced as an "emergency brake" in cells experiencing sustained replicative stress.

Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

NASA Astrophysics Data System (ADS)

Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

2015-07-01

Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

Proteomic changes during intestinal cell maturation in vivo

PubMed Central

Chang, Jinsook; Chance, Mark R.; Nicholas, Courtney; Ahmed, Naseem; Guilmeau, Sandra; Flandez, Marta; Wang, Donghai; Byun, Do-Sun; Nasser, Shannon; Albanese, Joseph M.; Corner, Georgia A.; Heerdt, Barbara G.; Wilson, Andrew J.; Augenlicht, Leonard H.; Mariadason, John M.

2008-01-01

Intestinal epithelial cells undergo progressive cell maturation as they migrate along the crypt-villus axis. To determine molecular signatures that define this process, proteins differentially expressed between the crypt and villus were identified by 2D-DIGE and MALDI-MS. Forty-six differentially expressed proteins were identified, several of which were validated by immunohistochemistry. Proteins upregulated in the villus were enriched for those involved in brush border assembly and lipid uptake, established features of differentiated intestinal epithelial cells. Multiple proteins involved in glycolysis were also upregulated in the villus, suggesting increased glycolysis is a feature of intestinal cell differentiation. Conversely, proteins involved in nucleotide metabolism, and protein processing and folding were increased in the crypt, consistent with functions associated with cell proliferation. Three novel paneth cell markers, AGR2, HSPA5 and RRBP1 were also identified. Notably, significant correlation was observed between overall proteomic changes and corresponding gene expression changes along the crypt-villus axis, indicating intestinal cell maturation is primarily regulated at the transcriptional level. This proteomic profiling analysis identified several novel proteins and functional processes differentially induced during intestinal cell maturation in vivo. Integration of proteomic, immunohistochemical, and parallel gene expression datasets demonstrate the coordinated manner in which intestinal cell maturation is regulated. PMID:18824147

Adrenergic factors involved in the control of crypt cell proliferation in jejunum and descending colon of mouse.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1983-01-01

The mitotic rates in the crypts of Lieberkühn of the proximal jejunum and descending colon of mouse, following different treatments, were measured using a stathmokinetic technique. Regression coefficients, representing mitotic rates, were then calculated by the method of least squares. Treatment with adrenaline, isoprenaline, phenylephrine, phentolamine, and yohimbine all resulted in decreased mitotic rate of jejunal and colonic crypt cells. Chemical sympathectomy and cryosympathectomy had a similar effect, and chemical sympathectomy was followed by a supersensitivity to clonidine. Intraperitoneal injection of metaraminol, clonidine, propranolol, prazosin, labetolol and simultaneous injection of propranolol and adrenaline all resulted in an increased rate of crypt cell proliferation in both jejunum and colon. A significant increase in mitotic rate was observed in both tissues at night. The amplitude of this diurnal variation was decreased in both jejunum and colon following chemical sympathectomy. In addition, the amplitude of this variation in jejunum was decreased after treatment with yohimbine or phentolamine. The results of the study suggest that the sympathetic nervous system stimulates epithelial cell proliferation in both the small and large intestine and that this effect is mediated by an alpha 2-adrenoceptor. By contrast, stimulation of alpha 1- and beta-adrenoceptors is inhibitory to cell proliferation in these tissues.

Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon

PubMed Central

Ochiai, Masako; Hippo, Yoshitaka; Izumiya, Masashi; Watanabe, Masatoshi; Nakagama, Hitoshi

2014-01-01

Dysplasia represents a preneoplastic status in multistep colon carcinogenesis. Whereas laborious preparation of thin sections is required for its diagnosis, we here show that newly defined aberrant crypt foci (ACF) simply mark the majority of the dysplasia on the whole colon. Specifically, decoloring of the azoxymethane-treated rat colon after scoring classical ACF (cACF) resulted in visualization of a subset of aberrant crypts that remained densely stained. They were morphologically classified into three subtypes, of which two with compressed luminal openings proved highly correlated with dysplasia. Accordingly, we designated those foci harboring either of the two crypt subtypes as dysplasia-associated ACF (dACF). By serially applying different detection methods for known preneoplastic lesions to the same colon, we showed that most dACF had already been identified as cACF, and a few newly identified dACF contained an entire population of more advanced lesions, such as flat ACF and mucin-depleted foci. Consequently, integrative scoring of cACF and dACF enabled capture of all early lesions of the colon. Furthermore, 94% of the dACF showed dysplasia and 90% of the dysplastic lesions proved to be dACF. Thus, dACF is a promising marker for dysplasia, likely facilitating precise identification of the early stages of colon carcinogenesis. PMID:24827115

Quantitative analysis of ex vivo colorectal epithelium using an automated feature extraction algorithm for microendoscopy image data

PubMed Central

Prieto, Sandra P.; Lai, Keith K.; Laryea, Jonathan A.; Mizell, Jason S.; Muldoon, Timothy J.

2016-01-01

Abstract. Qualitative screening for colorectal polyps via fiber bundle microendoscopy imaging has shown promising results, with studies reporting high rates of sensitivity and specificity, as well as low interobserver variability with trained clinicians. A quantitative image quality control and image feature extraction algorithm (QFEA) was designed to lessen the burden of training and provide objective data for improved clinical efficacy of this method. After a quantitative image quality control step, QFEA extracts field-of-view area, crypt area, crypt circularity, and crypt number per image. To develop and validate this QFEA, a training set of microendoscopy images was collected from freshly resected porcine colon epithelium. The algorithm was then further validated on ex vivo image data collected from eight human subjects, selected from clinically normal appearing regions distant from grossly visible tumor in surgically resected colorectal tissue. QFEA has proven flexible in application to both mosaics and individual images, and its automated crypt detection sensitivity ranges from 71 to 94% despite intensity and contrast variation within the field of view. It also demonstrates the ability to detect and quantify differences in grossly normal regions among different subjects, suggesting the potential efficacy of this approach in detecting occult regions of dysplasia. PMID:27335893

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices

PubMed Central

Lee, Jeong-A; Kim, Mi-Kyung; Kim, Hyoung-Mi; Lee, Jong Kwon; Jeong, Jayoung; Kim, Young-Rok; Oh, Jae-Min; Choi, Soo-Jin

2015-01-01

Background Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics. Methods We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m2/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats. Results N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca2+, although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein–particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size. Conclusion We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size. PMID:25848250

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices.

PubMed

Lee, Jeong-A; Kim, Mi-Kyung; Kim, Hyoung-Mi; Lee, Jong Kwon; Jeong, Jayoung; Kim, Young-Rok; Oh, Jae-Min; Choi, Soo-Jin

2015-01-01

Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics. We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats. N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca(2+), although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein-particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size. We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption.

PubMed

Moran, A W; Al-Rammahi, M; Zhang, C; Bravo, D; Calsamiglia, S; Shirazi-Beechey, S P

2014-01-01

Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na(+)-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep intestinal segments to saccharin or neohesperidin dihydrochalcone evokes secretion of GLP-2, the gut hormone known to enhance intestinal glucose absorption and mucosal growth. Artificial sweeteners, such as Sucram, at small concentrations are potent activators of T1R2-T1R3 (600-fold>glucose). This, combined with oral bioavailability of T1R2-T1R3 and the understanding that artificial sweetener-induced receptor activation evokes GLP-2 release (thus leading to increased SGLT1 expression and mucosal growth), make this receptor a suitable target for dietary manipulation. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ground-penetrating radar investigation of St. Leonard's Crypt under the Wawel Cathedral (Cracow, Poland) - COST Action TU1208

NASA Astrophysics Data System (ADS)

Benedetto, Andrea; Pajewski, Lara; Dimitriadis, Klisthenis; Avlonitou, Pepi; Konstantakis, Yannis; Musiela, Małgorzata; Mitka, Bartosz; Lambot, Sébastien; Żakowska, Lidia

2016-04-01

The Wawel ensemble, including the Royal Castle, the Wawel Cathedral and other monuments, is perched on top of the Wawel hill immediately south of the Cracow Old Town, and is by far the most important collection of buildings in Poland. St. Leonard's Crypt is located under the Wawel Cathedral of St Stanislaus BM and St Wenceslaus M. It was built in the years 1090-1117 and was the western crypt of the pre-existing Romanesque Wawel Cathedral, so-called Hermanowska. Pope John Paul II said his first Mass on the altar of St. Leonard's Crypt on November 2, 1946, one day after his priestly ordination. The interior of the crypt is divided by eight columns into three naves with vaulted ceiling and ended with one apse. The tomb of Bishop Maurus, who died in 1118, is in the middle of the crypt under the floor; an inscription "+ MAVRVS EPC MCXVIII +" indicates the burial place and was made in 1938 after the completion of archaeological works which resulted in the discovery of this tomb. Moreover, the crypt hosts the tombs of six Polish kings and heroes: Michał Korybut Wiśniowiecki (King of the Polish-Lithuanian Commonwealth), Jan III Sobieski (King of the Polish-Lithuanian Commonwealth and Commander at the Battle of Vienna), Maria Kazimiera (Queen of the Polish-Lithuanian Commonwealth and consort to Jan III Sobieski), Józef Poniatowski (Prince of Poland and Marshal of France), Tadeusz Kościuszko (Polish general, revolutionary and a Brigadier General in the American Revolutionary War) and Władysław Sikorski (Prime Minister of the Polish Government in Exile and Commander-in-Chief of the Polish Armed Forces). The adjacent six crypts and corridors host the tombs of the other Polish kings, from Sigismund the Old to Augustus II the Strong, their families and several Polish heroes. In May 2015, the COST (European COoperation in Science and Technology) Action TU1208 "Civil engineering applications of Ground Penetrating Radar" organised and offered a Training School (TS) on the "Applications of Ground Penetrating Radar in urban areas: the sensitive case of historical cities." The Action TU1208 is coordinated by "Roma Tre University" (Rome, Italy) and the TS was hosted by the Cracow University of Technology (Cracow, Poland). It was attended by 25 PhD students and early-career investigators coming from Albania, Belgium, Germany, Italy, Poland, Romania, Russia and Slovenia. Trainers and Trainees had the great honour and privilege to carry out practical sessions in St Leonard's Crypt, in cooperation with the companies Restauro (Toruń, Poland) and Geoservice (Athens, Greece). Over the centuries, city centres have been continuously changing, developing and adapting to the requirements of society, architectural planning and advancing technology. Under the pressure of urbanisation, many cities and towns have significantly expanded and the limited space in their centres has been exploited more intensively. The shallow subsurface of historical cities is nowadays a very complicated scenario including reams of pipes, cables, rubble, bars and slabs of reinforced concrete, backfilled excavation trenches and pits, cellars, wells, cavities, tunnels, graves, walls and foundations of former houses, churches, monasteries, town fortifications, along with several other modern and ancient structures and manufacts. For the prospection of such a diversified, multilayered, intricate and complex underground environment, both for archaeological and civil-engineering purposes, Ground Penetrating Radar (GPR) is a very effective non-destructive geophysical method. GPR is a powerful tool not only for the prospection of subsurface but also for the non-invasive testing of historical buildings, fountains, historical bridges, sculptures, frescoes, pottery and other objects collected in museums: it can give information about their state of preservation, it can significantly help to address a restoration project properly, and sometimes it can also help to achieve information of historical interest. The TS presented an insight into the challenges, advantages and potential of GPR prospection in historical cities. Data examples from urban historical centres were presented and discussed. An introduction to electromagnetic modelling of GPR was provided. To widen the perspective, the school included an introduction to urban remote sensing, describing how high-resolution satellite imagery or alternative sources of image date can be exploited for urban feature extraction, to analyse population, energy use, and other aspects of the urban environment. In this work, data collected in St Leonard's Crypt will be presented for the first time. The activities focused on surveying the floor of the crypt, in order to obtain an image of the tomb of Bishop Maurus, verify whether further cavities were present and collect information about the subsurface of the crypt. GPR scans were taken on a 20 cm x 20 cm grid. Subsequently, an interesting area of smaller extent was chosen, where further data were collected on a 10 cm x 10 cm grid. We found out that the tomb of Bishop Maurus is shifted with respect to the inscription placed in the middle of the crypt and supposed to indicate its position. We could also detect the presence of another large cavity and estimate their size. All measurements were performed by using a CX-12 GPR pulsed system of MALA Geoscience. Acknowledgement The Authors are deeply grateful to the Parish of the Cathedral of St. Stanislaus BM and St. Wenceslas M, Cracow, Poland, for authorizing us to carry out the practical sessions of the Training School in St. Leonard's Crypt under the Wawel Cathedral. This was for all Trainers and Trainees a unique, touching and unforgettable experience. The Authors thank COST (www.cost.eu) for funding the Action TU1208 "Civil engineering applications of Ground Penetrating Radar" (www.GPRadar.eu) and for its constant support to the Action.

Development of a high-efficiency, gas-fired, absorption heat pump for residental and small-commercial applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, B.A.

1990-09-01

The purpose of the total project is to develop a gas-fired absorption heat pump for residential and small-commercial applications that will produce at least 1.6 Btu of heating and 0.7 Btu of cooling per Btu of heat content in the gas being burned. The primary technology advances that can be used to attain the new goals are higher efficiency cycles, increased flue efficiency, and better fluids. Flue efficiency technology is well developed, and fan-assisted combustion systems with condensing heat exchangers can limit flue and insulation losses to the 10% range. If this 10% loss assumption is made, the resulting targetmore » cycle COPs are 1.78 in heating mode and 0.78 in cooling mode at the ARI rating conditions. The objective of Phase 1 was to analyze working fluids and absorption-cycle concepts that are capable of performing at the target COPs and are potentially competitive with existing space-conditioning products in cost, operating life, and reliability. Six advanced cycles were evaluated with ammonia/water as the fluid pair. Then additional analysis was performed with other fluid pairs to determine whether cycle ranking would change depending on which fluid was used. It was concluded that the preferred cycle/fluid was the generator-absorber heat exchange (GAX) cycle using ammonia/water as the fluid pair. A cost estimate made by an independent manufacturing engineering firm for a residential heat pump based on the cycle/fluid combination determined that the GAX heat pump could be cost competitive with existing products. 20 refs., 28 figs., 2 tabs.« less

NDELA and nickel modulation of triazine disposition in skin.

PubMed

Baynes, Ronald E; Brooks, James D; Barlow, Beth M; Riviere, Jim E

2005-10-01

Cutting fluids can become contaminated with metals (e.g., nickel, Ni) and nitrosamines (e.g., N-nitrosodiethanolamine, NDELA) and there is concern that these classes of contaminants can modulate dermal disposition and ultimately the toxicity of cutting fluid additives, such as irritant biocides (e.g., triazine). Biocides are added to these formulations to prevent bacterial degradation of commercial cutting fluids. The purpose of this study was to assess the dermal absorption and skin deposition of 14C-triazine when topically applied to porcine skin in an in vitro flow-through diffusion cell system as aqueous soluble oil (mineral oil, MO) or aqueous synthetic (polyethylene glycol, PEG) mixtures. 14C-Triazine mixtures were formulated with NDELA and/or Ni, or with a combination of three additional cutting fluid additives; namely, 5% linear alkylbenzene sulfonate (LAS), 5% triethanolamine (TEA) and 5% sulfurized ricinoleic acid. Neither Ni nor NDELA was absorbed during these 8-h studies. However, 14C-triazine absorption ranged from 2.72 to 3.29% dose in MO and 2.29-2.88% dose in PEG with significantly greater triazine absorption in MO than PEG when all additives and contaminates were present. The difference between these two diluents was most pronounced when NDELA and/or Ni were present in cutting fluids. These contaminants also enhanced triazine deposition on the skin surface and skin tissues especially with PEG-based mixtures. In essence, the dermal disposition of irritant biocides could be dependent on whether the worker is exposed to a soluble oil or synthetic fluid when these contaminants are present. Workers should therefore not only be concerned about dermatotoxicity of these contaminants, but also the modulated dermal disposition of cutting fluid additives when these contaminants are present in cutting fluid formulations.

Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system.

PubMed

Cromer, W E; Zawieja, D C

2018-05-01

Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II + immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development. Copyright © 2018 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Light absorption cell combining variable path and length pump

DOEpatents

Prather, William S.

1993-01-01

A device for use in making spectrophotometric measurements of fluid samples. In particular, the device is a measurement cell containing a movable and a fixed lens with a sample of the fluid therebetween and through which light shines. The cell is connected to a source of light and a spectrophotometer via optic fibers. Movement of the lens varies the path length and also pumps the fluid into and out of the cell. Unidirectional inlet and exit valves cooperate with the movable lens to assure a one-way flow of fluid through the cell. A linear stepper motor controls the movement of the lens and cycles it from a first position closer to the fixed lens and a second position farther from the fixed lens, preferably at least 10 times per minute for a nearly continuous stream of absorption spectrum data.

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed

Dennis, V W; Brazy, P C

1978-08-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport.

A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

PubMed

Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

2018-05-30

The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

Incidence and evolution of subretinal precipitates in optic disc pit maculopathy.

PubMed

Chatziralli, Irini; Theodossiadis, George; Brouzas, Dimitrios; Theodossiadis, Panagiotis

2017-06-26

To study the evolution of subretinal precipitates coexistent with optic disc pit (ODP) maculopathy from their appearance at baseline examination until their absorption after successful treatment. Participants in this retrospective, multicenter study were 42 patients with ODP maculopathy, in whom complete ocular examination was performed, including visual acuity (VA) measurement, slit-lamp examination, color or red-free fundus photography, and optical coherence tomography at baseline after surgical treatment. Out of 42 cases, 17 (40.5%) cases of ODP maculopathy, which were examined between 2002 and 2015, were found to have subretinal precipitates associated with multilayer fluid accumulation at baseline. Precipitates were located at the outer part of the photoreceptor layer and remained for 3-6 months after successful treatment and absorption of subretinal fluid. The mean VA was 0.99 ± 0.21 logMAR at baseline and improved to 0.54 ± 0.25 logMAR at the final examination. Macular precipitates in association with signs of disease chronicity, such as multilayer fluid accumulation, became evident at baseline examination. Precipitates' disappearance in 15 out of 17 cases coincided with the absorption of subretinal fluid. The relative low VA at baseline probably could be attributed to the chronicity of the disease.

Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

PubMed Central

Pretlow, T. P.; O'Riordan, M. A.; Spancake, K. M.; Pretlow, T. G.

1993-01-01

Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues. Images Figure 1 PMID:8506941

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters.

PubMed

Tetteh, Paul W; Basak, Onur; Farin, Henner F; Wiebrands, Kay; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; de Sauvage, Frederic; van Es, Johan H; van Oudenaarden, Alexander; Clevers, Hans

2016-02-04

Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an Alpi-IRES-CreERT2 (Alpi(CreER)) knockin allele for lineage tracing. Marked clones consist entirely of enterocytes and are all lost from villus tips within days. Genetic fate-mapping of Alpi(+) cells before or during targeted ablation of Lgr5-expressing stem cells generated numerous long-lived crypt-villus "ribbons," indicative of dedifferentiation of enterocyte precursors into Lgr5(+) stems. By single-cell analysis of dedifferentiating enterocytes, we observed the generation of Paneth-like cells and proliferative stem cells. We conclude that the highly proliferative, short-lived enterocyte precursors serve as a large reservoir of potential stem cells during crypt regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced absorption cycle computer model

NASA Astrophysics Data System (ADS)

Grossman, G.; Wilk, M.

1993-09-01

Absorption heat pumps have received renewed and increasing attention in the past two decades. The rising cost of electricity has made the particular features of this heat-powered cycle attractive for both residential and industrial applications. Solar-powered absorption chillers, gas-fired domestic heat pumps, and waste-heat-powered industrial temperature boosters are a few of the applications recently subjected to intensive research and development. The absorption heat pump research community has begun to search for both advanced cycles in various multistage configurations and new working fluid combinations with potential for enhanced performance and reliability. The development of working absorption systems has created a need for reliable and effective system simulations. A computer code has been developed for simulation of absorption systems at steady state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system's components and property subroutines containing thermodynamic properties of the working fluids. The user conveys to the computer an image of his cycle by specifying the different subunits and their interconnections. Based on this information, the program calculates the temperature, flow rate, concentration, pressure, and vapor fraction at each state point in the system, and the heat duty at each unit, from which the coefficient of performance (COP) may be determined. This report describes the code and its operation, including improvements introduced into the present version. Simulation results are described for LiBr-H2O triple-effect cycles, LiCl-H2O solar-powered open absorption cycles, and NH3-H2O single-effect and generator-absorber heat exchange cycles. An appendix contains the user's manual.

Analysis of advanced conceptual designs for single-family-size absorption chillers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macriss, R.A.; Zawacki, T.S.; Kouo, M.T.

1978-01-01

The objective of this research study is the development of radically new fluid systems, specifically tailored to the needs and requirements of solar-absorption cooling for single-family-size residences. Progress is reported.

N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice.

PubMed

Amrouche-Mekkioui, Ilhem; Djerdjouri, Bahia

2012-09-15

The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150 mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

Induction of the Tumor-Suppressor p16INK4a within Regenerative Epithelial Crypts in Ulcerative Colitis1

PubMed Central

Furth, Emma E; Gustafson, Karen S; Dai, Charlotte Y; Gibson, Steven L; Menard-Katcher, Paul; Chen, Tina; Koh, Jim; Enders, Greg H

2006-01-01

Abstract p16INK4a is a major tumor-suppressor protein, but its regulation and settings of fuction remain poorly understood. To explore the notion that p16 is induced in vivo in response to replicative stress, we examined p16 expression in tissues from human ulcerative colitis (UC; n = 25) and normal controls (n = 20). p16 was expressed strongly in UC-associated neoplasms (n = 17), as seen previously in sporadic colonic neoplasms. In non-neoplastic UC epithelium, p16 was expressed in 33% of crypts (the proliferative compartment) compared to < 1% of normal controls. p16 expression did not correlate with degree of inflammation but did correlate with the degree of crypt architecture distortion (P = .002)—a reflection of epithelial regeneration. In coimmunofluorescence studies with Ki67, p16 expression was associated with cell cycle arrest (P < .001). Both UC and normal crypts displayed evidence for the activation of the DNA damage checkpoint pathway, and p16 was induced in primary cultures of normal epithelial cells by ionizing irradiation (IR). However, induction by IR displayed delayed kinetics, implying that p16 is not an immediate target of the checkpoint pathway. These findings support a model in which p16 is induced as an “emergency brake” in cells experiencing sustained replicative stress. PMID:16820088

Solution Synthesis, Structure, and CO2 Reduction Reactivity of a Scandium(II) Complex, {Sc[N(SiMe3 )2 ]3 }.

PubMed

Woen, David H; Chen, Guo P; Ziller, Joseph W; Boyle, Timothy J; Furche, Filipp; Evans, William J

2017-02-13

The first crystallographically characterizable complex of Sc 2+ , [Sc(NR 2 ) 3 ] - (R=SiMe 3 ), has been obtained by LnA 3 /M reactions (Ln=rare earth metal; A=anionic ligand; M=alkali metal) involving reduction of Sc(NR 2 ) 3 with K in the presence of 2.2.2-cryptand (crypt) and 18-crown-6 (18-c-6) and with Cs in the presence of crypt. Dark maroon [K(crypt)] + , [K(18-c-6)] + , and [Cs(crypt)] + salts of the [Sc(NR 2 ) 3 ] - anion are formed, respectively. The formation of this oxidation state of Sc is also indicated by the eight-line EPR spectra arising from the I=7/2 45 Sc nucleus. The Sc(NR 2 ) 3 reduction differs from Ln(NR 2 ) 3 reactions (Ln=Y and lanthanides) in that it occurs under N 2 without formation of isolable reduced dinitrogen species. [K(18-c-6)][Sc(NR 2 ) 3 ] reacts with CO 2 to produce an oxalate complex, {K 2 (18-c-6) 3 }{[(R 2 N) 3 Sc] 2 (μ-C 2 O 4 -κ 1 O:κ 1 O'')}, and a CO 2 - radical anion complex, [(R 2 N) 3 Sc(μ-OCO-κ 1 O:κ 1 O')K(18-c-6)] n . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium.

PubMed

Sato, Toshiro; Stange, Daniel E; Ferrante, Marc; Vries, Robert G J; Van Es, Johan H; Van den Brink, Stieneke; Van Houdt, Winan J; Pronk, Apollo; Van Gorp, Joost; Siersema, Peter D; Clevers, Hans

2011-11-01

We previously established long-term culture conditions under which single crypts or stem cells derived from mouse small intestine expand over long periods. The expanding crypts undergo multiple crypt fission events, simultaneously generating villus-like epithelial domains that contain all differentiated types of cells. We have adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Based on the mouse small intestinal culture system, we optimized the mouse and human colon culture systems. Addition of Wnt3A to the combination of growth factors applied to mouse colon crypts allowed them to expand indefinitely. Addition of nicotinamide, along with a small molecule inhibitor of Alk and an inhibitor of p38, were required for long-term culture of human small intestine and colon tissues. The culture system also allowed growth of mouse Apc-deficient adenomas, human colorectal cancer cells, and human metaplastic epithelia from regions of Barrett's esophagus. We developed a technology that can be used to study infected, inflammatory, or neoplastic tissues from the human gastrointestinal tract. These tools might have applications in regenerative biology through ex vivo expansion of the intestinal epithelia. Studies of these cultures indicate that there is no inherent restriction in the replicative potential of adult stem cells (or a Hayflick limit) ex vivo. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs

PubMed Central

Davis, Michael E; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L; Gulizia, James M; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E; Mirvish, Sidney S

2012-01-01

Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17–34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5–6, with P < 0.01 for both ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon. PMID:22293095

Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury.

PubMed

Chandrakesan, Parthasarathy; May, Randal; Weygant, Nathaniel; Qu, Dongfeng; Berry, William L; Sureban, Sripathi M; Ali, Naushad; Rao, Chinthalapally; Huycke, Mark; Bronze, Michael S; Houchen, Courtney W

2016-11-23

Crypt epithelial survival and regeneration after injury require highly coordinated complex interplay between resident stem cells and diverse cell types. The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA damage response for cell survival/self-renewal after radiation-induced injury is unclear. Intestinal epithelial cells (IECs) were isolated and purified and utilized for experimental analysis. We found that small intestinal crypts of Villin Cre ;Dclk1 f/f mice were hypoplastic and more apoptotic 24 h post-total body irradiation, a time when stem cell survival is p53-independent. Injury-induced ATM mediated DNA damage response, pro-survival genes, stem cell markers, and self-renewal ability for survival and restitution were reduced in the isolated intestinal epithelial cells. An even greater reduction in these signaling pathways was observed 3.5 days post-TBI, when peak crypt regeneration occurs. We found that interaction with Dclk1 is critical for ATM and COX2 activation in response to injury. We determined that Dclk1 expressing tuft cells regulate the whole intestinal epithelial cells following injury through paracrine mechanism. These findings suggest that intestinal tuft cells play an important role in regulating the ATM mediated DNA damage response, for epithelial cell survival/self-renewal via a Dclk1 dependent mechanism, and these processes are indispensable for restitution and function after severe radiation-induced injury.

Embryonic Development of the Light Organ of the Sepiolid Squid Euprymna scolopes Berry.

PubMed

Montgomery, M K; McFall-Ngai, M

1993-06-01

The sepiolid squid Euprymna scolopes maintains luminous bacterial symbionts of the species Vibrio fischeri in a bilobed light organ partially embedded in the ventral surface of the ink sac. Anatomical and ultrastructural observations of the light organ during embryogenesis indicate that the organ begins development as a paired proliferation of the mesoderm of the hindgut-ink sac complex. Three-dimensional reconstruction of the incipient light organ of a newly hatched juvenile revealed the presence of three pairs of sacculate crypts, each crypt joined to a pore on the surface of the light organ by a ciliated duct. The crypts, which become populated with bacterial symbionts within hours after the juvenile hatches, appear to result from sequential paired invaginations of the surface epithelium of the hindgut-ink sac complex during embryogenesis. A pair of anterior and a pair of posterior ciliated epithelial appendages, which may facilitate infection of the incipient light organ with symbiotic bacteria, develop by extension and growth of the surface epithelium. The ink sac and reflector develop dorsal to the crypts and together function to direct luminescence ventrally. These two accessory tissues are present at the time of hatching, although changes in their overall structure accompany growth and maturation of the light organ. A third accessory tissue, the muscle-derived lens, appears during post-hatch maturation of the light organ.

Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development

PubMed Central

Uchiyama, Kazuhiko; Sakiyama, Toshio; Hasebe, Takumu; Musch, Mark W.; Miyoshi, Hiroyuki; Nakagawa, Yasushi; He, Tong-Chuan; Lichtenstein, Lev; Naito, Yuji; Itoh, Yoshito; Yoshikawa, Toshikazu; Jabri, Bana; Stappenbeck, Thaddeus; Chang, Eugene B.

2016-01-01

Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation. PMID:27561676

[Metaplasic Paneth cells in ulcerative colitis].

PubMed

Bedini, Oscar Alfredo; Naves, Ariel; San Miguel, Patricia; Quispe, Arturo; Guida, Carolina

2014-01-01

Paneth cells are normally present in small intestine, but its appearance in other areas of the gastrointestinal tract is related to chronic inflammatory processes. In our study we retrospectively examined 29 patients with diagnosis of ulcerative colitis, from the files of Instituto de Histopatología de Rosario, and from the casuistry of two authors (O.B. and P.S.M.), during two years. Biopsies corresponded to rectal or sigmoid mucosa and were stained with H.E. Distal Paneth cells in rectum and/or sigmoid colon were found in 60% of patients. This finding was related to the time of evolution of the disease (median 7 years for patients with Paneth cells and 3 years for patients without Paneth cells). With more time of evolution, there were more number of affected crypts and more number of Paneth cells. Some of the patients with longer evolution had 2-5 crypts with Paneth cells (up to 11 Paneth cells). When the time of evolution of the disease was longer, we found an irregular distribution of Paneth cells, with migration from the depth of the crypt to highest crypt levels. There was a relationship between the number of Paneth cells and the degree of leukocyte infiltration of the mucosa. We observed a direct correlation of the presence of Paneth cells with the time of evolution of the disease and with the leukocyte infiltration of the mucosa.

Changes in the oviducal epithelium during the estrous cycle in the marsupial Monodelphis domestica

PubMed Central

Kress, Annetrudi; Morson, Gianni

2007-01-01

The Monodelphis oviduct can be divided into four anatomical segments: preampulla (comprising fimbriae and infundibulum), ampulla, isthmus with crypts and uterotubal junction. Ovaries are enclosed in a periovarial sac, the bursa, and in some specimens tubules of an epoophoron could be identified. In both structures non-ciliated cells develop small translucent vesicles, which accumulate in the cell apices and presumably produce fluid as often seen in the bursa and in the tubules of the epooophoron. These vesicles do not stain with Alcian blue or PAS. The same applies also to the non-ciliated cells of the fimbriae. The oviducal epithelium of ampulla and the surface epithelium of the isthmus consisting of ciliated and non-ciliated, secretory cells undergo considerable changes during the estrous cycle. Proestrus shows low numbers of ciliated cells, some are in the process of neo-ciliogenesis, non-ciliated cells carry solitary cilia and few remnant secretory granules from the previous cycle may be found. At estrus the amount of ciliated cells in ampulla and isthmus has increased, most non-cililated cells lost the solitary cilia, developed longer microvilli and formed numerous secretory granules in their cell apices. At postestrus secretory products, often surrounded by membranes, are extruded into the oviducal lumen and contribute towards egg coat formation. First signs of deciliation processes are apparent. Solitary cilia reappear. At metestrus only few secretory cells are left with some secretory material. The lumen is often filled with shed cilia and cell apices. Proliferation of basal bodies within non-secretory cells indicate the formation of new ciliated cells. The non-ciliated epithelial cells of the isthmic crypts form no secretory granules but accumulate a great number of translucent vesicles, which in contrast to the secretory granules do not stain with Alcian blue or PAS. PMID:17883438

Hydrogen peroxide inhibits Ca2+-dependent chloride secretion across colonic epithelial cells via distinct kinase signaling pathways and ion transport proteins

PubMed Central

Chappell, Alfred E.; Bunz, Michael; Smoll, Eric; Dong, Hui; Lytle, Christian; Barrett, Kim E.; McCole, Declan F.

2018-01-01

Reactive oxygen species (ROS) are key mediators in a number of inflammatory conditions, including inflammatory bowel disease (IBD). ROS, including hydrogen peroxide (H2O2), modulate intestinal epithelial ion transport and are believed to contribute to IBD-associated diarrhea. Intestinal crypt fluid secretion, driven by electrogenic Cl− secretion, hydrates and sterilizes the crypt, thus reducing bacterial adherence. Here, we show that pathophysiological concentrations of H2O2 inhibit Ca2+-dependent Cl− secretion across T84 colonic epithelial cells by elevating cytosolic Ca2+, which contributes to activation of two distinct signaling pathways. One involves recruitment of the Ca2+-responsive kinases, Src and Pyk-2, as well as extracellular signal-regulated kinase (ERK). A separate pathway recruits p38 MAP kinase and phosphoinositide 3-kinase (PI3-K) signaling. The ion transport response to Ca2+-dependent stimuli is mediated in part by K+ efflux through basolateral K+ channels and Cl− uptake by the Na+-K+-2Cl− cotransporter, NKCC1. We demonstrate that H2O2 inhibits Ca2+-dependent basolateral K+ efflux and also inhibits NKCC1 activity independently of inhibitory effects on apical Cl− conductance. Thus, we have demonstrated that H2O2 inhibits Ca2+-dependent Cl− secretion through multiple negative regulatory signaling pathways and inhibition of specific ion transporters. These findings increase our understanding of mechanisms by which inflammation disturbs intestinal epithelial function and contributes to intestinal pathophysiology.—Chappell, A. E., Bunz, M., Smoll, E., Dong, H., Lytle, C., Barrett, K. E., McCole, D. F. Hydrogen peroxide inhibits Ca2+-dependent chloride secretion across colonic epithelial cells via distinct kinase signaling pathways and ion transport proteins. FASEB J. 22, 000–000 (2008) PMID:18211955

Light absorption cell combining variable path and length pump

DOEpatents

Prather, W.S.

1993-12-07

A device is described for use in making spectrophotometric measurements of fluid samples. In particular, the device is a measurement cell containing a movable and a fixed lens with a sample of the fluid there between and through which light shines. The cell is connected to a source of light and a spectrophotometer via optic fibers. Movement of the lens varies the path length and also pumps the fluid into and out of the cell. Unidirectional inlet and exit valves cooperate with the movable lens to assure a one-way flow of fluid through the cell. A linear stepper motor controls the movement of the lens and cycles it from a first position closer to the fixed lens and a second position farther from the fixed lens, preferably at least 10 times per minute for a nearly continuous stream of absorption spectrum data. 2 figures.

Three-Dimensional Flow of an Oldroyd-B Fluid with Variable Thermal Conductivity and Heat Generation/Absorption

PubMed Central

Shehzad, Sabir Ali; Alsaedi, Ahmed; Hayat, Tasawar; Alhuthali, M. Shahab

2013-01-01

This paper looks at the series solutions of three dimensional boundary layer flow. An Oldroyd-B fluid with variable thermal conductivity is considered. The flow is induced due to stretching of a surface. Analysis has been carried out in the presence of heat generation/absorption. Homotopy analysis is implemented in developing the series solutions to the governing flow and energy equations. Graphs are presented and discussed for various parameters of interest. Comparison of present study with the existing limiting solution is shown and examined. PMID:24223780

Spatial nonlinear absorption of Alfven waves by dissipative plasma taking account bremsstrahlung

NASA Astrophysics Data System (ADS)

Taiurskii, A. A.; Gavrikov, M. B.

2016-10-01

We study numerically the nonlinear absorption of a plane Alfven wave falling on the stationary boundary of dissipative plasma. This absorption is caused by such factors as the magnetic viscosity, hydrodynamic viscosity, and thermal conductivity of electrons and ions, bremsstrahlung and energy exchange between plasma components. The relevance of this investigation is due to some works, published in 2011, with regard to the heating mechanism of the solar corona and solar wind generation as a result of the absorption of plasma Alfven waves generated in the lower significantly colder layers of the Sun. Numerical analysis shows that the absorption of Alfven waves occurs at wavelengths of the order of skin depth, in which case the classical MHD equations are inapplicable. Therefore, our research is based on equations of two-fluid magnetohydrodynamics that take into account the inertia of the electrons. The implicit difference scheme proposed here for calculating plane-parallel flows of two-fluid plasma reveals a number of important patterns of absorption and thus allows us to study the dependence of the absorption on the Alfven wave frequency and the electron thermal conductivity and viscosity, as well as to evaluate the depth and the velocity of plasma heating during the penetration of Alfven waves interacting with dissipative plasma.

Polycomb Repressive Complex 2 Enacts Wnt Signaling in Intestinal Homeostasis and Contributes to the Instigation of Stemness in Diseases Entailing Epithelial Hyperplasia or Neoplasia.

PubMed

Oittinen, Mikko; Popp, Alina; Kurppa, Kalle; Lindfors, Katri; Mäki, Markku; Kaikkonen, Minna U; Viiri, Keijo

2017-02-01

Canonical Wnt/β-catenin signaling regulates the homeostasis of intestinal epithelium by controlling the balance between intestinal stem cell self-renewal and differentiation but epigenetic mechanisms enacting the process are not known. We hypothesized that epigenetic regulator, Polycomb Repressive Complex-2 (PRC2), is involved in Wnt-mediated epithelial homeostasis on the crypt-villus axis and aberrancies therein are implicated both in celiac disease and in intestinal malignancies. We found that PRC2 establishes repressive crypt and villus specific trimethylation of histone H3 lysine 27 (H3K27me3) signature on genes responsible for, for example, nutrient transport and cell killing in crypts and, for example, proliferation and differentiation in mature villi, suggesting that PRC2 facilitates the Wnt-governed intestinal homeostasis. When celiac patients are on gluten-containing diet PRC2 is out-of-bounds active and consequently its target genes were found affected in intestinal epithelium. Significant set of effective intestinal PRC2 targets are also differentially expressed in colorectal adenoma and carcinomas. Our results suggest that PRC2 gives rise and maintains polar crypt and villus specific H3K27me3 signatures. As H3K27me3 is a mark enriched in developmentally important genes, identified intestinal PRC2 targets are possibly imperative drivers for enterocyte differentiation and intestinal stem cell maintenance downstream to Wnt-signaling. Our work also elucidates the mechanism sustaining the crypt hyperplasia in celiac disease and suggest that PRC2-dependent fostering of epithelial stemness is a common attribute in intestinal diseases in which epithelial hyperplasia or neoplasia prevails. Finally, this work demonstrates that in intestine PRC2 represses genes having both pro-stemness and pro-differentiation functions, fact need to be considered when designing epigenetic therapies including PRC2 as a drug target. Stem Cells 2017;35:445-457. © 2016 AlphaMed Press.

Characterization of the cell polarity gene crumbs during the early development and maintenance of the squid-vibrio light organ symbiosis.

PubMed

Peyer, Suzanne M; Heath-Heckman, Elizabeth A C; McFall-Ngai, Margaret J

2017-11-01

The protein Crumbs is a determinant of apical-basal cell polarity and plays a role in apoptosis of epithelial cells and their protection against photodamage. Using the squid-vibrio system, a model for development of symbiotic partnerships, we examined the modulation of the crumbs gene in host epithelial tissues during initiation and maintenance of the association. The extracellular luminous symbiont Vibrio fischeri colonizes the apical surfaces of polarized epithelia in deep crypts of the Euprymna scolopes light organ. During initial colonization each generation, symbiont harvesting is potentiated by the biochemical and biophysical activity of superficial ciliated epithelia, which are several cell layers from the crypt epithelia where the symbionts reside. Within hours of crypt colonization, the symbionts induce the cell death mediated regression of the remote superficial ciliated fields. However, the crypt cells directly interacting with the symbiont are protected from death. In the squid host, we characterized the gene and encoded protein during light organ morphogenesis and in response to symbiosis. Features of the protein sequence and structure, phylogenetic relationships, and localization patterns in the eye supported assignment of the squid protein to the Crumbs family. In situ hybridization revealed that the crumbs transcript shows opposite expression at the onset of symbiosis in the two different regions of the light organ: elevated levels in the superficial epithelia were attenuated whereas low levels in the crypt epithelia were turned up. Although a rhythmic association in which the host controls the symbiont population over the day-night cycle begins in the juvenile upon colonization, cycling of crumbs was evident only in the adult organ with peak expression coincident with maximum symbiont population and luminescence. Our results provide evidence that crumbs responds to symbiont cues that induce developmental apoptosis and to symbiont population dynamics correlating with luminescence-based stress throughout the duration of the host-microbe association.

Increased intestinal absorption in the rat caused by sodium lauryl sulphate, and its possible relation to the cAMP system.

PubMed

Briseid, G; Briseid, K; Kirkevold, K

1976-01-01

The increases in the absorption of ouabain, phenolsulphonphthalein and pralidoxime caused by 17 mM sodium lauryl sulphate (SLS) from jejunal loops of anaesthetized rats were significantly reduced if sodium and chloride (Briseid et al., 1974) or chloride and bicarbonate were replaced by other ions in the loop fluid. Separate substitutions of sodium, chloride of bicarbonate did not significantly alter the SLS-caused absorption, except that the substitution of choline for sodium reduced the absorption of pralidoxime, both in the presence and in the absence of SLS. The increases in the absorption of phenolsulphonphthalein and pralidoxime caused by SLS were potentiated by theophylline (25 mM) and reduced by imidazole (25 mM). The addition of dibutyryl cyclic AMP (2.5 mM) to the loop fluid increased this absorption of the test substances. This effect was reduced by imidazole, but under the experimental conditions it was not potentiated by theophylline. Determinations of cyclic AMP in the rat intestinal mucosa showed that the level of this substance was significantly higher in the presence than in the absence of SLS. The experimental conditions were as described for the absorption experiments. It is concluded that the data obtained support the idea of an increased level of cyclic AMP as the main basis for the effect of SLS on the absorption.

THE INDUCTION OF ABERRANT CRYPT FOCI (ACF) IN MALE AND FEMALE F344/N RATS BY BROMOCHLOROACETIC ACID (BCA) ADMINISTERED IN THE DRINKING WATER

EPA Science Inventory

The Induction of Aberrant Crypt Foci (ACF) in Male and Female F344/N Rats by Bromochloroacetic Acid (BCA) Administered in the Drinking Water.

M.H. George1, D. Delker1, D.R. Geter1, C.Herbert2, J. Roycroft3, R. Melnick3, D.W.
Rosenberg4, and A.B. DeAngelo1. 1USEPA, Resea...

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

PubMed Central

Tutton, P. J.; Barkla, D. H.

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours. PMID:7362778

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

PubMed

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

Correlation of bone defect dimensions with healing outcome one year after apical surgery.

PubMed

von Arx, Thomas; Hänni, Stefan; Jensen, Simon Storgård

2007-09-01

This clinical study prospectively evaluated the healing outcome 1 year after apical surgery in relation to bony crypt dimensions measured intraoperatively. The study cohort included 183 teeth in an equal number of patients. For statistical analysis, results were dichotomized (healed versus non-healed cases). The overall success rate was 83% (healed cases). Healing outcome was not significantly related to the level and height of the facial bone plate. In contrast, a significant difference was found for the mean size of the bony crypt when healed cases (395 mm(3)) were compared with non-healed cases (554 mm(3)). In addition, healed cases had a significantly shorter mean distance (4.30 mm) from the facial bone surface to the root canal (horizontal access) compared with non-healed cases (5.13 mm). With logistic regression, however, the only parameter found to be significantly related to healing outcome was the length of the access window to the bony crypt.

Examples of Mathematical Modeling

PubMed Central

Johnston, Matthew D.; Edwards, Carina M.; Bodmer, Walter F.; Maini, Philip K.; Chapman, S. Jonathan

2008-01-01

Mathematical modeling is being increasingly recognized within the biomedical sciences as an important tool that can aid the understanding of biological systems. The heavily regulated cell renewal cycle in the colonic crypt provides a good example of how modeling can be used to find out key features of the system kinetics, and help to explain both the breakdown of homeostasis and the initiation of tumorigenesis. We use the cell population model by Johnston et al.5 to illustrate the power of mathematical modeling by considering two key questions about the cell population dynamics in the colonic crypt. We ask: how can a model describe both homeostasis and unregulated growth in tumorigenesis; and to which parameters in the system is the model most sensitive? In order to address these questions, we discuss what type of modeling approach is most appropriate in the crypt. We use the model to argue why tumorigenesis is observed to occur in stages with long lag phases between periods of rapid growth, and we identify the key parameters. PMID:17873520

Studies on the reactivity of [Ge9]4- towards [Fe(cot)(CO)3]: synthesis and characterization of [Ge8Fe(CO)3]3- and of the anionic organometallic species [Fe(cot)(CO)3]-.

PubMed

Zhou, Binbin; Goicoechea, Jose M

2010-09-24

Reaction of cyclooctatetraene (COT) iron(II) tricarbonyl, [Fe(cot)(CO)(3)], with one equivalent of K(4)Ge(9) in ethylenediamine (en) yielded the cluster anion [Ge(8)Fe(CO)(3)](3-) which was crystallographically-characterized as a [K(2,2,2-crypt)](+) salt in [K(2,2,2-crypt)](3)[Ge(8)Fe(CO)(3)]. The chemically-reduced organometallic species [Fe(η(3)-C(8)H(8))(CO)(3)](-) was also isolated as a side-product from this reaction as [K(2,2,2-crypt)][Fe(η(3)-C(8)H(8))(CO)(3)]. Both species were further characterized by EPR and IR spectroscopy and electrospray mass spectrometry. The [Ge(8)Fe(CO)(3)](3-) cluster anion represents an unprecedented functionalized germanium Zintl anion in which the nine-atom precursor cluster has lost a vertex, which has been replaced by a transition-metal moiety.

Location and description of spiral-shaped microorganisms in the normal rat cecum

USGS Publications Warehouse

Davis, Charles P.; Mulcahy, D.; Takeuchi, A.; Savage, D.C.

1972-01-01

Some indigenous microorganisms have been shown to localize in certain anatomical sites of the digestive tract of mammals. We studied the ceca of normal adult rats by light and electron microscopy to determine whether any specific bacterial population localizes in this area. All rats studied showed that the crypt was packed with organisms whose morphological character differs from those of the cecal lumen. Organisms localized in the crypt were often identified topographically close to the microvilli of the epithelial cells. These organisms could be differentiated into three types according to their characteristic ultrastructure. Type 1 was a thin spiral-shaped microbe that resembled a Borrelia. Type 2 possessed helically coiled fibers and flagella-like appendages. Type 3 was spiral-shaped but lacked axial fibers. Types 1 and 2 were both capable of penetrating through the crypt epithelium into the lamina propria where they were found in either phagocytes or extracellular locations. These observations are discussed in relation to other host-microflora localization patterns.

Unsteady Sisko magneto-nanofluid flow with heat absorption and temperature dependent thermal conductivity: A 3D numerical study

NASA Astrophysics Data System (ADS)

Khan, Masood; Ahmad, Latif; Gulzar, M. Mudassar

2018-03-01

The impact of temperature dependent thermal conductivity and convective surface conditions on unsteady 3D Sisko nanofluid flow over a stretching surface is studied in the presence of heat generation/absorption and magnetic field. The numerical solution of nonlinear coupled equations has been carried out to explore the properties of different physical profiles of the fluid flow with varying of parameters. Specifically, the application of generalized Biot numbers and heat generation/absorption parameter in the sketching of temperature and concentration profiles are explored. The effect of all three parameters is noticed in the increasing order for shear thinning (0 < n < 1) and for shear thickening (n > 1) fluids. Moreover, the influence of Biot number γ1 on heat and mass transfer rates, are found in the enhancement and diminishing conducts respectively, in both cases of shear thinning as well as shear thickening fluids and a reverse trend is observed with the variation of Biot number γ2 . Additionally, the present results are validated through skin friction, heat and mass transfer rate values with the comparable values in the existing previous values.

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds.

PubMed

Fröhlich, Eleonore; Mercuri, Annalisa; Wu, Shengqian; Salar-Behzadi, Sharareh

2016-01-01

Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.

Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema

PubMed Central

Solymosi, Esther A.; Kaestle-Gembardt, Stefanie M.; Vadász, István; Wang, Liming; Neye, Nils; Chupin, Cécile Julie Adrienne; Rozowsky, Simon; Ruehl, Ramona; Tabuchi, Arata; Schulz, Holger; Kapus, Andras; Morty, Rory E.; Kuebler, Wolfgang M.

2013-01-01

Alveolar fluid clearance driven by active epithelial Na+ and secondary Cl− absorption counteracts edema formation in the intact lung. Recently, we showed that impairment of alveolar fluid clearance because of inhibition of epithelial Na+ channels (ENaCs) promotes cardiogenic lung edema. Concomitantly, we observed a reversal of alveolar fluid clearance, suggesting that reversed transepithelial ion transport may promote lung edema by driving active alveolar fluid secretion. We, therefore, hypothesized that alveolar ion and fluid secretion may constitute a pathomechanism in lung edema and aimed to identify underlying molecular pathways. In isolated perfused lungs, alveolar fluid clearance and secretion were determined by a double-indicator dilution technique. Transepithelial Cl− secretion and alveolar Cl− influx were quantified by radionuclide tracing and alveolar Cl− imaging, respectively. Elevated hydrostatic pressure induced ouabain-sensitive alveolar fluid secretion that coincided with transepithelial Cl− secretion and alveolar Cl− influx. Inhibition of either cystic fibrosis transmembrane conductance regulator (CFTR) or Na+-K+-Cl− cotransporters (NKCC) blocked alveolar fluid secretion, and lungs of CFTR−/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride reproduced alveolar fluid and Cl− secretion that were again CFTR-, NKCC-, and Na+-K+-ATPase–dependent. Our findings show a reversal of transepithelial Cl− and fluid flux from absorptive to secretory mode at hydrostatic stress. Alveolar Cl− and fluid secretion are triggered by ENaC inhibition and mediated by NKCC and CFTR. Our results characterize an innovative mechanism of cardiogenic edema formation and identify NKCC1 as a unique therapeutic target in cardiogenic lung edema. PMID:23645634

Acoustic radiation force acting on elastic and viscoelastic spherical shells placed in a plane standing wave field.

PubMed

Mitri, F G

2005-08-01

The theory of the acoustic radiation force acting on elastic spherical shells suspended in a plane standing wave field is developed in relation to their thickness and the content of their hollow regions. The theory is modified to include the effect of a hysteresis type of absorption of compressional and shear waves in the material. The fluid-loading effect on the acoustic radiation force function Y(st) is analyzed as well. Results of numerical calculations are presented for a number of elastic and viscoelastic materials, with the hollow region filled with water or air. These results show how the damping due to absorption, the change of the interior fluid inside the shells' hollow regions, and the exterior fluid surrounding their structures, affect the acoustic radiation force.

Secretagogue stimulation enhances NBCe1 (electrogenic Na(+)/HCO(3)(-) cotransporter) surface expression in murine colonic crypts.

PubMed

Yu, Haoyang; Riederer, Brigitte; Stieger, Nicole; Boron, Walter F; Shull, Gary E; Manns, Michael P; Seidler, Ursula E; Bachmann, Oliver

2009-12-01

A Na(+)/HCO(3)(-) cotransporter (NBC) is located in the basolateral membrane of the gastrointestinal epithelium, where it imports HCO(3)(-) during stimulated anion secretion. Having previously demonstrated secretagogue activation of NBC in murine colonic crypts, we now asked whether vesicle traffic and exocytosis are involved in this process. Electrogenic NBCe1-B was expressed at significantly higher levels than electroneutral NBCn1 in colonic crypts as determined by QRT-PCR. In cell surface biotinylation experiments, a time-dependent increase in biotinylated NBCe1 was observed, which occurred with a peak of +54.8% after 20 min with forskolin (P < 0.05) and more rapidly with a peak of +59.8% after 10 min with carbachol (P < 0.05) and which corresponded well with the time course of secretagogue-stimulated colonic bicarbonate secretion in Ussing chamber experiments. Accordingly, in isolated colonic crypts pretreated with forskolin and carbachol for 10 min, respectively, and subjected to immunohistochemistry, the NBCe1 signal showed a markedly stronger colocalization with the E-cadherin signal, which was used as a membrane marker, compared with the untreated control. Cytochalasin D did not change the observed increase in membrane abundance, whereas colchicine alone enhanced NBCe1 membrane expression without an additional increase after carbachol or forskolin, and LY294002 had a marked inhibitory effect. Taken together, our results demonstrate a secretagogue-induced increase of NBCe1 membrane expression. Vesicle traffic and exocytosis might thus represent a novel mechanism of intestinal NBC activation by secretagogues.

Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi

PubMed Central

Parker, Aimee; Maclaren, Oliver J.; Fletcher, Alexander G.; Muraro, Daniele; Kreuzaler, Peter A.; Byrne, Helen M.; Maini, Philip K.; Watson, Alastair J. M.; Pin, Carmen

2017-01-01

The functional integrity of the intestinal epithelial barrier relies on tight coordination of cell proliferation and migration, with failure to regulate these processes resulting in disease. It is not known whether cell proliferation is sufficient to drive epithelial cell migration during homoeostatic turnover of the epithelium. Nor is it known precisely how villus cell migration is affected when proliferation is perturbed. Some reports suggest that proliferation and migration may not be related while other studies support a direct relationship. We used established cell-tracking methods based on thymine analog cell labeling and developed tailored mathematical models to quantify cell proliferation and migration under normal conditions and when proliferation is reduced and when it is temporarily halted. We found that epithelial cell migration velocities along the villi are coupled to cell proliferation rates within the crypts in all conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cell migration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus. This methodology can be applied to interrogate intestinal epithelial dynamics and characterize situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models.—Parker, A., Maclaren, O. J., Fletcher, A. G., Muraro, D., Kreuzaler, P. A., Byrne, H. M., Maini, P. K., Watson, A. J. M., Pin, C. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi. PMID:27811059

Azoxymethane protects intestinal stem cells and reduces crypt epithelial mitosis through a COX-1-dependent mechanism.

PubMed

Riehl, Terrence E; George, Robert J; Sturmoski, Mark A; May, Randal; Dieckgraefe, Brian; Anant, Shrikant; Houchen, Courtney W

2006-12-01

Azoxymethane (AOM) is a potent DNA-damaging agent and carcinogen that induces intestinal and colonic tumors in rodents. Evaluation of the stem cell population by colony formation assay reveals that, within 8 h after treatment, AOM (10 mg/kg) elicited a prosurvival response. In wild-type (WT) mice, AOM treatment induced a 2.5-fold increase in intestinal crypt stem cell survival. AOM treatment increased stem cell survival in cyclooxygenase (COX)-2(-/-) but not COX-1(-/-) mice, confirming a role of COX-1 in the AOM-induced increase in stem cell survival. COX-1 mRNA and protein expression as well as COX-1-derived PGE(2) synthesis were increased 8 h after AOM treatment. Immunohistochemical staining of COX-1 demonstrated expression of the enzyme in the crypt epithelial cells, especially in the columnar epithelial cells between the Paneth cells adjacent to the stem cell zone. WT mice receiving AOM exhibited increased intestinal apoptosis and a simultaneous reduction in crypt mitotic figures within 8 h of injection. There were no significant differences in baseline or AOM-induced intestinal epithelial apoptosis between WT and COX-1(-/-) mice, but there was a complete reversal of the AOM-mediated reduction in mitosis in COX-1(-/-) mice. This suggests that COX-1-derived PGE(2) may play a key role in the early phase of intestinal tumorigenesis in response to DNA damage and suggests that COX-1 may be a potential therapeutic target in this model of colon cancer.

An alternative for rapid administration of medication and fluids in the emergency setting using a novel device.

PubMed

Lyons, Neal; Nejak, Daniel; Lomotan, Nadine; Mokszycki, Robert; Jamieson, Stephen; McDowell, Marc; Kulstad, Erik

2015-08-01

Routes of administration for medications and fluids in the acute care setting have primarily focused on oral, intravenous, or intraosseous routes, but, in many patients, none of these routes is optimal. A novel device (Macy Catheter; Hospi Corp) that offers an easy route for administration of medications or fluids via rectal mucosal absorption (proctoclysis) has recently become available in the palliative care market; we describe here the first known uses of this device in the emergency setting. Three patients presenting to the hospital with conditions limiting more typical routes of medication or fluid administration were treated with this new device; patients were administered water for hydration, lorazepam for treatment of alcohol withdrawal, ondansetron for nausea, acetaminophen for fever, aspirin for antiplatelet effect, and methimazole for hyperthyroidism. Placement of the device was straightforward, absorption of administered medications (judged by immediacy of effects, where observable) was rapid, and use of the device was well tolerated by patients, suggesting that this device may be an appealing alternative route to medication and fluid administration for a variety of indications in acute and critical care settings.

Time-dependent oral absorption models

NASA Technical Reports Server (NTRS)

Higaki, K.; Yamashita, S.; Amidon, G. L.

2001-01-01

The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.

Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp; Umeda, Sachiko; Yasuda, Takeshi

2013-02-01

Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93Gmore » could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage. Therefore, Q40P/S47I/H93G is pharmacologically one of the most promising candidates for clinical applications for radiation-induced gastrointestinal syndrome.« less

Estimation of alga growth stage and lipid content growth rate

NASA Technical Reports Server (NTRS)

Embaye, Tsegereda N. (Inventor); Trent, Jonathan D. (Inventor)

2012-01-01

Method and system for estimating a growth stage of an alga in an ambient fluid. Measured light beam absorption or reflection values through or from the alga and through an ambient fluid, in each of two or more wavelength sub-ranges, are compared with reference light beam absorption values for corresponding wavelength sub-ranges for in each alga growth stage to determine (1) which alga growth stage, if any, is more likely and (2) whether estimated lipid content of the alga is increasing or has peaked. Alga growth is preferably terminated when lipid content has approximately reached a maximum value.

Thermal energy transformer

NASA Technical Reports Server (NTRS)

Berdahl, C. M.; Thiele, C. L. (Inventor)

1979-01-01

For use in combination with a heat engine, a thermal energy transformer is presented. It is comprised of a flux receiver having a first wall defining therein a radiation absorption cavity for converting solar flux to thermal energy, and a second wall defining an energy transfer wall for the heat engine. There is a heat pipe chamber interposed between the first and second walls having a working fluid disposed within the chamber and a wick lining the chamber for conducting the working fluid from the second wall to the first wall. Thermal energy is transferred from the radiation absorption cavity to the heat engine.

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed Central

Dennis, V W; Brazy, P C

1978-01-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport. PMID:670399

Lubiprostone targets prostanoid signaling and promotes ion transporter trafficking, mucus exocytosis, and contractility.

PubMed

Jakab, Robert L; Collaco, Anne M; Ameen, Nadia A

2012-11-01

Lubiprostone is a chloride channel activator in clinical use for the treatment of chronic constipation, but the mechanisms of action of the drug are poorly understood. The aim of this study was to determine whether lubiprostone exerts secretory effects in the intestine by membrane trafficking of ion transporters and associated machinery. Immunolabeling and quantitative fluorescence intensity were used to examine lubiprostone-induced trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR), sodium/potassium-coupled chloride co-transporter 1 (NKCC1), electrogenic sodium/bicarbonate co-transporter 1 (NBCe1), down-regulated in adenoma (DRA), putative anion transporter 1 (PAT1), sodium/proton exchanger 3 (NHE3), Ca(2+) activated chloride channel 2 (ClC-2) serotonin and its transporter SERT, E prostanoid receptors EP4 and EP1, sodium/potassium ATPase (Na-K-ATPase) and protein kinase A (PKA). The effects of lubiprostone on mucus exocytosis in rat intestine and human rectosigmoid explants were also examined. Lubiprostone induced contraction of villi and proximal colonic plicae and membrane trafficking of transporters that was more pronounced in villus/surface cells compared to the crypt. Membrane trafficking was determined by: (1) increased membrane labeling for CFTR, PAT1, NKCC1, and NBCe1 and decreased membrane labeling for NHE3, DRA and ClC-2; (2) increased serotonin, SERT, EP4, EP1 and PKA labeling in enterochromaffin cells; (3) increased SERT, EP4, EP1, PKA and Na-K-ATPase in enterocytes; and (4) increased mucus exocytosis in goblet cells. These data suggest that lubiprostone can target serotonergic, EP4/PKA and EP1 signaling in surface/villus regions; stimulate membrane trafficking of CFTR/NBCe1/NKCC1 in villus epithelia and PAT1/NBCe1/NKCC1 in colonic surface epithelia; suppress NHE3/DRA trafficking and fluid absorption; and enhance mucus-mobilization and mucosal contractility.

Lubiprostone targets prostanoid signaling and promotes ion transporter trafficking, mucus exocytosis and contractility

PubMed Central

Jakab, Robert L.; Collaco, Anne M.; Ameen, Nadia A.

2012-01-01

Background and Aim Lubiprostone is a chloride channel activator in clinical use for the treatment of chronic constipation, but the mechanisms of action of the drug are poorly understood. The aim of this study was to determine whether lubiprostone exerts secretory effects in the intestine by membrane trafficking of ion transporters and associated machinery. Methods Immunolabeling and quantitative fluorescence intensity were used to examine lubiprostone-induced trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR), sodium/potassium-coupled chloride co-transporter 1 (NKCC1), electrogenic sodium/bicarbonate co-transporter 1 (NBCe1), down-regulated in adenoma (DRA), putative anion transporter 1 (PAT1), sodium/proton exchanger 3 (NHE3), Ca2+ activated chloride channel 2 (ClC-2) serotonin and its transporter SERT, E prostanoid receptors EP4 and EP1, sodium/potassium ATPase (Na-K-ATPase) and protein kinase A (PKA). The effects of lubiprostone on mucus exocytosis in rat intestine and human rectosigmoid explants were also examined. Results Lubiprostone induced contraction of villi and proximal colonic plicae and membrane trafficking of transporters that was more pronounced in villus/surface cells compared to the crypt. Membrane trafficking was determined by: (1) increased membrane labeling for CFTR, PAT1, NKCC1, and NBCe1 and decreased membrane labeling for NHE3, DRA and ClC-2; (2) increased serotonin, SERT, EP4, EP1 and PKA labeling in enterochromaffin cells; (3) increased SERT, EP4, EP1, PKA and Na-K-ATPase in enterocytes; (4) and increased mucus exocytosis in goblet cells. Conclusion These data suggest that lubiprostone can target serotonergic, EP4/PKA and EP1 signaling in surface/villus regions; stimulate membrane trafficking of CFTR/NBCe1/NKCC1 in villus epithelia and PAT1/NBCe1/NKCC1 in colonic surface epithelia; suppress NHE3/DRA trafficking and fluid absorption; enhance mucus-mobilization and mucosal contractility. PMID:22923315

Water redistribution in experimentally deformed natural milky quartz single crystals—Implications for H2O-weakening processes

NASA Astrophysics Data System (ADS)

Stünitz, H.; Thust, A.; Heilbronner, R.; Behrens, H.; Kilian, R.; Tarantola, A.; Fitz Gerald, J. D.

2017-02-01

Natural quartz single crystals were experimentally deformed in two orientations: (1) ⊥ to one prism plane and (2) in O+ orientation at 900 and 1000°C, 1.0 and 1.5 GPa, and strain rates of 1 × 10-6 s-1. In addition, hydrostatic and annealing experiments were performed. The starting material was milky quartz, which consisted of dry quartz with a large number of fluid inclusions of variable size up to several 100 µm. During pressurization fluid inclusions decrepitated producing much smaller fluid inclusions. Deformation on the sample scale is anisotropic due to dislocation glide on selected slip systems and inhomogeneous due to an inhomogeneous distribution of fluid inclusions. Dislocation glide is accompanied by minor dynamic recovery. Strongly deformed regions show a pointed broad absorption band in the 3400 cm-1 region consisting of a superposition of bands of molecular H2O and three discrete absorption bands (at 3367, 3400, and 3434 cm-1). In addition, there is a discrete absorption band at 3585 cm-1, which only occurs in deformed regions and reduces or disappears after annealing, so that this band appears to be associated with dislocations. H2O weakening in inclusion-bearing natural quartz crystals is assigned to the H2O-assisted dislocation generation and multiplication. Processes in these crystals represent recycling of H2O between fluid inclusions, cracking and crack healing, incorporation of structurally bound H in dislocations, release of H2O from dislocations during recovery, and dislocation generation at very small fluid inclusions. The H2O weakening by this process is of disequilibrium nature because it depends on the amount of H2O available.

Energy absorption is reduced with oleic acid supplements in human short bowel syndrome.

PubMed

Compher, Charlene W; Kinosian, Bruce P; Rubesin, Stephen E; Ratcliffe, Sarah J; Metz, David C

2009-01-01

Oleic acid premeal supplements have been described as a method to trigger the ileal brake and thus lengthen transit time and the opportunity for nutrient absorption. The aims of this study were to determine whether oleic acid supplements would lengthen transit time and improve absorption of nutrients in study participants with short bowel syndrome as well as affect diarrhea or patient weight. A double-blind, controlled, random-order crossover trial was conducted in 8 study participants with longstanding and severe short bowel syndrome, employing blue food color appearance, breath hydrogen testing, and radio-opaque markers as measures of transit time. Absorption of energy, protein, fat, and fluid was conducted by classic nutrient balance methods. Diarrhea was estimated by daily stool weight and number of bowel actions. Although 8 patients were enrolled, only 7 completed the study. Transit time was not significantly different between oleic acid and placebo treatment, although peptide YY levels trended higher with the oleic acid treatment. Energy absorption was reduced 14% by oleic acid, significantly more than the 3% reduction by placebo. Fat, protein, and fluid absorption was not changed significantly. Neither diarrhea nor patient body weight was changed by oleic acid. Energy absorption is reduced by oleic acid supplements in severe short bowel syndrome. The study may have lacked power to determine whether oleic acid affects diarrhea or body weight.

The Effects of Void Geometry and Contact Angle on the Absorption of Liquids into Porous Calcium Carbonate Structures.

PubMed

Ridgway, Cathy J.; Schoelkopf, Joachim; Matthews, G. Peter; Gane, Patrick A. C.; James, Philip W.

2001-07-15

The absorption (permeation) of alcohols into porous blocks of calcium carbonate has been studied experimentally and with a computer model. The experimental measurement was of change in apparent weight of a block with time after contact with liquid. The modeling used the previously developed 'Pore-Cor' model, based on unit cells of 1000 cubic pores connected by cylindrical throats. To gain some insight into absorption into voids of complex geometry, and to provide a representation of heterogeneities in surface interaction energy, the cylindrical throats were converted to double cones. Relative to cylinders, such geometries caused hold-ups of the percolation of nonwetting fluids with respect to increasing applied pressure, and a change in the rate of absorption of wetting fluids. Both the measured absorption of the alcohols and the simulated absorption of the alcohols and of water showed significant deviations from that predicted by an effective hydraulic radius approximation. The simulation demonstrated the development of a highly heterogeneous wetting front, and of preferred wetting pathways that were perturbed by inertial retardation. The findings are useful in the design of high-performance, low-waste pigments for paper coatings, and environmentally friendly printing inks, as well as in wider industrial, environmental, and geological contexts. Copyright 2001 Academic Press.

Simulation of phenomena occurring during digestion of foods

NASA Astrophysics Data System (ADS)

Bakalis, Serafim; Jaime-Fonseca, Monica R.; Fryer, Peter

2015-01-01

The increasing incidence of dietary related diseases, such as obesity and diabetes, emphasize the importance to understand digestion and absorption of nutrients and to develop models that could be able to predict the food behavior through the gastrointestinal tract. In order to achieve this, an in vitro Small Intestine Model (SIM) was used to build starch digestion and glucose absorption as function of food viscosity. The effect of mixing and food formulation was evaluated and correlated to changes on glucose absorption. Significant differences on glucose delivery rates were found between the control and fluids containing viscous biopolymers. Results showed that the segmentation motion significantly increases (up to 30%) glucose rate of absorption across the membrane and that the influence of segmentation decreases as viscosity increases. Furthermore, it has been demonstrated that addition of about 0.5 % (w/v) guar gum can result in a threefold decrease of absorption rate and mass transfer. Velocity fields obtained using Computational Fluid Dynamics (CFD) showed the effect of segmentation on nutrients absorption. Velocities profiles indicated that concentric contractions results in an increasing of micromixing and thus enhances mass transfer. This in vitro behaviour could be correlated within blood glucose levels in humans to understand the mechanisms by which biopolymers improves glucose tolerance.

Fluid synthesis and structure of a new polymorphic modification of boron nitride

NASA Astrophysics Data System (ADS)

Pokropivny, V. V.; Smolyar, A. S.; Ovsiannikova, L. I.; Pokropivny, A. V.; Kuts, V. A.; Lyashenko, V. I.; Nesterenko, Yu. V.

2013-04-01

A new previously unknown phase of boron nitride with a hardness of 0.41-0.63 GPa has been pre-pared by the supercritical fluid synthesis. The presence of a new phase is confirmed by the X-ray spectra and IR absorption spectra, where new reflections and bands are distinguished. The fundamental reflection of the X-ray diffraction pattern is d = 0.286-0.291 nm, and the characteristic band in the infrared absorption spectrum is observed at 704 cm-1. The X-ray diffraction pattern and the experimental and theoretical infrared absorption spectra show that a new synthesized boron nitride phase can be a cluster crystal (space group 211) with a simple cubic lattice. Cage clusters of a fullerene-like morphology B24N24 with point symmetry O are arranged in lattice sites.

Significant consequences of heat generation/absorption and homogeneous-heterogeneous reactions in second grade fluid due to rotating disk

NASA Astrophysics Data System (ADS)

Hayat, Tasawar; Qayyum, Sumaira; Alsaedi, Ahmed; Ahmad, Bashir

2018-03-01

Flow of second grade fluid by a rotating disk with heat and mass transfer is discussed. Additional effects of heat generation/absorption are also analyzed. Flow is also subjected to homogeneous-heterogeneous reactions. The convergence of computed solution is assured through appropriate choices of initial guesses and auxiliary parameters. Investigation is made for the effects of involved parameters on velocities (radial, axial, tangential), temperature and concentration. Skin friction and Nusselt number are also analyzed. Graphical results depict that an increase in viscoelastic parameter enhances the axial, radial and tangential velocities. Opposite behavior of temperature is observed for larger values of viscoelastic and heat generation/absorption parameters. Concentration profile is increasing function of Schmidt number, viscoelastic parameter and heterogeneous reaction parameter. Magnitude of skin friction and Nusselt number are enhanced for larger viscoelastic parameter.

Surface wave energy absorption by a partially submerged bio-inspired canopy.

PubMed

Nové-Josserand, C; Castro Hebrero, F; Petit, L-M; Megill, W M; Godoy-Diana, R; Thiria, B

2018-03-27

Aquatic plants are known to protect coastlines and riverbeds from erosion by damping waves and fluid flow. These flexible structures absorb the fluid-borne energy of an incoming fluid by deforming mechanically. In this paper we focus on the mechanisms involved in these fluid-elasticity interactions, as an efficient energy harvesting system, using an experimental canopy model in a wave tank. We study an array of partially-submerged flexible structures that are subjected to the action of a surface wave field, investigating in particular the role of spacing between the elements of the array on the ability of our system to absorb energy from the flow. The energy absorption potential of the canopy model is examined using global wave height measurements for the wave field and local measurements of the elastic energy based on the kinematics of each element of the canopy. We study different canopy arrays and show in particular that flexibility improves wave damping by around 40%, for which half is potentially harvestable.

Effects of glucocorticoid hormones on cell proliferation in dimethylhydrazine-induced tumours in rat colon.

PubMed

Tutton, P J; Barkla, D H

1981-01-01

Adrenocortical hormones have previously been shown to influence cell proliferation in many tissues. In this report, their influence on cell proliferation in the colonic crypt epithelium and in colonic adenocarcinomata is compared. Colonic tumour cell proliferation was found to be retarded following adrenalectomy and this retardation was reversible by administration of hydrocortisone, or by administration of synthetic steroids with predominantly glucocorticoid activity. Tumour cell proliferation in adrenalectomized rats was not promoted by the mineralocorticoid hormone aldosterone. Neither adrenalectomy, nor adrenocortical hormone treatment, significantly influenced colonic crypt cell proliferation.

Actions of Hydrogen Sulfide on Sodium Transport Processes across Native Distal Lung Epithelia (Xenopus laevis)

PubMed Central

Erb, Alexandra; Althaus, Mike

2014-01-01

Hydrogen sulfide (H2S) is well known as a highly toxic environmental chemical threat. Prolonged exposure to H2S can lead to the formation of pulmonary edema. However, the mechanisms of how H2S facilitates edema formation are poorly understood. Since edema formation can be enhanced by an impaired clearance of electrolytes and, consequently, fluid across the alveolar epithelium, it was questioned whether H2S may interfere with transepithelial electrolyte absorption. Electrolyte absorption was electrophysiologically measured across native distal lung preparations (Xenopus laevis) in Ussing chambers. The exposure of lung epithelia to H2S decreased net transepithelial electrolyte absorption. This was due to an impairment of amiloride-sensitive sodium transport. H2S inhibited the activity of the Na+/K+-ATPase as well as lidocaine-sensitive potassium channels located in the basolateral membrane of the epithelium. Inhibition of these transport molecules diminishes the electrochemical gradient which is necessary for transepithelial sodium absorption. Since sodium absorption osmotically facilitates alveolar fluid clearance, interference of H2S with the epithelial transport machinery provides a mechanism which enhances edema formation in H2S-exposed lungs. PMID:24960042

Gastrointestinal assimilation of Cu during digestion of a single meal in the freshwater rainbow trout (Oncorhynchus mykiss).

PubMed

Nadella, Sunita R; Bucking, Carol; Grosell, Martin; Wood, Chris M

2006-08-01

Gastrointestinal processing and assimilation of Cu in vivo was investigated by sequential chyme analysis over a 72 h period following ingestion of a single satiation meal (3% body weight) of commercial trout food (Cu content=0.42 micromol g(-1)) by adult rainbow trout. Leaded glass ballotini beads incorporated into the food and detected by X-ray radiography were employed as an inert marker in order to quantify net Cu absorption or secretion in various parts of the tract. Cu concentrations in the supernatant (fluid phase) fell from about 0.06 micromol mL(-1) (63 microM) in the stomach at 2 h to about 0.003 micromol mL(-1) (3 microM) in the posterior intestine at 72 h. Cu concentrations in the solid phase were 10 to 30-fold higher than in the fluid phase, and increased about 4-fold from the stomach at 2 h to the posterior intestine at 72 h. By reference to the inert marker, overall net Cu absorption from the ingested food by 72 h was about 50%. The mid-intestine, and posterior intestine emerged as important sites of net Cu and water absorption and a potential role for the stomach in this process was also indicated. The anterior intestine was a site of large net Cu addition to the chyme, probably due to large net additions of Cu-containing fluids in the form of bile and other secretions in this segment. The results provide valuable information about sites of Cu absorption and realistic concentrations of Cu in chyme fluid for future in vitro mechanistic studies on Cu transport in the trout gastrointestinal tract.

Comparison of in vitro digestive fluid extraction and traditional in vivo approaches as measures of polycyclic aromatic hydrocarbon bioavailability from sediments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weston, D.P.; Mayer, L.M.

1998-05-01

The bioavailability of particle-associated contaminants was measured by a new approach that employs the digestive fluid of deposit feeders to solubilize contaminants in vitro. The proportion of contaminant solubilized by digestive fluid of the polychaete Arenicola brasiliensis was considered a measure of bioavailability and was contrasted with other, more traditional measures (i.e., uptake clearance, bioaccumulation factor, and absorption efficiency). There was generally good agreement among the four methods on the relative bioavailability of benzo[a]pyrene from six sandy sediments. Measures of phenanthrene bioavailability did not show strong correlations due to both a more limited data set and perhaps greater importance ofmore » uptake from the dissolved phase. The bioavailability of spiked polycyclic aromatic hydrocarbons (PAHs) differed from that of equivalent in situ-contaminated PAH but not in a predictable and consistent manner. By direct measurement of PAH content of recently ingested sediments collected from the foregut the authors were able to quantify the importance of particle-selective feeding in increasing PAH content of ingested material relative to the bulk, ambient sediments. In most instances, the effect of selective feeding by A. brasiliensis was minimal, increasing PAH content of ingested material <20% above the ambient sediments. Absorption efficiencies of PAH during gut passage were determined by direct measurement of PAH concentration in sediments at various points along the digestive tract. Overall digestive absorption efficiencies were similar to the extent of in vitro solubilization by digestive fluids from the same sediments. These data suggest that extent of solubilization of sediment-bound contaminants during gut passage is a critical constraint on uptake and that absorption efficiency, with respect to the solubilized fraction, approaches 100%.« less

Physicochemical determinants of linear alkylbenzene sulfonate (LAS) disposition in skin exposed to aqueous cutting fluid mixtures.

PubMed

Baynes, Ronald E; Brooks, James D; Barlow, Beth M; Riviere, Jim E

2002-06-01

Linear alkylbenzene sulfonate (LAS) is added to cutting fluid formulations to enhance the performance of metal machining operations, but this surfactant can cause contact dermatitis in workers involved in these operations. The purpose of this study was to determine how cutting fluid additives influence dermal disposition of 14C-LAS in mineral oil- or polyethylene glycol 200 (PEG)-based mixtures when topically applied to silastic membranes and porcine skin in an in vitro flow-through diffusion cell system. 14C-LAS mixtures were formulated with three commonly used cutting fluid additives; 0 or 2% triazine (TRI), 0 or 5% triethanolamine (TEA), and 0 or 5% sulfurized ricinoleic acid (SRA). LAS absorption was limited to less than a 0.5% dose and the additives in various combinations influenced the physicochemical characteristics of the dosing mixture. LAS was more likely to partition into the stratum corneum (SC) in mineral oil mixtures, and LAS absorption was significantly greater in the complete mixture. TRI enhanced LAS transport, and the presence of SRA decreased LAS critical micelle concentration (CMC) which reduced LAS monomers available for transport. TEA increased mixture viscosity, and this may have negated the apparent enhancing properties of TRI in several mixtures. In summary, physicochemical interactions in these mixtures influenced availability of LAS for absorption and distribution in skin, and could ultimately influence toxicological responses in skin.

HPLC analysis of 6-mercaptopurine and metabolites in extracellular body fluids.

PubMed

Rudy, J L; Argyle, J C; Winick, N; Van Dreal, P

1988-09-01

A convenient HPLC assay, which allows for the simultaneous measurement in extracellular fluids of 6-mercaptopurine and four of its metabolites, 6-thioguanine, 6-mercaptopurine riboside, 6-thioxanthine and 6-thiouric acid is described. Solid phase extraction allows for the clean isolation of analytes from plasma, urine or cerebrospinal fluid. The simultaneous determination of 6-mercaptopurine and some of its major metabolites in extracellular fluids may contribute to the monitoring of patient compliance, bioavailability, and individual variation in metabolism and absorption.

Mitotic and apoptotic activity in colorectal neoplasia.

PubMed

Kohoutova, Darina; Pejchal, Jaroslav; Bures, Jan

2018-05-18

Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p < 0.05. Transformation of non-a-A into a-A did not lead to any further significant increase in apoptotic activity, but was related to significant increase in mitotic activity in upper part of crypts and superficial compartment. A significant decrease in apoptotic activity was detected in all three comparments of CRC samples compared to a-A; p < 0.05. No differences in mitotic and apoptotic activity between biopsies in healthy controls and biopsy samples from healthy mucosa in patients with colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype.

PubMed

De Lisle, Robert C; Mueller, Racquel; Roach, Eileen

2010-09-15

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Cftr(tm1UNC) (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

PubMed Central

2010-01-01

Background Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Methods Cftrtm1UNC (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Results Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. Conclusions These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion. PMID:20843337

The Delayed Effects of Acute Radiation Syndrome: Evidence of Long-Term Functional Changes in the Clonogenic Cells of the Small Intestine.

PubMed

Booth, Catherine; Tudor, Gregory L; Katz, Barry P; MacVittie, Thomas J

2015-11-01

Long term or residual damage post-irradiation has been described for many tissues. In hematopoietic stem cells (HSC), this is only revealed when the HSC are stressed and required to regenerate and repopulate a myeloablated host. Such an assay cannot be used to assess the recovery potential of previously irradiated intestinal stem cells (ISC) due to their incompatibility with transplantation. The best approximation to the HSC assay is the crypt microcolony assay, also based on clonogen survival. In the current study, the regenerative capacity of intestinal clonogenic cells in mice that had survived 13 Gy irradiation (with 5% bone marrow shielding to allow survival through the hematopoietic syndrome) and were then aged for 200 d was compared to previously unirradiated age-matched controls. Interestingly, at 200 d following 13 Gy, there remained a statistically significant reduction in crypts present in the various small intestinal regions (illustrating that the gastrointestinal epithelium had not fully recovered despite the 200-d interval). However, upon re-irradiation on day 196, those mice previously irradiated had improved crypt survival and regeneration compared to the age-matched controls. This was evident in all regions of the small intestine following 11-13 Gy re-exposure. Thus, there were either more clonogens per crypt within those previously irradiated and/or those that were present were more radioresistant (possibly because a subpopulation was more quiescent). This is contrary to the popular belief that previously irradiated animals may have an impaired/delayed regenerative response and be more radiosensitive.

Overlapping DNA Methylation Dynamics in Mouse Intestinal Cell Differentiation and Early Stages of Malignant Progression

PubMed Central

Forn, Marta; Díez-Villanueva, Anna; Merlos-Suárez, Anna; Muñoz, Mar; Lois, Sergi; Carriò, Elvira; Jordà, Mireia; Bigas, Anna; Batlle, Eduard; Peinado, Miguel A.

2015-01-01

Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart. PMID:25933092

TLR9 agonist protects mice from radiation-induced gastrointestinal syndrome.

PubMed

Saha, Subhrajit; Bhanja, Payel; Liu, Laibin; Alfieri, Alan A; Yu, Dong; Kandimalla, Ekambar R; Agrawal, Sudhir; Guha, Chandan

2012-01-01

Radiation-induced gastrointestinal syndrome (RIGS) is due to the clonogenic loss of crypt cells and villi depopulation, resulting in disruption of mucosal barrier, bacterial invasion, inflammation and sepsis. Intestinal macrophages could recognize invading bacterial DNA via TLR9 receptors and transmit regenerative signals to the neighboring crypt. We therefore investigated whether systemic administration of designer TLR9 agonist could ameliorate RIGS by activating TLR9. Male C57Bl6 mice were distributed in four experimental cohorts, whole body irradiation (WBI) (8.4-10.4 Gy), TLR9 agonist (1 mg/kg s.c.), 1 h pre- or post-WBI and TLR9 agonist+WBI+iMyd88 (pretreatment with inhibitory peptide against Myd88). Animals were observed for survival and intestine was harvested for histological analysis. BALB/c mice with CT26 colon tumors in abdominal wall were irradiated with 14 Gy single dose of whole abdominal irradiation (AIR) for tumor growth study. Mice receiving pre-WBI TLR9 agonist demonstrated improvement of survival after 10.4 Gy (p<0.03), 9.4 Gy (p<0.008) and 8.4 Gy (p<0.002) of WBI, compared to untreated or iMyd88-treated controls. Post-WBI TLR9 agonist mitigates up to 8.4 Gy WBI (p<0.01). Histological analysis and xylose absorption test demonstrated significant structural and functional restitution of the intestine in WBI+TLR9 agonist cohorts. Although, AIR reduced tumor growth, all animals died within 12 days from RIGS. TLR9 agonist improved the survival of mice beyond 28 days post-AIR (p<0.008) with significant reduction of tumor growth (p<0.0001). TLR9 agonist treatment could serve both as a prophylactic or mitigating agent against acute radiation syndrome and also as an adjuvant therapy to increase the therapeutic ratio of abdominal Radiation Therapy for Gastro Intestinal malignancies.

Measurement of translymphatic fluid absorption using technetium-99m human serum albumin diethylenetriamine pentaacetic acid in continuous ambulatory peritoneal dialysis patients.

PubMed

Terawaki, Hiroyuki; Nakayama, Masaaki; Seto, Kazuhiko; Yoshimura, Kazunobu; Hasegawa, Toshio

2004-08-01

We have established a new method of measuring translymphatic fluid absorption (TLA) using technetium-99m ((99m)Tc) human serum albumin diethylenetriamine pentaacetic acid ((99m)Tc-HSAD) that can be used commonly in clinical practice. This new method was applied in 13 continuous ambulatory peritoneal dialysis patients (11 males and two females) who had various peritoneal permeability and capacities for peritoneal transport of water. (99m)Tc-HSAD 740MBq was injected in 2 L of peritoneal dialysis fluid with 2.5% glucose, mixed well, and administered intraperitoneally. The fluid was drained extraperitoneally after 4 h and TLA was determined by the in vivo loss of (99m)Tc-HSAD. TLA was 1.41 +/- 1.11 mL/min (mean +/- SD; range, 0.27-3.69 mL/min). The estimated reduction rate by TLA in trans-peritoneally removed fluid ranged from 14.2 to 84.4%, indicating that TLA could have an extremely significant negative effect in some cases on total drainage volume. The present study, using new tracer (99m)Tc-HSAD, could confirm a large individual difference in TLA, indicating TLA as an important contributing factor for fluid-removal failure in continuous ambulatory peritoneal dialysis patients.

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside of the crypt base stem cell niche

PubMed Central

Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc Castro; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen James; Greten, Florian R; Wang, Lai Mun; East, James Edward; Tomlinson, Ian; Leedham, Simon John

2015-01-01

Hereditary mixed polyposis syndrome (HMPS) is characterised by the development of mixed morphology colorectal tumours and is caused by a 40 kb duplication that results in aberrant epithelial expression of the mesenchymal Bone Morphogenetic Protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell-fate, that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem-cell properties in Lgr5 negative (non-expressing) progenitor cells that have exited the stem-cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem-cell is not the sole cell-of-origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic pre-malignant lesions with a hitherto unknown pathogenesis and these lesions can be considered the sporadic equivalents of HMPS polyps. PMID:25419707

Transient, heat-induced thermal resistance in the small intestine of mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hume, S.P.; Marigold, J.C.L.

Heat-induced thermal resistance has been investigated in mouse jejunum by assaying crypt survival 24 h after treatment. Hyperthermia was achieved by immersing an exteriorized loop of intestine in a bath of Krebs-Ringer solution. Two approaches have been used. In the first, thermal survival curves were obtained following single hyperthermal treatments at temperatures in the range 42 to 44/sup 0/C. Transient thermal resistance, inducted by a plateau in the crypt survival curve, developed during heating at temperatures around 42.5/sup 0/C after 60 to 80 min. In the second series of experiments, a priming heat treatment (40.0, 41.0, 41.5, or 42.0/sup 0/Cmore » for 60 min) was followed at varying intervals by a test treatment at 43.0/sup 0/C. A transient resistance to the second treatment was induced, the extent and time of development being dependent upon the priming treatment. Crypt survival curves for thermally resistant intestine showed an increase in thermal D/sub 0/ and a decrease in n compared with curves from previously unheated intestine.« less

Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

PubMed Central

Kang, Sung Yoon Catherine; Kannan, Nagarajan; Zhang, Lewei; Martinez, Victor; Rosin, Miriam P.; Eaves, Connie J.

2015-01-01

Summary Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation. PMID:26527383

Effects of spaceflight on the proliferation of jejunal mucosal cells

NASA Technical Reports Server (NTRS)

Phillips, Robert W.; Moeller, C. L.; Sawyer, Heywood R.; Smirnov, K. L.

1991-01-01

The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity due to microgravity conditions encountered during spaceflight would be demonstrable in cells and tissues characterized by a rapid rate of turnover. Jejunal mucosal cells were chosen as a model since these cells are among the most rapidly proliferating in the body. Accordingly, the percentage of mitotic cells present in the crypts of Lieberkuhn in each of 5 rats flown on the COSMOS 2044 mission were compared to the percentage of mitotic cells present in the crypts in rats included in each of 3 ground control groups (i.e., vivarium, synchronous and caudal-elevated). No significant difference (p greater than .05) was detected in mitotic indices between the flight and vivarium group. Although the ability of jejunal mucosal cells to divide by mitosis was not impaired in flight group, there was, however, a reduction in the length of villi and depth of crypts. The concommitant reduction in villus length and crypth depth in the flight group probably reflects changes in connective tissue components within the core of villi.

The protective effects of fermented kefir milk on azoxymethane-induced aberrant crypt formation in mice colon.

PubMed

Melo, Aline Freitas de Paula; Mendonça, Monique Culturato Padilha; Rosa-Castro, Raquel de Mendonça

2018-06-01

Kefir is a probiotic fermented milk product produced from grains with a complex composition of bacteria and yeasts that live in a symbiotic association. Anti-proliferative, anti-inflammatory, and anti-mutagenic effects are some of the health beneficial properties of kefir grains. The present study was conducted to evaluate whether regular consumption of kefir milk would be capable of preventing the development of pre-neoplastic lesions induced by azoxymethane (AOM). Aberrant crypt foci were induced in BALB-c mice via 2 subcutaneous injections of azoxymethane (15 mg/kg) and kefir was administered by daily gavage for 8 weeks (5 ml/kg). Additionally, bacterial growth was monitored in pasteurized and ultra-high temperature (UHT) treated milk to compare different fermentation conditions. Our results showed that UHT milk presented better growth of Lactobacillus acidophilus colonies. The aberrant crypt foci were attenuated by approximately 43% (height) and 20% (width) in the kefir group compared to AOM group, suggesting that kefir treatment may contribute to prevent and control the growth of intestinal neoplastic cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fluid mechanics of eating, swallowing and digestion - overview and perspectives.

PubMed

Engmann, Jan; Burbidge, Adam S

2013-02-26

From a very simplistic viewpoint, the human digestive system can be regarded as a long tube (with dramatic variations in diameter, cross-section, wall properties, pumping mechanisms, regulating valves and in-line sensors). We single out a few fluid mechanical phenomena along the trajectory of a food bolus from the mouth to the small intestine and discuss how they influence sensorial perception, safe transport, and nutrient absorption from a bolus. The focus is on lubrication flows between the tongue and palate, the oropharyngeal stage of swallowing and effects of flow on absorption in the small intestine. Specific challenges and opportunities in this research area are highlighted.

Determination of aluminum in biological fluids by furnace atomic absorption spectrophotometry.

PubMed

Johnson, K E; Treble, R G

1992-01-01

Detailed procedures were developed for the furnace atomic absorption spectrophotometry (FAAS) determination of aluminum (Al) in serum, urine, cerebrospinal fluid (CSF), and proportionated dialysate. Of particular note were the use of Mg (NO3)2.6H2O as a matrix modifier and the employment of the standard additions routine in analysis. The accuracy of the method(s) used is supported by work with assayed controls and by recovery studies. The use of a "clean room" was shown to be unnecessary. Normal serum, urine, and CSF Al ranges observed were 4.8-8.9, 5.1-9.1, and 1.0-5.8 micrograms L-1 respectively.

Development and application of bio-sample quantification to evaluate stability and pharmacokinetics of inulin-type fructo-oligosaccharides from Morinda Officinalis.

PubMed

Chi, Liandi; Chen, Lingxiao; Zhang, Jiwen; Zhao, Jing; Li, Shaoping; Zheng, Ying

2018-07-15

Inulin-type fructooligosaccharides (FOS) purified from Morinda Officinalis, with degrees of polymerization (DP) from 3 to 9, have been approved in China as an oral prescribed drug for mild and moderate depression episode, while the stability and oral absorption of this FOS mixtures are largely unknown. As the main active component and quality control marker for above FOS, DP5 was selected as the representative FOS in this study. Desalting method by ion exchange resin was developed to treat bio-sample, followed by separation and quantification by high performance liquid chromatography-charged aerosol detector. Results showed that the DP5 was stepwisely hydrolyzed in simulated gastric fluid and gut microbiota, while maintained stable in intestinal fluid. DP5 has poor permeability across Caco-2 monolayer with P app of 5.22 × 10 -7  cm/s, and very poor oral absorption with bioavailability of (0.50 ± 0.12)% in rat. In conclusion, FOS in Morinda Officinalis demonstrated poor chemical stability in simulated gastric fluid and human gut microbiota, and low oral absorption in rats. Copyright © 2018 Elsevier B.V. All rights reserved.

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

PubMed Central

Fröhlich, Eleonore; Mercuri, Annalisa; Wu, Shengqian; Salar-Behzadi, Sharareh

2016-01-01

Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily. PMID:27445817

Fiber optic fluid detector

DOEpatents

Angel, S.M.

1987-02-27

Particular gases or liquids are detected with a fiber optic element having a cladding or coating of a material which absorbs the fluid or fluids and which exhibits a change of an optical property, such as index of refraction, light transmissiveness or fluoresence emission, for example, in response to absorption of the fluid. The fluid is sensed by directing light into the fiber optic element and detecting changes in the light, such as exit angle changes for example, that result from the changed optical property of the coating material. The fluid detector may be used for such purposes as sensing toxic or explosive gases in the atmosphere, measuring ground water contamination or monitoring fluid flows in industrial processes, among other uses. 10 figs.

Triple-effect absorption chiller cycle: A step beyond double-effect cycles

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeVault, R.C.

1990-01-01

Many advanced'' absorption cycles have been proposed during the current century. Of the hundreds of absorption cycles which have been patented throughout the world, all commercially manufactured products for air conditioning buildings have been variations of just two basic absorption cycles: single-effect and condenser-coupled double-effect cycles. The relatively low cooling coefficients of performance (COPs) inherent in single-effect and double-effect cycles limits the economic applicability of absorption air conditioners (chillers) in the United States. A triple-effect absorption chiller cycle is discussed. This cycle uses two condensers and two absorbers to achieve the triple effect.'' Depending on the absorption fluids selected, thismore » triple-effect cycle is predicted to improve cooling COPs by 18% to 60% compared with the equivalent double-effect cycle. This performance improvement is obtained without increasing the total amount of heat-transfer surface area needed for the heat exchangers. A comparison between the calculated performances of a double-effect cycle and a triple-effect cycle (both using ammonia-water (NH{sub 3}/H{sub 2}O) as the absorption fluid pair) is presented. The triple-effect cycle is predicted to have an 18% higher cooling COP (1.41 compared with 1.2 for a double-effect), lower pressure (47.70 atm (701 psi) instead of 68.05 atm (1000 psi)), significantly reduced pumping power (less than one-half that of the double-effect cycle), and potentially lower construction cost (33% less total heat exchange needed). Practical implications for this triple-effect cycle are discussed. 16 refs., 5 figs., 1 tab.« less

Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lasalvia, Maria; Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari; Castellani, Stefano

The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalizedmore » airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in the plasmamembrane. • CFTR overexpression changes morphology and actin organization. • CFBE cells absorb more apical fluid than wild type bronchial epithelial cells. • Fluid absorption is increased by disorganization of actin cytoskeleton.« less

Should Workers Avoid Consumption of Chilled Fluids in a Hot and Humid Climate?

PubMed

Brearley, Matt B

2017-12-01

Despite provision of drinking water as the most common method of occupational heat stress prevention, there remains confusion in hydration messaging to workers. During work site interactions in a hot and humid climate, workers commonly report being informed to consume tepid fluids to accelerate rehydration. When questioned on the evidence supporting such advice, workers typically cite that fluid absorption is delayed by ingestion of chilled beverages. Presumably, delayed absorption would be a product of fluid delivery from the gut to the intestines, otherwise known as gastric emptying. Regulation of gastric emptying is multifactorial, with gastric volume and beverage energy density the primary factors. If gastric emptying is temperature dependent, the impact of cooling is modest in both magnitude and duration (≤ 5 minutes) due to the warming of fluids upon ingestion, particularly where workers have elevated core temperature. Given that chilled beverages are most preferred by workers, and result in greater consumption than warm fluids during and following physical activity, the resultant increased consumption of chilled fluids would promote gastric emptying through superior gastric volume. Hence, advising workers to avoid cool/cold fluids during rehydration appears to be a misinterpretation of the research. More appropriate messaging to workers would include the thermal benefits of cool/cold fluid consumption in hot and humid conditions, thereby promoting autonomy to trial chilled beverages and determine personal preference. In doing so, temperature-based palatability would be maximized and increase the likelihood of workers maintaining or restoring hydration status during and after their work shift.

A strategy for isolation of cDNAs encoding proteins affecting human intestinal epithelial cell growth and differentiation: characterization of a novel gut-specific N-myristoylated annexin.

PubMed

Wice, B M; Gordon, J I

1992-01-01

The human intestinal epithelium is rapidly and perpetually renewed as the descendants of multipotent stem cells located in crypts undergo proliferation, differentiation, and eventual exfoliation during a very well organized migration along the crypt to villus axis. The mechanisms that establish and maintain this balance between proliferation and differentiation are largely unknown. We have utilized HT-29 cells, derived from a human colon adenocarcinoma, as a model system for identifying gene products that may regulate these processes. Proliferating HT-29 cells cultured in the absence of glucose (e.g., using inosine as the carbon source) have some of the characteristics of undifferentiated but committed crypt epithelial cells while postconfluent cells cultured in the absence of glucose resemble terminally differentiated enterocytes or goblet cells. A cDNA library, constructed from exponentially growing HT-29 cells maintained in inosine-containing media, was sequentially screened with a series of probes depleted of sequences encoding housekeeping functions and enriched for intestine-specific sequences that are expressed in proliferating committed, but not differentiated, epithelial cells. Of 100,000 recombinant phage surveyed, one was found whose cDNA was derived from an apparently gut-specific mRNA. It encodes a 316 residue, 35,463-D protein that is a new member of the annexin/lipocortin family. Other family members have been implicated in regulation of cellular growth and in signal transduction pathways. RNA blot and in situ hybridization studies indicate that the gene encoding this new annexin exhibits region-specific expression along both axes of the human gut: (a) highest levels of mRNA are present in the jejunum with marked and progressive reductions occurring distally; (b) its mRNA appears in crypt-associated epithelial cells and increases in concentration as they exit the crypt. Villus-associated epithelial cells continue to transcribe this gene during their differentiation/translocation up the villus. Immunocytochemical studies reveal that the intestine-specific annexin (ISA) is associated with the plasma membrane of undifferentiated, proliferating crypt epithelial cells as well as differentiated villus enterocytes. In polarized enterocytes, the highest concentrations of ISA are found at the apical compared to basolateral membrane. In vitro studies using an octapeptide derived from residues 2-9 of the primary translation product of ISA mRNA and purified myristoyl-CoA:protein N-myristoyltransferase suggested that it is N-myristoylated. In vivo labeling studies confirmed that myristate is covalently attached to ISA via a hydroxylamine resistant amide linkage. The restricted cellular expression and acylation of ISA distinguish it from other known annexins.(ABSTRACT TRUNCATED AT 400 WORDS)

Methods and apparatus for mid-infrared sensing

DOEpatents

Lin, Pao Tai; Cai, Yan; Agarwal, Anuradha Murthy; Kimerling, Lionel C.

2015-06-02

A chip-scale, air-clad semiconductor pedestal waveguide can be used as a mid-infrared (mid-IR) sensor capable of in situ monitoring of organic solvents and other analytes. The sensor uses evanescent coupling from a silicon or germanium waveguide, which is highly transparent in the mid-IR portion of the electromagnetic spectrum, to probe the absorption spectrum of fluid surrounding the waveguide. Launching a mid-IR beam into the waveguide exposed to a particular analyte causes attenuation of the evanescent wave's spectral components due to absorption by carbon, oxygen, hydrogen, and/or nitrogen bonds in the surrounding fluid. Detecting these changes at the waveguide's output provides an indication of the type and concentration of one or more compounds in the surrounding fluid. If desired, the sensor may be integrated onto a silicon substrate with a mid-IR light source and a mid-IR detector to form a chip-based spectrometer.

Experimental Evaluation of Equivalent-Fluid Models for Melamine Foam

NASA Technical Reports Server (NTRS)

Allen, Albert R.; Schiller, Noah H.

2016-01-01

Melamine foam is a soft porous material commonly used in noise control applications. Many models exist to represent porous materials at various levels of fidelity. This work focuses on rigid frame equivalent fluid models, which represent the foam as a fluid with a complex speed of sound and density. There are several empirical models available to determine these frequency dependent parameters based on an estimate of the material flow resistivity. Alternatively, these properties can be experimentally educed using an impedance tube setup. Since vibroacoustic models are generally sensitive to these properties, this paper assesses the accuracy of several empirical models relative to impedance tube measurements collected with melamine foam samples. Diffuse field sound absorption measurements collected using large test articles in a laboratory are also compared with absorption predictions determined using model-based and measured foam properties. Melamine foam slabs of various thicknesses are considered.

Peritoneal fluid transport in CAPD patients with different transport rates of small solutes.

PubMed

Sobiecka, Danuta; Waniewski, Jacek; Weryński, Andrzej; Lindholm, Bengt

2004-01-01

Continuous ambulatory peritoneal dialysis (CAPD) patients with high peritoneal solute transport rate often have inadequate peritoneal fluid transport. It is not known whether this inadequate fluid transport is due solely to a too rapid fall of osmotic pressure, or if the decreased effectiveness of fluid transport is also a contributing factor. To analyze fluid transport parameters and the effectiveness of dialysis fluid osmotic pressure in the induction of fluid flow in CAPD patients with different small solute transport rates. 44 CAPD patients were placed in low (n = 6), low-average (n = 13), high-average (n = 19), and high (n = 6) transport groups according to a modified peritoneal equilibration test (PET). The study involved a 6-hour peritoneal dialysis dwell with 2 L 3.86% glucose dialysis fluid for each patient. Radioisotopically labeled serum albumin was added as a volume marker.The fluid transport parameters (osmotic conductance and fluid absorption rate) were estimated using three mathematical models of fluid transport: (1) Pyle model (model P), which describes ultrafiltration rate as an exponential function of time; (2) model OS, which is based on the linear relationship of ultrafiltration rate and overall osmolality gradient between dialysis fluid and blood; and (3) model G, which is based on the linear relationship between ultrafiltration rate and glucose concentration gradient between dialysis fluid and blood. Diffusive mass transport coefficients (K(BD)) for glucose, urea, creatinine, potassium, and sodium were estimated using the modified Babb-Randerson-Farrell model. The high transport group had significantly lower dialysate volume and glucose and osmolality gradients between dialysate and blood, but significantly higher K(BD) for small solutes compared with the other transport groups. Osmotic conductance, fluid absorption rate, and initial ultrafiltration rate did not differ among the transport groups for model OS and model P. Model G yielded unrealistic values of fluid transport parameters that differed from those estimated by models OS and P. The K(BD) values for small solutes were significantly different among the groups, and did not correlate with fluid transport parameters for model OS. The difference in fluid transport between the different transport groups was due only to the differences in the rate of disappearance of the overall osmotic pressure of the dialysate, which was a combined result of the transport rate of glucose and other small solutes. Although the glucose gradient is the major factor influencing ultrafiltration rate, other solutes, such as urea, are also of importance. The counteractive effect of plasma small solutes on transcapillary ultrafiltration was found to be especially notable in low transport patients. Thus, glucose gradient alone should not be considered the only force that shapes the ultrafiltration profile during peritoneal dialysis. We did not find any correlations between diffusive mass transport coefficients for small solutes and fluid transport parameters such as osmotic conductance or fluid and volume marker absorption. We may thus conclude that the pathway(s) for fluid transport appears to be partly independent from the pathway(s) for small solute transport, which supports the hypothesis of different pore types for fluid and solute transport.

Storage of H.sub.2 by absorption and/or mixture within a fluid medium

DOEpatents

Berry, Gene David; Aceves, Salvador Martin

2007-03-20

For the first time, a hydrogen storage method, apparatus and system having a fluid mixture is provided. At predetermined pressures and/or temperatures within a contained substantially fixed volume, the fluid mixture can store a high density of hydrogen molecules, wherein a predetermined phase of the fluid mixture is capable of being withdrawn from the substantially fixed volume for use as a vehicle fuel or energy storage having reduced and/or eliminated evaporative losses, especially where storage weight, vessel cost, vessel shape, safety, and energy efficiency are beneficial.

The Failure of Absorption of DC Silicone Fluid 703 from the Gastrointestinal Tract of Rats

PubMed Central

Paul, J.; Pover, W. F. R.

1960-01-01

The intestinal absorption of silicone fluid 703, a methyl phenyl polysiloxane, has been studied in the rat. This silicone was chosen for the present investigation because of its lipid-like character and its solubility in olive oil. The experimental findings demonstrate that very little, if any, silicone is absorbed when fed in olive oil. No silicone was found in the lymph lipids of cannulated rats fed the silicone, and balance experiments by recovery of the organosilicon compound and triglyceride after feeding to rats for three hours showed that 85% of silicone fluid 703 was recovered from the gastrointestinal tract, whereas 70% of the fed triglyceride was absorbed. The unabsorbed silicone was concentrated chiefly in the intestinal lumen. Balance experiments by recovery of the organosilicon compound after long-term feeding gave recoveries of 96% of the silicone. This amount was recovered entirely from the lower part of the gastrointestinal tract and the faeces. No silicon fluid 703 was found in the liver, kidneys, or fat depots. The urine contained no soluble silica. PMID:14430986

Real-time X-ray Imaging of Lung Fluid Volumes in Neonatal Mouse Lung.

PubMed

Van Avermaete, Ashley E; Trac, Phi T; Gauthier, Theresa W; Helms, My N

2016-07-18

At birth, the lung undergoes a profound phenotypic switch from secretion to absorption, which allows for adaptation to breathing independently. Promoting and sustaining this phenotype is critically important in normal alveolar growth and gas exchange throughout life. Several in vitro studies have characterized the role of key regulatory proteins, signaling molecules, and steroid hormones that can influence the rate of lung fluid clearance. However, in vivo examinations must be performed to evaluate whether these regulatory factors play important physiological roles in regulating perinatal lung liquid absorption. As such, the utilization of real time X-ray imaging to determine perinatal lung fluid clearance, or pulmonary edema, represents a technological advancement in the field. Herein, we explain and illustrate an approach to assess the rate of alveolar lung fluid clearance and alveolar flooding in C57BL/6 mice at post natal day 10 using X-ray imaging and analysis. Successful implementation of this protocol requires prior approval from institutional animal care and use committees (IACUC), an in vivo small animal X-ray imaging system, and compatible molecular imaging software.

Influence of Aloe vera on water absorption and enzymatic in vitro degradation of alginate hydrogel films.

PubMed

Pereira, Rúben F; Carvalho, Anabela; Gil, M H; Mendes, Ausenda; Bártolo, Paulo J

2013-10-15

This study investigates the influence of Aloe vera on water absorption and the in vitro degradation rate of Aloe vera-Ca-alginate hydrogel films, for wound healing and drug delivery applications. The influence of A. vera content (5%, 15% and 25%, v/v) on water absorption was evaluated by the incubation of the films into a 0.1 M HCl solution (pH 1.0), acetate buffer (pH 5.5) and simulated body fluid solution (pH 7.4) during 24h. Results show that the water absorption is significantly higher for films containing high A. vera contents (15% and 25%), while no significant differences are observed between the alginate neat film and the film with 5% of A. vera. The in vitro enzymatic degradation tests indicate that an increase in the A. vera content significantly enhances the degradation rate of the films. Control films, incubated in a simulated body fluid solution without enzymes, are resistant to the hydrolytic degradation, exhibiting reduced weight loss and maintaining its structural integrity. Results also show that the water absorption and the in vitro degradation rate of the films can be tailored by changing the A. vera content. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vanadium inhibits DNA-protein cross-links and ameliorates surface level changes of aberrant crypt foci during 1,2-dimethylhydrazine induced rat colon carcinogenesis.

PubMed

Kanna, P Suresh; Saralaya, M G; Samanta, K; Chatterjee, M

2005-01-01

The trace mineral vanadium inhibits cancer development in a variety of experimental animal models. The present study was to gain insight into a putative anticancer effect of vanadium in a rat model of colon carcinogenesis. The in vivo study was intended to clarify the effect of vanadium on DNA-protein cross-links (DPC), surface level changes of aberrant crypt foci (ACF) and biotransformation status during 1,2-dimethylhydrazine (1,2-DMH) induced preneoplastic rat colon carcinogenesis. The comet assay showed statistically higher mean base values of DNA-protein mass (p<0.01) and mean frequencies of tailed cells (p<0.001) in the carcinogen-induced group after treatment with proteinase K. Treatment with vanadium in the form of ammonium monovanadate supplemented ad libitum in drinking water for the entire experimental period caused a significant (p<0.02) reduction (40%) in DNA-protein cross-links in colon cells. Further, the biotransformation status of vanadium was ascertained measuring the drug metabolising enzymes, glutathione S-transferase (GST) and cytochrome P-450 (Cyt P-450). Significantly, there was an increase in glutathione S-transferase and cytochrome P-450 levels (p<0.01 and p<0.02, respectively) in rats supplemented with vanadium as compared to their carcinogen controls. As an endpoint marker, we also evaluated the effect of vanadium on surface level changes of aberrant crypt foci induced by 1,2-DMH by scanning electron microscopy. Animals induced with 1,2-DMH and supplemented with vanadium showed a marked improvement in colonic architecture with less number of aberrant crypt foci in contrast to the animals induced with 1,2-DMH alone, thereby exhibiting its anti-carcinogenicity by modulating the markers studied herein.

A water-soluble extract from cultured medium of Ganoderma lucidum (Reishi) mycelia attenuates the small intestinal injury induced by anti-cancer drugs

PubMed Central

KASHIMOTO, NAOKI; ISHII, SATOMI; MYOJIN, YUKI; USHIJIMA, MITSUYASU; HAYAMA, MINORU; WATANABE, HIROMITSU

2010-01-01

The present study investigated whether a water-soluble extract from the culture medium of Ganoderma lucidum (Reishi) mycelia (MAK) is able to protect the small intestine against damage induced by anti-cancer drugs. Six-week-old male B6C3F1/Crlj mice were fed a basal diet (MF) alone or with various doses of MAK or Agarics blazei Murrill (AGA) beginning one week before treatment with the anti-cancer drugs. Mice were sacrificed 3.5 days after injection of the anti-cancer drug, the small intestine was removed and tissue specimens were examined for the regeneration of small intestinal crypts. In experiment 1, the number of regenerative crypts after the administration of 5-fluorouracil (5FU) intravenously (250 mg/kg) or intraperitoneally (250 or 500 mg/kg) was compared after treatment with MAK or AGA. MAK protected against 5FU-induced small intestinal injury whereas AGA did not. In experiment 2, we investigated the protective effect of MAK against small intestinal injury induced by the anti-cancer drugs: UFT (tegafur with uracil; 1,000 mg/kg, orally), cisplatin (CDDP; 12.5 and 25 mg/kg, intraperitoneally), cyclophosphamide (CPA; 250 mg/kg, orally) and gefitinib (Iressa; 2,000 and 4,000 mg/kg, orally). UFT and CDDP decreased the number of regenerative crypts, but treatment with MAK attenuated the extent of UFT- or CDDP-induced small intestinal injury. CPA or Iressa plus MAK up-regulated crypt regeneration. The present results indicate that MAK ameliorates the small intestinal injury caused by several anti-cancer drugs, suggesting that MAK is a potential preventive agent against this common adverse effect of chemotherapy. PMID:22966257

Immunohistochemical and morphometric analysis of intestinal full-thickness biopsy samples from cats with lymphoplasmacytic inflammatory bowel disease.

PubMed

Marsilio, S; Kleinschmidt, S; Nolte, I; Hewicker-Trautwein, M

2014-05-01

The distribution and numbers of CD3(+) T lymphocytes, immunoglobulin(+) plasma cells and calprotectin (L1)(+) macrophages was analyzed in full-thickness, formalin-fixed biopsy samples from the small intestine (duodenum, jejunum and ileum) and from the colon from nine cats with clinical signs of inflammatory bowel disease (IBD). All animals had lymphoplasmacytic enteritis or lymphoplasmacytic enterocolitis. Equivalent samples from the same intestinal regions from 12 healthy pet cats served as controls. Labelled cells in the lamina propria were counted by computer-aided morphometry. The different cell types were similarly distributed in both groups, but there were differences in their numbers. There were more CD3(+) T cells in the duodenum and jejunum of cats with IBD; however, the difference was only significant for the duodenum. There were significantly more IgA(+) cells in the duodenal crypt region. There were significantly more IgG(+) cells in the lower jejunal crypt region. Plasma cells expressing IgM were decreased in cats with IBD, but the difference was not significant. L1(+) macrophages were significantly decreased in the lower crypt area of the colon in cats with IBD and there was a trend to decreased L1(+) cells in the upper crypt area of the duodenum and jejunum. Comparison of the results of this study with previous findings on endoscopically-obtained duodenal biopsy samples from cats with IBD revealed some differences. These discrepancies might relate to differences between control cat populations, types of biopsy samples, methodological factors such as different counting techniques and the activity of the disease at the time of sampling. Copyright © 2014 Elsevier Ltd. All rights reserved.

The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes.

PubMed

Winkelmann, Isabel; Diehl, Daniela; Oesterle, Doris; Daniel, Hannelore; Wenzel, Uwe

2007-07-01

Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2-dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism.

The Sommersdorf mummies—An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany

PubMed Central

Kellinghaus, Manuel; Jackowski, Christian; Shved, Natallia; Rühli, Frank; Maixner, Frank; Zink, Albert; Rosendahl, Wilfried; Lösch, Sandra

2017-01-01

Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle’s church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases. PMID:28859116

Sodium Selenite Radiosensitizes Hormone-Refractory Prostate Cancer Xenograft Tumors but Not Intestinal Crypt Cells In Vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian Junqiang; Ning Shouchen; Knox, Susan J., E-mail: sknox@stanford.ed

Purpose: We have previously shown that sodium selenite (SSE) increases radiation-induced cell killing of human prostate carcinoma cells in vitro. In this study we further evaluated the in vivo radiosensitizing effect of SSE in prostate cancer xenograft tumors and normal radiosensitive intestinal crypt cells. Methods and Materials: Immunodeficient (SCID) mice with hormone-independent LAPC-4 (HI-LAPC-4) and PC-3 xenograft tumors (approximately 200 mm{sup 3}) were divided into four groups: control (untreated), radiation therapy (XRT, local irradiation), SSE (2 mg/kg, intraperitoneally, 3 times/week), and XRT plus SSE. The XRT was given at the beginning of the regimen as a single dose of 5more » Gy for HI-LAPC-4 tumors and a single dose of 7 Gy followed by a fractional dose of 3 Gy/d for 5 days for PC-3 tumors. The tumor volume was measured 3 times per week. The radiosensitizing effect of SSE on normal intestinal epithelial cells was assessed by use of a crypt cell microcolony assay. Results: In the efficacy study, SSE alone significantly inhibited the tumor growth in HI-LAPC-4 tumors but not PC-3 tumors. Sodium selenite significantly enhanced the XRT-induced tumor growth inhibition in both HI-LAPC-4 and PC-3 tumors. In the toxicity study, SSE did not affect the intestinal crypt cell survival either alone or in combination with XRT. Conclusions: Sodium selenite significantly enhances the effect of radiation on well-established hormone-independent prostate tumors and does not sensitize the intestinal epithelial cells to radiation. These results suggest that SSE may increase the therapeutic index of XRT for the treatment of prostate cancer.« less

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage

PubMed Central

Seiler, Kristen M; Schenhals, Erica L; von Furstenberg, Richard J; Allena, Bhavya K; Smith, Brian J; Scaria, Denny; Bresler, Michele N; Dekaney, Christopher M; Henning, Susan J

2015-01-01

The goals of this study were to document the proliferative response of intestinal stem cells (ISCs) during regeneration after damage from doxorubicin (DXR) and to characterize the signals responsible for ISC activation. To this end, jejuni from DXR-treated mice were harvested for histology, assessment of ISC numbers and proliferation by flow cytometry, crypt culture, and RNA analyses. Histology showed that crypt depth and width were increased 4 days after DXR. At this time point, flow cytometry on tissue collected 1 hour after EdU administration revealed increased numbers of CD24loUEA− ISCs and increased percentage of ISCs cycling. In culture, crypts harvested from DXR-treated mice were equally proliferative as those of control mice. Addition of subepithelial intestinal tissue (SET) collected 4 days after DXR elicited increased budding (1.4 ± 0.3 vs. 5.1 ± 1.0 buds per enteroid). Microarray analysis of SET collected 4 days after DXR revealed 1,030 differentially expressed transcripts. Cross comparison of Gene Ontology terms considered relevant to ISC activation pointed to 10 candidate genes. Of these the epidermal growth factor (EGF) family member amphiregulin and the BMP antagonist chordin-like 2 were chosen for further study. In crypt culture, amphiregulin alone did not elicit significant budding, but amphiregulin in combination with BMP antagonism showed marked synergism (yielding 6.3 ± 0.5 buds per enteroid). These data suggest a critical role for underlying tissue in regulating ISC behavior after damage, and point to synergism between amphiregulin and chordin-like 2 as factors which may account for activation of ISCs in the regenerative phase. PMID:25693894

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clouston, Laura J.; Bernales, Varinia; Carlson, Rebecca K.

Expanding a family of cobalt bimetallic complexes, we report the synthesis of the Ti(III) metalloligand, Ti[N(o-(NCH2P(iPr)2)C6H4)3] (abbreviated as TiL), and three heterobimetallics that pair cobalt with an early transition metal ion: CoTiL (1), K(crypt-222)[(N2)CoVL] (2), and K(crypt-222)[(N2)CoCrL] (3). The latter two complexes, along with previously reported K(crypt-222)[(N2)CoAlL] and K(crypt-222)[(N2)Co2L], constitute an isostructural series of cobalt bimetallics that bind dinitrogen in an end-on fashion, i.e. [(N2)CoML]-. The characterization of 1–3 includes cyclic voltammetry, X-ray crystallography, and infrared spectroscopy. The [CoTiL]0/– reduction potential is extremely negative at -3.20 V versus Fc+/Fc. In the CoML series where M is a transition metal, themore » reduction potentials shift anodically as M is varied across the first-row period. Among the [(N2)CoML]- compounds, the dinitrogen ligand is weakly activated, as evidenced by N–N bond lengths between 1.110(8) and 1.135(4) Å and by N–N stretching frequencies between 1971 and 1995 cm–1. Though changes in νN2 are subtle, the extent of N2 activation decreases across the first-row period. A correlation is found between the [CoML]0/– reduction potentials and N2 activation, where the more cathodic potentials correspond to lower N–N frequencies. Theoretical calculations of the [(N2)CoML]- complexes reveal important variations in the electronic structure and Co–M interactions, which depend on the exact nature of the supporting metal ion, M.« less

Live imaging of symbiosis: spatiotemporal infection dynamics of a GFP-labelled Burkholderia symbiont in the bean bug Riptortus pedestris

PubMed Central

Kikuchi, Yoshitomo; Fukatsu, Takema

2014-01-01

Many insects possess endosymbiotic bacteria inside their body, wherein intimate interactions occur between the partners. While recent technological advancements have deepened our understanding of metabolic and evolutionary features of the symbiont genomes, molecular mechanisms underpinning the intimate interactions remain difficult to approach because the insect symbionts are generally uncultivable. The bean bug Riptortus pedestris is associated with the betaproteobacterial Burkholderia symbiont in a posterior region of the midgut, which develops numerous crypts harbouring the symbiont extracellularly. Distinct from other insect symbiotic systems, R. pedestris acquires the Burkholderia symbiont not by vertical transmission but from the environment every generation. By making use of the cultivability and the genetic tractability of the symbiont, we constructed a transgenic Burkholderia strain labelled with green fluorescent protein (GFP), which enabled detailed observation of spatiotemporal dynamics and the colonization process of the symbiont in freshly prepared specimens. The symbiont live imaging revealed that, at the second instar, colonization of the symbiotic midgut M4 region started around 6 h after inoculation (hai). By 24 hai, the symbiont cells appeared in the main tract and also in several crypts of the M4. By 48 hai, most of the crypts were colonized by the symbiont cells. By 72 hai, all the crypts were filled up with the symbiont cells and the symbiont localization pattern continued during the subsequent nymphal development. Quantitative PCR of the symbiont confirmed the infection dynamics quantitatively. These results highlight the stinkbug-Burkholderia gut symbiosis as an unprecedented model for comprehensive understanding of molecular mechanisms underpinning insect symbiosis. PMID:24103110

GM-CSF produced by non-hematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa1,2

PubMed Central

Egea, Laia; McAllister, Christopher S.; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F.

2012-01-01

GM-CSF is a growth factor that promotes the survival and activation of macrophages and granulocytes, and dendritic cell (DC) differentiation and survival in vitro. The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn’s disease in humans and colitis in murine models has been considered mainly to reflect its activity on myeloid cells. We used GM-CSF deficient (GM-CSF−/−) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS) at doses that resulted in little epithelial damage and mucosal ulceration in wild type (WT) mice resulted in marked colon ulceration and delayed ulcer healing in GM-CSF−/− mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF−/− mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF−/− mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Non-hematopoietic cells and not myeloid cells produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury as revealed by bone marrow chimera and DC depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell produced GM-CSF has a novel non-redundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium. PMID:23325885

Chemoprevention of 1,2-dimethylhydrazine-induced colonic preneoplastic lesions in Fischer rats by 6-methylsulfinylhexyl isothiocyanate, a wasabi derivative

PubMed Central

KUNO, TOSHIYA; HIROSE, YOSHINOBU; YAMADA, YASUHIRO; IMAIDA, KATSUMI; TATEMATSU, KENJIRO; MORI, YUKIO; MORI, HIDEKI

2010-01-01

The preventive effects of dietary exposure to a wasabi derivative 6-methylsulfinylhexyl isothiocyanate (6-MSITC) during the initiation and post-initiation phases on the development of 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF), and β-catenin-accumulated crypts (BCAC) were investigated in male F344 rats. To induce ACF and BCAC, rats were given four weekly subcutaneous injections of DMH (40 mg/kg body weight). The rats also received diets containing 200 or 400 ppm 6-MSITC during the initiation or post-initiation phases. The experiment was terminated 12 weeks after the start. DMH exposure produced a substantial number of ACF (323.8±69.7/colon) and BCAC (3.80±1.05/cm2) at the end of the study. Dietary administration of 6-MSITC at a dose of 400 ppm during the initiation phase caused a significant reduction in the total number of ACF (52% reduction, P<0.0001), larger ACF (4 or more crypt ACF) (58% reduction, P<0.001) and BCAC (76% reduction, P<0.00001). The dietary exposure to 6-MSITC significantly reduced the size (crypt multiplicity) of BCAC during both initiation and post-initiation treatment when compared to group 1 treated with DMH alone. Immunohistochemically, 6-MSITC administration lowered the proliferating cell nuclear antigen labeling index in ACF and BCAC. In addition, protein levels of hepatic cytochrome P-450 isozymes at 24 h after 6-MSITC exposure were significantly suppressed (P<0.01). The results indicated that 6-MSITC exerted chemopreventive effects in the present short-term colon carcinogenesis bioassay, through alterations in cell proliferation activity and drug metabolizing enzyme levels. PMID:22966293

Chemoprevention of 1,2-dimethylhydrazine-induced colonic preneoplastic lesions in Fischer rats by 6-methylsulfinylhexyl isothiocyanate, a wasabi derivative.

PubMed

Kuno, Toshiya; Hirose, Yoshinobu; Yamada, Yasuhiro; Imaida, Katsumi; Tatematsu, Kenjiro; Mori, Yukio; Mori, Hideki

2010-03-01

The preventive effects of dietary exposure to a wasabi derivative 6-methylsulfinylhexyl isothiocyanate (6-MSITC) during the initiation and post-initiation phases on the development of 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF), and β-catenin-accumulated crypts (BCAC) were investigated in male F344 rats. To induce ACF and BCAC, rats were given four weekly subcutaneous injections of DMH (40 mg/kg body weight). The rats also received diets containing 200 or 400 ppm 6-MSITC during the initiation or post-initiation phases. The experiment was terminated 12 weeks after the start. DMH exposure produced a substantial number of ACF (323.8±69.7/colon) and BCAC (3.80±1.05/cm(2)) at the end of the study. Dietary administration of 6-MSITC at a dose of 400 ppm during the initiation phase caused a significant reduction in the total number of ACF (52% reduction, P<0.0001), larger ACF (4 or more crypt ACF) (58% reduction, P<0.001) and BCAC (76% reduction, P<0.00001). The dietary exposure to 6-MSITC significantly reduced the size (crypt multiplicity) of BCAC during both initiation and post-initiation treatment when compared to group 1 treated with DMH alone. Immunohistochemically, 6-MSITC administration lowered the proliferating cell nuclear antigen labeling index in ACF and BCAC. In addition, protein levels of hepatic cytochrome P-450 isozymes at 24 h after 6-MSITC exposure were significantly suppressed (P<0.01). The results indicated that 6-MSITC exerted chemopreventive effects in the present short-term colon carcinogenesis bioassay, through alterations in cell proliferation activity and drug metabolizing enzyme levels.

Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.

PubMed

Carr, Jacquelyn S; King, Stephanie; Dekaney, Christopher M

2017-01-01

While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.

Early establishment of epithelial apoptosis in the developing human small intestine.

PubMed

Vachon, P H; Cardin, E; Harnois, C; Reed, J C; Vézina, A

2000-12-01

In the adult small intestine, the dynamic renewal of the epithelium is characterized by a sequence of cell production in the crypts, cell maturation and cell migration to the tip of villi, where apoptosis is undertaken. Little is known about enterocytic apoptosis during development. In man, intestinal architectural features and functions are acquired largely by mid-gestation (18-20 wks); the question whether the establishment of enterocytic apoptotic processes parallels or not the acquisition of other intestinal functional features remains open. In the present study, we approached this question by examining enterocytic apoptosis during development of the human jejunum (9-20 wks gestation), using the ISEL (in situ terminal uridine deoxynucleotidyl nick-end labelling) method. Between 9 and 17 wks, apoptotic enterocytes were not evidenced. However, beginning at the 18 wks stage, ISEL-positive enterocytes were regularly observed at the tip of villi. Since the Bcl-2 family of proteins constitutes a critical checkpoint in apoptosis, acting upstream of the apoptotic machinery, we investigated the expression of six Bcl-2 homologs (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak, Bad) and one non-homologous associated molecule (Bag-1). By immunofluorescence, we found that all homologs analyzed were expressed by enterocytes between 9 and 20 wks. However, Bcl-2 homologs underwent a gradual compartmentalization of epithelial expression along the maturing crypt-villus axis, to establish gradients of expression by 18-20 wks. Western blot analyses indicated that the expression levels of Bcl-2 homologs were modulated during morphogenesis of the crypt-villus axis, in parallel to their gradual compartmentalization of expression. Altogether, these data suggest that regulatory mechanisms of human enterocytic apoptosis become established by mid-gestation (18-20 wks) and coincide with the maturation of the crypt-villus axis of cell proliferation, differentiation and renewal.

CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice.

PubMed

Riehl, Terrence E; Santhanam, Srikanth; Foster, Lynne; Ciorba, Matthew; Stenson, William F

2015-12-01

Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3-8 wk of age to wild-type, CD44(-/-), and TLR4(-/-) mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5(+) stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5(+) reporter mice from postnatal day 7 to day 14 decreased Lgr5(+) cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5(+) stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4. Copyright © 2015 the American Physiological Society.

Relationship between iris surface features and angle width in Asian eyes.

PubMed

Sidhartha, Elizabeth; Nongpiur, Monisha Esther; Cheung, Carol Y; He, Mingguang; Wong, Tien Yin; Aung, Tin; Cheng, Ching-Yu

2014-10-23

To examine the associations between iris surface features with anterior chamber angle width in Asian eyes. In this prospective cross-sectional study, we recruited 600 subjects from a large population-based study, the Singapore Epidemiology of Eye Diseases (SEED) study. We obtained standardized digital slit-lamp iris photographs and graded the iris crypts (by number and size), furrows (by number and circumferential extent), and color (higher grade denoting darker iris). Vertical and horizontal cross-sections of anterior chamber were imaged using anterior segment optical coherence tomography. Angle opening distance (AOD), angle recess area (ARA), and trabecular-iris space area (TISA) were measured using customized software. Associations of the angle width with the iris surface features in the subject's right eyes were assessed using linear regression analysis. A total of 464 eyes of the 464 subjects (mean age: 57.5 ± 8.6 years) had complete and gradable data for crypts and color, and 423 eyes had gradable data for furrows. After adjustment for age, sex, ethnicity, pupil size, and corneal arcus, higher crypt grade was independently associated with wider AOD750 (β [change in angle width per grade higher] = 0.018, P = 0.023), ARA750 (β = 0.022, P = 0.049), and TISA750 (β = 0.011, P = 0.019), and darker iris was associated narrower ARA750 (β = -0.025, P = 0.044) and TISA750 (β = -0.013, P = 0.011). Iris surface features, assessed and measured from slit-lamp photographs, correlated well with anterior chamber angle width; irises with more crypts and lighter color were associated with wider angle. These findings may provide another imaging modality to assess angle closure risk based on iris surface features. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.

PubMed

Fedirko, Veronika; Bostick, Roberd M; Long, Qi; Flanders, W Dana; McCullough, Marjorie L; Sidelnikov, Eduard; Daniel, Carrie R; Rutherford, Robin E; Shaukat, Aasma

2010-01-01

The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms.

ADAM10 Regulates Notch Function in Intestinal Stem Cells of Mice

PubMed Central

Tsai, Yu-Hwai; VanDussen, Kelli L.; Sawey, Eric T.; Wade, Alex W.; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G.; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C.; Samuelson, Linda C.; Dempsey, Peter J.

2014-01-01

BACKGROUND & AIMS ADAM10 is a cell surface sheddase that regulates physiological processes including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. METHODS We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10f/f mice) and conditional (Vil-CreER;Adam10f/f and Lgr5-CreER;Adam10f/f mice) deletion of ADAM10. We performed cell lineage tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26NICD) or mice with intestine-specific disruption of Notch (Rosa26DN-MAML), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. RESULTS Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26NICD and Rosa26DN-MAML mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage tracing experiments showed that ADAM10 is required for survival of Lgr5+ crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. CONCLUSIONS ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. PMID:25038433

Operation of a cascade air conditioning system with two-phase loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Yinshan; Wang, Jinliang; Zhao, Futao

A method of operating a heat transfer system includes starting operation of a first heat transfer fluid vapor/compression circulation loop including a fluid pumping mechanism, a heat exchanger for rejecting thermal energy from a first heat transfer fluid, and a heat absorption side of an internal heat exchanger. A first conduit in a closed fluid circulation loop circulates the first heat transfer fluid therethrough. Operation of a second two-phase heat transfer fluid circulation loop is started after starting operation of the first heat transfer fluid circulation loop. The second heat transfer fluid circulation loop transfers heat to the first heatmore » transfer fluid circulation loop through the internal heat exchanger and includes a heat rejection side of the internal heat exchanger, a liquid pump, and a heat exchanger evaporator. A second conduit in a closed fluid circulation loop circulates a second heat transfer fluid therethrough.« less

The impact of irrigating fluid absorption on blood coagulation in patients undergoing transurethral resection of the prostate

PubMed Central

Shin, Hyun-Jung; Na, Hyo-Seok; Jeon, Young-Tae; Park, Hee-Pyoung; Nam, Sun-Woo; Hwang, Jung-Won

2017-01-01

Abstract Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM). A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol–0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath. The effects on coagulation were assessed by pre- and postoperative laboratory blood tests, including hemoglobin, hematocrit, platelet count, international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time, electrolyte, and ROTEM. INTEM-clotting time (INTEM-CT) was significantly lengthened by 14% (P = 0.001). INTEM-α-angle was significantly decreased by 3% (P = 0.011). EXTEM-clot formation time was significantly prolonged by 18% (P = 0.008), and EXTEM-maximum clot firmness (EXTEM-MCF) was significantly decreased by 4% (P = 0.010). FIBTEM-MCF was also significantly decreased by 13% (P = 0.015). Moreover, hemoglobin (P < 0.001), hematocrit (P < 0.001), platelet counts (P < 0.001), potassium (P = 0.024), and ionized calcium (P = 0.004) were significantly decreased, while PT-INR (P = 0.001) was significantly increased after surgery. The amount of irrigating fluid absorbed was significantly associated with the weight of resected prostatic tissue (P = 0.001) and change of INTEM-CT (P < 0.001). As shown by the ROTEM analysis, the irrigating fluid absorbed during TURP impaired the blood coagulation cascade by creating a disruption in the coagulation factor activity or by lowering the coagulation factor concentration via dilution. PMID:28079789

The impact of irrigating fluid absorption on blood coagulation in patients undergoing transurethral resection of the prostate: A prospective observational study using rotational thromboelastometry.

PubMed

Shin, Hyun-Jung; Na, Hyo-Seok; Jeon, Young-Tae; Park, Hee-Pyoung; Nam, Sun-Woo; Hwang, Jung-Won

2017-01-01

Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM).A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol-0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath. The effects on coagulation were assessed by pre- and postoperative laboratory blood tests, including hemoglobin, hematocrit, platelet count, international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time, electrolyte, and ROTEM.INTEM-clotting time (INTEM-CT) was significantly lengthened by 14% (P = 0.001). INTEM-α-angle was significantly decreased by 3% (P = 0.011). EXTEM-clot formation time was significantly prolonged by 18% (P = 0.008), and EXTEM-maximum clot firmness (EXTEM-MCF) was significantly decreased by 4% (P = 0.010). FIBTEM-MCF was also significantly decreased by 13% (P = 0.015). Moreover, hemoglobin (P < 0.001), hematocrit (P < 0.001), platelet counts (P < 0.001), potassium (P = 0.024), and ionized calcium (P = 0.004) were significantly decreased, while PT-INR (P = 0.001) was significantly increased after surgery. The amount of irrigating fluid absorbed was significantly associated with the weight of resected prostatic tissue (P = 0.001) and change of INTEM-CT (P < 0.001).As shown by the ROTEM analysis, the irrigating fluid absorbed during TURP impaired the blood coagulation cascade by creating a disruption in the coagulation factor activity or by lowering the coagulation factor concentration via dilution.

Time-lapse integrated geophysical imaging of magmatic injections and fluid-induced fracturing causing Campi Flegrei 1983-84 Unrest

NASA Astrophysics Data System (ADS)

De Siena, Luca; Crescentini, Luca; Amoruso, Antonella; Del Pezzo, Edoardo; Castellano, Mario

2016-04-01

Geophysical precursors measured during Unrest episodes are a primary source of geophysical information to forecast eruptions at the largest and most potentially destructive volcanic calderas. Despite their importance and uniqueness, these precursors are also considered difficult to interpret and unrepresentative of larger eruptive events. Here, we show how novel geophysical imaging and monitoring techniques are instead able to represent the dynamic evolution of magmatic- and fluid-induced fracturing during the largest period of Unrest at Campi Flegrei caldera, Italy (1983-1984). The time-dependent patterns drawn by microseismic locations and deformation, once integrated by 3D attenuation tomography and absorption/scattering mapping, model injections of magma- and fluid-related materials in the form of spatially punctual microseismic bursts at a depth of 3.5 km, west and offshore the city of Pozzuoli. The shallowest four kilometres of the crust work as a deformation-based dipolar system before and after each microseismic shock. Seismicity and deformation contemporaneously focus on the point of injection; patterns then progressively crack the medium directed towards the second focus, a region at depths 1-1.5 km south of Solfatara. A single high-absorption and high-scattering aseismic anomaly marks zones of fluid storage overlying the first dipolar centre. These results provide the first direct geophysical signature of the processes of aseismic fluid release at the top of the basaltic basement, producing pozzolanic activity and recently observed via rock-physics and well-rock experiments. The microseismicity caused by fluids and gasses rises to surface via high-absorption north-east rising paths connecting the two dipolar centres, finally beingq being generally expelled from the maar diatreme Solfatara structure. Geophysical precursors during Unrest depict how volcanic stress was released at the Campi Flegrei caldera during its period of highest recorded seismicity and deformation; they may work as a template for modelling future events in the case the volcano was approaching eruption conditions.

Absorption-emission optrode and methods of use thereof

DOEpatents

Hirschfeld, T.B.

1990-05-29

A method and apparatus are described for monitoring the physical and chemical properties of a sample fluid by measuring an optical signal generated by a fluorescent substance and modulated by an absorber substance. The emission band of the fluorescent substance overlaps the absorption band of the absorber substance, and the degree of overlap is dependent on the physical and chemical properties of the sample fluid. The fluorescent substance and absorber substance are immobilized on a substrate so that an effective number of molecules thereof are sufficiently close for resonant energy transfer to occur, thereby providing highly efficient modulation of the fluorescent emissions of the fluorescent substance by the absorber substance. 4 figs.

Metabolic consequences of fluid shifts induced by microgravity

NASA Technical Reports Server (NTRS)

Cintron, N. M.; Lane, H. W.; Leach, C. S.

1990-01-01

The effects of fluid redistribution induced by weightlessness on the fluid and electrolyte regulation, the maintenance of optimum nutritional status, and on pharmacodynamics (i.e., the absorption, distribution, and elimination of pharmacologic agents) are examined on the basis of published data on flights aboard Skylab and Space Shuttle. Data are presented on changes in plasma osmolarity and the content of antinuclear factor, serum glucose, and the salivary scopolamine concentrations after oral administration before and during space flights.

Protective versus promotional effects of white tea and caffeine on PhIP-induced tumorigenesis and β-catenin expression in the rat

PubMed Central

Wang, Rong; Dashwood, W. Mohaiza; Löhr, Christiane V.; Fischer, Kay A.; Pereira, Clifford B.; Louderback, Mandy; Nakagama, Hitoshi; Bailey, George S.; Williams, David E.; Dashwood, Roderick H.

2009-01-01

A 1 year carcinogenicity bioassay was conducted in rats treated with three short cycles of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)/high-fat (HF) diet, followed by 2% white tea (wt/vol), 0.05% epigallocatechin-3-gallate (EGCG) or 0.065% caffeine as sole source of fluid intake. Thirty-two percent of the PhIP/HF controls survived to 1 year, compared with 50, 48.7 and 18.2% in groups given white tea, EGCG and caffeine, respectively. After 1 year, PhIP/HF controls had tumors in the colon, skin, small intestine, Zymbal’s gland, salivary gland and pancreas. For all sites combined, excluding the colon, tumor incidence data were as follows: PhIP/HF 69.5%, PhIP/HF + EGCG 48.7%, PhIP/HF + white tea 46.9% and PhIP/HF + caffeine 13.3%. Unexpectedly, a higher incidence of colon tumors was detected in rats post-treated with white tea (69%) and caffeine (73%) compared with the 42% incidence in PhIP/HF controls. In the colon tumors, β-catenin mutations were detected at a higher frequency after caffeine posttreatment, and there was a shift toward more tumors harboring substitutions of Gly34 with correspondingly high protein and messenger RNA expression seen for both β-catenin and c-Myc. c-Myc expression exhibited concordance with tumor promotion, and there was a concomitant increase in cell proliferation versus apoptosis in colonic crypts. A prior report described suppression of PhIP-induced colonic aberrant crypts by the same test agents, but did not incorporate a HF diet. These findings are discussed in the context of epidemiological data which do not support an adverse effect of tea and coffee on colon tumor outcome—indeed, some such studies suggest a protective role for caffeinated beverages. PMID:18283038

Intestinal absorption of copper: influence of carbohydrates.

PubMed

Wapnir, R A; Balkman, C

1992-02-01

Macronutrients can modulate the intestinal absorption of trace elements by binding the metal or altering mucosal function. We investigated whether certain simple and complex carbohydrates modify copper (Cu) absorption, using an in vivo perfusion technique in the rat. Corn syrup solids, which contain a mixture of glucose polymers of diverse length, added at either 20 or 50 mosm/kg enhanced Cu absorption from a 31.5 microM (2 mg/liter) Cu solution (128 +/- 11 and 130 +/- 11 pmol/min x cm, respectively, vs 101 +/- 4 pmol/min x cm, P less than 0.05, in the absence of carbohydrate). This was concomitant with a stimulation of net water absorption (1.05 +/- 0.08 and 0.84 +/- 0.08 microliter/min x cm, respectively, vs 0.63 +/- 0.02 microliter/min x cm with no carbohydrate, P less than 0.05). Glucose, fructose, lactose, or sucrose had no influence on Cu absorption, although they altered water exchanges, an effect attributable to a reduction of the outflow component of fluid recirculation. Low concentrations of lactose resulted in a greater accumulation of Cu in the intestinal mucosa (8.75 +/- 0.71 micrograms/g vs 5.77 +/- 0.68 micrograms/g for controls, P less than 0.05). Hence, solutes that moderately stimulate mucosa-to-serosa fluid influx in a progressive manner, such as glucose polymers, may contribute to functionally increase Cu absorption. Conversely, conditions which tend to reduce water inflow or increase water outflow across the small intestinal mucosa, as may occur with high lactose diets or in cases of chronic diarrhea, may have negative effects.

Coupled optical-thermal-fluid and structural analyses of novel light-trapping tubular panels for concentrating solar power receivers

NASA Astrophysics Data System (ADS)

Ortega, Jesus D.; Christian, Joshua M.; Yellowhair, Julius E.; Ho, Clifford K.

2015-09-01

Traditional tubular receivers used in concentrating solar power are formed using tubes connected to manifolds to form panels; which in turn are arranged in cylindrical or rectangular shapes. Previous and current tubular receivers, such as the ones used in Solar One, Solar Two, and most recently the Ivanpah solar plants, have used a black paint coating to increase the solar absorptance of the receiver. However, these coatings degrade over time and must be reapplied, increasing the receiver maintenance cost. This paper presents the thermal efficiency evaluation of novel receiver tubular panels that have a higher effective solar absorptance due to a light-trapping effect created by arranging the tubes in each panel into unique geometric configurations. Similarly, the impact of the incidence angle on the effective solar absorptance and thermal efficiency is evaluated. The overarching goal of this work is to achieve effective solar absorptances of ~90% and thermal efficiencies above 85% without using an absorptance coating. Several panel geometries were initially proposed and were down-selected based on structural analyses considering the thermal and pressure loading requirements of molten salt and supercritical carbon-dioxide receivers. The effective solar absorptance of the chosen tube geometries and panel configurations were evaluated using the ray-tracing modeling capabilities of SolTrace. The thermal efficiency was then evaluated by coupling computational fluid dynamics with the ray-tracing results using ANSYS Fluent. Compared to the base case analysis (flat tubular panel), the novel tubular panels have shown an increase in effective solar absorptance and thermal efficiency by several percentage points.

Carborundum, a bulk similar to dietary fibers but chemically inert, does not decrease colon carcinogenesis.

PubMed

Corpet, D E; Taché, S; Peiffer, G

1997-03-19

Dietary fibers might lower the risk of colorectal cancer, maybe because of their bulking effect. We tested the protection afforded by an inert bulk against carcinogenesis. Thirty rats received an azoxymethane injection and were allocated to a control diet, or to a diet supplemented with 10% carborundum. After 100 days the colons were scored for aberrant crypt foci. Compared to controls, the fecal weight was doubled in carborundum-fed rats (P < 0.001), but the aberrant crypt foci multiplicity was not changed (P = 0.92). The results do not support the hypothesis that intestinal dilution by an inert bulk can protect against colon cancer.

Serotonin receptors influencing cell proliferation in the jejunal crypt epithelium and in colonic adenocarcinomas.

PubMed

Tutton, P J; Barkla, D H

1986-01-01

Serotonin has previously been shown to stimulate cell proliferation in the jejunal crypt epithelium and in colonic tumours. The original classification of serotonin receptors into D and M groups was not conductive to the understanding of these observations. The more recent classification of serotonin receptors into 5HT1 and 5HT2 groups is considered in this report. On the balance of evidence it appears that similar receptors mediate the response to serotonin in the two tissues under consideration and that these receptors resemble those of the 5HT1 group. Such receptors are usually positively linked to adenylate cyclase.

Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.

PubMed Central

Batman, P A; Miller, A R; Forster, S M; Harris, J R; Pinching, A J; Griffin, G E

1989-01-01

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV. Images Fig 1 Fig 2 PMID:2703544

Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet.

PubMed

Abiko, Yukie; Kojima, Takashi; Murata, Masaki; Tsujiwaki, Mitsuhiro; Takeuchi, Masaya; Sawada, Norimasa; Mori, Michio

2013-12-01

DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

Impaired Cell Volume Regulation in Intestinal Crypt Epithelia of Cystic Fibrosis Mice

NASA Astrophysics Data System (ADS)

Valverde, M. A.; O'Brien, J. A.; Sepulveda, F. V.; Ratcliff, R. A.; Evans, M. J.; Colledge, W. H.

1995-09-01

Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl^- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl^- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl^- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K^+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl^- secretion.

Scap is required for sterol synthesis and crypt growth in intestinal mucosa.

PubMed

McFarlane, Matthew R; Cantoria, Mary Jo; Linden, Albert G; January, Brandon A; Liang, Guosheng; Engelking, Luke J

2015-08-01

SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synthesis of sterols and fatty acids is reduced, but mice are otherwise healthy. To determine whether Scap loss is tolerated in the intestine, we generated a mouse model (Vil-Scap(-)) in which tamoxifen-inducible Cre-ER(T2), a fusion protein of Cre recombinase with a mutated ligand binding domain of the human estrogen receptor, ablates Scap in intestinal mucosa. After 4 days of tamoxifen, Vil-Scap(-) mice succumb with a severe enteropathy and near-complete collapse of intestinal mucosa. Organoids grown ex vivo from intestinal crypts of Vil-Scap(-) mice are readily killed when Scap is deleted by 4-hydroxytamoxifen. Death is prevented when culture medium is supplemented with cholesterol and oleate. These data show that, unlike the liver, the intestine requires Scap to sustain tissue integrity by maintaining the high levels of lipid synthesis necessary for proliferation of intestinal crypts. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Sampling the light-organ microenvironment of Euprymna scolopes: description of a population of host cells in association with the bacterial symbiont Vibrio fischeri.

PubMed

Nyholm, S V; McFall-Ngai, M J

1998-10-01

The symbiosis between the squid Euprymna scolopes and the luminous bacterium Vibrio fischeri has a pronounced diel rhythm, one component of which is the venting of the contents of the light organ into the surrounding seawater each day at dawn. In this study, we explored the use of this behavior to sample the microenvironment of the light-organ crypts. Intact crypt contents, which emerge from the lateral pores of the organ as a thick paste-like exudate, were collected from anesthetized host animals that had been exposed to a light cue. Microscopy revealed that the expelled material is composed of a conspicuous population of host cells in association with the bacterial symbionts, all of which are embedded in a dense acellular matrix that strongly resembles the bacteria-based biofilms described in other systems. Assays of the viability of expelled crypt cells revealed no dead bacterial symbionts and a mixture of live and dead host cells. Analyses of the ultrastructure, biochemistry, and phagocytic activity of a subset of the host cell population suggested that some of these cells are macrophage-like molluscan hemocytes.

Experiment K-7-17: Effects of Spaceflight on the Proliferation of Jejunal Mucosal Cells

NASA Technical Reports Server (NTRS)

Phillips, R. W.; Moeller, C. L.; Sawyer, H. R.; Smirnov, K. L.

1994-01-01

The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity due to microgravity conditions encountered during spaceflight would be demonstrable in cells and tissues characterized by a rapid rate of turnover. Jejunal mucosal cells were chosen as a model since these cells are among the most rapidly proliferating in the body. Accordingly, the percentage of mitotic cells present in the crypts of Lieberkuhn in each of 5 rats flown on the COSMOS 2044 mission were compared to the percentage of mitotic cells present in the crypts in rats included in each of 3 ground control groups (i.e., vivarium, synchronous and caudal-elevated). No significant difference (p greater than .05) was detected in mitotic indices between the flight and vivarium group. Although the ability of jejunal mucosal cells to divide by mitosis was not impaired in flight group, there was, however, a reduction in the length of villi and depth of crypts. The concommitant reduction in villus length and crypth depth in the flight group probably reflects changes in connective tissue components within the core of villi.

Comparing a discrete and continuum model of the intestinal crypt

PubMed Central

Murray, Philip J.; Walter, Alex; Fletcher, Alex G.; Edwards, Carina M.; Tindall, Marcus J.; Maini, Philip K.

2011-01-01

The integration of processes at different scales is a key problem in the modelling of cell populations. Owing to increased computational resources and the accumulation of data at the cellular and subcellular scales, the use of discrete, cell-level models, which are typically solved using numerical simulations, has become prominent. One of the merits of this approach is that important biological factors, such as cell heterogeneity and noise, can be easily incorporated. However, it can be difficult to efficiently draw generalisations from the simulation results, as, often, many simulation runs are required to investigate model behaviour in typically large parameter spaces. In some cases, discrete cell-level models can be coarse-grained, yielding continuum models whose analysis can lead to the development of insight into the underlying simulations. In this paper we apply such an approach to the case of a discrete model of cell dynamics in the intestinal crypt. An analysis of the resulting continuum model demonstrates that there is a limited region of parameter space within which steady-state (and hence biologically realistic) solutions exist. Continuum model predictions show good agreement with corresponding results from the underlying simulations and experimental data taken from murine intestinal crypts. PMID:21411869

GLUT-5 expression in neonatal rats: crypt-villus location and age-dependent regulation.

PubMed

Jiang, L; David, E S; Espina, N; Ferraris, R P

2001-09-01

The rat fructose transporter normally appears after completion of weaning but can be precociously induced by early feeding of a high-fructose diet. In this study, the crypt-villus site, the metabolic nature of the signal, and the age dependence of induction were determined. In weaning rats fed high-glucose pellets, GLUT-5 mRNA expression was modest, localized mainly in the upper three-fourths of the villus, and there was little expression in the villus base. When fed high-fructose pellets, GLUT-5 mRNA expression was two to three times greater in all regions except the villus base. Intestinal perfusion in vivo of a nonmetabolizable fructose analog, 3-O-methylfructose, tended to increase fructose uptake rate and moderately increased GLUT-5 mRNA abundance but had no effect on glucose uptake rates and SGLT1 mRNA abundance. Gavage feeding of high-fructose, but not high-glucose, solutions enhanced fructose uptake only in pups > or =14 days, suggesting that GLUT-5 regulation is markedly age dependent. Fructose or its metabolites upregulate GLUT-5 expression in all enterocytes, except those in the crypt and villus base and in pups <14 days old.

In vitro dermal absorption of pyrethroid pesticides in human and rat skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hughes, Michael F., E-mail: hughes.michaelf@epa.go; Edwards, Brenda C.

2010-07-15

Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4 h. At 24 h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skinmore » and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using in vitro dermal absorption data for risk assessment.« less

Stimulation of Intestinal Cl- Secretion Through CFTR by Caffeine Intake in Salt-Sensitive Hypertensive Rats.

PubMed

Wei, Xiao; Lu, Zongshi; Yang, Tao; Gao, Peng; Chen, Sijiao; Liu, Daoyan; Zhu, Zhiming

2018-03-16

High salt consumption is a major risk factor for hypertension, and sodium homeostasis is regulated by both intestinal sodium absorption and urinary sodium excretion. Chronic caffeine intake has been reported to attenuate salt-sensitive hypertension by promoting urinary sodium excretion; however, its exact role in intestinal sodium absorption remains unknown. Here, we investigated whether and how chronic caffeine consumption antagonizes salt-sensitive hypertension by inhibiting intestinal sodium absorption. Dahl salt-sensitive rats were fed 8% NaCl chow and 0.1% caffeine in their drinking water for 15 days. The blood pressure and fecal sodium content were measured. The effect of caffeine on the movement of Cl- in enterocyte cells was determined with the Ussing chamber assay. Rats that were treated with caffeine displayed significantly lower mean blood pressure and higher fecal sodium content than the controls. Consistent with these findings, caffeine intake decreased fluid absorption by the intestine in the fluid perfusion experiment. Further, the results from the Ussing chamber assay indicated that caffeine promoted Cl- secretion through enterocyte apical cystic fibrosis transmembrane conductance regulator (CFTR), and thus inhibited sodium absorption. Moreover, depletion of cAMP or inhibition of CFTR completely abolished the effect of caffeine on Cl- secretion. The results indicate that chronic caffeine consumption reduces sodium absorption by promoting CFTR-mediated Cl- secretion in the intestine, which contributes to the anti-hypertensive effect of caffeine in salt-sensitive rats. © 2018 The Author(s). Published by S. Karger AG, Basel.

Protein detection system

DOEpatents

Fruetel, Julie A [Livermore, CA; Fiechtner, Gregory J [Bethesda, MD; Kliner, Dahv A. V. [San Ramon, CA; McIlroy, Andrew [Livermore, CA

2009-05-05

The present embodiment describes a miniature, microfluidic, absorption-based sensor to detect proteins at sensitivities comparable to LIF but without the need for tagging. This instrument utilizes fiber-based evanescent-field cavity-ringdown spectroscopy, in combination with faceted prism microchannels. The combination of these techniques will increase the effective absorption path length by a factor of 10.sup.3 to 10.sup.4 (to .about.1-m), thereby providing unprecedented sensitivity using direct absorption. The coupling of high-sensitivity absorption with high-performance microfluidic separation will enable real-time sensing of biological agents in aqueous samples (including aerosol collector fluids) and will provide a general method with spectral fingerprint capability for detecting specific bio-agents.

Fiber optic fluid detector

DOEpatents

Angel, S. Michael

1989-01-01

Particular gases or liquids are detected with a fiber optic element (11, 11a to 11j) having a cladding or coating of a material (23, 23a to 23j) which absorbs the fluid or fluids and which exhibits a change of an optical property, such as index of refraction, light transmissiveness or fluoresence emission, for example, in response to absorption of the fluid. The fluid is sensed by directing light into the fiber optic element and detecting changes in the light, such as exit angle changes for example, that result from the changed optical property of the coating material. The fluid detector (24, 24a to 24j) may be used for such purposes as sensing toxic or explosive gases in the atmosphere, measuring ground water contamination or monitoring fluid flows in industrial processes, among other uses.

Peritoneal fluid transport: mechanisms, pathways, methods of assessment.

PubMed

Waniewski, Jacek

2013-11-01

Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chao; Xu, Zhijie; Lai, Kevin

Part 1 of this paper presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO2) capture. To generate data for WWC model validation, CO2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work can account for both chemical absorption and desorption of CO2 in MEA. In addition, the overall mass transfer coefficient predictedmore » using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry's constant and gas diffusivity in the non-reacting nitrous oxide (N2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO2 reaction rate constants after using the N2O/CO2 analogy method. The calibrated model can be used to predict the CO2 mass transfer in a WWC for a wider range of operating conditions.« less

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

DOE PAGES

Wang, Chao; Xu, Zhijie; Lai, Kevin; ...

2017-10-24

Part 1 of this paper presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO2) capture. To generate data for WWC model validation, CO2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work can account for both chemical absorption and desorption of CO2 in MEA. In addition, the overall mass transfer coefficient predictedmore » using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry's constant and gas diffusivity in the non-reacting nitrous oxide (N2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO2 reaction rate constants after using the N2O/CO2 analogy method. The calibrated model can be used to predict the CO2 mass transfer in a WWC for a wider range of operating conditions.« less

The imaging and modelling of the physical processes involved in digestion and absorption.

PubMed

Schulze, K S

2015-02-01

The mechanical activity of the gastro-intestinal tract serves to store, propel and digest food. Contractions disperse particles and transform solids and secretions into the two-phase slurry called chyme; movements of the intestine deliver nutrients to mucosal sites of absorption, and from the submucosa into the lymphatic and portal venous circulation. Colonic motor activity helps to extract fluid and electrolytes from chyme and to compound and compact luminal debris into faeces for elimination. We outline how dynamic imaging by ultrasound and magnetic resonance can demonstrate intestinal flow processes critical to digestion like mixing, dilution, swelling, dispersion and elution. Computational fluid mechanics enables a numerical rendition of the forces promoting digestion: pressure and flow fields, the shear stresses dispersing particles or the effectiveness of bolus mixing can be calculated. These technologies provide new insights into the mechanical processes that promote digestion and absorption. © 2014 This article is a U.S. Government work and is in the public domain in the USA.

Radiant energy absorption studies for laser propulsion. [gas dynamics

NASA Technical Reports Server (NTRS)

Caledonia, G. E.; Wu, P. K. S.; Pirri, A. N.

1975-01-01

A study of the energy absorption mechanisms and fluid dynamic considerations for efficient conversion of high power laser radiation into a high velocity flow is presented. The objectives of the study are: (1) to determine the most effective absorption mechanisms for converting laser radiation into translational energy, and (2) to examine the requirements for transfer of the absorbed energy into a steady flow which is stable to disturbances in the absorption zone. A review of inverse Bremsstrahlung, molecular and particulate absorption mechanisms is considered and the steady flow and stability considerations for conversion of the laser power to a high velocity flow in a nozzle configuration is calculated. A quasi-one-dimensional flow through a nozzle was formulated under the assumptions of perfect gas.

Ultrasonically Encoded Photoacoustic Flowgraphy in Biological Tissue

NASA Astrophysics Data System (ADS)

Wang, Lidai; Xia, Jun; Yao, Junjie; Maslov, Konstantin I.; Wang, Lihong V.

2013-11-01

Blood flow speed is an important functional parameter. Doppler ultrasound flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of millimeters per second) in deep tissue. To address this challenge, we developed ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal tagging with photoacoustic imaging. Focused ultrasound generates a confined heat source in acoustically absorptive fluid. Thermal waves propagate with the flow and are directly visualized in pseudo color using photoacoustic computed tomography. The Doppler shift is employed to calculate the flow speed. This method requires only acoustic and optical absorption, and thus is applicable to continuous fluid. A blood flow speed as low as 0.24mm·s-1 was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue.

Molecular architecture underlying fluid absorption by the developing inner ear

PubMed Central

Honda, Keiji; Kim, Sung Huhn; Kelly, Michael C; Burns, Joseph C; Constance, Laura; Li, Xiangming; Zhou, Fei; Hoa, Michael; Kelley, Matthew W; Morell, Robert J

2017-01-01

Mutations of SLC26A4 are a common cause of hearing loss associated with enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we show that the mouse endolymphatic sac absorbs fluid in an SLC26A4-dependent fashion. Fluid absorption was sensitive to ouabain and gadolinium but insensitive to benzamil, bafilomycin and S3226. Single-cell RNA-seq analysis of pre- and postnatal endolymphatic sacs demonstrates two types of differentiated cells. Early ribosome-rich cells (RRCs) have a transcriptomic signature suggesting expression and secretion of extracellular proteins, while mature RRCs express genes implicated in innate immunity. The transcriptomic signature of mitochondria-rich cells (MRCs) indicates that they mediate vectorial ion transport. We propose a molecular mechanism for resorption of NaCl by MRCs during development, and conclude that disruption of this mechanism is the root cause of hearing loss associated with EES. PMID:28994389

Squeeze strengthening of magnetorheological fluids using mixed mode operation

NASA Astrophysics Data System (ADS)

Becnel, A. C.; Sherman, S. G.; Hu, W.; Wereley, N. M.

2015-05-01

This research details a novel method of increasing the shear yield stress of magnetorheological fluids by combining shear and squeeze modes of operation to manipulate particle chain structures, so-called squeeze strengthening. Using a custom built Searle cell magnetorheometer, which is a model device emulating a rotary magnetorheological energy absorber (MREA), the contribution of squeeze strengthening to the total controllable yield force is experimentally investigated. Using an eccentric rotating inner cylinder, characterization data from large (1 mm) and small (0.25 mm) nominal gap geometries are compared to investigate the squeeze strengthening effect. Details of the experimental setup and method are presented, and a hybrid model is used to explain experimental trends. This study demonstrates that it is feasible, utilizing squeeze strengthening to increase yield stress, to either (1) design a rotary MREA of a given volume to achieve higher energy absorption density (energy absorbed normalized by active fluid volume), or (2) reduce the volume of a given rotary MREA to achieve the same energy absorption density.

The effect of in-service aerospace contaminants on X-band dielectric properties of a bismaleimide/quartz composite

NASA Astrophysics Data System (ADS)

Rodriguez, Luis A.; García, Carla; Grace, Landon R.

2015-05-01

The impact of three common aerospace in-service liquid contaminants on the X-band dielectric properties of a polymer composite radar protecting structure (radome) is investigated and quantified. The dielectric properties of the composite laminate are critical to radar transparency, and thus performance, of the radome structure. Further, polymer composites are highly susceptible to absorption of liquids. As such, the effect of common aerospace contaminants on the dielectric properties of composite laminates is crucial. Measurement of relative permittivity and loss tangent via a split-post dielectric resonant technique at 10 GHz is used to determine the effect of water, deicing fluid, and propylene glycol absorption in a three-ply quartz-reinforced bismaleimide laminate. Additionally, fluid uptake kinetics are investigated as a function of liquid type. An approximately linear relationship between fluid content and relative permittivity is observed for all three contaminant types. A 1% increase in contaminant content by weight results in a 7.8%, 4.5%, and 2.5% increase in relative permittivity of the material due to water, deicing fluid, and propylene glycol, respectively. A more significant impact is seen in material loss tangent, where a 1% increase in contaminant content by weight is responsible for a 378.5%, 593.0%, and 441.5% increase in loss tangent due to the aforementioned fluids, respectively. A fluid uptake weight content of 1.31%, 3.41%, and 4.28% is achieved for water, deicing fluid, and propylene glycol respectively, at approximately 1300 hours exposure. Based on the reported observations, the dielectric property degradation of composite laminates due to these commonly used fluids is of significant concern for in-service aircraft radar systems routinely exposed to these contaminants.

The influence of body position on cerebrospinal fluid pressure gradient and movement in cats with normal and impaired craniospinal communication.

PubMed

Klarica, Marijan; Radoš, Milan; Erceg, Gorislav; Petošić, Antonio; Jurjević, Ivana; Orešković, Darko

2014-01-01

Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension.

Gastrointestinal Epithelial Organoid Cultures from Postsurgical Tissues.

PubMed

Hahn, Soojung; Yoo, Jongman

2017-08-17

An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells. Thus far, gastrointestinal organoids have been extensively used for generating gastrointestinal disease models. This protocol describes the method of isolating a gland or crypt using stomach or colon tissue after surgery and establishing them into gastroids or colonoids.

Gastrointestinal citrate absorption in nephrolithiasis

NASA Technical Reports Server (NTRS)

Fegan, J.; Khan, R.; Poindexter, J.; Pak, C. Y.

1992-01-01

Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

LiCl Dehumidifier LiBr absorption chiller hybrid air conditioning system with energy recovery

DOEpatents

Ko, Suk M.

1980-01-01

This invention relates to a hybrid air conditioning system that combines a solar powered LiCl dehumidifier with a LiBr absorption chiller. The desiccant dehumidifier removes the latent load by absorbing moisture from the air, and the sensible load is removed by the absorption chiller. The desiccant dehumidifier is coupled to a regenerator and the desiccant in the regenerator is heated by solar heated hot water to drive the moisture therefrom before being fed back to the dehumidifier. The heat of vaporization expended in the desiccant regenerator is recovered and used to partially preheat the driving fluid of the absorption chiller, thus substantially improving the overall COP of the hybrid system.

FTIR quantification of industrial hydraulic fluids in perchloroethylene

NASA Technical Reports Server (NTRS)

Mehta, Narinder K.

1993-01-01

The purpose of this summer research project was to investigate whether perchloroethylene can be used as a solvent for the quantitative analysis of industrial hydraulic fluids by infrared spectroscopy employing Beer's law. Standard calibration curves using carbon-hydrogen stretching (generic) and ester absorption peaks were prepared for a series of standard dilutions at low ppm levels of concentration of seven hydraulic fluids in perchloroethylene. The absorbance spectras were recorded with 1.5-10 mm fixed and variable path length sample cells made of potassium bromide. The results indicate that using ester infrared spectral peak, it is possible to detect about 20 ppm of the hydraulic fluid in perchloroethylene.

WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals.

PubMed

Powell, Robin H; Behnke, Michael S

2017-05-15

Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance. © 2017. Published by The Company of Biologists Ltd.

Fluctuations of cell population in a colonic crypt

NASA Astrophysics Data System (ADS)

Pei, Qi-ming; Zhan, Xuan; Yang, Li-jian; Bao, Chun; Cao, Wei; Li, An-bang; Rozi, Anvar; Jia, Ya

2014-03-01

The number of stem cells in a colonic crypt is often very small, which leads to large intrinsic fluctuations in the cell population. Based on the model of cell population dynamics with linear feedback in a colonic crypt, we present a stochastic dynamics of the cell population [including stem cells (SCs), transit amplifying cells (TACs), and fully differentiated cells (FDCs)]. The Fano factor, covariance, and susceptibility formulas of the cell population around the steady state are derived by using the Langevin theory. In the range of physiologically reasonable parameter values, it is found that the stationary populations of TACs and FDCs exhibit an approximately threshold behavior as a function of the net growth rate of TACs, and the reproductions of TACs and FDCs can be classified into three regimens: controlled, crossover, and uncontrolled. With the increasing of the net growth rate of TACs, there is a maximum of the relative intrinsic fluctuations (i.e., the Fano factors) of TACs and FDCs in the crossover region. For a fixed differentiation rate and the net growth rate of SCs, the covariance of fluctuations between SCs and TACs has a maximum in the crossover region. However, the susceptibilities of both TACs and FDCs to the net growth rate of TACs have a minimum in the crossover region.

Screening for in vitro and in vivo antitumor activities of the mushroom Agaricus blazei.

PubMed

Ziliotto, Liane; Pinheiro, Fabriciano; Barbisan, Luís Fernando; Rodrigues, Maria Aparecida Marchesan

2009-01-01

We have investigated the in vitro antitumor activity of the mushroom Agaricus blazei Murill on human cancer cell lines as well as its potential anticancer activity in a model of rat colon carcinogenesis. The in vitro anticancer analysis was performed using 9 human cancer cell lines incubated with organic and aqueous extracts of A. blazei. Antitumor activity was observed with the dichloromethane/methanol and hexanic extracts of A. blazei at 250 mu g/ml for all cancer cell lines tested. No antiproliferative/cytotoxic activities were detected for the aqueous, methanol, ethyl acetate, or n-butanolic extracts. In the in vivo analysis, crude A. blazei was given orally after carcinogen treatment in a rat medium-term study (20 weeks) of colon carcinogenesis using aberrant crypt foci (ACF) as biomarker. Male Wistar rats were given dimethylhydrazine (DMH) and then were fed A. blazei at 5% in the diet until Week 20. ACF were scored for number and crypt multiplicity. A. blazei intake did not suppress ACF development or crypt multiplicity induced by DMH. No differences in tumor incidence in the colon were observed among the DMH-treated groups. Our results indicate that employing A. blazei in the diet does not have a suppressive effect on colon carcinogenesis.

Requirement of alveolar bone formation for eruption of rat molars

PubMed Central

Wise, Gary E.; He, Hongzhi; Gutierrez, Dina L.; Ring, Sherry; Yao, Shaomian

2011-01-01

Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (BMP6), was inhibited by injection of the 1st mandibular molar of the rat with an siRNA targeted against BMP6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption either was delayed or completely inhibited (7 molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced as compared to the erupted first molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that BMP6 may be an essential gene for promoting this growth. PMID:21896048

Phylogenetically Diverse Burkholderia Associated with Midgut Crypts of Spurge Bugs, Dicranocephalus spp. (Heteroptera: Stenocephalidae).

PubMed

Kuechler, Stefan Martin; Matsuura, Yu; Dettner, Konrad; Kikuchi, Yoshitomo

2016-06-25

Diverse phytophagous heteropteran insects, commonly known as stinkbugs, are associated with specific gut symbiotic bacteria, which have been found in midgut cryptic spaces. Recent studies have revealed that members of the stinkbug families Coreidae and Alydidae of the superfamily Coreoidea are consistently associated with a specific group of the betaproteobacterial genus Burkholderia, called the "stinkbug-associated beneficial and environmental (SBE)" group, and horizontally acquire specific symbionts from the environment every generation. However, the symbiotic system of another coreoid family, Stenocephalidae remains undetermined. We herein investigated four species of the stenocephalid genus Dicranocephalus. Examinations via fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM) revealed the typical arrangement and ultrastructures of midgut crypts and gut symbionts. Cloning and molecular phylogenetic analyses of bacterial genes showed that the midgut crypts of all species are colonized by Burkholderia strains, which were further assigned to different subgroups of the genus Burkholderia. In addition to the SBE-group Burkholderia, a number of stenocephalid symbionts belonged to a novel clade containing B. sordidicola and B. udeis, suggesting a specific symbiont clade for the Stenocephalidae. The symbiotic systems of stenocephalid bugs may provide a unique opportunity to study the ongoing evolution of symbiont associations in the stinkbug-Burkholderia interaction.

Chemopreventive effects of Ku-jin tea against AOM-induced precancerous colorectal lesions in rats and metabolomic analysis.

PubMed

Bi, Wu; Liu, Haibo; Shen, Jie; Zhang, Ling-Hua; Li, Pei; Peng, Bing; Cao, Li; Zhang, Pengfei; He, Chunnian; Xiao, Peigen

2017-11-21

Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.

Phylogenetically Diverse Burkholderia Associated with Midgut Crypts of Spurge Bugs, Dicranocephalus spp. (Heteroptera: Stenocephalidae)

PubMed Central

Kuechler, Stefan Martin; Matsuura, Yu; Dettner, Konrad; Kikuchi, Yoshitomo

2016-01-01

Diverse phytophagous heteropteran insects, commonly known as stinkbugs, are associated with specific gut symbiotic bacteria, which have been found in midgut cryptic spaces. Recent studies have revealed that members of the stinkbug families Coreidae and Alydidae of the superfamily Coreoidea are consistently associated with a specific group of the betaproteobacterial genus Burkholderia, called the “stinkbug-associated beneficial and environmental (SBE)” group, and horizontally acquire specific symbionts from the environment every generation. However, the symbiotic system of another coreoid family, Stenocephalidae remains undetermined. We herein investigated four species of the stenocephalid genus Dicranocephalus. Examinations via fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM) revealed the typical arrangement and ultrastructures of midgut crypts and gut symbionts. Cloning and molecular phylogenetic analyses of bacterial genes showed that the midgut crypts of all species are colonized by Burkholderia strains, which were further assigned to different subgroups of the genus Burkholderia. In addition to the SBE-group Burkholderia, a number of stenocephalid symbionts belonged to a novel clade containing B. sordidicola and B. udeis, suggesting a specific symbiont clade for the Stenocephalidae. The symbiotic systems of stenocephalid bugs may provide a unique opportunity to study the ongoing evolution of symbiont associations in the stinkbug-Burkholderia interaction. PMID:27265344

Analysis of iris surface features in populations of diverse ancestry

PubMed Central

Edwards, Melissa; Cha, David; Krithika, S.; Johnson, Monique; Parra, Esteban J.

2016-01-01

There are many textural elements that can be found in the human eye, including Fuchs’ crypts, Wolfflin nodules, pigment spots, contraction furrows and conjunctival melanosis. Although iris surface features have been well-studied in populations of European ancestry, the worldwide distribution of these traits is poorly understood. In this paper, we develop a new method of characterizing iris features from photographs of the iris. We then apply this method to a diverse sample of East Asian, European and South Asian ancestry. All five iris features showed significant differences in frequency between the three populations, indicating that iris features are largely population dependent. Although none of the features were correlated with each other in the East and South Asian groups, Fuchs’ crypts were significantly correlated with contraction furrows and pigment spots and contraction furrows were significantly associated with pigment spots in the European group. The genetic marker SEMA3A rs10235789 was significantly associated with Fuchs’ crypt grade in the European, East Asian and South Asian samples and a borderline association between TRAF3IP1 rs3739070 and contraction furrow grade was found in the European sample. The study of iris surface features in diverse populations may provide valuable information of forensic, biomedical and ophthalmological interest. PMID:26909168

Population pharmacokinetic modeling of furosemide in patients with hypertension and fluid overload conditions.

PubMed

Kodati, Devender; Yellu, Narsimhareddy

2017-06-01

Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL). The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh -1 and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Regulation of ENaC and CFTR expression with K+ channel modulators and effect on fluid absorption across alveolar epithelial cells.

PubMed

Leroy, Claudie; Privé, Anik; Bourret, Jean-Charles; Berthiaume, Yves; Ferraro, Pasquale; Brochiero, Emmanuelle

2006-12-01

In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J Physiol Lung Cell Mol Physiol 286: L1027-L1037, 2004), we identified an ATP-sensitive K(+) (K(ATP)) channel in alveolar epithelial cells, formed by inwardly rectifying K(+) channel Kir6.1/sulfonylurea receptor (SUR)2B subunits. We found that short applications of K(ATP), voltage-dependent K(+) channel KvLQT1, and calcium-activated K(+) (K(Ca)) channel modulators modified Na(+) and Cl(-) currents in alveolar monolayers. In addition, it was shown previously that a K(ATP) opener increased alveolar liquid clearance in human lungs by a mechanism possibly related to epithelial sodium channels (ENaC). We therefore hypothesized that prolonged treatment with K(+) channel modulators could induce a sustained regulation of ENaC activity and/or expression. Alveolar monolayers were treated for 24 h with inhibitors of K(ATP), KvLQT1, and K(Ca) channels identified by PCR. Glibenclamide and clofilium (K(ATP) and KvLQT1 inhibitors) strongly reduced basal transepithelial current, amiloride-sensitive Na(+) current, and forskolin-activated Cl(-) currents, whereas pinacidil, a K(ATP) activator, increased them. Interestingly, K(+) inhibitors or membrane depolarization (induced by valinomycin in high-K(+) medium) decreased alpha-, beta-, and gamma-ENaC and CFTR mRNA. alpha-ENaC and CFTR proteins also declined after glibenclamide or clofilium treatment. Conversely, pinacidil augmented ENaC and CFTR mRNAs and proteins. Since alveolar fluid transport was found to be driven, at least in part, by Na(+) transport through ENaC, we tested the impact of K(+) channel modulators on fluid absorption across alveolar monolayers. We found that glibenclamide and clofilium reduced fluid absorption to a level similar to that seen in the presence of amiloride, whereas pinacidil slightly enhanced it. Long-term regulation of ENaC and CFTR expression by K(+) channel activity could benefit patients with pulmonary diseases affecting ion transport and fluid clearance.

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chao; Xu, Zhijie; Lai, Kevin

The first part of this paper (Part 1) presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO2) capture. To generate data for WWC model validation, CO2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work has the ability to account for both chemical absorption and desorption of CO2 in MEA. In addition,more » the overall mass transfer coefficient predicted using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry’s constant and gas diffusivity in the non-reacting nitrous oxide (N2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO2 reaction rate constants after using the N2O/CO2 analogy method. The calibrated model can be used to predict the CO2 mass transfer in a WWC for a wider range of operating conditions.« less

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chao; Xu, Zhijie; Lai, Kevin

Part 1 of this paper presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO 2) capture. In this study, to generate data for WWC model validation, CO 2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work can account for both chemical absorption and desorption of CO 2 in MEA. In addition,more » the overall mass transfer coefficient predicted using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO 2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry's constant and gas diffusivity in the non-reacting nitrous oxide (N 2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO 2 reaction rate constants after using the N 2O/CO 2 analogy method. Finally, the calibrated model can be used to predict the CO 2 mass transfer in a WWC for a wider range of operating conditions.« less

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

DOE PAGES

Wang, Chao; Xu, Zhijie; Lai, Kevin; ...

2017-10-24

Part 1 of this paper presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO 2) capture. In this study, to generate data for WWC model validation, CO 2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work can account for both chemical absorption and desorption of CO 2 in MEA. In addition,more » the overall mass transfer coefficient predicted using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO 2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry's constant and gas diffusivity in the non-reacting nitrous oxide (N 2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO 2 reaction rate constants after using the N 2O/CO 2 analogy method. Finally, the calibrated model can be used to predict the CO 2 mass transfer in a WWC for a wider range of operating conditions.« less

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Histological variations in juvenile polyp phenotype correlate with genetic defect underlying juvenile polyposis

PubMed Central

van Hattem, W. Arnout; Langeveld, Danielle; de Leng, Wendy W. J.; Morsink, Folkert H.; van Diest, Paul J.; Iacobuzio-Donahue, Christine A.; Giardiello, Francis M.; Offerhaus, G. Johan A.; Brosens, Lodewijk A. A.

2011-01-01

Background Juvenile polyps are distinct hamartomatous malformations of the gastrointestinal tract that may occur in the heritable juvenile polyposis syndrome (JPS) or sporadically. Histologically, juvenile polyps are characterised by a marked increase of the stromal cell compartment but, an epithelial phenotype has also been reported. JPS has an increased risk of colorectal cancer but sporadic juvenile polyps do not. In 50–60% of JPS patients a germline mutation of the TGF-β/BMP pathway genes SMAD4 or BMPR1A is found. This study compares the histological phenotype of juvenile polyps with a SMAD4 or BMPR1A germline mutation and sporadic juvenile polyps. Methods H&E slides of 65 JPS polyps and 25 sporadic juvenile polyps were reviewed for histological features and dysplasia. Systematic random crypt and stroma counts were obtained by count stereology and a crypt-stroma ratio was determined. All polyps were subsequently categorised as type A (crypt-stroma ratio <1.00) or type B (crypt-stroma ratio ≥1.00), the latter referring to the epithelial phenotype. Cell cycle activity was assessed using immunohistochemistry of the proliferation marker Ki67, and mutation analysis was conducted for KRAS and APC to determine the involvement of the adenoma-carcinoma sequence. Results Juvenile polyps with a SMAD4 germline mutation were predominantly type B, whereas, type A was more common among juvenile polyps with a BMPR1A germline mutation, but this distinction could not be ascribed to differences in cell cycle activity. Dysplasia was equally common in JPS polyps with either a SMAD4 or BMPR1A germline mutation, where the involvement of the adenoma-carcinoma sequence does not seem to play a distinct role. Conclusion juvenile polyps in the setting of JPS exhibit distinct phenotypes correlating with the underlying genetic defect. PMID:21412070

Is the presence of 6 or fewer crypt apoptotic bodies sufficient for diagnosis of graft versus host disease? A decade of experience at a single institution.

PubMed

Lin, Jingmei; Fan, Rong; Zhao, Zijin; Cummings, Oscar W; Chen, Shaoxiong

2013-04-01

Histopathology assessment is crucial for the diagnosis of graft versus host disease (GVHD), as the presence of crypt apoptosis is the cardinal criterion required. However, crypt apoptosis is not limited to GVHD; it also occurs in other conditions such as infection, drug reaction, or inflammatory reactions unrelated to GVHD. To better determine whether the presence of 6 or fewer apoptotic bodies is sufficient for the diagnosis of GVHD, we retrospectively reviewed 78 colon biopsies from 66 patients who received either hematopoietic stem cell (HSCT) or cord blood cell transplantation and whose colon biopsies exhibited apoptotic bodies. Among them, 41 cases contained 6 or fewer apoptotic bodies in the colon biopsy. These biopsies were compared with 141 colon biopsy controls that showed no significant pathologic changes as well as 16 colon biopsies with cytomegalovirus colitis from patients without a history of bone marrow transplantation. Among the 41 cases reviewed, 7 patients had coexisting GVHD in other organs (skin or liver). However, gastrointestinal symptoms of at least 4 HSCT patients whose colon biopsies contained 6 or fewer apoptotic bodies completely resolved in the absence of further intervention for GVHD. The discrepancy between pathologic findings and the clinical course may be due to confounding factors, such as infection or medication-induced injury. Our data suggest that identifying 6 or fewer crypt apoptotic bodies in colon biopsies from HSCT patients is worth reporting in order to alert the clinicians of the possibility of GVHD but not sufficient to render a diagnosis on the pathologic grounds alone. The colon biopsies containing 6 or fewer apoptotic bodies represent a heterogenous group. We suggest this group to be classified as indeterminate for GVHD, instead of diagnosing GVHD outright. Synthesis of all clinical, endoscopic, and pathologic information, including the status of infection, coexisting GVHD involvement in the other organs, and medication, is essential for confirmation of the diagnosis of GVHD.

ADAM10 regulates Notch function in intestinal stem cells of mice.

PubMed

Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

2014-10-01

A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Plum polyphenols inhibit colorectal aberrant crypt foci formation in rats: potential role of the miR-143/protein kinase B/mammalian target of rapamycin axis.

PubMed

Banerjee, Nivedita; Kim, Hyemee; Talcott, Stephen T; Turner, Nancy D; Byrne, David H; Mertens-Talcott, Susanne U

2016-10-01

The nutritional prevention of aberrant crypt foci by polyphenols may be a crucial step to dietary cancer prevention. The objective of this study was to determine the underlying mechanisms that contribute to the anti-inflammatory and antitumorigenic properties of plum (Prunus salicina L.) polyphenols, including chlorogenic acid and neochlorogenic acid, in azoxymethane (AOM)-treated rats. The hypothesis was that plum polyphenolics suppress AOM-induced aberrant crypt foci formation through alterations in the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and relative micro-RNA expressions. Sprague-Dawley rats (n=10/group) received plum beverage (1346mg gallic acid equivalents/L) or a control beverage ad libitum for 10 weeks with subcutaneous injections of AOM (15mg/kg) at weeks 2 and 3. Results show that the consumption of the plum beverage decreased the number of dysplastic aberrant crypt foci by 48% (P<.05) and lowered proliferation of mucosal cells by 24% (P<.05). The plum beverage decreased the activity of glutathione peroxidase, superoxide dismutase, and catalase in mucosal scrapings, as well as the superoxide dismutase activity in serum. The results were accompanied by a down-regulation of proinflammatory enzymes nuclear factor κB, nitric oxide synthase, cyclooxygenase-2, and vascular cell adhesion molecule 1 messenger RNA. Plum inhibited the expression of AKT and mTOR messenger RNA, phosphorylated AKT, mTOR, and hypoxia-inducible factor-1α protein levels, and the ratio of the phosphorylated/total protein expression of mTOR. Also, the plum beverage increased the expression of miR-143, which is involved in the regulation of AKT. These results suggest that plum polyphenols may exhibit a chemopreventive potential against colon carcinogenesis by impacting the AKT/mTOR pathway and miR-143. Copyright © 2016 Elsevier Inc. All rights reserved.

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

PubMed

Torlakovic, Emina Emilia; Gomez, Jose D; Driman, David K; Parfitt, Jeremy R; Wang, Chang; Benerjee, Tama; Snover, Dale C

2008-01-01

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, chi test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to "ectopic crypts" and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between SSA and TSA, because these architectural abnormalities may well be a reflection of abnormalities in genetically programmed mucosal development.

Comparisons of lanthanide/actinide +2 ions in a tris(aryloxide)arene coordination environment† †Electronic supplementary information (ESI) available: Additional computational details, spectroscopic information, crystallographic data collection, structure solution, and refinement (PDF), X-ray diffraction details of compounds 1-Ln (Ln = Nd, Gd, Dy, and Er), 2-Nd, 2-Ln/3-Ln (Ln = Gd, Dy, Er), 2-Dy/4-Dy, and 5-Dy/6-Dy. CCDC (CIF, 1538987–1538995 and 1566075 for 2-Dy/3-Dy), and DFT-optimized structural coordinates for 2-Nd and 2-Gd. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc02337e Click here for additional data file. Click here for additional data file. Click here for additional data file.

PubMed Central

Fieser, Megan E.; Palumbo, Chad T.; La Pierre, Henry S.; Halter, Dominik P.; Voora, Vamsee K.; Ziller, Joseph W.

2017-01-01

A new series of Ln3+ and Ln2+ complexes has been synthesized using the tris(aryloxide)arene ligand system, ((Ad,MeArO)3mes)3–, recently used to isolate a complex of U2+. The triphenol precursor, (Ad,MeArOH)3mes, reacts with the Ln3+ amides, Ln(NR2)3 (R = SiMe3), to form a series of [((Ad,MeArO)3mes)Ln] complexes, 1-Ln. Crystallographic characterization was achieved for Ln = Nd, Gd, Dy, and Er. The complexes 1-Ln can be reduced with potassium graphite in the presence of 2.2.2-cryptand (crypt) to form highly absorbing solutions with properties consistent with Ln2+ complexes, [K(crypt)][((Ad,MeArO)3mes)Ln], 2-Ln. The synthesis of the Nd2+ complex [K(crypt)][((Ad,MeArO)3mes)Nd], 2-Nd, was unambiguously confirmed by X-ray crystallography. In the case of the other lanthanides, crystals were found to contain mixtures of 2-Ln co-crystallized with either a Ln3+ hydride complex, [K(crypt)][((Ad,MeArO)3mes)LnH], 3-Ln, for Ln = Gd, Dy, and Er, or a hydroxide complex, [K(crypt)][((Ad,MeArO)3mes)Ln(OH)], 4-Ln, for Ln = Dy. A Dy2+ complex with 18-crown-6 as the potassium chelator, [K(18-crown-6)(THF)2][((Ad,MeArO)3mes)Dy], 5-Dy, was isolated as a co-crystallized mixture with the Dy3+ hydride complex, [K(18-crown-6)(THF)2][((Ad,MeArO)3mes)DyH], 6-Dy. Structural comparisons of 1-Ln and 2-Ln are presented with respect to their uranium analogs and correlated with density functional theory calculations on their electronic structures. PMID:29163894

Effect of glycine and glucose on sodium and water absorption in patients with cholera

PubMed Central

Nalin, D. R.; Cash, R. A.; Rahman, M.; Yunus, Md.

1970-01-01

Electrolyte solutions containing glucose, glycine, or a combination of the two were absorbed sufficiently well from the intestine to supply maintenance fluid and the electrolytes required by cholera patients. Data on net absorption and duration and volume of diarrhoea show that a solution containing both glucose and glycine provides more effective therapy than solutions containing either glucose or glycine alone. PMID:5473608

Cycle simulation of the low-temperature triple-effect absorption chiller with vapor compression unit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J.S.; Lee, H.

1999-07-01

The construction of a triple-effect absorption chiller machine using the lithium bromide-water solution as a working fluid is strongly limited by corrosion problems caused by the high generator temperature. In this work, three new cycles having the additional vapor compression units were suggested in order to lower the generator temperature of a triple-effect absorption chiller. Each new cycle has one compressor located at the different position which was used to elevate the pressure of the refrigerant vapor. Computer simulations were carried out in order to examine both the basic triple-effect cycle and three new cycles. All types of triple-effect absorptionmore » chiller cycles were found to be able to lower the temperature of high-temperature generator to the more favorable operation range. The COPs of three cycles calculated by considering the additional compressor works showed a small level of decrease or increase compared with that of the basic triple-effect cycle. Consequently, a low-temperature triple-effect absorption chiller can be possibly constructed by adapting one of three new cycles. A great advantage of these new cycles over the basic one is that the conventionally used lithium bromide-water solution can be successfully used as a working fluid without the danger of corrosion.« less

CFTR is restricted to a small population of high expresser cells that provide a forskolin-sensitive transepithelial Cl- conductance in the proximal colon of the possum, Trichosurus vulpecula.

PubMed

Fan, Shujun; Harfoot, Natalie; Bartolo, Ray C; Butt, A Grant

2012-04-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is central to anion secretion in both the possum and eutherian small intestine. Here, we investigated its role in the possum proximal colon, which has novel transport properties compared with the eutherian proximal colon. Despite considerable CFTR expression, high doses of the CFTR activator forskolin (EC(50)≈10 μmol l(-1)) were required for a modest, CFTR-dependent increase in short-circuit current (I(sc)) in the proximal colon. Presumably, this is because CFTR is restricted to the apical membrane of a small population of CFTR high expresser (CHE) cells in the surface and upper crypt epithelium. Furthermore, although the forskolin-stimulated I(sc) was dependent on serosal Na(+), Cl(-) and HCO(3)(-), consistent with anion secretion, inhibition of the basolateral Na-K-2Cl(-) (NKCC1) or Na-HCO(3) (pNBCe1) cotransporters did not prevent it. Therefore, although NKCC1 and pNBCe1 are expressed in the colonic epithelium they do not appear to be expressed in CHE cells. At low doses (IC(50)≈1 μmol l(-1)), forskolin also decreased the transepithelial conductance (G(T)) of the colon through inhibition of a 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid-sensitive anion conductance in the basolateral membrane of the CHE cells. This conductance is arranged in series with CFTR in the CHE cells and, therefore, the CHE cells provide a transepithelial Cl(-) conductance for passive Cl(-) absorption across the epithelium. Inhibition of the basolateral Cl(-) conductance of the CHE cells by forskolin will inhibit Na(+) absorption by restricting the movement of its counter-ion Cl(-), assisting in the conversion of the tissue from an absorptive to a secretory state.

Absorption heat pump system

DOEpatents

Grossman, Gershon; Perez-Blanco, Horacio

1984-01-01

An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

Absorption-heat-pump system

DOEpatents

Grossman, G.; Perez-Blanco, H.

1983-06-16

An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

Extrinsic extinction cross-section in the multiple acoustic scattering by fluid particles

NASA Astrophysics Data System (ADS)

Mitri, F. G.

2017-04-01

Cross-sections (and their related energy efficiency factors) are physical parameters used in the quantitative analysis of different phenomena arising from the interaction of waves with a particle (or multiple particles). Earlier works with the acoustic scattering theory considered such quadratic (i.e., nonlinear) quantities for a single scatterer, although a few extended the formalism for a pair of scatterers but were limited to the scattering cross-section only. Therefore, the standard formalism applied to viscous particles is not suitable for the complete description of the cross-sections and energy balance of the multiple-particle system because both absorption and extinction phenomena arise during the multiple scattering process. Based upon the law of the conservation of energy, this work provides a complete comprehensive analysis for the extrinsic scattering, absorption, and extinction cross-sections (i.e., in the far-field) of a pair of viscous scatterers of arbitrary shape, immersed in a nonviscous isotropic fluid. A law of acoustic extinction taking into consideration interparticle effects in wave propagation is established, which constitutes a generalized form of the optical theorem in multiple scattering. Analytical expressions for the scattering, absorption, and extinction cross-sections are derived for plane progressive waves with arbitrary incidence. The mathematical expressions are formulated in partial-wave series expansions in cylindrical coordinates involving the angle of incidence, the addition theorem for the cylindrical wave functions, and the expansion coefficients of the scatterers. The analysis shows that the multiple scattering cross-section depends upon the expansion coefficients of both scatterers in addition to an interference factor that depends on the interparticle distance. However, the extinction cross-section depends on the expansion coefficients of the scatterer located in a particular system of coordinates, in addition to the interference term. Numerical examples illustrate the analysis for two viscous fluid circular cylindrical cross-sections immersed in a non-viscous fluid. Computations for the (non-dimensional) scattering, absorption, and extinction cross-section factors are performed with particular emphasis on varying the angle of incidence, the interparticle distance, and the sizes, and the physical properties of the particles. A symmetric behavior is observed for the dimensionless multiple scattering cross-section, while asymmetries arise for both the dimensionless absorption and extinction cross-sections with respect to the angle of incidence. The present analysis provides a complete analytical and computational method for the prediction of cross-section and energy efficiency factors in multiple acoustic scattering of plane waves of arbitrary incidence by a pair of scatterers. The results can be used as a priori information in the direct or inverse characterization of multiple scattering systems such as acoustically engineered fluid metamaterials with reconfigurable periodicities, cloaking devices, liquid crystals, and other applications.

Transmissible Gastroenteritis in Feeder Pigs: Observations on the Jejunal Epithelium of Normal Feeder Pigs and Feeder Pigs Infected with TGE Virus

PubMed Central

Morin, M.; Morehouse, L. G.

1974-01-01

Light and electron microscopy findings in the jejunal mucosa of the normal feeder pig and feeder pigs infected with transmissible gastroenteritis (TGE) virus are reported. Villi in the mid jejunum of the normal feeder pig were elongated, finger shaped and covered with a layer of columnar absorptive cells with a well developed and regular brush border. Severe lesions of villous atrophy were present in all jejunal segments of feeder swine killed 96 hours post infection with TGE virus. Atrophic villi were covered by flat to cuboidal cells with a poorly developed brush border in some areas. In other segments, cells varied in appearance from sub-columnar to columnar type of near normal appearance. The ultrastructure of the jejunal absorptive cells in the normal feeder pig was found to be similar to that described for the jejunal cells of other adult mammals. There were no significant indications of high pinocytotic activity. The epithelial cells covering the atrophic villi of TGE infected pigs had a fine structure similar to that described for the crypt cells, ranging in appearance from very immature to moderately differentiated cells. Microvilli were very short, decreased markedly in number and irregular in arrangement. The terminal web was poorly developed. Strands of rough endoplasmic reticulum were markedly diminished and an increase in free ribosomes was noted. The significance of these observations in explaining pathogenesis of TGE in feeder pigs is discussed. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8. PMID:4277743

[Effects of glucagon-like peptide 2 on the adaptation of residual small bowel in a rat model of short bowel syndrome].

PubMed

Wu, Guo-Hao; Chen, Ji; Li, Hang; Wu, Zhao-Han

2006-09-01

To investigate the effects of glucagon-like peptide 2 (GLP-2) on the morphology and functional adaptation of the residual small bowel in rat model of short bowel syndrome. Twenty rats with 75% of the midjejunoileum removed were randomly divided into two groups, and received intra-peritoneal injection of GLP-2(250 micro*gd*kg-1*d-1) or subcutaneous injection saline(0.5 ml, twice one day) after operation. On postoperative day 6, the morphological changes of the residual jejunum and ileum, the expression of proliferating cell nuclear antigen(PCNA), and the mRNA expressions of Na-D-glucose cotransporters (SGLT1) and peptide cotransporters (PEPT1) were determined. The intestinal glucose absorption data per unit length as well as per unit weight of ileum were measured by in vivo circulatory perfusion experiment. The morphological parameters of the residual gut such as the thickness of mucosa, height of villus, depth of crypt, and PCNA positive index were significantly higher, while the apoptosis rate per unit of mucosal square was significantly lower in GLP-2 treatment group than those in the control group. The expressions of mRNA SGTLl and PEPT1 in the residual ileum were significantly higher than those in the control group. There was no significant difference in glucose absorption rate per gram of mucosal wet weight between the two groups (P > 0.05). GLP-2 could improve morphological and functional adaptation of the residual small bowel by stimulating enterocyte proliferation and decreasing enterocyte apoptosis in short bowel syndrome.

Study to define behavior of liquid lubricants in an elastohydrodynamic contact

NASA Technical Reports Server (NTRS)

Lauer, J. L.

1974-01-01

The spectra of an ester and a saturated hydrocarbon polymer were obtained at pressures ranging from ambient to 2 GN/sq m (20 kilobar) and at temperatures between ambient and 180 C in absorption and between 150 C and 210 C in emission. To simulate contact conditions the fluids were contained in the tiny sample volume of a diamond cell, i.e., the hole in a metal spacer separating two diamonds pressed against each other in a nut crackerlike arrangement. Pressures could be deduced from bandshifts and states of aggregation from bandwidths in the fluorescence spectrum of a ruby crystal immersed in the fluids. An infrared Fourier transform spectrometer was used with attachments specially designed to analyze the radiation passed through the sample and both diamonds (absorption technique) or the radiation emanating from the heated sample and passing through only one diamond (emission technique). The latter technique is applicable to operating EHD contacts. Spectral changes pointing to possible glass transitions and composition changes were observed. Emission and absorption spectra were generally equivalent. Some emission bandshapes appear to be temperature sensitive enough to be useful as internal temperature probes.

Artificial sweat enhances dermal transfer of chlorpyrifos from treated nylon carpet fibers.

PubMed

Williams, Ryan L; Reifenrath, William G; Krieger, Robert I

2005-01-01

The dermal transfer and absorption of 14C-ring-chlorpyrifos from nylon carpet fibers was measured in skin penetration-evaporation cells with excised pig skin. Prior to application, synthetic sweat was applied to skin in half of the cells. Radioactivity was measured in receptor fluid, dermis, epidermis, tape stripping samples, and vapor trap samples during a 24-h period. The sum of radiolabel recovered from the dermis and receptor fluid represented the absorbed dose. There was no significant difference (p > 0.05) in percutaneous absorption between cells that received the synthetic sweat application and "dry" cells (1.3 +/- 0.3% of applied dose). There was significantly more (p < 0.05) radiolabel recovered from tape stripping (5.4 +/- 2.1 vs. 2.8 +/- 0.6%) and in the epidermis (4.5 +/- 0.8 vs. 3.1 +/- 0.3%) from cells that received the synthetic sweat application, which indicated synthetic sweat facilitated transfer of chlorpyrifos from a treated substrate to the skin surface. The measured value for percutaneous absorption of chlorpyrifos agreed with the value predicted from an empirical model previously developed for nitro compound-containing soil.

Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon.

PubMed

Mereto, E; Ghia, M; Brambilla, G

1996-03-19

Anthraquinone glycosides of Senna and Cascara were investigated for their ability to induce aberrant crypt foci (ACF) in the rat colon mucosa, which are considered putative preneoplastic lesions. Dietary exposure to high doses of these glycosides for 56 successive days did not cause the appearance of ACF or increase in incidence of ACF induced by 1,2-dimethyl-hydrazine (DMH). However, in rats treated with both DMH and the highest dose of glycosides, the average number of aberrant crypts per focus, considered a consistent predictor of tumor outcome, was higher than in rats given DMH alone. These findings suggest that Senna and Cascara glycoside might behave as weak promoters in rat colon carcinogenesis.

Fatal winter dysentery with severe anemia in an adult cow.

PubMed

Natsuaki, Sumiko; Goto, Keiichi; Nakamura, Kikuyasu; Yamada, Manabu; Ueo, Hiroshi; Komori, Toshihiro; Shirakawa, Hitomi; Uchinuno, Yukinori

2007-09-01

An adult dairy cow fatally affected with winter dysentery was investigated pathologically and virologically. The cow had severe anemia and diarrhea with massive blood. Pathologically, the loss of surface epithelial cells and necrosis of crypt epithelial cells in the large intestine were observed. Bovine coronavirus (BCV) antigen was observed in necrotic crypt epithelial cells of the large intestine. Virus particles were found in the necrotic epithelial cells of the large intestine. Virologically, BCV was isolated from the feces of the dead cow. The dead cow had no serum antibody against BCV although the co-habitants did. These suggest that severe infection of BCV in the cow without the BCV antibody accompanied by severe hemorrhagic anemia resulted in the cow's death.

Generation of energy

DOEpatents

Kalina, Alexander I.

1984-01-01

A method of generating energy which comprises utilizing relatively lower temperature available heat to effect partial distillation of at least portion of a multicomponent working fluid stream at an intermediate pressure to generate working fluid fractions of differing compositions. The fractions are used to produce at least one main rich solution which is relatively enriched with respect to the lower boiling component, and to produce at least one lean solution which is relatively improverished with respect to the lower boiling component. The pressure of the main rich solution is increased whereafter it is evaporated to produce a charged gaseous main working fluid. The main working fluid is expanded to a low pressure level to release energy. The spent low pressure level working fluid is condensed in a main absorption stage by dissolving with cooling in the lean solution to regenerate an initial working fluid for reuse.

Concomitant bidirectional transport during peritoneal dialysis can be explained by a structured interstitium

PubMed Central

Waniewski, Jacek; Flessner, Michael F.; Lindholm, Bengt

2016-01-01

Clinical and animal studies suggest that peritoneal absorption of fluid and protein from dialysate to peritoneal tissue, and to blood and lymph circulation, occurs concomitantly with opposite flows of fluid and protein, i.e., from blood to dialysate. However, until now a theoretical explanation of this phenomenon has been lacking. A two-phase distributed model is proposed to explain the bidirectional, concomitant transport of fluid, albumin and glucose through the peritoneal transport system (PTS) during peritoneal dialysis. The interstitium of this tissue is described as an expandable two-phase structure with phase F (water-rich, colloid-poor region) and phase C (water-poor, colloid-rich region) with fluid and solute exchange between them. A low fraction of phase F is assumed in the intact tissue, which can be significantly increased under the influence of hydrostatic pressure and tissue hydration. The capillary wall is described using the three-pore model, and the conditions in the peritoneal cavity are assumed commencing 3 min after the infusion of glucose 3.86% dialysis fluid. Computer simulations demonstrate that peritoneal absorption of fluid into the tissue, which occurs via phase F at the rate of 1.8 ml/min, increases substantially the interstitial pressure and tissue hydration in both phases close to the peritoneal cavity, whereas the glucose-induced ultrafiltration from blood occurs via phase C at the rate of 15 ml/min. The proposed model delineating the phenomenon of concomitant bidirectional transport through PTS is based on a two-phase structure of the interstitium and provides results in agreement with clinical and experimental data. PMID:26945084

Transmission loss of orthogonally rib-stiffened double-panel structures with cavity absorption.

PubMed

Xin, F X; Lu, T J

2011-04-01

The transmission loss of sound through infinite orthogonally rib-stiffened double-panel structures having cavity-filling fibrous sound absorptive materials is theoretically investigated. The propagation of sound across the fibrous material is characterized using an equivalent fluid model, and the motions of the rib-stiffeners are described by including all possible vibrations, i.e., flexural displacements, bending, and torsional rotations. The effects of fluid-structure coupling are account for by enforcing velocity continuity conditions at fluid-panel interfaces. By taking full advantage of the periodic nature of the double-panel, the space-harmonic approach and virtual work principle are applied to solve the sets of resultant governing equations, which are eventually truncated as a finite system of simultaneous algebraic equations and numerically solved insofar as the solution converges. To validate the proposed model, a comparison between the present model predictions and existing numerical and experimental results for a simplified version of the double-panel structure is carried out, with overall agreement achieved. The model is subsequently employed to explore the influence of the fluid-structure coupling between fluid in the cavity and the two panels on sound transmission across the orthogonally rib-stiffened double-panel structure. Obtained results demonstrate that this fluid-structure coupling affects significantly sound transmission loss (STL) at low frequencies and cannot be ignored when the rib-stiffeners are sparsely distributed. As a highlight of this research, an integrated optimal algorithm toward lightweight, high-stiffness and superior sound insulation capability is proposed, based on which a preliminary optimal design of the double-panel structure is performed.

Eldercare at Home: Constipation

MedlinePlus

... much bran too quickly may cause diarrhea, excess gas (flatus), stomach cramps, and reduce absorption into the body of certain vitamins. Drink plenty of water Liquids like water and juice add fluid to the ...

The Influence of Body Position on Cerebrospinal Fluid Pressure Gradient and Movement in Cats with Normal and Impaired Craniospinal Communication

PubMed Central

Radoš, Milan; Erceg, Gorislav; Petošić, Antonio; Jurjević, Ivana

2014-01-01

Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension. PMID:24748150

Modeling of Ti-W Solidification Microstructures Under Additive Manufacturing Conditions

NASA Astrophysics Data System (ADS)

Rolchigo, Matthew R.; Mendoza, Michael Y.; Samimi, Peyman; Brice, David A.; Martin, Brian; Collins, Peter C.; LeSar, Richard

2017-07-01

Additive manufacturing (AM) processes have many benefits for the fabrication of alloy parts, including the potential for greater microstructural control and targeted properties than traditional metallurgy processes. To accelerate utilization of this process to produce such parts, an effective computational modeling approach to identify the relationships between material and process parameters, microstructure, and part properties is essential. Development of such a model requires accounting for the many factors in play during this process, including laser absorption, material addition and melting, fluid flow, various modes of heat transport, and solidification. In this paper, we start with a more modest goal, to create a multiscale model for a specific AM process, Laser Engineered Net Shaping (LENS™), which couples a continuum-level description of a simplified beam melting problem (coupling heat absorption, heat transport, and fluid flow) with a Lattice Boltzmann-cellular automata (LB-CA) microscale model of combined fluid flow, solute transport, and solidification. We apply this model to a binary Ti-5.5 wt pct W alloy and compare calculated quantities, such as dendrite arm spacing, with experimental results reported in a companion paper.

ABSIM. Simulation of Absorption Systems in Flexible and Modular Form

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grossman, G.

1994-06-01

The computer code has been developed for simulation of absorption systems at steady-state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system`s components. When all the equations have been established, a mathematical solver routine is employed to solve them simultaneously. Property subroutines contained in a separate data base serve to provide thermodynamic properties of the working fluids. The code is user-oriented and requires a relatively simple input containing the given operating conditions and the working fluid atmore » each state point. the user conveys to the computer an image of the cycle by specifying the different components and their interconnections. Based on this information, the program calculates the temperature, flowrate, concentration, pressure and vapor fraction at each state point in the system and the heat duty at each unit, from which the coefficient of performance may be determined. A graphical user-interface is provided to facilitate interactive input and study of the output.« less

ABSIM. Simulation of Absorption Systems in Flexible and Modular Form

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grossman, G.

1994-06-01

The computer code has been developed for simulation of absorption systems at steady-state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system's components. When all the equations have been established, a mathematical solver routine is employed to solve them simultaneously. Property subroutines contained in a separate data base serve to provide thermodynamic properties of the working fluids. The code is user-oriented and requires a relatively simple input containing the given operating conditions and the working fluid atmore » each state point. the user conveys to the computer an imagev of the cycle by specifying the different components and their interconnections. Based on this information, the program calculates the temperature, flowrate, concentration, pressure and vapor fraction at each state point in the system and the heat duty at each unit, from which the coefficient of performance may be determined. A graphical user-interface is provided to fcilitate interactive input and study of the output.« less

Bicarbonate absorption stimulates active calcium absorption in the rat proximal tubule.

PubMed Central

Bomsztyk, K; Calalb, M B

1988-01-01

To evaluate the effect of luminal bicarbonate on calcium reabsorption, rat proximal tubules were perfused in vivo. Perfusion solution contained mannitol to reduce water flux to zero. Total Ca concentration was measured by atomic absorption spectrometry, Ca ion concentration in the tubule lumen (CaL2+) and the peritubular capillary (CaP2+), and luminal pH (pHL) with ion-selective microelectrodes and transepithelial voltage (VTE) with conventional microelectrodes. When tubules were perfused with buffer-free Cl-containing solution, net Ca absorption (JCa) averaged 3.33 pmol/min. Even though VTE was 1.64 mV lumen-positive, CaL2+, 1.05 mM, did not fall below the concentration in the capillary blood, 1.07 mM. When 27 mM of Cl was replaced with HCO3, there was luminal fluid acidification. Despite a decrease in VTE and CaL2+, JCa increased to 7.13 pmol/min, indicating that the enhanced JCa could not be accounted for by the reduced electrochemical gradient, delta CCa. When acetazolamide or an analogue of amiloride was added to the HCO3 solution, JCa was not different from the buffer-free solution, suggesting that HCO3-stimulated JCa may be linked to acidification. To further test this hypothesis, we used 27 mM Hepes as the luminal buffer. With Hepes there was luminal fluid acidification and JCa was not different from the buffer-free solution but delta CCa was significantly reduced, indicating enhanced active calcium transport. We conclude from the results of the present study that HCO3 stimulates active Ca absorption, a process that may be linked to acidification-mediated HCO3 absorption. PMID:3366902

Role of aquaporin and sodium channel in pleural water movement.

PubMed

Jiang, Jinjun; Hu, Jie; Bai, Chunxue

2003-12-16

The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or isosmolar fluid was infused into the pleural space in anesthetized wildtype and AQP1 null mice. Pleural fluid was sampled at specified times to quantify the osmolality and volume. The sodium channel activator terbutaline increased isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride decreased it by 15%, but had no effect on osmotically driven water transport. AQP1 deletion significantly decreased osmotic water transport in pleural space by twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous injection of HgCl2 decreased osmotic pleural water movement by 43%. These results provided evidence for a role of a sodium channel in pleural fluid absorption; AQP1 plays a major role in osmotic liquid transport but it does not affect isosmolar fluid clearance.

Fluid dynamic modelling of renal pelvic pressure during endoscopic stone removal

NASA Astrophysics Data System (ADS)

Oratis, Alexandros; Subasic, John; Bird, James; Eisner, Brian

2015-11-01

Endoscopic kidney stone removal procedures are known to increase internal pressure in the renal pelvis, the kidney's urinary collecting system. High renal pelvic pressure incites systemic absorption of irrigation fluid, which can increase the risk of postoperative fever and sepsis or the unwanted absorption of electrolytes. Urologists choose the appropriate surgical procedure based on patient history and kidney stone size. However, no study has been conducted to compare the pressure profiles of each procedure, nor is there a precise sense of how the renal pelvic pressure scales with various operational parameters. Here we develop physical models for the flow rates and renal pelvic pressure for various procedures. We show that the results of our models are consistent with existing urological data on each procedure and that the models can predict pressure profiles where data is unavailable.

Bioavailability of Tetracycline and Doxycycline in Fasted and Nonfasted Subjects

PubMed Central

Welling, Peter G.; Koch, Patricia A.; Lau, Curtis C.; Craig, William A.

1977-01-01

The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline. PMID:856000

Absorption heat pump for space applications

NASA Technical Reports Server (NTRS)

Nguyen, Tuan; Simon, William E.; Warrier, Gopinath R.; Woramontri, Woranun

1993-01-01

In the first part, the performance of the Absorption Heat Pump (AHP) with water-sulfuric acid and water-magnesium chloride as two new refrigerant-absorbent fluid pairs was investigated. A model was proposed for the analysis of the new working pairs in a heat pump system, subject to different temperature lifts. Computer codes were developed to calculate the Coefficient of Performance (COP) of the system with the thermodynamic properties of the working fluids obtained from the literature. The study shows the potential of water-sulfuric acid as a satisfactory replacement for water-lithium bromide in the targeted temperature range. The performance of the AHP using water-magnesium chloride as refrigerant-absorbent pair does not compare well with those obtained using water-lithium bromide. The second part concentrated on the design and testing of a simple ElectroHydrodynamic (EHD) Pump. A theoretical design model based on continuum electromechanics was analyzed to predict the performance characteristics of the EHD pump to circulate the fluid in the absorption heat pump. A numerical method of solving the governing equations was established to predict the velocity profile, pressure - flow rate relationship and efficiency of the pump. The predicted operational characteristics of the EHD pump is comparable to that of turbomachinery hardware; however, the overall efficiency of the electromagnetic pump is much lower. An experimental investigation to verify the numerical results was conducted. The pressure - flow rate performance characteristics and overall efficiency of the pump obtained experimentally agree well with the theoretical model.

Integrating sphere-based photoacoustic setup for simultaneous absorption coefficient and Grüneisen parameter measurements of biomedical liquids

NASA Astrophysics Data System (ADS)

Villanueva, Yolanda; Hondebrink, Erwin; Petersen, Wilma; Steenbergen, Wiendelt

2015-03-01

A method for simultaneously measuring the absorption coefficient μa and Grüneisen parameter Γ of biological absorbers in photoacoustics is designed and implemented using a coupled-integrating sphere system. A soft transparent tube with inner diameter of 0.58mm is used to mount the liquid absorbing sample horizontally through the cavity of two similar and adjacent integrating spheres. One sphere is used for measuring the sample's μa using a continuous halogen light source and a spectrometer fiber coupled to the input and output ports, respectively. The other sphere is used for simultaneous photoacoustic measurement of the sample's Γ using an incident pulsed light with wavelength of 750nm and a flat transducer with central frequency of 5MHz. Absolute optical energy and pressure measurements are not necessary. However, the derived equations for determining the sample's μa and Γ require calibration of the setup using aqueous ink dilutions. Initial measurements are done with biological samples relevant to biomedical imaging such as human whole blood, joint and cyst fluids. Absorption of joint and cyst fluids is enhanced using a contrast agent like aqueous indocyanine green dye solution. For blood sample, measured values of μa = 0.580 +/- 0.016 mm-1 and Γ = 0.166 +/- 0.006 are within the range of values reported in literature. Measurements with the absorbing joint and cyst fluid samples give Γ values close to 0.12, which is similar to that of water and plasma.

Colonic stem cell data are consistent with the immortal model of stem cell division under non-random strand segregation.

PubMed

Walters, K

2009-06-01

Colonic stem cells are thought to reside towards the base of crypts of the colon, but their numbers and proliferation mechanisms are not well characterized. A defining property of stem cells is that they are able to divide asymmetrically, but it is not known whether they always divide asymmetrically (immortal model) or whether there are occasional symmetrical divisions (stochastic model). By measuring diversity of methylation patterns in colon crypt samples, a recent study found evidence in favour of the stochastic model, assuming random segregation of stem cell DNA strands during cell division. Here, the effect of preferential segregation of the template strand is considered to be consistent with the 'immortal strand hypothesis', and explore the effect on conclusions of previously published results. For a sample of crypts, it is shown how, under the immortal model, to calculate mean and variance of the number of unique methylation patterns allowing for non-random strand segregation and compare them with those observed. The calculated mean and variance are consistent with an immortal model that incorporates non-random strand segregation for a range of stem cell numbers and levels of preferential strand segregation. Allowing for preferential strand segregation considerably alters previously published conclusions relating to stem cell numbers and turnover mechanisms. Evidence in favour of the stochastic model may not be as strong as previously thought.

Oleuropein Prevents Azoxymethane-Induced Colon Crypt Dysplasia and Leukocytes DNA Damage in A/J Mice.

PubMed

Sepporta, Maria Vittoria; Fuccelli, Raffaela; Rosignoli, Patrizia; Ricci, Giovanni; Servili, Maurizio; Fabiani, Roberto

2016-08-19

Previous studies have shown that the precursor of olive oil secoiridoids, Oleuropein (OL) has several in vitro chemopreventive properties. OL inhibits proliferation and induces apoptosis in breast, thyroid, prostate, and colorectal cancer (CRC) cells. Much less is known about the effects of OL on animal models of carcinogenesis. In this study, we investigated the ability of OL to prevent the azoxymethane (AOM)-induced colon cancer upset and DNA damage in mice. Animals, fed with a basal diet either enriched or not with OL (125 mg/kg), were injected with AOM (10 mg/kg, once a week for 6 weeks) and sacrificed after either 7 weeks for histological analysis of colon crypt dysplasia and evaluation of DNA damage in leukocytes or 17 weeks for counting the macroscopically observable colon tumors. An OL-enriched diet prevented the AOM-induced preneoplastic lesions in different colon segments, reducing the severity of crypt dysplasia and DNA damage in peripheral leukocytes. In addition, OL significantly reduced the AOM-induced tumor incidence from 57% to 14% (P < .05, chi-square test) in the medial colon segment. This study shows that OL is able to prevent CRC and DNA damage in mice treated with the carcinogen AOM. These results stimulate further human cancer prevention studies with OL-enriched food supplements that are actually available on the market.

Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis.

PubMed

Brown, Jeffrey B; Lee, Goo; Managlia, Elizabeth; Grimm, Gery R; Dirisina, Ramanarao; Goretsky, Tatiana; Cheresh, Paul; Blatner, Nichole R; Khazaie, Khashayarsha; Yang, Guang-Yu; Li, Linheng; Barrett, Terrence A

2010-02-01

Mesalamine is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) in which condition it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that mesalamine reduces beta-catenin-associated progenitor cell activation, Akt-phosphorylated beta-catenin(Ser552) (P-beta-catenin), and colitis-induced dysplasia (CID). Effects of mesalamine on P-beta-catenin staining and function were assessed by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in biopsy specimens of CUC in mild or "refractory" severe mucosal inflammation. Effects of mesalamine on epithelial proliferation and activation of Akt and beta-catenin were assessed in interleukin (IL)-10(-/-) colitis and CID by immunohistochemistry and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon. Data from IL-10(-/-) and human colitis samples show that mesalamine reduced Akt activation and P-beta-catenin levels in the middle and upper crypt. Reductions in P-beta-catenin in CUC biopsy specimens with severe inflammation suggested that mesalamine reduced P-beta-catenin levels in tissue refractory to mesalamine's anti-inflammatory effects. In IL-10(-/-) mice, mesalamine reduced CID concordant with inhibition of crypt Akt and beta-catenin signaling. The results are consistent with the model that mesalamine contributes to chemoprevention in CAC by reducing beta-catenin signaling within intestinal progenitors.

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine.

PubMed

Muglia, C; Mercer, N; Toscano, M A; Schattner, M; Pozner, R; Cerliani, J P; Gobbi, R Papa; Rabinovich, G A; Docena, G H

2011-05-26

Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1(-/-)) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1(-/-) mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function.

Study of dynamic emission spectra from lubricant films in an elastohydrodynamic contact using Fourier transform spectroscopy

NASA Technical Reports Server (NTRS)

Lauer, J. L.

1978-01-01

Infrared emission spectra were obtained through a diamond window from lubricating fluids in an operating sliding elastohydrodynamic contact and analyzed by comparison with static absorption spectra under similar pressures. Different loads, shear rates and temperatures were used. Most of the spectra exhibited polarization characteristics, indicating directional alignment of the lubricant in the EHD contact. Among the fluids studied were a "traction" fluid, an advanced ester, and their mixtures, a synthetic paraffin, a naphthenic reference fluid (N-1), both neat and containing 1 percent of p-tricresyl phosphate as an anti-wear additive, and a C-ether. Traction properties were found to be nearly proportional to mixture composition for traction fluid and ester mixtures. The anti-wear additive reduced traction and fluid temperature under low loads but increased them under higher loads, giving rise to formation of a friction polymer.

Modeling of a Von Platen-Munters diffusion absorption refrigeration cycle

NASA Astrophysics Data System (ADS)

Agostini, Bruno; Agostini, Francesco; Habert, Mathieu

2016-09-01

This article presents a thermodynamical model of a Von-Platen diffusion absorption refrigeration cycle for power electronics applications. It is first validated by comparison with data available in the literature for the classical water-ammonia-helium cycle for commercial absorption fridges. Then new operating conditions corresponding to specific ABB applications, namely high ambient temperature and new organic fluids combinations compatible with aluminium are simulated and discussed. The target application is to cool power electronics converters in harsh environments with high ambient temperature by providing refrigeration without compressor, for passive components losses of about 500 W, with a compact and low cost solution.

Hydrodynamic modeling of laser interaction with micro-structured targets

DOE PAGES

Velechovsky, Jan; Limpouch, Jiri; Liska, Richard; ...

2016-08-03

A model is developed for numerical simulations of laser absorption in plasmas made of porous materials, with particular interest in low-density foams. Laser absorption is treated on two spatial scales simultaneously. At the microscale, the expansion of a thin solid pore wall is modeled in one dimension and the information obtained is used in the macroscale fluid simulations for the description of the plasma homogenization behind the ionization front. This two-scale laser absorption model is implemented in the arbitrary Lagrangian–Eulerian hydrocode PALE. In conclusion, the numerical simulations of laser penetration into low-density foams compare favorably with published experimental data.

Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Lerner, Aaron; Sabo, Edmund; Krausz, Michael M; Siplovich, Leonardo; Coran, Arnold G; Mogilner, Jorge; Shiloni, Eitan

2003-07-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal morphology and intestinal absorptive function. The purpose of the present study was to determine the effect of enteral ARG supplementation on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Thirty male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-ARG rats underwent bowel resection and were treated with ARG given in the drinking water (2%). Parameters of intestinal adaptation, enterocyte proliferation and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-ARG animals had a lower jejunal and ileal mucosal weight, jejunal mucosal DNA and protein, ileal mucosal protein, jejunal villus height, jejunal and ileal crypt depth, and enterocyte proliferation index and a greater enterocyte apoptosis compared to SBS untreated animals. We conclude that in a rat model of SBS enteral L-arginine inhibits structural intestinal adaptation. Possible mechanism for this effect may be decreased cell proliferation and increased cell apoptosis.

Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation

PubMed Central

Davis, Reema B.; Kechele, Daniel O.; Blakeney, Elizabeth S.; Pawlak, John B.

2017-01-01

Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor–like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy. Upon indomethacin challenge, Calcrlfl/fl/Prox1-CreERT2 mice demonstrated persistent inflammation and failure to recover and thrive. The epithelium and crypts of Calcrlfl/fl/Prox1-CreERT2 mice exhibited exacerbated hallmarks of disease progression, and the lacteals demonstrated an inability to absorb lipids. Furthermore, we identified Calcrl/adrenomedullin signaling as an essential upstream regulator of the Notch pathway, previously shown to be critical for intestinal lacteal maintenance and junctional integrity. In conclusion, lymphatic insufficiency and lymphangiectasia caused by loss of lymphatic Calcrl exacerbates intestinal recovery following mucosal injury and underscores the importance of lymphatic function in promoting recovery from intestinal inflammation. PMID:28352669

First conclusions about results of GPR investigations in the Church of the Assumption of the Blessed Virgin Mary in Kłodzko, Poland

NASA Astrophysics Data System (ADS)

Chernov, Anatolii; Dziubacki, Dariusz; Cogoni, Martina; Bądescu, Alexandru

2018-03-01

The article presents results of a ground penetrating radar (GPR) investigation carried out in the Church of the Assumption of the Blessed Virgin Mary in Kłodzko, Poland, dating from the 14th to 16th centuries. Due to the 20th century wars, the current state of knowledge about the history of the church is still poor. Under the floor of the Catholic temple, unknown structures might exist. To verify the presence of underground structures such as crypts and tombs, a GPR survey was carried out in chapels and aisles with 500 and 800 MHz GPR shielded antennas. Numerous anomalies were detected. It was concluded that those under the chapels were caused by the presence of crypts beneath the floor.

Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis.

PubMed

Bormann, Felix; Rodríguez-Paredes, Manuel; Lasitschka, Felix; Edelmann, Dominic; Musch, Tanja; Benner, Axel; Bergman, Yehudit; Dieter, Sebastian M; Ball, Claudia R; Glimm, Hanno; Linhart, Heinz G; Lyko, Frank

2018-06-12

Colorectal adenomas are precursor lesions of colorectal cancers and represent clonal amplifications of single cells from colonic crypts. DNA methylation patterns specify cell-type identity during cellular differentiation and, therefore, provide opportunities for the molecular analysis of tumors. We have now analyzed DNA methylation patterns in colorectal adenomas and identified three biologically defined subclasses that describe different intestinal crypt differentiation stages. Importantly, colorectal carcinomas could be classified into the same methylation subtypes, reflecting their shared cell types of origin with adenomas. Further data analysis also revealed significantly reduced overall survival for one of the subtypes. Our results provide a concept for understanding the methylation patterns observed in colorectal cancer and provide opportunities for tumor subclassification and patient stratification. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Iris texture traits show associations with iris color and genomic ancestry.

PubMed

Quillen, Ellen E; Guiltinan, Jenna S; Beleza, Sandra; Rocha, Jorge; Pereira, Rinaldo W; Shriver, Mark D

2011-01-01

This study seeks to identify associations among genomic biogeographic ancestry (BGA), quantitative iris color, and iris texture traits contributing to population-level variation in these phenotypes. DNA and iris photographs were collected from 300 individuals across three variably admixed populations (Portugal, Brazil, and Cape Verde). Two raters scored the photos for pigmentation spots, Fuchs' crypts, contraction furrows, and Wolflinn nodes. Iris color was quantified from RGB values. Maximum likelihood estimates of individual BGA were calculated from 176 ancestry informative markers. Pigmentation spots, Fuchs' crypts, contraction furrows, and iris color show significant positive correlation with increasing European BGA. Only contraction furrows are correlated with iris color. The relationship between BGA and iris texture illustrates a genetic contribution to this population-level variation. Copyright © 2011 Wiley-Liss, Inc.

In vitro percutaneous absorption and metabolism of Bisphenol A (BPA) through fresh human skin.

PubMed

Toner, Frank; Allan, Graham; Dimond, Stephen S; Waechter, John M; Beyer, Dieter

2018-03-01

Bisphenol A (BPA) is a high production volume compound. It is mainly used as a monomer to make polymers for various applications including food-contact materials. The primary route of exposure to BPA in the general population is through oral intake (EFSA 2015) however, other potential sources of exposure have also been identified, such as dermal contact. In the present study, the percutaneous absorption through human skin has been investigated in an in vitro study according to OECD TG 428 (Skin Absorption: In Vitro Method). In order to investigate potential dermal BPA metabolism during absorption, radiolabelled BPA was applied to fresh, metabolically competent, human skin samples (ring labelled 14 C BPA concentrations tested were 2.4, 12, 60 and 300mg/L). Measured as total radioactivity the mean absorbed dose (receptor compartment) ranged from 1.7-3.6% of the applied doses and the dermal delivery (epidermis+dermis+receptor compartment), sometimes also named bioavailable dose was 16-20% of the applied doses, with the majority of the radioactivity associated with epidermis compared to dermis and receptor fluid. No metabolism was observed in any of the epidermis samples; however some metabolism was observed in dermis and receptor fluid samples with formation of BPA-glucuronide and BPA-sulfate, and some polar metabolites. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

46 CFR 58.30-25 - Accumulators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pressure vessel in which energy is stored under high pressure in the form of a gas or a gas and hydraulic... result in contamination of the hydraulic fluid and loss of gas through absorption. (c) Each accumulator...

46 CFR 58.30-25 - Accumulators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pressure vessel in which energy is stored under high pressure in the form of a gas or a gas and hydraulic... result in contamination of the hydraulic fluid and loss of gas through absorption. (c) Each accumulator...

46 CFR 58.30-25 - Accumulators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pressure vessel in which energy is stored under high pressure in the form of a gas or a gas and hydraulic... result in contamination of the hydraulic fluid and loss of gas through absorption. (c) Each accumulator...

46 CFR 58.30-25 - Accumulators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pressure vessel in which energy is stored under high pressure in the form of a gas or a gas and hydraulic... result in contamination of the hydraulic fluid and loss of gas through absorption. (c) Each accumulator...

Biorelevant media resistant co-culture model mimicking permeability of human intestine.

PubMed

Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

2015-03-15

Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

Packaged integrated opto-fluidic solution for harmful fluid analysis

NASA Astrophysics Data System (ADS)

Allenet, T.; Bucci, D.; Geoffray, F.; Canto, F.; Couston, L.; Jardinier, E.; Broquin, J.-E.

2016-02-01

Advances in nuclear fuel reprocessing have led to a surging need for novel chemical analysis tools. In this paper, we present a packaged lab-on-chip approach with co-integration of optical and micro-fluidic functions on a glass substrate as a solution. A chip was built and packaged to obtain light/fluid interaction in order for the entire device to make spectral measurements using the photo spectroscopy absorption principle. The interaction between the analyte solution and light takes place at the boundary between a waveguide and a fluid micro-channel thanks to the evanescent part of the waveguide's guided mode that propagates into the fluid. The waveguide was obtained via ion exchange on a glass wafer. The input and the output of the waveguides were pigtailed with standard single mode optical fibers. The micro-scale fluid channel was elaborated with a lithography procedure and hydrofluoric acid wet etching resulting in a 150+/-8 μm deep channel. The channel was designed with fluidic accesses, in order for the chip to be compatible with commercial fluidic interfaces/chip mounts. This allows for analyte fluid in external capillaries to be pumped into the device through micro-pipes, hence resulting in a fully packaged chip. In order to produce this co-integrated structure, two substrates were bonded. A study of direct glass wafer-to-wafer molecular bonding was carried-out to improve detector sturdiness and durability and put forward a bonding protocol with a bonding surface energy of γ>2.0 J.m-2. Detector viability was shown by obtaining optical mode measurements and detecting traces of 1.2 M neodymium (Nd) solute in 12+/-1 μL of 0.01 M and pH 2 nitric acid (HNO3) solvent by obtaining an absorption peak specific to neodymium at 795 nm.

Fluid and electrolyte balance in ultra-endurance sport.

PubMed

Rehrer, N J

2001-01-01

It is well known that fluid and electrolyte balance are critical to optimal exercise performance and, moreover, health maintenance. Most research conducted on extreme sporting endeavour (>3 hours) is based on case studies and studies involving small numbers of individuals. Ultra-endurance sportsmen and women typically do not meet their fluid needs during exercise. However, successful athletes exercising over several consecutive days come close to meeting fluid needs. It is important to try to account for all factors influencing bodyweight changes, in addition to fluid loss, and all sources of water input. Increasing ambient temperature and humidity can increase the rate of sweating by up to approximately 1 L/h. Depending on individual variation, exercise type and particularly intensity, sweat rates can vary from extremely low values to more than 3 L/h. Over-hydration, although not frequently observed, can also present problems, as can inappropriate fluid composition. Over-hydrating or meeting fluid needs during very long-lasting exercise in the heat with low or negligible sodium intake can result in reduced performance and, not infrequently, hyponatraemia. Thus, with large rates of fluid ingestion, even measured just to meet fluid needs, sodium intake is vital and an increased beverage concentration [30 to 50 mmol/L (1.7 to 2.9 g NaCl/L) may be beneficial. If insufficient fluids are taken during exercise, sodium is necessary in the recovery period to reduce the urinary output and increase the rate of restoration of fluid balance. Carbohydrate inclusion in a beverage can affect the net rate of water assimilation and is also important to supplement endogenous reserves as a substrate for exercising muscles during ultra-endurance activity. To enhance water absorption, glucose and/or glucose-containing carbohydrates (e.g. sucrose, maltose) at concentrations of 3 to 5% weight/volume are recommended. Carbohydrate concentrations above this may be advantageous in terms of glucose oxidation and maintaining exercise intensity, but will be of no added advantage and, if hyperosmotic, will actually reduce the net rate of water absorption. The rate of fluid loss may exceed the capacity of the gastrointestinal tract to assimilate fluids. Gastric emptying, in particular, may be below the rate of fluid loss, and therefore, individual tolerance may dictate the maximum rate of fluid intake. There is large individual variation in gastric emptying rate and tolerance to larger volumes. Training to drink during exercise is recommended and may enhance tolerance.

Alternate working fluids for solar air conditioning applications

NASA Technical Reports Server (NTRS)

Evans, R. D.; Beck, J. K.

1978-01-01

An experimental investigation of sixteen different refrigerant-absorbent fluid pairs has been carried out in order to determine their suitability as the working fluid in a solar-powered absorption cycle air conditioner. The criteria used in the initial selection of a refrigerant-absorbent pair included: high affinity (large negative deviation from Raoult's Law), high solubility, low specific heat, low viscosity, stability, corrosive properties, safety, and cost. For practical solar considerations of a fluid pair, refrigerants were selected with low boiling points whereas absorbent fluids were selected with a boiling point considerably above that of the refrigerant. Additional restrictions are determined by the operating temperatures of the absorber and the generator; these temperatures were specified as 100 F (39 C) and 170 F (77 C). Data are presented for a few selected pressures at the specified absorber and generator temperatures.

Method for improving dissolution efficiency in gas-absorption and liquid extraction processes. [Patent application

DOEpatents

Kanak, B.E.; Stephenson, M.J.

1980-01-11

A method is described for improving dissolution efficiency in processes in which a feed fluid is introduced to a zone where it is contacted with a liquid solvent for preferentially removing a component of the feed and where part of the solvent so contacted undergoes transfer into the feed fluid to saturate the same. It has been found that such transfer significantly impairs dissolution efficiency. In accordance with the invention, an amount of the above-mentioned solvent is added to the feed fluid being introduced to the contact zone, the solvent being added in an amount sufficient to effect reduction or elimination of the above-mentioned transfer. Preferably, the solvent is added to the feed fluid in an amount saturating or supersaturating the feed fluid under the conditions prevailing in the contact zone.

Method for improving dissolution efficiency in gas-absorption and liquid extraction processes

DOEpatents

Kanak, Brant E.; Stephenson, Michael J.

1981-01-01

This invention is a method for improving dissolution efficiency in processes in which a feed fluid is introduced to a zone where it is contacted with a liquid solvent for preferentially removing a component of the feed and where part of the solvent so contacted undergoes transfer into the feed fluid to saturate the same. It has been found that such transfer significantly impairs dissolution efficiency. In accordance with the invention, an amount of the above-mentioned solvent is added to the feed fluid being introduced to the contact zone, the solvent being added in an amount sufficient to effect reduction or elimination of the above-mentioned transfer. Preferably, the solvent is added to the feed fluid in an amount saturating or supersaturating the feed fluid under the conditions prevailing in the contact zone.

Computational Evaluation of Mixtures of Hydrofluorocarbons and Deep Eutectic Solvents for Absorption Refrigeration Systems.

PubMed

Abedin, Rubaiyet; Heidarian, Sharareh; Flake, John C; Hung, Francisco R

2017-10-24

We used computational tools to evaluate three working fluid mixtures for single-effect absorption refrigeration systems, where the generator (desorber) is powered by waste or solar heat. The mixtures studied here resulted from combining a widely used hydrofluorocarbon (HFC) refrigerant, R134a, with three common deep eutectic solvents (DESs) formed by mixing choline chloride (hydrogen bond acceptor, HBA) with urea, glycerol, or ethylene glycol as the hydrogen bond donor (HBD) species. The COSMOtherm/TmoleX software package was used in combination with refrigerant data from NIST/REFPROP, to perform a thermodynamic evaluation of absorption refrigeration cycles using the proposed working fluid mixtures. Afterward, classical MD simulations of the three mixtures were performed to gain insight on these systems at the molecular level. Larger cycle efficiencies are obtained when R134a is combined with choline chloride and ethylene glycol, followed by the system where glycerol is the HBD, and finally that where the HBD is urea. MD simulations indicate that the local density profiles of all species exhibit very sharp variations in systems containing glycerol or urea; furthermore, the Henry's law constants of R134a in these two systems are larger than those observed for the HFC in choline chloride and ethylene glycol, indicating that R134a is more soluble in the latter DES. Interaction energies indicate that the R134a-R134a interactions are weaker in the system where ethylene glycol is the HBD, as compared to in the other DES. Radial distribution functions confirm that in all systems, the DES species do not form strong directional interactions (e.g., hydrogen bonds) with the R134a molecules. Relatively strong interactions are observed between the Cl anions and the hydrogen atoms in R134a; however, the atom-atom interactions between R134a and the cation and HBD species are weaker and do not play a significant role in the solvation of the refrigerant. In all systems, R134a has the largest diffusion coefficients, followed by the HBD, the anion and the cation; the diffusion coefficients are the largest in the systems containing ethylene glycol, followed by those having glycerol and urea. This work is our first step toward our long-term goal of designing and demonstrating optimal working fluid mixtures for use in absorption refrigeration systems. Our results suggest that COSMO-RS can be used to perform a rapid screening of a large number of working fluid mixtures, and select a few candidates for further exploration using molecular simulations and experiments. These latter approaches can be used to refine the accuracy of the COSMO-RS predictions, and to optimize the selection of optimal working fluid mixtures for demonstration in absorption refrigeration systems powered by solar or waste heat sources.

Long-term culture-induced phenotypic difference and efficient cryopreservation of small intestinal organoids by treatment timing of Rho kinase inhibitor.

PubMed

Han, Sung-Hoon; Shim, Sehwan; Kim, Min-Jung; Shin, Hye-Yun; Jang, Won-Suk; Lee, Sun-Joo; Jin, Young-Woo; Lee, Seung-Sook; Lee, Seung Bum; Park, Sunhoo

2017-02-14

To investigate a suitable long-term culture system and optimal cryopreservation of intestinal organoid to improve organoid-based therapy by acquiring large numbers of cells. Crypts were isolated from jejunum of C57BL/6 mouse. Two hundred crypts were cultured in organoid medium with either epidermal growth factor/Noggin/R-spondin1 (ENR) or ENR/CHIR99021/VPA (ENR-CV). For subculture, organoids cultured on day 7 were passaged using enzyme-free cell dissociation buffer (STEMCELL Technologies). The passage was performed once per week until indicated passage. For cryopreservation, undissociated and dissociated organoids were resuspended in freezing medium with or without Rho kinase inhibitor subjected to different treatment times. The characteristics of intestinal organoids upon extended passage and freeze-thaw were analyzed using EdU staining, methyl thiazolyl tetrazolium assay, qPCR and time-lapse live cell imaging. We established a three-dimensional culture system for murine small intestinal organoids using ENR and ENR-CV media. Both conditions yielded organoids with a crypt-villus architecture exhibiting Lgr5 + cells and differentiated intestinal epithelial cells as shown by morphological and biochemical analysis. However, during extended passage (more than 3 mo), a comparative analysis revealed that continuous passaging under ENR-CV conditions, but not ENR conditions induced phenotypic changes as observed by morphological transition, reduced numbers of Lgr5 + cells and inconsistent expression of markers for differentiated intestinal epithelial cell types. We also found that recovery of long-term cryopreserved organoids was significantly affected by the organoid state, i.e ., whether dissociation was applied, and the timing of treatment with the Rho-kinase inhibitor Y-27632. Furthermore, the retention of typical morphological characteristics of intestinal organoids such as the crypt-villus structure from freeze-thawed cells was observed by live cell imaging. The maintenance of the characteristics of intestinal organoids upon extended passage is mediated by ENR condition, but not ENR-CV condition. Identified long-term cryopreservation may contribute to the establishment of standardized cryopreservation protocols for intestinal organoids for use in clinical applications.

Interleukin-1 modulatory effect on the action of chemotherapeutic drugs and localized irradiation of the lip, duodenum, and tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaghloul, M.S.; Dorie, M.J.; Kallman, R.F.

1993-06-15

This study was conducted to examine the radioprotective and radiochemoprotective capabilities of interleukin 1[beta] (IL-1) on two acute-reacting normal tissues of the C3H mouse, the mucosa of the lip and the duodenum. Also assessed was the modulating effect of IL-1 on tumor growth in the same strain of mice. IL-1 was administered to C3H-Km mice in combination with fractionated irradiation, or with cyclophosphamide, cisplatin, or 5-fluorouracil (5FU) followed by irradiation. Normal tissue damage was evaluated in the mouse lip, using a subjective scoring system for tissue reaction, and in the duodenum, using the crypt cell survival assay. RIF-1 fibrosarcoma tumormore » response was assayed with the regrowth delay method. IL-1 protected against the acute reaction produced by fractionated irradiation in the lip mucosa, shifting the dose-response curve by 3.8 Gy. IL-1 was protective when injected intraperitoneally 24 hr before CY or c-DDP, which were given immediately before the first of five daily radiation dose fractions. The dose-response curves for cyclophosphamide and cisplatin were shifted 4.0 Gy and 1.6 Gy, respectively. IL-1 did not protect against 5FU toxicity when treatments were administered in that same sequence; however, when 5FU was given 4 or 8 hr before IL-1 and the first radiation dose fraction followed 20 or 16 hr later, there was significant protection and the curves were separated by 1.5 Gy or 3.5 Gy. IL-1 also protected duodenal crypt cells against the cytocidal effect of fractionated irradiation, with a dose difference of 1.5 Gy and an improvement of crypt survival of 11.7%. It was even more immediately before the first of five daily radiation doses, with the dose differences of 4.4 and 5.3 Gy, respectively, and improvements of crypt survival of 33.8 and 29.9%, respectively. There was no modification by IL-1 of the effect of irradiation alone on the RIF-1 tumor. 45 refs., 8 figs., 1 tab.« less

Intraspecific Competition Impacts Vibrio fischeri Strain Diversity during Initial Colonization of the Squid Light Organ

PubMed Central

Sun, Yan; LaSota, Elijah D.; Cecere, Andrew G.; LaPenna, Kyle B.; Larios-Valencia, Jessie; Wollenberg, Michael S.

2016-01-01

ABSTRACT Animal development and physiology depend on beneficial interactions with microbial symbionts. In many cases, the microbial symbionts are horizontally transmitted among hosts, thereby making the acquisition of these microbes from the environment an important event within the life history of each host. The light organ symbiosis established between the Hawaiian squid Euprymna scolopes and the bioluminescent bacterium Vibrio fischeri is a model system for examining how hosts acquire horizontally transmitted microbial symbionts. Recent studies have revealed that the light organ of wild-caught E. scolopes squid contains polyclonal populations of V. fischeri bacteria; however, the function and development of such strain diversity in the symbiosis are unknown. Here, we report our phenotypic and phylogenetic characterizations of FQ-A001, which is a V. fischeri strain isolated directly from the light organ of an E. scolopes individual. Relative to the type strain ES114, FQ-A001 exhibits similar growth in rich medium but displays increased bioluminescence and decreased motility in soft agar. FQ-A001 outcompetes ES114 in colonizing the crypt spaces of the light organs. Remarkably, we find that animals cocolonized with FQ-A001 and ES114 harbor singly colonized crypts, in contrast to the cocolonized crypts observed from competition experiments involving single genotypes. The results with our two-strain system suggest that strain diversity within the squid light organ is a consequence of diversity in the single-strain colonization of individual crypt spaces. IMPORTANCE The developmental programs and overall physiologies of most animals depend on diverse microbial symbionts that are acquired from the environment. However, the basic principles underlying how microbes colonize their hosts remain poorly understood. Here, we report our findings of bacterial strain competition within the coevolved animal-microbe symbiosis composed of the Hawaiian squid and bioluminescent bacterium Vibrio fischeri. Using fluorescent proteins to differentially label two distinct V. fischeri strains, we find that the strains are unable to coexist in the same niche within the host. Our results suggest that strain competition for distinct colonization sites dictates the strain diversity associated with the host. Our study provides a platform for studying how strain diversity develops within a host. PMID:27016564

Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PubMed

Ozkan, L; Ozuysal, S; Egeli, U; Adim, S B; Tunca, B; Aydemir, N; Ceçener, G; Ergül, E; Akpinar, G; Cimen, C; Engin, K; Ahmed, M M

2001-07-01

In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon

PubMed Central

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-01-01

AIM: To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. METHODS: Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS: Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. CONCLUSION: GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon. PMID:21734804

Effects of monochromatic light on mucosal mechanical and immunological barriers in the small intestine of broilers.

PubMed

Xie, D; Li, J; Wang, Z X; Cao, J; Li, T T; Chen, J L; Chen, Y X

2011-12-01

Our previous studies demonstrated that green and blue monochromatic lights were effective to stimulate immune response of the spleen in broilers. This study was designed to investigate the effects of monochromatic light on both gut mucosal mechanical and immunological barriers. A total of 120 Arbor Acre male broilers on post-hatching day (P) 0 were exposed to red light, green light (GL), blue light (BL), and white light (WL) for 49 d, respectively. As compared with broilers exposed to WL, the broilers exposed to GL showed that the villus height of small intestine was increased by 19.5% (P = 0.0205) and 38.8% (P = 0.0149), the crypt depth of small intestine was decreased by 15.1% (P = 0.0049) and 10.1% (P = 0.0005), and the ratios of villus height to crypt depth were increased by 39.3% (P < 0.0001) and 52.5% (P < 0.0001) at P7 and P21, respectively. Until P49, an increased villus height (33.6%, P = 0.0076), a decreased crypt depth (15.4%, P = 0.0201), and an increased villus height-to-crypt depth ratio (58.5%, P < 0.0001) were observed in the BL group as compared with the WL group. On the other hand, the numbers of intestinal intraepithelial lymphocytes (27.9%, P < 0.0001 and 37.0%, P < 0.0001), goblet cells (GC, 22.1%, P < 0.0001 and 18.1%, P < 0.0001), and IgA(+) cells (14.8%, P = 0.0543 and 47.9%, P = 0.0377) in the small intestine were significantly increased in the GL group as compared with the WL group at P7 and P21, respectively. The numbers of intestinal intraepithelial lymphocytes (36.2%, P < 0.0001), GC (26.5%, P < 0.0001), and IgA(+) cells (68.0%, P = 0.0177) in the BL group were also higher than those in the WL group at P49. These results suggest that both mucosal mechanical and immunological barriers of the small intestine may be improved by rearing broilers under GL at an early age and under BL at an older age.

Enhanced gastric stability of esomeprazole by molecular interaction and modulation of microenvironmental pH with alkalizers in solid dispersion.

PubMed

Van Nguyen, Hien; Baek, Namhyun; Lee, Beom-Jin

2017-05-15

Due to the instability of esomeprazole magnesium dihydrate (EPM), a proton pump inhibitor, in gastric fluid, enteric-coated dosage form is commonly used for therapeutic application. In this study, we prepared new gastric fluid resistant solid dispersions (SDs) containing alkalizers. Then, new mechanistic evidence regarding the effects of pharmaceutical alkalizers on the aqueous stability of EPM in simulated gastric fluid was investigated. The alkalizer-loaded SD were prepared by dissolving or dispersing EPM, hydroxypropyl methylcellulose (HPMC) 6 cps, and an alkalizer, in ethanol 50% (v/v) followed by spray drying. Nine different alkalizers were assessed for in vitro stability in two media, simulated gastric fluid (pH 1.2 buffer) and simulated intestinal fluid (pH 6.8 buffer). The microenvironmental pH (pH M ) was measured to evaluate the effect of the alkalizer on the pH M of SDs. Drug crystallinity and morphology of the SDs were also examined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The interactions among EPM, the polymer, and the alkalizer were elucidated by Fourier transform infrared (FTIR) spectroscopy. The in vivo absorption studies of the optimized alkalizer-containing SD and the enteric-coated reference tablet Nexium ® were then conducted in beagle dogs. Among alkalizers, MgO loaded in SDs proved to be the best alkalizer to stabilize EPM in simulated gastric fluid. pH M values of the alkalizer-containing SDs were significantly higher than that of the SD without alkalizer. The pH M values decreased in the following order: MgO, Na 2 CO 3 , Ca(OH) 2 , and no alkalizer. DSC and PXRD data exhibited a change in the drug crystallinity of the SDs from crystalline to amorphous form. SEM data showed a relatively spherical shape of the MgO-loaded SD compared to the less-defined shape of pure drug. FTIR indicated a strong molecular interaction among EPM, alkalizer and polymer; in particular, MgO showed the strongest interaction with EPM. It was evident that alkalizer interacts with benzimidazole ring and/or sulfonyl group of EPM for enhancing EPM stability in gastric fluid. Regarding the in vivo absorption studies in beagle dogs, the optimized SD (C16) was bioequivalent to the reference Nexium ® and had a considerable greater absorption at the early stages. The current alkalizer-containing SD could provide a promising approach for aqueous stabilization of acid-labile drugs without using enteric coating method. Copyright © 2017 Elsevier B.V. All rights reserved.

Physical aspects of heat generation/absorption in the second grade fluid flow due to Riga plate: Application of Cattaneo-Christov approach

NASA Astrophysics Data System (ADS)

Anjum, Aisha; Mir, N. A.; Farooq, M.; Javed, M.; Ahmad, S.; Malik, M. Y.; Alshomrani, A. S.

2018-06-01

The present article concentrates on thermal stratification in the flow of second grade fluid past a Riga plate with linear stretching towards a stagnation region. Heat transfer phenomenon is disclosed with heat generation/absorption. Riga plate is known as electromagnetic actuator which comprises of permanent magnets and alternating electrodes placed on a plane surface. Cattaneo-Christov heat flux model is implemented to analyze the features of heat transfer. This new heat flux model is the generalization of classical Fourier's law with the contribution of thermal relaxation time. For the first time heat generation/absorption effect is computed with non-Fourier's law of heat conduction (i.e., Cattaneo-Christov heat flux model). Transformations are used to obtain the governing non-linear ordinary differential equations. Approximate convergent solutions are developed for the non-dimensionalized governing problems. Physical features of velocity and temperature distributions are graphically analyzed corresponding to various parameters in 2D and 3D. It is noted that velocity field enhances with an increment of modified Hartman number while it reduces with increasing variable thickness parameter. Increment in modified heat generation parameter results in reduction of temperature field.

Improved bioavailability and antiasthmatic efficacy of poorly soluble curcumin-solid dispersion granules obtained using fluid bed granulation.

PubMed

Jang, Dong-Jin; Kim, Sung Tae; Lee, Kooyeon; Oh, Euichaul

2014-01-01

The intestinal absorption and antiasthmatic efficacy of poorly water-soluble curcumin (CUR), which has low solubility and permeability, was increased by fabricating solid dispersion granules (SDGs). The SDG containing CUR (SDG-CUR) was prepared by dispersing CUR in excess Cremophor RH40 as a solubilizer and Ryoto sugar ester L-1695 as an absorption enhancer using fluid bed granulation. We evaluated the physicochemical properties such as crystallinity and dissolution, pharmacokinetics, and antiasthmatic efficacy of SDG-CUR. Our results showed that CUR was molecularly dispersed, and the dissolution of SDG-CUR was significantly higher than that of native CUR. In addition, the blood concentration of SDG-CUR in rats was much higher than that of native CUR. Compared to CUR, SDG-CUR showed a 9.1- and 13.1-fold increase in area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. Further, SDG-CUR effectively alleviated airway hyperresponsiveness and levels of T-helper 2 cytokines (interleukin-4, interleukin-5, and interleukin-13) in a murine model of asthma. In conclusion, our results suggest that the SDGs could be considered as a potential oral formulation to enhance the absorption and efficacy of CUR.

Fluid mechanics relevant to flow through pretreatment of cellulosic biomass.

PubMed

Archambault-Léger, Véronique; Lynd, Lee R

2014-04-01

The present study investigates fluid mechanical properties of cellulosic feedstocks relevant to flow through (FT) pretreatment for biological conversion of cellulosic biomass. The results inform identifying conditions for which FT pretreatment can be implemented in a practical context. Measurements of pressure drop across packed beds, viscous compaction and water absorption are reported for milled and not milled sugarcane bagasse, switchgrass and poplar, and important factors impacting viscous flow are deduced. Using biomass knife-milled to pass through a 2mm sieve, the observed pressure drop was highest for bagasse, intermediate for switchgrass and lowest for poplar. The highest pressure drop was associated with the presence of more fine particles, greater viscous compaction and the degree of water absorption. Using bagasse without particle size reduction, the instability of the reactor during pretreatment above 140kg/m(3) sets an upper bound on the allowable concentration for continuous stable flow. Copyright © 2014. Published by Elsevier Ltd.

A small-volume PVTX system for broadband spectroscopic calibration of downhole optical sensors

NASA Astrophysics Data System (ADS)

Jones, Christopher Michael; Pelletier, Michael T.; Atkinson, Robert; Shen, Jing; Moore, Jeff; Anders, Jimmy; Perkins, David L.; Myrick, Michael L.

2017-07-01

An instrument is presented that is capable of measuring the optical spectrum (long-wave ultraviolet through short-wave mid-infrared) of fluids under a range of temperature and pressure conditions from ambient pressure up to 138 MPa (20 000 psi) and 422 K (300 °F) using ˜5 ml of fluid. Temperature, pressure, and density are measured in situ in real-time, and composition is varied by adding volatile and nonvolatile components. The stability and accuracy of the conditions are reported for pure ethane, and the effects of temperature and pressure on characteristic regions of the optical spectrum of ethane are illustrated after correction for temperature and pressure effects on the optical cell path length, as well as normalization to the measured density. Molar absorption coefficients and integrated molar absorption coefficients for several vibrational combination bands are presented.

Resonant excitation of coupled Rayleigh waves in a short and narrow fluid channel clad between two identical metal plates

DOE PAGES

García-Chocano, Victor M.; López-Rios, Tomás; Krokhin, Arkadii; ...

2011-12-23

Transmission of ultrasonic waves through a slit between two water immersed brass plates is studied for sub-wavelength plate thicknesses and slit apertures. Extraordinary high absorption is observed at discrete frequencies corresponding to resonant excitation of Rayleigh waves on the both sides of the channel. The coupling of the Rayleigh waves occurs through the fluid and the corresponding contribution to the dispersion has been theoretically derived and also experimentally confirmed. Symmetric and anti-symmetric modes are predicted but only the symmetric mode resonances have been observed. It follows from the dispersion equation that the coupled Rayleigh waves cannot be excited in amore » channel with apertures less than the critical one. The calculated critical aperture is in a good agreement with the measured acoustic spectra. These findings could be applied to design a broadband absorptive metamaterial.« less

Absorption sites of orally administered drugs in the small intestine.

PubMed

Murakami, Teruo

2017-12-01

In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method.

PubMed

Shi-Ying, Jin; Jin, Han; Shi-Xiao, Jin; Qing-Yuan, Lv; Jin-Xia, Bai; Chen, Hong-Ge; Rui-Sheng, Li; Wei, Wu; Hai-Long, Yuan

2014-01-01

To improve the absorption and bioavailability of baicalin using a nanocrystal (or nanosuspension) drug delivery system. A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of -34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 μg·mL(-1), was much higher than the baicalin-microcrystals and the physical mixture (135 and 86.4 μg·mL(-1), respectively). In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability (with the AUC(0-t) value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L(-1)·h(-1), respectively). The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Arsenic speciation and transport associated with the release of spent geothermal fluids in Mutnovsky field (Kamchatka, Russia)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilgen, Anastasia G.; Rychagov, Sergey N.; Trainor, Thomas P.

The use of geothermal fluids for the production of electricity poses a risk of contaminating surface waters when spent fluids are discharged into (near) surface environments. Arsenic (As) in particular is a common component in geothermal fluids and leads to a degradation of water quality when present in mobile and bioavailable forms. We have examined changes in arsenic speciation caused by quick transition from high temperature reducing conditions to surface conditions, retention mechanisms, and the extent of transport associated with the release of spent geothermal fluids at the Dachny geothermal fields (Mutnovsky geothermal region), Kamchatka, Russia -- a high temperaturemore » field used for electricity production. In the spent fluids, the arsenic concentration reaches 9 ppm, while in natural hot springs expressed in the vicinity of the field, the As concentration is typically below 10 ppb. The aqueous phase arsenic speciation was determined using Liquid Chromatography (LC) coupled to an Inductively Coupled Plasma Mass Spectrometer (ICP-MS). The arsenic speciation in the bottom sediments (< 65 {mu}m fraction) of the local surface waters was analyzed using X-ray Absorption Spectroscopy (XAS). Arsenic in the geothermal source fluids is predominantly found as As(III), while a mixture of As(III)/As(V) is found in the water and sediment of the Falshivaia River downstream from the power plant. The extent of elevated arsenic concentrations in water is limited by adsorption to the bottom sediment and dilution, as determined using Cl{sup -} from the deep well fluids as a tracer. Analysis of the Extended X-ray Absorption Fine Structure (EXAFS) spectra shows that sediment phase arsenic is associated with both Al- and Fe-rich phases with a bi-dentate corner sharing local geometry. The geothermal waste fluids released in the surface water create a localized area of arsenic contamination. The extent of transport of dissolved As is limited to {approx}7 km downstream from the source, while As associated with bottom sediment travels {approx}3 km farther.« less

[Changes in the peritoneum of the small intestine and diaphragm in experimental portal hypertension].

PubMed

Khoroshaev, V A; Vorozheĭkin, V M; Baĭbekov, I M

1991-04-01

Diaphragm and small intestine peritoneum morphology was studied in experimental portal hypertension in rats with the help of luminescent, transmission and scanning electron microscopy techniques. Structural organizations of these peritoneum portions and performance function were different: fluid transudation realized through the small intestine peritoneum and resorption occurred via diaphragm peritoneum. Morphological signs allowed to judge about the increasing of fluid transudation in abdominal cavity and diaphragmatic resorption in early period of portal hypertension. Morphological alterations appeared in peritoneum resorption sites (pumping diaphragmatic hatchs) according to progress of portal hypertension that indicated decompensation process of peritoneal fluid absorption and led to ascites.

High-fat diet affects gut nutrients transporters in hypo and hyperthyroid mice by PPAR-a independent mechanism.

PubMed

Losacco, Mariana Cerqueira; de Almeida, Carolina Fernanda Theodora; Hijo, Andressa Harumi Torelli; Bargi-Souza, Paula; Gama, Patricia; Nunes, Maria Tereza; Goulart-Silva, Francemilson

2018-06-01

High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition. C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days. The mice were euthanized and proximal intestine was removed to study GLUT2, GLUT5, PEPT1, FAT-CD36, FATP4, NPC1L1 and NHE3 distribution by Western blotting. Since PPAR-a is activated by fatty acids, which is abundant in the HFD, we also evaluated whether PPAR-a affects nutrients transporters. Thus, mice were treated with fenofibrate, a PPAR-a agonist. HFD decreased GLUT2, PEPT1, FAT-CD6 and NPC1L1, but increased NHE3, while GLUT5 and FATP4 remained unaltered. THs did not alter distribution of nutrients transporters neither in LFD nor in HFD groups, but they increased villi length and depth crypt in LFD and HFD, respectively. Fenofibrate did not affect content of nutrients transporters, excluding PPAR-a involvement on the HFD-induced changes. We assume that chronic HFD consumption reduced most of the nutrients transporters content in the small intestine of mice, which might limit the entrance of nutrients and gain weight. Since NHE3 promotes sodium absorption, and it was increased in HFD group, this finding could contribute to explain the hypertension observed in obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Supplementing formula-fed piglets with a low molecular weight fraction of bovine colostrum whey results in an improved intestinal barrier.

PubMed

De Vos, M; Huygelen, V; Van Raemdonck, G; Willemen, S; Fransen, E; Van Ostade, X; Casteleyn, C; Van Cruchten, S; Van Ginneken, C

2014-08-01

To test the hypothesis that a low molecular weight fraction of colostral whey could affect the morphology and barrier function of the small intestine, 30 3-d-old piglets (normal or low birth weight) were suckled (n = 5), artificially fed with milk formula (n = 5), or artificially fed with milk formula with a low molecular weight fraction of colostral whey (n = 5) until 10 d of age. The small intestine was sampled for histology (haematoxylin and eosin stain; anti-KI67 immunohistochemistry) and enzyme activities (aminopeptidase A, aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase, and sucrase). In addition, intestinal permeability was evaluated via a dual sugar absorption test and via the measurement of occludin abundance. Artificially feeding of piglets reduced final BW (P < 0.001), villus height (P < 0.001), lactase (P < 0.001), and dipeptidylpeptidase IV activities (P < 0.07), whereas crypt depth (P < 0.001) was increased. No difference was observed with regard to the permeability measurements when comparing artificially fed with naturally suckling piglets. Supplementing piglets with the colostral whey fraction did not affect BW, enzyme activities, or the outcome of the dual sugar absorption test. On the contrary, the small intestines of supplemented piglets had even shorter villi (P = 0.001) than unsupplemented piglets and contained more occludin (P = 0.002). In conclusion, at 10 d of age, no differences regarding intestinal morphology and permeability measurements were observed between the 2 BW categories. In both weight categories, the colostral whey fraction affected the morphology of the small intestine but did not improve the growth performances or the in vivo permeability. These findings should be acknowledged when developing formulated milk for neonatal animals with the aim of improving the performance of low birth weight piglets.

Absorption kinetics of flurbiprofen axetil microspheres in cerebrospinal fluid: A pilot study
.

PubMed

Zhang, Hong; Gu, Jian; Feng, Yi; An, Haiyan

2017-11-01

The purpose of this study is to investigate the absorption dynamics of flurbiprofen axetil in cerebrospinal fluid. We analyzed the concentrations of flurbiprofen in peripheral venous blood and cerebrospinal fluid (CSF) to explore the absorption dynamics of flurbiprofen axetil loaded in lipid microspheres in CSF. 72 adult patients who planned to undergo selective operations under spinal anesthesia or combined spinal-epidural anesthesia were intravenously injected with flurbiprofen axetil (1 mg/kg) and randomly divided into nine groups according to the sampling time after administration: 5 (T5), 10 (T10), 15 (T15), 20 (T20), 25 (T25), 30 (T30), 35 (T35), 40 (T40), and 45 minutes (T45). The CSF and venous blood samples collected from patients were analyzed by reverse-phase high-performance liquid chromatography to determine the concentrations of flurbiprofen. With the exception of 3 CSF samples in T5 and 4 CSF samples in T10, flurbiprofen was detected in all CSF and blood specimens. Significant differences between the CSF concentrations and CSF/plasma drug concentration ratios were observed among the nine time points (p < 0.001), whereas no significant difference in plasma concentration was found (p > 0.05). The findings suggest that lipid microspheres loaded with flurbiprofen can penetrate through the blood-brain barrier into CSF after intravenous injection. The fact that the flurbiprofen concentration rose continuously for 45 minutes after injection indicates that flurbiprofen-loaded lipid microspheres may exert analgesic action via the central nervous system.
.

Temperature Control in a Franz Diffusion Cell Skin Sonoporation Setup

NASA Astrophysics Data System (ADS)

Robertson, Jeremy; Becker, Sid

2017-11-01

In vitro experimental studies that investigate ultrasound enhanced transdermal drug delivery employ Franz diffusion cells. Because of absorption, the temperature of the coupling fluid often increases drastically during the ultrasound application. The current methodologies for controlling the coupling fluid temperature require either replacement of the coupling fluid during the experiment or the application of a time consuming duty cycle. This paper introduces a novel method for temperature control that allows for a wide variety of coupling fluid temperatures to be maintained. This method employs a peristaltic pump to circulate the coupling fluid through a thermoelectric cooling device. This temperature control method allowed for an investigation into the role of coupling fluid temperature on the inertial cavitation that impacts the skin aperture (inertial cavitation is thought to be the main cause of ultrasound induced skin permeability increase). Both foil pitting and passive cavitation detection experiments indicated that effective inertial cavitation activity decreases with increasing coupling fluid temperature. This finding suggests that greater skin permeability enhancement can be achieved if a lower coupling fluid temperature is maintained during skin insonation.

Detection of Unknown Crypts under the Floor in the Holy Trinity Church (Dominican Monastery) in Krakow, Poland

NASA Astrophysics Data System (ADS)

Strzępowicz, Anna; Łyskowski, Mikołaj; Ziętek, Jerzy; Tomecka-Suchoń, Sylwia

2018-03-01

The GPR surveying method belongs to non-invasive and quick geophysical methods, applied also in archaeological prospection. It allows for detecting archaeological artefacts buried under historical layers, and also those which can be found within buildings of historical value. Most commonly, just as in this particular case, it is used in churches, where other non-invasive localisation methods cannot be applied. In a majority of cases, surveys bring about highly positive results, enabling the site and size of a specific object to be indicated. A good example are the results obtained from the measurements carried out in the Basilica of Holy Trinity, belonging to the Dominican Monastery in Krakow. They allowed for confirming the location of the already existing crypts and for indicating so-far unidentified objects.

Senna and the formation of aberrant crypt foci and tumors in rats treated with azoxymethane.

PubMed

Borrelli, F; Capasso, R; Aviello, G; Di Carlo, G; Izzo, A A; Mascolo, N; Capasso, F

2005-06-01

Chronic use of anthraquinone laxatives has been blamed for the induction of habituation and the development of colonic cancer, but there are no definitive studies which have demonstrated this. To evaluate the carcinogenic potential of anthraquinones, the effect of long-term senna pod extract (SE) treatment on either healthy rats or rats treated with an initiating tumor agent (azoxymethane--AOM) has been studied. SE (30 and 60mg/kg), administered for 110 weeks, did not induce the development of aberrant crypt foci (ACF) and tumors in healthy rats. The development of ACF and tumors in rats treated with AOM were significantly reduced by SE (30 and 60 mg/kg). These results suggest that a chronic SE use does not predispose to colon cancer. By contrast, SE might exert an anti-tumoral activity on rat colon carcinogenesis.

The influence of androgens, anti-androgens, and castration on cell proliferation in the jejunal and colonic crypt epithelia, and in dimethylhydrazine-induced adenocarcinoma of rat colon.

PubMed

Tutton, P J; Barkla, D H

1982-01-01

Androgenic hormones have previously been shown to promote cell proliferation in the small intestine of rat and androgen receptors have been demonstrated in carcinomata of the large intestine of rat. In this study the influence of testosterone and of castration on epithelial cell proliferation in the small intestine, the large intestine and in dimethylhydrazine-induced colonic tumours is compared. Cell proliferation in the small intestine and in colonic tumours was accelerated by testosterone treatment, and cell proliferation in colonic tumours, but not in the small intestine, was retarded following castration. Cell proliferation in colonic tumours was also inhibited by the anti-androgenic drug, Flutamide. Testosterone and castration each failed to influence cell proliferation in the colonic crypt epithelium of both normal and carcinogen-treated animals.

Occupational arthropathy: evidence from the past.

PubMed Central

Waldron, H A; Cox, M

1989-01-01

The relation between osteoarthritis and occupation was examined in a group of skeletons from the crypt of Christ Church, Spitalfields, in east London used for burial between 1729 and 1869. Of the total of 968 discrete skeletons excavated, 367 had legible coffin plates giving details of name, age, sex, and date of death. Various sources were used to find the occupations of the group for which these details were known. As many of those buried in the crypt were Huguenots interest centred on the relation between weaving and osteoarthritis of the hands but none was found using a case-control study. Further analyses failed to show a relation between occupation and osteoarthritis of the shoulder or osteoarthritis at any site. There was a statistically significant association between non-manual occupations and osteoarthritis of the spine, the reasons for which are not yet clear. PMID:2818978

Spontaneous Aberrant Crypt Foci in Apc1638N Mice with a Mutant Apc Allele

PubMed Central

Pretlow, Theresa P.; Edelmann, Winfried; Kucherlapati, Raju; Pretlow, Thomas G.; Augenlicht, Leonard H.

2003-01-01

The Apc1638N/+ mouse has a chain-terminating mutation in one allele of the adenomatous polyposis coli (Apc) gene that is similar to most mutations observed in the human familial adenomatous polyposis syndrome. Aberrant crypt foci (ACF), the earliest identified neoplastic lesions in the colon, are morphologically abnormal structures that are identifiedmicroscopically in the grossly normal colonic mucosas of rodents treated with colon carcinogens and of human patients. The colons and cecums of 62 Apc1638N/+ mice were evaluated for the spontaneous occurrence of ACF and tumors. Both male and female mice were killed at different times between 5 and 28 weeks of age. Wild-type littermates, ie, Apc+/+ mice, at 22 to 26 weeks of age served as controls. ACF were identified in 97% of the Apc1638N/+ mice starting at 5 weeks of age and not in any wild-type littermates. Although the number of ACF increased with age (P < 0.0001), the average number of crypts per focus of the ACF did not increase significantly. In addition, wild-type Apc protein was detected by immunohistochemistry in all 22 ACF evaluated. Together these data suggest that heterozygous loss of Apc may be sufficient to initiate ACF in these mice and that these mice may be suitable models to study the interaction of environmental factors with an inherited mutation of the Apc gene that is associated with colon cancer. PMID:14578176

Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche.

PubMed

Wang, Yuli; Kim, Raehyun; Hinman, Samuel S; Zwarycz, Bailey; Magness, Scott T; Allbritton, Nancy L

2018-03-01

The relationship between intestinal stem cells (ISCs) and the surrounding niche environment is complex and dynamic. Key factors localized at the base of the crypt are necessary to promote ISC self-renewal and proliferation, to ultimately provide a constant stream of differentiated cells to maintain the epithelial barrier. These factors diminish as epithelial cells divide, migrate away from the crypt base, differentiate into the postmitotic lineages, and end their life span in approximately 7 days when they are sloughed into the intestinal lumen. To facilitate the rapid and complex physiology of ISC-driven epithelial renewal, in vivo gradients of growth factors, extracellular matrix, bacterial products, gases, and stiffness are formed along the crypt-villus axis. New bioengineered tools and platforms are available to recapitulate various gradients and support the stereotypical cellular responses associated with these gradients. Many of these technologies have been paired with primary small intestinal and colonic epithelial cells to re-create select aspects of normal physiology or disease states. These biomimetic platforms are becoming increasingly sophisticated with the rapid discovery of new niche factors and gradients. These advancements are contributing to the development of high-fidelity tissue constructs for basic science applications, drug screening, and personalized medicine applications. Here, we discuss the direct and indirect evidence for many of the important gradients found in vivo and their successful application to date in bioengineered in vitro models, including organ-on-chip and microfluidic culture devices.

Cdx1 and cdx2 expression during intestinal development.

PubMed

Silberg, D G; Swain, G P; Suh, E R; Traber, P G

2000-10-01

The intestine-specific transcription factors Cdx1 and Cdx2 are candidate genes for directing intestinal development, differentiation, and maintenance of the intestinal phenotype. This study focused on the complex patterns of expression of Cdx1 and Cdx2 during mouse gastrointestinal development. Embryonic and postnatal mouse tissues were analyzed by immunohistochemistry to determine protein expression of Cdx1 and Cdx2 in the developing intestinal tract. Cdx2 protein expression was observed at 9. 5 postcoitum (pc), whereas weak expression of Cdx1 protein was first seen at 12.5 pc in the distal developing intestine (hindgut). Expression of Cdx1 increased from 13.5 to 14.5 pc during the endoderm/epithelial transition with predominately distal expression. In contrast to Cdx1, there was intense expression of Cdx2 in all but the distal portions of the developing intestine. Cdx2 expression remained low in the distal colon throughout postnatal development. A gradient of expression formed in the crypt-villus axis, with Cdx1 primarily in the crypt and Cdx2 primarily in the villus. Direct comparison of the patterns of Cdx1 and Cdx2 protein expression during development as performed in this study provides new insights into their potential functional roles. The relative expression of Cdx1 to Cdx2 protein may be important in the anterior to posterior patterning of the intestinal epithelium and in defining patterns of proliferation and differentiation along the crypt-villus axis.

Regulators of Intestinal Epithelial Migration in Sepsis.

PubMed

Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

2018-02-08

The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

Cellular and molecular basis of tooth eruption

PubMed Central

Wise, GE

2009-01-01

Objectives Tooth eruption requires the presence of a dental follicle (DF), alveolar bone resorption for an eruption pathway, and alveolar bone formation at the base of the bony crypt. The objectives of our investigations have been to determine how the DF regulates both the osteoclastogenesis and osteogenesis needed for eruption. Material & Methods Multiple experimental methods have been employed. Results The DF regulates osteoclastogenesis and osteogenesis by regulating the expression of critical genes in both a chronological and spatial fashion. In the rat 1st mandibular molar there is a major burst of osteoclastogenesis at day 3 postnatally and a minor burst at day 10. At day 3, the DF maximally expresses colony-stimulating factor-1 (CSF-1) to down-regulate the expression of osteoprotegerin such that osteoclastogenesis can occur. At day 10, the minor burst of osteoclastogenesis is promoted by upregulation of VEGF and RANKL in the DF. Spatially, the bone resorption is in the coronal portion of the bony crypt and genes such as RANKL are expressed more in the coronal region of the DF than in its basal one-half. For osteogenesis, bone formation begins at day 3 at the base of the bony crypt and maximal growth is at days 9–14. Osteo-inductive genes such as BMP-2 appear to promote this and are expressed more in the basal half of the DF than in the coronal. Conclusion The osteoclastogenesis and osteogenesis needed for eruption are regulated by differential gene expression in the DF both chronologically and spatially. PMID:19419449

Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2008-11-01

The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.

Beneficial Biological Effects of Miso with Reference to Radiation Injury, Cancer and Hypertension

PubMed Central

Watanabe, Hiromitsu

2013-01-01

This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods. PMID:23914051

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine

PubMed Central

Muglia, C; Mercer, N; Toscano, M A; Schattner, M; Pozner, R; Cerliani, J P; Gobbi, R Papa; Rabinovich, G A; Docena, G H

2011-01-01

Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1−/−) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1−/− mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function. PMID:21614093

Plasma enteroglucagon and CCK levels and cell proliferation in defunctioned small bowel in the rat.

PubMed

Gornacz, G E; Ghatei, M A; Al-Mukhtar, M Y; Yeats, J C; Adrian, T E; Wright, N A; Bloom, S R

1984-11-01

Luminal nutrients exert a powerful trophic effect on small bowel mucosa. Recent evidence suggests that a circulating factor, possibly enteroglucagon, is also growth-promoting. In order to study the isolated effect of nonluminal influences on bowel mucosa, Thiry-Vella fistulae (TVF) were constructed in rats. Circulating enteric hormone concentrations were manipulated by resecting different lengths of remaining gut. Thirty-two male Wistar rats had either 25%, 50%, 75%, or 90% proximal small bowel resection. In each animal the first 25% of resected bowel was exteriorized as a Thiry-Vella fistula. Seven control rats underwent jejunal transection. Twelve days postoperatively the fasted animals were killed, and circulating and tissue concentrations of enteroglucagon and CCK were estimated by radioimmunoassay. Crypt-cell production rate was used as an index of cellular proliferation in the Thiry-Vella fistulae. Proximal small bowel defunctioned in the Thirty-Vella fistulae had a significantly lower crypt-cell production rate and enteroglucagon and CCK content than the equivalent segment in transected rats. Further small bowel resection produced a subsequent increase in circulating enteroglucagon and CCK concentrations, an increase in the Thiry-Vella fistula content of these hormones, and a doubling of the crypt-cell production rate in the Thiry-Vella fistulae. These results show that circulating enteroglucagon and CCK concentrations match closely with enterocyte production even when luminal influences are excluded. It is suggested that circulating factors may play a major role in postresectional ileal hyperplasia. This hyperplasia apparently affects endocrine cells as well as enterocytes.

Molecular Analysis of Single Tumor Glands Using the Crypt Isolation Method in Endometrial Carcinomas.

PubMed

Nagasawa, Takayuki; Sugai, Tamotsu; Shoji, Tadahiro; Habano, Wataru; Sugiyama, Toru

2016-11-01

Endometrial adenocarcinomas are characterized by the presence of many single tumor glands in which multiple genetic changes have accumulated. To elucidate the differences in molecular abnormalities among single tumor glands, individual tumor glands were analyzed and microsatellite alterations (loss of heterozygosity (LOH) and microsatellite instability [MSI]) were examined using the crypt isolation method in glands from each tumor from patients with endometrial carcinoma. Twenty-five patients with endometrial adenocarcinoma who underwent surgery were included in this study. We obtained cancerous individual isolated tumor glands from each patient using the crypt isolation method. For LOH and MSI analyses, we used 15 microsatellite markers (3p, 5q, 10q, 13q, 17p, 18q, BAT25, and BAT26) and the promoter regions of 6 genes (transforming growth factor beta receptor II, BAX, insulin-like growth factor II receptor, E2F4, MutS homolog 3, and MSH6). Loss of heterozygosity was detected in 8 (32%) of 25 patients, and MSI was detected in 9 (36%) of 25 patients. Some MSI-positive carcinomas had LOH in single tumor gland samples, and the coexistence of LOH and MSI was confirmed. In 16 (64%) of 25 cases, intratumoral genetic heterogeneity among single tumor gland samples was detected. By analyzing multiple single tumor glands within the same tumor, we found that endometrial adenocarcinoma was composed of various tumor glands with different molecular abnormalities, even in a limited region within the same tumor.

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease

PubMed Central

Schwerd, T.; Bryant, R. V.; Pandey, S.; Capitani, M.; Meran, L.; Cazier, J.-B.; Jung, J.; Mondal, K.; Parkes, M.; Mathew, CG; Fiedler, K.; McCarthy, D. J.; Sullivan, PB; Rodrigues, A.; Travis, SPL; Moore, C.; Sambrook, J.; Ouwehand, W. H.; Roberts, D. J.; Danesh, J.; Russell, R. K.; Wilson, D. C.; Kelsen, J. R.; Cornall, R.; Denson, L. A.; Kugathasan, S.; Knaus, U. G.; Goncalves Serra, E.; Anderson, C. A.; Duerr, R. H.; McGovern, D. P. B.; Cho, J.; Powrie, F.; Li, V. S. W.; Muise, A. M.; Uhlig, H. H.

2017-01-01

Genetic defects that affect intestinal epithelial barrier function can present with very early onset inflammatory bowel disease (VEOIBD). Using whole genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 paediatric patients identified further seven male IBD patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex-vivo colonic explants and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes. PMID:29091079

Effects of enteral immunonutrition on the maintenance of gut barrier function and immune function in pigs with severe acute pancreatitis.

PubMed

Zou, Xiao-Ping; Chen, Min; Wei, Wei; Cao, Jun; Chen, Lei; Tian, Mi

2010-01-01

This study evaluated the effects of enteral immunonutrition (EIN) supplemented with glutamine, arginine, and probiotics on gut barrier function and immune function in pigs with severe acute pancreatitis (SAP). The model was induced by retrograde injection of 5% sodium taurocholate and trypsin via the pancreatic duct. After induction of SAP, 18 pigs were randomly divided into 3 groups, in which either parenteral nutrition (PN), control enteral nutrition (CEN), or EIN was applied for 8 days. Serum and pancreatic fluid amylase concentration was determined. Intestinal permeability (lactulose to mannitol ratio) was measured by high-performance liquid chromatography, and plasma endotoxin was quantified by the chromogenic limulus amebocyte lysate technique. Samples of venous blood and organs were cultured using standard techniques. Pancreatitis severity and villi of ileum were scored according to histopathologic grading. Plasma T-lymphocyte subsets were measured by flow cytometry, and immunoglobulins (Igs) were determined via enzyme-linked immunosorbent assay. There were no significant differences in serum and pancreatic fluid amylases concentrations or in pancreatitis severity between any 2 of the 3 groups. Compared with PN and CEN, EIN significantly decreased intestinal permeability, plasma endotoxin concentration, and the incidence and magnitudes of bacterial translocation, but increased ileal mucosal thickness, villous height, crypt depth, and percentage of normal intestinal villi. Significant differences were found in CD3+, CD4+ lymphocyte subsets, the ratio of CD4+: CD8+ lymphocyte subsets, and serum IgA and IgG, but not IgM, between any 2 of the 3 groups. EIN maintained gut barrier function and immune function in pigs with SAP.

Kenaf seed supercritical fluid extract reduces aberrant crypt foci formation in azoxymethane-induced rats.

PubMed

Ghafar, Siti Aisyah Abd; Yazan, Latifah Saiful; Tahir, Paridah Md; Ismail, Maznah

2012-03-01

Kenaf (Hibiscus cannabinus) a plant of the family Malvaceae, is a valuable fiber plant native to India and Africa. Kenaf seeds contain alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E and other antioxidants with chemopreventive properties. In the present study we examined the hypothesis that kenaf seed 'supercritical fluid extract' (SFE) extract could suppress the early colon carcinogenesis in vivo by virtue of its bioactive compounds. To accomplish this goal, 60 male rats were randomly assigned to 5 groups which were (1) negative control group [not induced with azoxymethane (AOM)]; (2) positive control group (induced with AOM but received no treatment); (3) group treated with 500 mg/kg kenaf seed SFE extract; (4) group treated with 1000 mg/kg kenaf seed SFE extract; (5) group treated with 1500 mg/kg kenaf seed SFE extract. At 7 weeks of age, all rats except the negative control group received 15 mg/kg of AOM injection subcutaneously once a week for 2 weeks. Rats were euthanized at 13 weeks of the experiment. Number of ACF (mean±SD) ranged from 84.4±4.43 to 179.5±12.78 in group 2, 3, 4, 5. ACF reductions compared with the untreated group were 45.3, 51.4 and 53.1% in rats fed with 500, 1000 and 1500 mg/kg body weight, respectively. There were no significant differences in weight gain among groups. Our finding indicates that kenaf seed SFE extract reduced AOM-induced ACF in Sprague-Dawley male rats. Copyright © 2010 Elsevier GmbH. All rights reserved.

Accelerator mass spectrometry analysis of aroma compound absorption in plastic packaging materials

NASA Astrophysics Data System (ADS)

Stenström, Kristina; Erlandsson, Bengt; Hellborg, Ragnar; Wiebert, Anders; Skog, Göran; Nielsen, Tim

1994-05-01

Absorption of aroma compounds in plastic packaging materials may affect the taste of the packaged food and it may also change the quality of the packaging material. A method to determine the aroma compound absorption in polymers by accelerator mass spectrometry (AMS) is being developed at the Lund Pelletron AMS facility. The high sensitivity of the AMS method makes it possible to study these phenomena under realistic conditions. As a first test low density polyethylene exposed to 14C-doped ethyl acetate is examined. After converting the polymer samples with the absorbed aroma compounds to graphite, the {14C }/{13C } ratio of the samples is measured by the AMS system and the degree of aroma compound absorption is established. The results are compared with those obtained by supercritical fluid extraction coupled to gas chromatography (SFE-GC).

Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process.

PubMed

Kataoka, Makoto; Fukahori, Miho; Ikemura, Atsumi; Kubota, Ayaka; Higashino, Haruki; Sakuma, Shinji; Yamashita, Shinji

2016-04-01

The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of gastric pH on the oral absorption of poorly water-soluble drugs were consistent with observations in humans. In conclusion, the D/P system with the gastric phase may be a useful tool for better predicting the oral absorption of poorly water-soluble basic drugs. In addition, the effects of gastric pH on the oral absorption of poorly water-soluble drugs may be evaluated by the D/P system with and without the gastric phase. Copyright © 2016 Elsevier B.V. All rights reserved.

Time-domain simulation of nonlinear radiofrequency phenomena

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, Thomas G.; Austin, Travis M.; Smithe, David N.

Nonlinear effects associated with the physics of radiofrequency wave propagation through a plasma are investigated numerically in the time domain, using both fluid and particle-in-cell (PIC) methods. We find favorable comparisons between parametric decay instability scenarios observed on the Alcator C-MOD experiment [J. C. Rost, M. Porkolab, and R. L. Boivin, Phys. Plasmas 9, 1262 (2002)] and PIC models. The capability of fluid models to capture important nonlinear effects characteristic of wave-plasma interaction (frequency doubling, cyclotron resonant absorption) is also demonstrated.

Time-domain simulation of nonlinear radiofrequency phenomena

NASA Astrophysics Data System (ADS)

Jenkins, Thomas G.; Austin, Travis M.; Smithe, David N.; Loverich, John; Hakim, Ammar H.

2013-01-01

Nonlinear effects associated with the physics of radiofrequency wave propagation through a plasma are investigated numerically in the time domain, using both fluid and particle-in-cell (PIC) methods. We find favorable comparisons between parametric decay instability scenarios observed on the Alcator C-MOD experiment [J. C. Rost, M. Porkolab, and R. L. Boivin, Phys. Plasmas 9, 1262 (2002)] and PIC models. The capability of fluid models to capture important nonlinear effects characteristic of wave-plasma interaction (frequency doubling, cyclotron resonant absorption) is also demonstrated.

Phase-resolved reflectance spectroscopy on layered turbid media

NASA Astrophysics Data System (ADS)

Hielscher, Andreas H.; Liu, Hanli; Chance, Britton; Tittel, Frank K.; Jacques, Steven L.

1995-05-01

In this study, we investigate the influence of layered tissue structures on the phase-resolved reflectance. As a particular example, we consider the affect of the skin, skull, and meninges on noninvasive blood oxygenation determination of the brain. In this case, it's important to know how accurate one can measure the absorption coefficient of the brain through the enclosing layers of different tissues. Experiments were performed on layered gelatin tissue phantoms and the results compared to diffusion theory. It is shown that when a high absorbing medium is placed on top of a low absorbing medium, the absorption coefficient of the lower layer is accessible. In the inverse case, where a low absorbing medium is placed on top of a high absorbing medium, the absorption coefficient of the underlying medium can only be determined if the differences in the absorption coefficient are small, or the top layer is very thin. Investigations on almost absorption and scattering free layers, like the cerebral fluid filled arachnoid, reveal that the determination of the absorption coefficient is barely affected by these kinds of structures.

[Everted intestinal sac method for quick finding absorption ingredients of Wuzhuyu decoction].

PubMed

Gong, Muxin; Wang, Yaxun; Song, Yafang; Wang, Zhimin; Zhang, Qiwei; Wang, Weihao; Zhu, Jingjing

2010-06-01

To establish a method for quick finding the absorption ingredients of Wuzhuyu decoction in order to select the index to control its quality. The absorption of three concentration of Wuzhuyu decotion was investigated with the in vitro-everted intestinal sac model. The intestinal bag fluid of jejunum and ileum were collected in different time and the eight ingredients, which were evodiamine (Ev), rutaecarpine (Ru), limonin (Li), ginsenoside-Rb1, -Rg1, -Re (Rb1, Rg1, Re), isorhamnetin-3-O-beta-D-glucosyl(6''-->1'")-alpha-L-rhamnoside (Irs)and 6-gingerol (6-Gi), were detected by HPLC as the represent constituents in samples. Eight ingredients except Ru in samples could be detected, but Ev could not be detected in high concentration samples. The ratios between absorption ingredients were different from in Wuzhuyu decotion. The in vitro-everted intestinal sac canc absorb the ingredients of Wuzhuyu decotion selectivity. Compare with the ileum, the jejunum can provide the more absorption information and faster, the best test time is 60-90 min.

Drug Testing in Oral Fluid

PubMed Central

Drummer, Olaf H

2006-01-01

Over the last decade there have been considerable developments in the use of oral fluid (saliva) for drug testing. Oral fluid can provide a quick and non-invasive specimen for drug testing. However, its collection may be thwarted by lack of available fluid due to a range of physiological factors, including drug use itself. Food and techniques designed to stimulate production of oral fluid can also affect the concentration of drugs. Current applications are mainly focused on drugs of abuse testing in employees at workplaces where drug use has safety implications, in drivers of vehicles at the roadside and in other situations where drug impairment is suspected. Testing has included alcohol (ethanol) and a range of clinical tests eg antibodies to HIV, therapeutic drugs and steroids. Its main application has been for testing for drugs of abuse such as the amphetamines, cocaine and metabolites, opioids such as morphine, methadone and heroin, and for cannabis. Oral fluid concentrations of basic drugs such as the amphetamines, cocaine and some opioids are similar or higher than those in plasma. Tetrahydrocannabinol (THC), the major species present from cannabis use, displays similar concentrations in oral fluid compared to blood in the elimination phase. However, there is significant local absorption of the drug in the oral cavity which increases the concentrations for a period after use of drug. Depot effects occur for other drugs introduced into the body that allow local absorption, such as smoking of tobacco (nicotine), cocaine, amphetamines, or use of sub-lingual buprenorphine. Screening techniques are usually an adaptation of those used in other specimens, with an emphasis on the parent drug since this is usually the dominant species present in oral fluid. Confirmatory techniques are largely based on mass spectrometry (MS) with an emphasis on Liquid Chromatography-Mass Spectrometry (LC-MS), due to low sample volumes and the low detection limits required. Drug testing outside laboratory environments has become widespread and provides presumptive results within minutes of collection of specimens. This review focuses on the developments, particularly over the last 10 years, and outlines the roles and applications of testing for drugs in oral fluid, describes the difficulties associated with this form of testing and illustrates applications of oral fluid testing for specific drugs. PMID:17268583

Convection induced by selective absorption of radiation: A laboratory model of conditional instability

NASA Astrophysics Data System (ADS)

Krishnamurti, Ruby

1998-01-01

When there is internal heating in a fluid layer, convection can occur even if the static state is one of stable stratification. We have been investigating through laboratory experiments such a stably stratified layer of water which is heated above and cooled below. The water contains in dilute solution thymol blue (a pH indicator), which normally colors the water orange. It turns yellow if the pH is low, blue if the pH is high. A small DC voltage is applied across the layer, by using the bottom boundary as the positive electrode, the top boundary as the negative electrode. The hydroxyl ions formed near the bottom boundary cause the orange fluid to turn blue. The fluid layer is uniformly and steadily illuminated from above with light from a sodium vapor lamp. This radiation travels with negligible absorption through the orange fluid but is strongly absorbed by the blue fluid. The resultant warming of the blue fluid can lead to convective instability, with the blue fluid rising into warm upper layers, which it would continue to penetrate as long as it remains blue and as long as the radiative heating is sufficient to exceed the higher ambient temperatures above. This radiative heating occurs only in the blue rising flow; the sinking fluid is orange and is not heated. We have found that with a strongly stably stratified layer, convective plumes are unable to penetrate far and they remain shallow. However, for a weakly stratified layer, plumes grow tall and furthermore collect into a large convective cluster which persists as a steady coherent structure. The present paper deals also with the formulation of the governing equations to include the fluid-state-dependent heat source. A linear stability analysis shows that the critical Rayleigh number for onset of motion is drastically reduced. Furthermore, the cell size at onset is larger by a factor of √ 3/2 than in the classical Rayleigh-Benard convection problem. However, the laboratory fluid cells were much further broadened (by a factor of 8 or 10) when they penetrated into the stably stratified fluid above. In this case, the rising region is narrow and the sinking region is broad, so that downward vertical velocities are correspondingly small. In this way, the downwards-forced warm fluid has time to cool by conduction to the cold boundary. Steady finite amplitude solutions and their stability are analyzed and it is shown that there is a parameter range in which finite amplitude hexagonal cells are stable.

Surface waves in an incompressible fluid - Resonant instability due to velocity shear

NASA Technical Reports Server (NTRS)

Hollweg, Joseph V.; Yang, G.; Cadez, V. M.; Gakovic, B.

1990-01-01

The effects of velocity shear on the resonance absorption of incompressible MHD surface waves are studied. It is found that there are generally values of the velocity shear for which the surface wave decay rate becomes zero. In some cases, the resonance absorption goes to zero even for very small velocity shears. It is also found that the resonance absorption can be strongly enhanced at other values of the velocity shear, so the presence of flows may be generally important for determining the effects of resonance absorption, such as might occur in the interaction of p-modes with sunspots. Resonances leading to instability of the global surface mode can exist, and instability can occur for velocity shears significantly below the Kelvin-Helmholtz threshold. These instabilities may play a role in the development or turbulence in regions of strong velocity shear in the solar wind or the earth's magnetosphere.

Clone-preventive technique that features magnetic microfibers and cryptography

NASA Astrophysics Data System (ADS)

Matsumoto, Hiroyuki; Suzuki, Keiichi; Matsumoto, Tsutomu

1998-04-01

We have used the term 'clone' to refer to those things which are produced by methods such as counterfeiting, alteration, duplication or simulation. To satisfy the requirements of secure and low-cost techniques for preventing card fraud, we have recently developed a clone preventive system called 'FibeCrypt (Fiber Cryptosystem)' which utilizes physical characteristics. Each card has a canonical domain (i.e. a distinctive part), similar to fingerprints as the biometric measurement, made up of magnetic micro-fibers scattered randomly inside. We have applied cryptosystems to the system. FibeCrypt examines and authenticates the unique pattern of the canonical domain using pre-stored reference data and a digital signature. In our paper, the schemes and the features of this system are described in detail. The results of our examinations show the accuracy of authentication of the system. We conclude that this authentication technique which utilizes physical characteristics can be very effective for clone prevention in various fields.

A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.

PubMed

Buske, Peter; Galle, Jörg; Barker, Nick; Aust, Gabriela; Clevers, Hans; Loeffler, Markus

2011-01-06

We introduce a novel dynamic model of stem cell and tissue organisation in murine intestinal crypts. Integrating the molecular, cellular and tissue level of description, this model links a broad spectrum of experimental observations encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal competition.Using computational simulations we demonstrate that the model is capable of quantitatively describing and predicting the dynamic behaviour of the intestinal tissue during steady state as well as after cell damage and following selective gain or loss of gene function manipulations affecting Wnt- and Notch-signalling. Our simulation results suggest that reversibility and flexibility of cellular decisions are key elements of robust tissue organisation of the intestine. We predict that the tissue should be able to fully recover after complete elimination of cellular subpopulations including subpopulations deemed to be functional stem cells. This challenges current views of tissue stem cell organisation.

Endocrine cells in the denervated intestine

PubMed Central

Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

2000-01-01

This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

A European Mitochondrial Haplotype Identified in Ancient Phoenician Remains from Carthage, North Africa

PubMed Central

Matisoo-Smith, Elizabeth A.; Gosling, Anna L.; Boocock, James; Kardailsky, Olga; Kurumilian, Yara; Roudesli-Chebbi, Sihem; Badre, Leila; Morel, Jean-Paul; Sebaï, Leïla Ladjimi; Zalloua, Pierre A.

2016-01-01

While Phoenician culture and trade networks had a significant impact on Western civilizations, we know little about the Phoenicians themselves. In 1994, a Punic burial crypt was discovered on Byrsa Hill, near the entry to the National Museum of Carthage in Tunisia. Inside this crypt were the remains of a young man along with a range of burial goods, all dating to the late 6th century BCE. Here we describe the complete mitochondrial genome recovered from the Young Man of Byrsa and identify that he carried a rare European haplogroup, likely linking his maternal ancestry to Phoenician influenced locations somewhere on the North Mediterranean coast, the islands of the Mediterranean or the Iberian Peninsula. This result not only provides the first direct ancient DNA evidence of a Phoenician individual but the earliest evidence of a European mitochondrial haplogroup, U5b2c1, in North Africa. PMID:27224451

Evidence for Different Reaction Pathways for Liquid and Granular Micronutrients in a Calcareous Soil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hettiarachchi, Ganga M.; McLaughlin, Mike J.; Scheckel, Kirk G.

2008-06-16

The benefits of Mn and Zn fluid fertilizers over conventional granular products in calcareous sandy loam soils have been agronomically demonstrated. We hypothesized that the differences in the effectiveness between granular and fluid Mn and Zn fertilizers is due to different Mn and Zn reaction processes in and around fertilizer granules and fluid fertilizer bands. We used a combination of several synchrotron-based x-ray techniques, namely, spatially resolved micro-x-ray fluorescence (?-XRF), micro-x-ray absorption near edge structure spectroscopy (?-XANES), and bulk-XANES and -extended x-ray absorption fine structure (EXAFS) spectroscopy, along with several laboratory-based x-ray techniques to speciate different fertilizer-derived Mn and Znmore » species in highly calcareous soils to understand the chemistry underlying the observed differential behavior of fluid and granular micronutrient forms. Micro-XRF mapping of soil-fertilizer reactions zones indicated that the mobility of Mn and Zn from liquid fertilizer was greater than that observed for equivalent granular sources of these micronutrients in soil. After application of these micronutrient fertilizers to soil, Mn and Zn from liquid fertilizers were found to remain in comparatively more soluble solid forms, such as hydrated Mn phosphate-like, Mn calcite-like, adsorbed Zn-like, and Zn silicate-like phases, whereas Mn and Zn from equivalent granular sources tended to transform into comparatively less soluble solid forms such as Mn oxide-like, Mn carbonate-like, and Zn phosphate-like phases.« less

The Role of “Leakage” of Tubular Fluid in Anuria Due to Mercury Poisoning*

PubMed Central

Bank, Norman; Mutz, Bertrand F.; Aynedjian, Hagop S.

1967-01-01

The role of “leakage” of tubular fluid in anuria produced by mercury poisoning was studied in rats by micropuncture techniques. After an initial brisk diuresis, almost all animals were completely anuric 24 hours after HgCl2 injection. Lissamine green injected intravenously in the early stage of anuria appeared in the beginning of the proximal tubule, but the color became progressively lighter as the dye traversed the proximal convolutions. The dye was barely visible in the terminal segments of the proximal tubule; it did not appear at all in the distal tubules. These observations suggest that the proximal epithelium had become abnormally permeable to Lissamine green. Tubular fluid to plasma inulin (TF/PIn) ratios and inulin clearance were measured in individual nephrons at three sites: early proximal tubule, late proximal tubule, and distal tubule. It was found that TF/PIn ratios were abnormally low in the late proximal and distal tubules. Inulin clearance was normal at the beginning of the proximal tubule but fell by more than 60% by the late proximal convolutions. Thus, the proximal tubule had also become permeable to inulin. We conclude from these observations that anuria in mercury poisoning can occur in the presence of a normal glomerular filtration rate. The absence of urine flow appears to be due to complete absorption of the filtrate through an excessively permeable tubular epithelium. The driving force affecting this fluid absorption is probably the colloid oncotic pressure of the peritubular capillary blood. Images PMID:6025476