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Secretion Rate (secretion + rate)
Kinds of Secretion Rate Selected AbstractsRobust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy databaseDIABETES OBESITY & METABOLISM, Issue 10 2008R. E. Pratley Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [source] Effects of contaminated sediment on the epidermis of mummichog, Fundulus heteroclitusENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2000Laurent C. Mézin Abstract Secretion of mucus by epidermal goblet cells protects fish against many biological, physical, and chemical insults encountered in the environment. This study monitored changes in hemoglobin concentration in epidermal mucus and in the density, diameter, and mucus quality of epidermal goblet cells in the mummichog, Fundulus heteroclitus, following exposure to creosote-contaminated sediment from the Elizabeth River, Virginia, USA. Fish were exposed for 13 d in flow-through aquaria to either uncontaminated (US) or contaminated (CS) sediments and were sampled periodically. The condition index was lower and the mortality rate and the occurrence of epidermal lesions were higher in CS-exposed fish than in US-exposed fish. Hemoglobin contents in epidermal mucus from the former group were significantly higher than from the latter. Significant reductions in both size and density of goblet cells in CS-exposed fish suggested a mucus secretion rate exceeding its production rate. Significant changes in mucin types between treatments did not occur until day 13 and are not believed to be directly related to the creosote present in the contaminated sediment. These results all indicate that exposure to creosote-contaminated sediment had a profound and deleterious effect on fish health. [source] Evolution of morphogenesis in 360-million-year-old conodont chordates calibrated in daysEVOLUTION AND DEVELOPMENT, Issue 6 2008Jerzy Dzik SUMMARY Highly rhythmic increments of crown tissue are identifiable in conodont oral apparatus elements from the Late Devonian of the Holy Cross Mountains, Poland; individual laminae being of thickness comparable with daily increments of vertebrate tooth enamel and fish otoliths. Abundant occurrence of such specimens enables bed-by-bed (stratophenetic) studies of the process of evolution at the population level and quantitative presentation of the evolution of ontogeny in the sampled geological section covering several million years. The morphologic transformation is expressed as expansion of a juvenile asymmetry to later stages of the ontogeny and in decrease of the mature element width, which was due to a change of the mineral tissue secretion rate. It was not just a simple extension of a juvenile character into the later stage of the ontogeny (heterochrony) but rather a true developmental novelty. The evolution was gradual and very slow. The proposed quantitative approach to growth increments in the mineral skeleton of ancient chordates introduces real-time units to evolutionary developmental studies connected with direct paleontological evidence on the course of evolution. [source] Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgarisEXPERIMENTAL DERMATOLOGY, Issue 10 2009Bodo C. Melnik Abstract:, It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion counts and facial sebum secretion rate have been reported. IGF-1 stimulates 5,-reductase, adrenal and gonadal androgen synthesis, androgen receptor signal transduction, sebocyte proliferation and lipogenesis. Milk consumption results in a significant increase in insulin and IGF-1 serum levels comparable with high glycaemic food. Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b. Acne is proposed to be an IGF-1-mediated disease, modified by diets and smoking increasing insulin/IGF1-signalling. Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling. Persistent acne in adulthood with high IGF-1 levels may be considered as an indicator for increased risk of cancer, which may require appropriate dietary intervention as well as treatment with insulin-sensitizing agents. [source] EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded ,1-antitrypsinGENES TO CELLS, Issue 5 2006Nobuko Hosokawa Misfolded glycoproteins are degraded by a mechanism known as ERAD (ER-associated degradation) after retrotranslocation out of the endoplasmic reticulum (ER). This mechanism plays an important role in ER quality control. We previously reported that an ER membrane protein, EDEM, accelerates ERAD of a misfolded ,1-antitrypsin variant, null (Hong Kong) (NHK), suggesting that EDEM may function as an acceptor of terminally misfolded glycoproteins. In this study, we constructed several genetically manipulated cell lines to test this hypothesis. EDEM expression did not alter the secretion rate of properly folded molecules and the forced retention of wild-type ,1-antitrypsin in the ER did not cause its association with EDEM, suggesting that EDEM may function as a molecular chaperone. To examine this possibility, we analyzed the effect of EDEM over-expression on the structure of NHK, and found that the accumulation of covalent NHK dimers was selectively prevented by the over-expression of EDEM. Co-expression of NHK with two other ER membrane proteins, calnexin and H+/K+ -ATPase (, subunit), did not inhibit NHK dimer formation or accelerate NHK ERAD. These results indicate that EDEM may maintain the retrotranslocation competence of NHK by inhibiting aggregation so that unstable misfolded proteins can be accommodated by the dislocon for ERAD. [source] Effect of exercise, aging and functional capacity on acute secretory immunoglobulin A response in elderly people over 75 years of ageGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2009Yuzuru Sakamoto Background: Age-associated decline in immune function and regulation, referred to as immunosenescence, brings about an increased incidence of infectious diseases in the aged; however, there are few data on the effect of aging and exercise on mucosal immune function in elderly people. Moreover, there is no evidence on whether the change in functional capacity affects mucosal immunity in elderly people. Therefore, the aim of the present study was to examine the effects of exercise, aging and functional capacity on mucosal immune function in elderly people over 75 years of age. Methods: The subjects were 92 community-dwelling elderly women aged over 75 years who lived in a rural community in Miyagi Prefecture. The subjects periodically performed approximately 20 min of low intensity exercise. Saliva samples were collected before and after exercise, and saliva flow (SF), secretory immunoglobulin A (SIgA) concentration (SIgA-C) and SIgA secretion rate (SIgA-SR) were determined. The Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) was used to measure functional capacity. Results: In comparison with before exercise, SF, SIgA-C and SIgA-SR were significantly increased after exercise in elderly subjects. In addition, when low and high value groups of resting SIgA levels were compared, acute SIgA responses were observed only in the low value group; however, there was no significant effect of aging and decline in functional capacity on exercise-induced SIgA response. Conclusion: These results suggest that resting SIgA levels influence the mucosal immune function response to exercise in elderly people over 75 years of age. [source] A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency,HUMAN MUTATION, Issue 1 2004Marilyn M. Gordon Abstract Congenital intrinsic factor (IF) deficiency is a disorder characterized by megaloblastic anemia due to the absence of gastric IF (GIF, GenBank NM_005142) and GIF antibodies, with probable autosomal recessive inheritance. Most of the reported patients are isolated cases without genetic studies of the parents or siblings. Complete exonic sequences were determined from the PCR products generated from genomic DNA of five affected individuals. All probands had the identical variant (g.68A>G) in the second position of the fifth codon in the coding sequence of the gene that introduces a restriction enzyme site for Msp I and predicts a change in the mature protein from glutamine5 (CAG) to arginine5 (CGG). Three subjects were homozygous for this base exchange and two subjects were heterozygous, one of which was apparently a compound heterozygote at positions 1 and 2 of the fifth codon ([g.67C>G] + [g.68A>G]). The other patient, heterozygous for position 2, had one heterozygous unaffected parent. Most parents were heterozygous for this base exchange, confirming the pattern of autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF was mutated at base pair g.68 (A>G) and expressed in COS-7 cells. The apparent size, secretion rate, and sensitivity to pepsin hydrolysis of the expressed IF were similar to native IF. The allelic frequency of g.68A>G was 0.067 and 0.038 in two control populations. This sequence aberration is not the cause of the phenotype, but is associated with the genotype of congenital IF deficiency and could serve as a marker for inheritance of this disorder. Hum Mutat 23:85,91, 2004. © 2003 Wiley-Liss, Inc. [source] Experimental determination of the periodicity of incremental features in enamelJOURNAL OF ANATOMY, Issue 1 2006T. M. Smith Abstract Vital labelling of hard tissues was used to examine the periodicity of features of dental enamel microstructure. Fluorescent labels were administered pre- and postnatally to developing macaques (Macaca nemestrina), which were identified histologically in dentine and related to accentuated lines in enamel, allowing for counts of features within known-period intervals. This study demonstrates that cross-striations represent a daily rhythm in enamel secretion, and suggests that intradian lines are the result of a similar 12-h rhythm. Retzius lines were found to have a regular periodicity within individual dentitions, and laminations appear to represent a daily rhythm that also shows 12-h subdivisions. The inclusion of intradian lines and laminations represents the first empirical evidence for their periodicities in primates; these features frequently complicate precise measurements of secretion rate and Retzius line periodicity, which are necessary for determination of crown formation time. The biological basis of incremental feature formation is not completely understood; long-period features may result from interactions between short-period rhythms, although this does not explain the known range of Retzius line periodicities within humans or among primates. Studies of the genetic, neurological and hormonal basis of incremental feature formation are needed to provide more insight into their physiological and structural basis. [source] Secretion of RANTES (CCL5) and interleukin-10 from mesenteric adipose tissue and from creeping fat in Crohn's disease: Regulation by steroid treatmentJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2006Andreas Schäffler Abstract Background:, Creeping fat represents a characteristic feature of Crohn's disease (CD) and adipose tissue is currently being recognized as a complex compartment secreting highly active molecules. Pro- or anti-inflammatory adipose tissue-derived secretory products (adipocytokines) might play a role in the pathogenesis of CD. Methods:, Adipose tissue specimens were obtained from creeping fat contiguous to the involved intestine of 10 patients with CD. Mesenteric adipose tissue specimens resected in 13 patients with colon cancer (CC) and in seven patients with diverticulitis (DIV) served as controls. Three fat tissue specimens per well and n = 6,8 wells per patient were incubated ex vivo for 24 h. The release of regulated on activation, T-cell expressed and secreted (RANTES) and interleukin (IL)-10 into the supernatant was measured by ELISA. Results:, Both RANTES and IL-10 secretion could be demonstrated from total adipose tissue explants. The RANTES secretion is increased from creeping fat in CD (3691 ± 597 pg/g fat per 24 h) when compared to mesenteric adipose tissue from patients with CC (1690 ± 191 pg/g fat per 24 h; P < 0.0001) or DIV (1672 ± 336 pg/g fat per 24 h; P < 0.0001). In contrast, IL-10 secretion is downregulated significantly only in patients with DIV (1418 ± 180 pg/g fat per 24 h; P = 0.016) when compared to CC patients (2368 ± 259 pg/g fat per 24 h). Crohn's disease patients receiving steroids had a higher secretion rate of RANTES and IL-10. Conclusions:, Both RANTES and IL-10 secretion can be detected from mesenteric adipose tissue and from creeping fat. The elevated RANTES and IL-10 secretion from creeping fat in CD is not due to a CD-specific effect but caused by steroid treatment. [source] Vascular endothelial growth factor secretion from mesenteric adipose tissue and from creeping fat in Crohn's diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2006Andreas Schäffler Abstract Background:, Creeping fat represents a characteristic feature of Crohn's disease (CD), and adipose tissue secretes adipocytokines and chemokines/growth factors such as vascular endothelial growth factor (VEGF). Because VEGF serum levels and mucosal VEGF expression is elevated in CD patients, the aim of the present paper was to investigate creeping fat-derived VEGF secretion in CD. Material and Methods:, Adipose tissue was obtained from creeping fat of 10 patients with CD. Mesenteric adipose tissue was resected from 13 patients with colon cancer (CC) and from seven patients with diverticulitis (DIV). Three fat tissue specimens per well, and several wells (6,8) per patient were incubated ex vivo for 24 h. The release of VEGF into the supernatant was measured by ELISA. Results:, There was stable VEGF secretion from mesenteric adipose tissue of patients with CC or DIV and from creeping fat of patients with CD. Whereas the VEGF secretion rate was not different between patients with CD (465 ± 98 pg/g fat per 24 h) and CC (399 ± 48 pg/g fat per 24 h), VEGF secretion was significantly reduced in patients suffering from DIV (115 ± 41 pg/g fat per 24 h; P < 0.0001 and P = 0.001, respectively). The CD patients treated with steroids had significantly lower VEGF secretion rates (294 ± 42 pg/g fat per 24 h) than CD patients not receiving steroids (607 ± 105 pg/g fat per 24 h; P = 0.001). Conclusions:, Creeping fat is an important source of VEGF secretion. The characteristics of the inflammatory changes in CD might be due to the lack of VEGF downregulation that is seen in DIV. [source] The relationship between salivary secretion rate and masticatory efficiencyJOURNAL OF ORAL REHABILITATION, Issue 1 2004T. Ishijima summary, In order to elucidate the relationship between the salivary secretion rate and masticatory efficiency, experimental hypo- and hyper-salivation were produced by the administration of atropine sulphate presenting an anticholinergic effect and pilocarpine hydrochloride having a muscarine effect orally in 10 healthy fully dentates. To confirm the pharmaceutical effect of these drugs, the unstimulated whole salivary secretion rate during 10 min, and masticatory efficiency using the sieve method were measured before and after medication. The unstimulated whole salivary secretion rate during 10 min decreased significantly by the administration of atropine sulphate (P < 0·05), and increased significantly by pilocarpine hydrochloride (P < 0·01). The masticatory efficiency after atropine sulphate medication was significantly lower than that before (P < 0·01). The increase in salivary secretion by pilocarpine hydrochloride did not lead to a higher masticatory efficiency. The evidence supports the understanding that saliva plays an important role in masticatory function. [source] Salivary IgA subclasses and bacteria-reactive IgA in patients with aggressive periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2002S. Hägewald The local salivary immunoglobulin A (IgA) response in patients with aggressive periodontitis to oral microorganisms and its role for the pathogenesis has not been determined. This study investigated the hypothesis that aggressive periodontitis patients have impaired oral secretory immunity. Our test group was made-up of 19 aggressive periodontitis patients and 19 age- and gender-matched periodontally healthy controls. Total IgA, IgA subclass 1, IgA subclass 2 and IgA reactive to Actinobacillus actinomycetemcomitans Y4, Treponema denticola ATCC 35404 and Candida albicans DSM 3454 were determined by enzyme-linked immunosorbent assay in whole unstimulated and stimulated saliva. A statistically significantly lower concentration and secretion rate of total salivary IgA (P < 0.01) and IgA1 (P < 0.001) was found in the aggressive periodontitis group in resting and stimulated saliva. A decrease of IgA2 (P < 0.05) was seen in resting saliva. Although only minor differences were detected in the concentration and secretion of bacteria-reactive IgA in both groups, the proportion of bacteria-reactive IgA from the total IgA was significantly higher (P < 0.01) in the aggressive periodontitis group in all three microorganisms tested. Our results indicate an inhibition of total secretory IgA. In particular an IgA subclass 1-specific decrease in aggressive periodontitis was noted, while the bacteria-reactive humoral immune system in saliva was activated. The role of the decrease of IgA1 immunoglobulins in aggressive periodontitis with respect to susceptibility for periodontal diseases has to be elucidated. [source] Salivary anticandidal activity and saliva composition in an HIV-infected cohortMOLECULAR ORAL MICROBIOLOGY, Issue 5 2001A. L. Lin This study investigated salivary anticandidal activity and salivary composition in stimulated whole saliva of 18 advanced HIV-infected patients and compared these values to healthy controls. Stimulated whole saliva from HIV-infected patients showed decreased anticandidal activity. The flow rate was reduced by 40% as compared with controls. The saliva flow rate for HIV-infected patients who had recoverable yeast in their saliva was reduced as compared to HIV-infected patients without recoverable yeast. For HIV-infected patients, the saliva concentrations of lactoferrin, secretory IgA and Cl, were increased while the secretion rate of lysozyme, total protein and K+ were reduced. There was no difference in any parameter as a function of taking the antifungal drug fluconazole. There was no association between salivary anticandidal activity and any salivary component. This study shows reduced anticandidal activity and salivary flow rate in HIV-infected patients. These alterations may contribute to their increased incidence of oral candidal infections. [source] Energy substrates in bovine oviduct and uterine fluid and blood plasma during the oestrous cycleMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2008S.A. Hugentobler Abstract Up to 40 percent of cattle embryos die within 3 weeks of fertilization but there is little or no published information on the composition of the oviduct and uterine fluids essential for their survival during this time. We have measured the concentrations of the energy substrates, glucose, lactate, and pyruvate in cattle oviduct fluid on Days 0, 2, 4, and 6 and uterine fluid on Days 6, 8, and 14 of the oestrous cycle and corresponding blood samples. Oviduct and uterine fluids were collected in situ. Glucose concentrations in oviduct and uterine fluids were similar on all days and lower than in plasma (P,<,0.05). Oviduct lactate concentration was up to eightfold higher than uterine or plasma concentration (P,<,0.01). Oviduct pyruvate concentrations were similar on all days and lower than plasma concentrations on Days 0 and 2 (P,<,0.005). Pyruvate concentrations were similar in the uterus and in plasma except on Day 14 when the concentration in plasma was higher (P,<,0.05). There were no associations between systemic progesterone or oestradiol and glucose, lactate or pyruvate. There was a linear positive relationship (P,<,0.001) between oviduct fluid secretion rate and oviduct glucose concentration and a linear negative relationship (P,<,0.001) between oviduct fluid secretion rate and oviduct lactate, but no association between uterine fluid secretion rate and energy substrates. The different concentrations and associations between the energy substrates in oviduct and uterine fluids and blood plasma indicate a differential regulation of the secretion of these energy substrates by the oviduct and uterine epithelium. Mol. Reprod. Dev. 75: 496,503, 2008. © 2007 Wiley-Liss, Inc. [source] Pilocarpine treatment in a mixed cohort of xerostomic patientsORAL DISEASES, Issue 1 2007DJ Aframian Objective:, To compare the effect of a single 5-mg dose of pilocarpine hydrochloride on the salivary flow rate in three groups of xerostomic patients. Subjects and methods:, Forty-five patients were divided into three groups according to the etiology of their xerostomia: (i) radiotherapy; (ii) Sjögren's syndrome; and (iii) sialosis and xerogenic medications. Following the oral administration of a 5-mg pilocarpine hydrochloride tablet blood pressure, heart rate, body temperature and saliva secretion rates were monitored hourly for 3 h and adverse events were reported. Results:, The most significant and persistent elevation of salivary flow rate was observed in the sialosis/drug-induced group followed by the Sjögren's syndrome group. The radiotherapy group presented a significant elevation of salivary secretion rate after 1 and 2 h, but returned to baseline at 3 h. No significant changes in vital signs were reported, except for low diastolic pressure measured at 1 h in the radiotherapy group. Several adverse events were recorded throughout the trial; however, only one patient withdrew from the study. Conclusion:, Treatment with pilocarpine hydrochloride tablets may improve saliva secretion in patients taking xerogenic medications and/or suffering from metabolic sialosis expanding the beneficial potential of this sialogogue. [source] Pilocarpine for the treatment of salivary glands' impairment caused by radioiodine therapy for thyroid cancerORAL DISEASES, Issue 3 2006DJ Aframian Objectives:, To study the effect of single-dose pilocarpine hydrochloride 5 mg on the whole unstimulated and stimulated salivary flow in patients suffering from thyroid cancer treated with radioiodine therapy, and to investigate the changes in vital signs during the treatment. Subjects and methods:, Five such patients were referred with complaints of dry mouth, rampant caries, and pain in the parotid gland region or history of chronic recurrent suppurative sialodenitis. A single dose of 5 mg pilocarpine hydrochloride was administered to each patient and blood pressure, heart rate, body temperature and salivary secretion rate were monitored at 1, 2 and 3 h. Results:, A significant elevation of unstimulated and stimulated saliva flow rate was observed in four patients without significant alteration of the monitored vital signs. Conclusions:, Treatment with pilocarpine hydrochloride may be beneficial in the case of impaired salivary function in patients treated with radioiodine. [source] Signal pathways regulating hyaluronan secretion into static and cycled synovial joints of rabbitsTHE JOURNAL OF PHYSIOLOGY, Issue 17 2009K. R. Ingram Joint lubrication, synovial fluid conservation and many pathophysiological processes depend on hyaluronan (HA). Intra-articular HA injection and exercise, which stimulates articular HA production, ameliorate osteoarthritis. We therefore investigated the pathways regulating movement-stimulated articular HA secretion rate () in vivo. Endogenous HA was removed from the knee joint cavity of anaesthetised rabbits by washout. Joints were then cycled passively or remained static for 5 h, with/without intra-articular agonist/inhibitor, after which newly secreted HA was harvested for analysis. Movement almost doubled . Similar or larger increases were elicited in static joints by the intra-articular Ca2+ ionophore ionomycin, prostaglandin E2, cAMP-raising agents, serine/threonine phosphatase inhibitor and activation of protein kinase C (PKC). PKC-stimulated secretion was inhibited by the PKC inhibitor bisindolylmaleimide I and inhibitors of the downstream kinases MEK-ERK (U0126, PD98059). These agents inhibited movement-stimulated secretion of HA (MSHA) only when the parallel p38 kinase path was simultaneously inhibited by SB203580 (ineffective alone). The phospholipase C inhibitor U73122 almost fully blocked MSHA (P= 0.001, n= 10), without affecting static . The ENaC channel blocker amiloride inhibited MSHA, whereas other inhibitors of stretch-activated channels (Gd3+, ruthenium red, SKF96365) did not. It is proposed that MSHA may be mediated by PLC activation, leading to activation of parallel PKC,MEK,ERK and p38 kinase pathways. [source] Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl, channel geneTHE JOURNAL OF PHYSIOLOGY, Issue 1 2002Jorge Arreola Salivary gland acinar cells shrink when Cl, currents are activated following cell swelling induced by exposure to a hypotonic solution or in response to calcium-mobilizing agonists. The molecular identity of the Cl, channel(s) in salivary cells involved in these processes is unknown, although ClC-3 has been implicated in several tissues as a cell-volume-sensitive Cl, channel. We found that cells isolated from mice with targeted disruption of the Clcn3 gene undergo regulatory volume decrease in a fashion similar to cells from wild-type littermates. Consistent with a normal regulatory volume decrease response, the magnitude and the kinetics of the swell-activated Cl, currents in cells from ClC-3-deficient mice were equivalent to those from wild-type mice. It has also been suggested that ClC-3 is activated by Ca2+ -calmodulin-dependent protein kinase II; however, the magnitude of the Ca2+ -dependent Cl, current was unchanged in the Clcn3,/- animals. In addition, we observed that ClC-3 appeared to be highly expressed in the smooth muscle cells of glandular blood vessels, suggesting a potential role for this channel in saliva production by regulating blood flow, yet the volume and ionic compositions of in vivo stimulated saliva from wild-type and null mutant animals were comparable. Finally, in some cells ClC-3 is an intracellular channel that is thought to be involved in vesicular acidification and secretion. Nevertheless, the protein content of saliva was unchanged in Clcn3,/- mice. Our results demonstrate that the ClC-3 Cl, channel is not a major regulator of acinar cell volume, nor is it essential for determining the secretion rate and composition of saliva. [source] ORIGINAL ARTICLE: Characterization of Cytokine Production by Human Term Placenta Macrophages In VitroAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2008Oleg Pavlov Problem, Macrophages are apparently the only immune cells within placenta villi, yet functions of these cells remain obscure. It has been postulated that placental macrophages accomplish regulatory roles at the fetal,maternal interface by means of wide variety of secreted cytokines. We attempt to analyze the patterns of cytokine production in an isolated population of placental macrophages. Method of study, Macrophages were obtained from term placentas in the absence of spontaneous labor. The basal and lipopolysaccharide (LPS)-stimulated levels of intracellular cytokines were detected by flow cytometry. The basal cytokine secretion was determined by BDÔCytometry Bead Array (BD Biosciences, San Diego, CA, USA). Results, Intracellular IL-1,, IL-1,, IL-6, and TNF, were detected in 31, 27, 4, and 3% CD68+ cells, respectively. Stimulation with LPS increased the proportions of cytokine-producing CD68+ cells to 48, 50, 28, and 49%, respectively. Under basal conditions, levels of released TNF, and IL-6, respectively, were 20- and 25-fold higher when compared with IL-1, while IL-10 was secreted in small but detectable amounts. When a secretory activity was estimated for cytokine-producing cells, the secretion rate for TNF, and IL-6 overwhelmingly surpassed that for IL-1, (TNF,:IL-6:IL-1, ratio was 192:145:1). Conclusion, These results suggest functional heterogeneity of the placental macrophage population and contribute to the elucidation of regulatory roles of these cells in gestation. [source] Effects of acute or chronic exposure to dietary organic anions on secretion of methotrexate and salicylate by Malpighian tubules of Drosophila melanogaster larvaeARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2010Sarah Chahine Abstract The effects of dietary exposure to organic anions on the physiology of isolated Malpighian tubules and on tubule gene expression were examined using larvae of Drosophila melanogaster. Acute (24,h) or chronic (7,d) exposure to type I organic anions (fluorescein or salicylate) was associated with increased fluid secretion rates and increased fluxes of both salicylate and the type II organic anion methotrexate. By contrast, chronic exposure to dietary methotrexate was associated with increased fluid secretion rate and increased flux of methotrexate, but not salicylate. Exposure to methotrexate in the diet resulted in increases in the expression of a multidrug efflux transporter gene (MET; CG30344) in the Malpighian tubules. There were also increases in expression of genes for either a Drosophila multidrug resistance,associated protein (dMRP; CG6214) or an organic anion transporting polypeptide (OATP; CG3380), depending on the concentration of methotrexate in the diet. Exposure to salicylate in the diet was associated with an increase in expression of dMRP and with decreases of MET and OATP. Exposure to dietary salicylate or methotrexate was also associated with different patterns of expression of heat shock protein genes. The results suggest that exposure to specific type I or type II organic anions has multiple effects and results not only in increased organic anion transport but also in increased rates of inorganic ion transport, which drives osmotically-obliged fluid secretion. Increased fluid secretion may enhance secretion of organic anions by eliminating diffusive backflux from the tubule lumen to the hemolymph. © 2010 Wiley Periodicals, Inc. [source] Control of the release of digestive enzymes in the larvae of the fall armyworm, Spodoptera frugiperdaARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2010Digali Lwalaba Abstract There is a basal level of enzyme activity for trypsin, aminopeptidase, amylase, and lipase in the gut of unfed larval (L6) Spodoptera frugiperda. Trypsin activity does not decrease with non-feeding, possibly because of the low protein levels in plants along with high amino acid requirements for growth and storage (for later reproduction in adults). Therefore, trypsin must always be present so that only a minimal protein loss via egestion occurs. Larvae, however, adjust amylase activity to carbohydrate ingestion, and indeed amylase activity is five-fold higher in fed larvae compared to unfed larvae. Gut lipase activity is low, typical of insects with a high carbohydrate diet. A flat-sheet preparation of the ventriculus was used to measure the release of enzymes in response to specific nutrients and known brain/gut hormones in S. frugiperda. Sugars greatly increase (>300%) amylase release, but starch has no effect. Proteins and amino acids have little or no effect on trypsin or aminopeptidase release. The control of enzyme release in response to food is likely mediated through neurohormones. Indeed, an allatostatin (Spofr-AS A5) inhibits amylase and trypsin, and allatotropin (Manse- AT) stimulates amylase and trypsin release. Spofr-AS A5 also inhibits ileum myoactivity and Manse-AT stimulates myoactivity. The epithelial secretion rate of amylase and trypsin was about 20% of the amount of enzyme present in the ventricular lumen, which, considering the efficient counter-current recycling of enzymes, suggests that the secretion rate is adequate to replace egested enzymes. © 2009 Wiley Periodicals, Inc. [source] Improvement of Metabolic Performance of Cultured Hepatocytes by High Oxygen Tension in the AtmosphereARTIFICIAL ORGANS, Issue 1 2001Kennichi Yanagi Abstract: Maintaining metabolic functions of cultured hepatocytes at higher levels is an essential requirement for the development of a bioartificial liver. We investigated the effect of oxygen tension (10,40%) of the medium on immobilization efficiency and metabolic functions of cultured hepatocytes obtained from a rat for up to 4 days. Immobilization efficiencies of cultures in 10% oxygen showed a significantly lower value from those for the other conditions. The ammonium metabolic rate and the albumin secretion rate were significantly improved with an increase of dissolved oxygen tension for up to 2 days. These values remained similar in the later stage of the culture. The urea secretion rate showed similar values in all conditions. In conclusion, higher oxygen tension improved immobilization efficiency and metabolic functions of cultured rat hepatocytes in the earlier stage of culture for up to 2 days. [source] Pharmacodynamics of glucose regulation by methylprednisolone.BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009II. normal rats Abstract A physiologic pharmacodynamic model was developed to jointly describe the effects of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal rats. Six groups of animals were given MPL intravenously at 0, 10 and 50,mg/kg, or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3,mg/kg/h. Plasma concentrations of MPL, corticosterone (CST), glucose and insulin were determined at various times up to 72,h after injection and 336,h after infusion. The pharmacokinetics of MPL was described by a two-compartment model. A circadian rhythm for CST was found in untreated rats with a stress-altered baseline caused by handling, which was captured by a circadian harmonic secretion rate with an increasing mesor. All drug treatments caused CST suppression. Injection of MPL caused temporary increases in glucose over 4,h. Insulin secretion was thereby stimulated yielding a later peak around 6,h. In turn, insulin can normalize glucose. However, long-term dosing caused continuous hyperglycemia during and after infusion. Hyperinsulinemia was achieved during infusion, but diminished immediately after dosing despite the high glucose concentration. The effects of CST and MPL on glucose production were described with a competitive stimulation function. A disease progression model incorporating reduced endogenous glucose uptake/utilization was used to describe glucose metabolism under different treatments. The results exemplify the roles of endogenous and exogenous hormones in mediating glucose dynamics. The pharmacokinetic/pharmacodynamic model is valuable for quantitating diabetogenic effects of corticosteroid treatments and provides mechanistic insights into the hormonal control of the metabolic system. Copyright © 2009 John Wiley & Sons, Ltd. [source] A population analysis of VEGF transgene expression and secretionBIOTECHNOLOGY & BIOENGINEERING, Issue 5 2008Golnaz Karoubi Abstract The induction of therapeutic angiogenesis with gene therapy approaches has received considerable interest and some limited clinical success. A major drawback to this approach is a lack of understanding of the pharmacokinetics of therapeutic protein delivery. This has become increasingly more relevant as recent studies have illustrated a defined therapeutic window for angiogenic protein secretion into the local microenvironment. For cell based gene therapies, with cells widely distributed throughout the tissue, this implies that any individual cell must attain a specific secretion rate to produce a local angiogenic response. Here we report a reproducible technique enabling the study of growth factor secretion from individual cells following transient plasmid transfection. We demonstrate significant variability in single cell vascular endothelial growth factor (VEGF) secretion with the majority of total protein secretion arising from a small subpopulation of transfected cells. We demonstrate that VEGF secretion is linearly correlated to intracellular plasmid copy number and protein secretion does not appear to reach saturation within the cell population. The selection of gene therapy approaches that optimize individual cell secretion profiles may be essential for the development of effective gene therapies. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc. [source] In vitro liver model using microfabricated scaffolds in a modular bioreactorBIOTECHNOLOGY JOURNAL, Issue 2 2010Bruna Vinci Abstract Hepatocyte function on 3-D microfabricated polymer scaffolds realised with the pressure-activated microsyringe was tested under static and dynamic conditions. The dynamic cell culture was obtained using the multicompartment modular bioreactor system. Hepatocyte cell density, glucose consumption, and albumin secretion rate were measured daily over a week. Cells seeded on scaffolds showed an increase in cell density compared with monolayer controls. Moreover, in dynamic culture, cell metabolic function increased three times in comparison with static monolayer cultures. These results suggest that cell density and cell-cell interactions are mediated by the architecture of the substrate, while the endogenous biochemical functions are regulated by a sustainable supply of nutrients and interstitial-like flow. Thus, a combination of 3-D scaffolds and dynamic flow conditions are both important for the development of a hepatic tissue model for applications in drug testing and regenerative medicine. [source] Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH)CLINICAL ENDOCRINOLOGY, Issue 6 2008Ammon Handisurya Summary Objective To evaluate ,-cell function and insulin sensitivity in subjects with overt (OH) and subclinical hypothyroidism (SH) before and after T4 replacement therapy. Background Disturbances in glucose metabolism have been observed in hypothyroid states. However, the clinical significance and potential reversibility of these alterations by T4 replacement therapy remain to be elucidated especially in patients with SH. Design and patients Parameters of glucose metabolism have been investigated in subjects with OH (n = 12) and SH (n = 11). Insulin sensitivity has been assessed by the euglycaemic,hyperinsulinaemic clamp technique and ,-cell function by mathematical modelling of data derived from an oral glucose tolerance test. Results Fasting and dynamic glycaemia as assessed by the AUCGlucose remained unaltered following substitution therapy (P > 0·05). Insulin sensitivity significantly improved only in subjects with OH (P < 0·05). Fasting insulin and proinsulin concentrations increased proportionally in both groups (P < 0·05) with the proinsulin : insulin ratio remaining unchanged (P > 0·05). Total insulin secretion was higher in OH before initiation of therapy (P < 0·05). In both groups, dynamic parameters including total insulin secretion, hepatic insulin extraction and the adaptation index were significantly attenuated (P < 0·05) after restoration of thyroid function, whereas the disposition index and the basal insulin secretion rate remained unaltered (P > 0·05). Conclusion In summary, SH and OH are characterized by attenuated basal plasma insulin levels and increased glucose-induced insulin secretion. T4 replacement therapy partially ameliorates the insulin secretion profile and reduces the demand on pancreatic ,-cells after glucose challenge to an extent that exceeds any effect attributable to the improvement in insulin sensitivity. [source] Hormone response to bidirectional selection on social behaviorEVOLUTION AND DEVELOPMENT, Issue 5 2010Gro V. Amdam SUMMARY Behavior is a quantitative trait determined by multiple genes. Some of these genes may have effects from early development and onward by influencing hormonal systems that are active during different life-stages leading to complex associations, or suites, of traits. Honey bees (Apis mellifera) have been used extensively in experiments on the genetic and hormonal control of complex social behavior, but the relationships between their early developmental processes and adult behavioral variation are not well understood. Bidirectional selective breeding on social food-storage behavior produced two honey bee strains, each with several sublines, that differ in an associated suite of anatomical, physiological, and behavioral traits found in unselected wild type bees. Using these genotypes, we document strain-specific changes during larval, pupal, and early adult life-stages for the central insect hormones juvenile hormone (JH) and ecdysteroids. Strain differences correlate with variation in female reproductive anatomy (ovary size), which can be influenced by JH during development, and with secretion rates of ecdysteroid from the ovaries of adults. Ovary size was previously assigned to the suite of traits of honey bee food-storage behavior. Our findings support that bidirectional selection on honey bee social behavior acted on pleiotropic gene networks. These networks may bias a bee's adult phenotype by endocrine effects on early developmental processes that regulate variation in reproductive traits. [source] Temporal, spatial and biotic variations in extrafloral nectar secretion by Macaranga tanariusFUNCTIONAL ECOLOGY, Issue 6 2000Heil M. Abstract 1Many plants produce extrafloral nectar (EFN) to nourish ants and other animals which defend them against herbivores. We aimed to find reasons for the high variability in amounts of EFN produced by most plant species. We investigated the influence of several biotic and abiotic factors (time of day, leaf age, nectar removal and leaf damage) on secretion rates of EFN in the common south-east Asian pioneer tree species, Macarangatanarius (L.) Muell. Arg. 2In most experiments leaves were washed with pure water and bagged in nets to protect them against nectar-collecting insects, and nectar was collected and quantified 24 h later. Six soluble sugars and up to eight amino acids were detected in nectar samples derived from untreated, field-grown plants. Total amounts of soluble substances varied more than the relative composition of EFN. 3Nectar secretion rates were highest on young, expanded leaves. A diurnal pattern with a secretion peak in the first 2 h after dusk was detected in the field. Nectar removal had a positive effect and its accumulation a negative effect on further EFN production. Artificial leaf damage (punching leaves with a needle or removing parts of the leaf blade with scissors) led to a significant induction of EFN production for the next 3 days. 4Extrafloral nectar of M. tanarius was secreted in complex patterns influenced by different biotic and abiotic factors; its production appeared to be adapted temporally and spatially in order to ensure optimal use of invested resources. [source] Quantifying anomalous intestinal sterol uptake, lymphatic transport, and biliary secretion in Abcg8,/, mice,,HEPATOLOGY, Issue 4 2007Helen H. Wang Sitosterolemia is caused by mutations in either ABCG5 or ABCG8, but simultaneous mutations of these genes have never been observed. To explore whether ABCG8, the sterol efflux (hemi-)transporter, plays a major role in determining intestinal absorption efficiency and hepatic secretion rates of cholesterol and sitostanol, we performed direct measurements of the absorption and lymphatic transport of these sterols in mice with chronic biliary and lymphatic fistulae, as well as the transport rates of radiolabeled cholesterol and sitostanol from plasma high-density lipoprotein (HDL) into bile in male Abcg8,/, and wild-type mice. We observed that the absorption and lymphatic transport rates of radiolabeled cholesterol and sitostanol were increased by ,40% and ,500%, respectively, in Abcg8,/, mice in the setting of constant intraduodenal infusion of micellar taurocholate and lecithin. Both strains displayed identical intestinal Npc1l1 expression levels and small intestinal transit rates. After 45 minutes of intraduodenal infusion, acute intestinal uptake rates of trace [14C]cholesterol and [3H]sitostanol were essentially similar in both groups of mice with intact biliary secretion. Furthermore, in wild-type mice, mass transport rate of [3H]sitostanol from plasma HDL into bile was significantly faster than that of [14C]cholesterol; however, no [3H]sitostanol and only traces of [14C]cholesterol were detected in bile of Abcg8,/, mice. Conclusion: Deletion of the Abcg8 gene alone significantly increases the mass of intestinal cholesterol and sitostanol absorption and reduces but does not eliminate hepatic secretion of cholesterol. Moreover, the mutation has no influence on acute uptake of cholesterol and sitostanol by the enterocyte nor small intestinal transit time. (HEPATOLOGY 2007;45:998,1006.) [source] Vascular endothelial growth factor secretion from mesenteric adipose tissue and from creeping fat in Crohn's diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2006Andreas Schäffler Abstract Background:, Creeping fat represents a characteristic feature of Crohn's disease (CD), and adipose tissue secretes adipocytokines and chemokines/growth factors such as vascular endothelial growth factor (VEGF). Because VEGF serum levels and mucosal VEGF expression is elevated in CD patients, the aim of the present paper was to investigate creeping fat-derived VEGF secretion in CD. Material and Methods:, Adipose tissue was obtained from creeping fat of 10 patients with CD. Mesenteric adipose tissue was resected from 13 patients with colon cancer (CC) and from seven patients with diverticulitis (DIV). Three fat tissue specimens per well, and several wells (6,8) per patient were incubated ex vivo for 24 h. The release of VEGF into the supernatant was measured by ELISA. Results:, There was stable VEGF secretion from mesenteric adipose tissue of patients with CC or DIV and from creeping fat of patients with CD. Whereas the VEGF secretion rate was not different between patients with CD (465 ± 98 pg/g fat per 24 h) and CC (399 ± 48 pg/g fat per 24 h), VEGF secretion was significantly reduced in patients suffering from DIV (115 ± 41 pg/g fat per 24 h; P < 0.0001 and P = 0.001, respectively). The CD patients treated with steroids had significantly lower VEGF secretion rates (294 ± 42 pg/g fat per 24 h) than CD patients not receiving steroids (607 ± 105 pg/g fat per 24 h; P = 0.001). Conclusions:, Creeping fat is an important source of VEGF secretion. The characteristics of the inflammatory changes in CD might be due to the lack of VEGF downregulation that is seen in DIV. [source] | |||||||||||||