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Secretory Capacity (secretory + capacity)
Selected AbstractsEffects of short-term food deprivation on orexin-A-induced intestinal bicarbonate secretion in comparison with related secretagoguesACTA PHYSIOLOGICA, Issue 3 2010G. Flemström Abstract Studies of gastrointestinal physiology in humans and intact animals are usually conducted after overnight fast. We compared the effects of orexin-A, vasoactive intestinal polypeptide (VIP), melatonin, serotonin, uroguanylin, ghrelin and prostaglandin E2 (PGE2) on duodenal bicarbonate secretion in fed and overnight fasted animals. This review is a summary of our findings. Secretagogues were administered by intra-arterial infusion or luminally (PGE2). Enterocyte intracellular calcium ([Ca2+]i) signalling was studied by fluorescence imaging. Total RNA was extracted, reverse transcripted to cDNA and expression of orexin receptors measured by quantitative real-time PCR. Orexin-A stimulates the duodenal secretion in continuously fed animals but not in food-deprived animals. Similarly, short-term fasting causes a 100-fold decrease in the amount of the muscarinic agonist bethanechol required for stimulation of secretion. In contrast, fasting does not affect secretory responses to intra-arterial VIP, melatonin, serotonin, uroguanylin and ghrelin, or that to luminal PGE2. Orexin-A induces [Ca2+]i signalling in enterocytes from fed rats but no significant [Ca2+]i responses occur in enterocytes from fasted animals. In addition, overnight fasting decreases the expression of mucosal orexin receptors. Short-term food deprivation thus decreases duodenal expression of orexin receptors and abolishes the secretory response to orexin-A as well as orexin-A-induced [Ca2+]i signalling. Fasting, furthermore, decreases mucosal sensitivity to bethanechol. The absence of declines in secretory responses to other secretagogues tested strongly suggests that short-term fasting does not affect the secretory capacity of the duodenal mucosa in general. Studies of intestinal secretion require particular evaluation with respect to feeding status. [source] Maternal transmission of diabetesDIABETIC MEDICINE, Issue 2 2002J. C. Alcolado Abstract Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNAleu(UUR) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non-autoimmune ,-cell failure. Specific treatment with Coenzyme Q10 or L-carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena. [source] Morphometric and immunohistochemical study of the abomasum of red deer during prenatal developmentJOURNAL OF ANATOMY, Issue 3 2007A. J. Masot Abstract The red deer is well suited to scientific study, given its economic importance as an animal to be hunted, and because it has a rich genetic heritage. However, there has been little research into the prenatal development of the stomach of ruminants in general, and none for the red deer. For this reason, we undertook histological evaluation of the ontogenesis of the abomasum in red deer. Histomorphometric and immunohistochemical analyses were carried out on 50 embryos and fetuses from the initial stages of prenatal life until birth. The animals were divided for test purposes into five experimental groups: group I [1.4,3.6 cm crown,rump length (CRL); 30,60 days, 1,25% of gestation]; group II (4.5,7.2 cm CRL; 67,90 days, 25,35% of gestation); group III (8,19 cm CRL; 97,135 days, 35,50% of gestation); group IV (21,33 cm CRL; 142,191 days, 50,70% of gestation) group V (36,40 cm CRL; 205,235 days, 75,100% of gestation). In the organogenesis of the primitive gastric tube of red deer, differentiation of the abomasum took place at 67 days, forming a three-layered structure: the epithelial layer (pseudostratified), pluripotential blastemic tissue and serosa. The abomasal wall displayed the primitive folds of the abomasum and by 97 days abomasal peak areas were observed on the fold surface. At 135 days the abomasal surface showed a single mucous cylindrical epithelium, and gastric pits were observed in the spaces between abomasal areas. At the bottom of these pits the first outlines of glands could be observed. The histodifferentiation of the lamina propria-submucosa, tunica muscularis and serosa showed patterns similar to those described for the forestomach of red deer. The abomasum of red deer during prenatal life, especially from 67 days of gestation, was shown to be an active structure with full secretory capacity. Its histological development, its secretory capacity (as revealed by the presence of neutral mucopolysaccharides) and its neuroendocrine nature (as revealed by the presence of positive non-neuronal enolase cells and the neuropeptides vasoactive intestinal peptide and neuropeptide Y) were in line with the development of the rumen, reticulum and omasum. Gastrin-immunoreactive cells first appeared in the abomasum at 142 days, and the number of positive cells increased during development. As for the number of gastrin cells, plasma gastrin concentrations increased throughout prenatal life. However, its prenatal development was later than that of the abomasum in sheep, goat and cow. [source] Regulation of IgE-receptor expression, IgE occupancy and secretory capacity of mast cellsAPMIS, Issue 10 2000XIAO-JUN Chen Mast cells play an important role in initiating and modulating allergic and inflammatory reactions. Their responsiveness is determined by three important factors: the expression of IgE receptors on the cell surface, the IgE occupancy of these receptors, and the intrinsic secretory capacity of the cells. In this review, we will summarise some findings relevant to these three aspects of mast cell function, and discuss possible regulatory mechanisms. It appears that the genetic background as well as environmental factors influence all three of these components of the response. T cells appear to play an important role in regulating the IgE-receptor expression and also, independently, the intrinsic secretory capacity of mast cells via an unidentified route, possibly involving the secretory signal transduction chain directly. IgE itself appears to have an important role in the regulation of IgE-receptor expression, as indicated by the upregulation of receptors in vitro in the presence of IgE, and the absence of IgE-binding capacity of mast cells in IL-4 gene knockout mice, lacking IgE production. The IgE-receptors of mast cells are saturated to a high degree under different normal conditions, without an obvious relation to antigenic stimulation, also in athymic animals. We have suggested that this basal IgE content on mast cells may be the result of an antigen-independent production of IgE directed by the mast cells themselves and serving regulatory purposes, modifying the secretory response and preventing a massive possibly harmful degranulation. [source] Using a GnRH agonist to obtain an index of testosterone secretory capacity in the cockatiel (Nymphicus hollandicus) and sulphur-crested cockatoo (Cacatua galerita)AUSTRALIAN VETERINARY JOURNAL, Issue 1-2 2010EM Lovas Objective Validation of a stimulation test for determining the steroidogenic capacity of the parrot testis. The major aim was to characterise testosterone secretion after injection of a gonadotropin-releasing hormone agonist (GnRHa), then use the test to investigate seasonal reproduction in the male cockatiel. Procedure A synthetic GnRHa (buserelin; 8.0 µg of peptide/kg bodyweight) was injected IM into male cockatiels (n = 7) and sulphur-crested cockatoos (n = 3) and serial blood samples collected at 0, 30, 60, 90 and 120 min after administration. Once validated, the technique was subsequently used to examine seasonal changes (23 months) in the testosterone profile of a captive cockatiel population. Results Injection of buserelin resulted in a significant increase in the testosterone concentration of cockatiel plasma, with maximal concentrations occurring at approximately 60 (1.33 ± 0.08 ng/mL) to 90 min (1.22 ± 0.08 ng/mL) after injection. Although no clear pattern of seasonal variation in testosterone secretion was detected in cockatiel plasma, samples taken 60 and 90 min after administration showed a significant increase in all seasons. Injection of buserelin in the sulphur-crested cockatoo also resulted in increased testosterone secretion, with maximal concentrations obtained after 90 min. Conclusion Buserelin can be used to obtain a reliable index of the prevailing testosterone capacity of the cockatiel and cockatoo testis. With further studies, this test may be incorporated into clinical assessment of reproductive status. [source] Molecular engineering of exocytic vesicle traffic enhances the productivity of Chinese hamster ovary cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009Ren-Wang Peng Abstract A complex vesicle trafficking system manages the precise and regulated distribution of proteins, membranes and other molecular cargo between cellular compartments as well as the secretion of (heterologous) proteins in mammalian cells. Sec1/Munc18 (SM) proteins are key components of the system by regulating membrane fusion. However, it is not clear how SM proteins contribute to the overall exocytosis. Here, functional analysis of the SM protein Sly1 and Munc18c suggested a united, positive impact upon SNARE-based fusion of ER-to-Golgi- and Golgi-to-plasma membrane-addressed exocytic vesicles and increased the secretory capacity of different therapeutic proteins in Chinese hamster ovary cells up to 40 pg/cell/day. Sly1- and Munc18c-based vesicle traffic engineering cooperated with Xbp-1-mediated ER/Golgi organelle engineering. Our study supports a model for united function of SM proteins in stimulating vesicle trafficking machinery and provides a generic secretion engineering strategy to improve biopharmaceutical manufacturing of important protein therapeutics. Biotechnol. Bioeng. 2009;102: 1170-1181. © 2008 Wiley Periodicals, Inc. [source] Regulation of XBP-1 signaling during transient and stable recombinant protein production in CHO cellsBIOTECHNOLOGY PROGRESS, Issue 2 2010Sebastian C. Y. Ku Abstract X-box binding protein 1 (XBP-1) is a key regulator of cellular unfolded protein response (UPR). The spliced isoform of XBP-1, XBP-1S, is a transcription activator, which is expressed only when UPR is induced. However, the impact of recombinant protein production on the regulation of XBP-1 signaling in CHO cells is not well understood. In this report, we cloned the Chinese hamster XBP-1 homolog to aid the investigation of the interplay between protein productivity, culture conditions, and endogenous XBP-1 signaling in CHO cells. Interestingly, expression of XBP-1S is detected in the non-producing and unstressed CHO-K1 cells. Transient expression of recombinant erythropoietin reveals a positive correlation between XBP-1 mRNA abundance and protein production level. However, such a correlation is not observed in batch cultivation of stable producing cell lines. The increased XBP-1 splicing is detected in late-phase cultures, suggesting that induction of XBP-1S may be a result of nutrient limitations or other environmental stresses rather than that of increased intracellular accumulation of recombinant proteins. Our data suggest that XBP-1 is a key determinant for the secretory capacity of CHO cells. Understanding its dynamic regulation hence provides a rational basis for cellular engineering strategies to improve recombinant protein secretion. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Relationship between adult dark spermatogonia and secretory capacity of Leydig cells in cryptorchidismBJU INTERNATIONAL, Issue 5 2007Dragana Zivkovic In a paper from Switzerland, the authors describe the relationship between adult dark spermatogonia and the secretory capacity of Leydig cells in cryptorchidism. OBJECTIVE To examine whether hormonal therapy before orchidopexy affects the histology of the testis and to assess the responsiveness of the Leydig cells, as it has been shown that although basal plasma testosterone levels are within the ,normal' range in cryptorchid boys there is an insufficient increase of testosterone after a human chorionic gonadotrophin (hCG) stimulation in ,,30% of cryptorchid boys. PATIENTS AND METHODS In all, 55 boys (aged 1,7 years) with a unilateral undescended testis were included in the study and divided into two groups. Group I (32 boys) received hormonal therapy before orchidopexy; 17 boys received a long-acting LHRH analogue (buserelin) administered as a nasal spray in doses of 20 µg/day for 28 days, followed by 1500 IU hCG intramuscularly (i.m.) once a week for 3 weeks, and the remaining 15 received 1500 IU hCG i.m. once a week for 3 weeks. Group II (33 boys) had orchidopexy alone. During orchidopexy biopsies were taken from the undescended and contralateral descended testes of the boys in both groups for histological analyses. Variations in the number of adult dark (Ad) spermatogonia per tubule (Ad/T) were assessed and testosterone levels were measured during the course of the hormonal therapy (before treatment, 14 days after initiation of buserelin administration, 24 h after each hCG injection, and 3 months after cessation of therapy). RESULTS In group I, 17 boys (53%) had a ,normal' Ad/T after hormonal treatment vs only six (18%) in group II after orchidopexy alone (P = 0.019). In the hormonally treated boys (group I) we compared the testosterone values 24 h after the second injection of hCG (when the response was most pronounced). Those with a normal Ad/T had a mean (sd) testosterone level of 199.5 (97.6) ng/dL vs 99.6 (85) ng/dL in those with an inadequate Ad/T response to hormonal therapy (P < 0.003). CONCLUSION We have confirmed that there are two subgroups of cryptorchid boys. Patients with a sufficient Leydig cell secretory capacity will have normal testicular histology and Ad spermatogonia count after hormonal treatment. While those with a suboptimal Leydig cell capacity will have a low Ad spermatogonia count and consequently poor prognosis for future fertility, despite successful surgery. As to whether different types and durations of the hormonal therapy in patients with impaired Leydig cell response could lead to improved testicular histology and consequently improved prognosis for future fertility, remains to be answered. [source] The novel use of the human nasal epithelial cell line RPMI 2650 as an in vitro model to study the influence of allergens and cytokines on transforming growth factor-, gene expression and protein releaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2005R. J. Salib Summary Background The epithelial accumulation of mast cells is a feature of allergic rhinitis and this has been linked to the expression of the known mast cell chemoattractant transforming growth factor-, (TGF-,) at this site. Little is known concerning the regulation of TGF-, gene expression or protein release by nasal epithelial cells. To address this we have utilized the RPMI 2650 human nasal epithelial cell line, which has some features that closely resemble normal nasal epithelium and has been reported to secrete a TGF-,-like molecule. Objectives To investigate the regulation of TGF-, gene expression and protein secretion in RPMI 2650 nasal epithelial cells following exposure to allergens (house dust mite (HDM) and grass pollen) and mast cell associated T-helper type 2 (Th2) cytokines (IL-4, IL-13, and TNF-,). Methods Light and scanning electron microscopy was used to evaluate the morphology of RPMI 2650 cells in culture, enzyme-linked immunosorbent assay was used to investigate their TGF-, secretory capacity and the identification of the TGF-, isotype(s) involved, flow cytometry was used to demonstrate the presence of TGF-, receptors on the RPMI 2650 cells, and the quantitative real-time TaqMan PCR was used to measure TGF-, gene expression. Results TGF-,2 was identified as the main isotype secreted by the RPMI 2650 cells. HDM allergens and TNF-, increased both TGF-, gene expression and protein release from these cells, whereas grass pollen, IL-4, and IL-13 were without effect. Conclusions The RPMI 2650 nasal epithelial cell line represents a valid in vitro model to evaluate the regulation of TGF-, biology. In this system HDM allergens have stimulatory activity that is fundamentally different from that of grass pollen allergens, and the Th2 cytokines IL-4 and IL-13 are without effect. The ability of TNF-, to up-regulate both TGF-, gene expression and protein release indicates that mast cell,epithelial interactions concerning TGF-, are bi-directional and this may be fundamental to epithelial immunoregulation. The availability of a model system, such as the RPMI 2650 cells, will enable the early evaluation of future novel and targeted interventions directed toward the aberrant responses of upper airway structural cells. [source] Endocrine responses to ghrelin in adult patients with isolated childhood-onset growth hormone deficiencyCLINICAL ENDOCRINOLOGY, Issue 6 2002Gianluca Aimaretti Summary objective Ghrelin, a 28 amino acid acylated peptide, is a natural ligand of the GH secretagogues (GHS) receptor (GHS-R), which is specific for synthetic GHS. Similar to synthetic GHS, ghrelin strongly stimulates GH secretion but also displays significant stimulatory effects on lactotroph and corticotroph secretion. It has been hypothesized that isolated GH deficiency (GHD) could reflect hypothalamic impairment that would theoretically involve defect in ghrelin activity. patients In the present study, we verified the effects of ghrelin (1 µg/kg i.v.) on GH, PRL, ACTH and cortisol levels in adult patients with isolated severe GHD [five males and one female, age (mean ± SEM) 24·7 ± 2·6 years, BMI 25·7 ± 2·7 kg/m2]. In all patients, the GH response to insulin-induced hypoglycaemia (ITT, 0·1 IU regular insulin i.v.) and GH releasing hormone (GHRH) (1 µg/kg i.v.) + arginine (ARG, 0·5 g/kg i.v.) was also studied. The hormonal responses in GHD were compared with those in age-matched normal subjects (NS, seven males, age 28·6 ± 2·9 years, BMI 22·1 ± 0·8 kg/m2). results IGF-I levels in GHD were markedly lower than in NS (69·8 ± 11·3 vs. 167·9 ± 19·2 µg/l, P < 0·003). Ghrelin administration induced significant increase in GH, PRL, ACTH and cortisol levels in all GHD. In GHD, the GH response to ghrelin was higher (P < 0·05) than that to GHRH + ARG, which, in turn, was higher (P < 0·05) than that to ITT (9·2 ± 4·1 vs. 5·3 ± 1·7 vs. 1·4 ± 0·4 µg/l). These GH (1 µg/l = 2 mU/l) responses in GHD were markedly lower (P < 0·0001) than those in NS (ghrelin vs. GHRH + ARG vs. ITT 92·1 ± 16·7 vs. 65·3 ± 8·9 vs. 17·7 ± 3·5 µg/l). In GHD, the highest individual peak GH response to ghrelin was markedly lower than the lowest peak GH response in NS (28·5 vs. 42·9 µg/l). GHD and NS showed overlapping PRL (1 µg/l = 32 mU/l) (10·0 ± 1·4 vs. 14·9 ± 2·2 µg/l), ACTH (22·3 ± 5·3 vs. 18·7 ± 4·6 pmol/l) and cortisol responses (598·1 ± 52·4 vs. 486·9 ± 38·9 nmol/l). conclusions This study shows that ghrelin is one of the most powerful provocative stimuli of GH secretion, even in those patients with isolated severe GHD. In this condition, however, the somatotroph response is markedly reduced while the lactotroph and corticotroph responsiveness to ghrelin is fully preserved, indicating that this endocrine activity is fully independent of mechanisms underlying the GH-releasing effect. These results do not support the hypothesis that ghrelin deficiency is a major cause of isolated GH deficiency but suggest that ghrelin might represent a reliable provocative test to evaluate the maximal GH secretory capacity provided that appropriate cut-off limits are assumed. [source] | |||||||||||||