| 1. |
- Bjurberg, Maria, et al.
(författare)
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Early changes in 2-deoxy-2-[18F]fluoro-D-glucose metabolism in squamous-cell carcinoma during chemotherapy in vivo and in vitro.
- 2009
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Ingår i: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 24:3, s. 327-332
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to investigate early changes in uptake of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) in vivo and in vitro in a squamous-cell carcinoma (SCC) cell line originating from a human head and neck SCC during cytotoxic therapy with respect to metabolism in tumor cells and in surrounding stromal tissue. MATERIALS AND METHODS: In 60 nude mice with xenografted SCC, 50 animals were treated with cisplatin. Early changes in the tumor FDG uptake following therapy were evaluated sequentially with phosphor imaging. Using this technique, areas with focal hypermetabolism were detected. The cells creating the focal hypermetabolism were then identified histopathologically on the corresponding sections. In addition, early FDG uptake versus the number of viable tumor cells was measured in vitro following cisplatin treatment. RESULTS: An early transient increase in FDG uptake in tumor cells was seen on day 1 in treated tumors, followed by a rapid decrease confirmed by subsequent tumor regression. This metabolic flare was present in all treated tumors but not in the controls. In vitro, an increase in FDG uptake per cell was observed. CONCLUSIONS: Our results provide new insights into the early metabolic changes in squamous-cell carcinomas subjected to cytotoxic therapy and thus contribute to the discussion on the feasibility of early predictive PET studies.
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| 2. |
- Andersson, Amelie, et al.
(författare)
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Expression and motor effects of secretin in small and large intestine of the rat
- 2000
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 21:11, s. 94-1687
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Tidskriftsartikel (refereegranskat)abstract
- Immunocytochemistry and in situ hybridization revealed abundant secretin expressing cells on duodenal villi with a gradual decrease throughout the small intestines of the rat. They were absent in pancreas, stomach and colon. Secretin caused relaxation of rat intestinal longitudinal muscle in vitro. Studies on colon revealed that the secretin-evoked response was unaffected by apamin, tetrodotoxin, L-NAME, VIP or PACAP pretreatment; secretin itself caused desensitization. Addition of VIP or PACAP when the secretin-evoked relaxation was maximal evoked a further relaxation suggesting the presence of distinct receptors. Secretin causes relaxation via activation of secretin receptors located on the smooth muscle and not via any of the related VIP/PACAP receptors.
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| 3. |
- Arciszewski, M B, et al.
(författare)
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Effects of vasoactive intestinal peptide and galanin on survival of cultured porcine myenteric neurons
- 2005
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 125:1-3, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- Enteric neuronal plasticity is probably fundamental in order to withstand injury or changes in intestinal activity. The role of the neuropeptides in neuroprotection is still enigmatic. The expression of galanin and vasoactive intestinal peptide (VIP) and the effects of the two peptides on survival of small intestinal porcine myenteric neurons cultured for 6 days were studied. Immunocytochemistry and cell counting were used to evaluate the numbers of surviving neurons and their expression of galanin and VIP. To reflect the in vivo situation, cryostat sections of porcine mid-jejunum were used. A concentration-dependent and marked increase in neuronal survival was noted when neurons were grown in the presence of VIP (10(-8) - 10(-6) M), whereas addition of galanin (10(-8) - 10(-6) M) slightly decreased neuronal survival. A dramatic increase in the proportions of myenteric neurons containing VIP or galanin immunoreactivity occurred during culturing. The presence of VIP further increased the number of galanin-expressing neurons. A majority of the galanin-immunoreactive neurons lacked VIP, while all VIP-immunoreactive neurons contained galanin. In conclusion, culturing porcine myenteric neurons in the presence of VIP increases, while the presence of galanin reduces, survival. Culturing significantly increased the proportion of neurons expressing VIP and/or galanin; the presence of VIP further increased the number of galanin-expressing neurons.
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| 4. |
- Arciszewski, Marcin, et al.
(författare)
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Lipopolysaccharide induces cell death in cultured porcine myenteric neurons.
- 2005
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 50:9, s. 1661-1668
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Tidskriftsartikel (refereegranskat)abstract
- Enteric bacteria execute, via lipopolysaccharide (LPS), a pathogenic role in intestinal inflammation. The effects of LPS on survival and neurotransmitter expression in cultured porcine myenteric neurons were investigated. Myenteric neurons were isolated and cultured for 6 days in medium, in LPS (100 ng/ml) with or without α-ketoglutarate or the nitric oxide synthase (NOS) inhibitor L-NAME, in α-ketoglutarate or in the NO donor SNAP. Neuronal survival and expression of vasoactive intestinal peptide (VIP) and NOS were evaluated by immunocytochemistry. Addition of LPS significantly decreased neuronal survival; only 40% survived, compared to controls run in parallel. The LPS-induced neurotoxic effect was not counteracted by the simultaneous presence of α-ketoglutarate or L-NAME. Either SNAP or α-ketoglutarate influenced neuronal survival. Culturing, particularly in the presence of LPS, markedly increased the proportion of VIP-immunoreactive neurons; NOS-immunoreactive neurons were unchanged. The reported LPS-induced neurotoxicity indicates loss of enteric neurons as a consequence of intestinal inflammation.
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| 5. |
- Arciszewski, MB, et al.
(författare)
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Vasoactive intestinal peptide rescues cultured rat myenteric neurons from lipopolysaccharide induced cell death
- 2008
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 146:1-3, s. 218-223
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Tidskriftsartikel (refereegranskat)abstract
- The role of the enteric nervous system in intestinal inflammation is not fully understood and the plethora of cellular activities concurrently ongoing in vivo renders intelligible studies difficult. In order to explore possible effects of bacterial lipopolysaccharide (LPS) on enteric neurons we utilised cultured myenteric neurons from rat small intestine. Exposure to LPS caused markedly reduced neuronal survival and increased neuronal expression of vasoactive intestinal peptide (VIP), while the expression of Toll-like receptor 4 (TLR4) was unchanged. TLR4 was expressed in approximately 35% of all myenteric neurons irrespective of if they were cultured in the presence or absence of LPS. In neurons cultured in medium, without LPS, 50% of all TLR4-immunoreactive neurons contained also VIP. Addition of LPS to the neuronal cultures markedly increased the proportion of TLR4-immunoreactive neurons also expressing VIP, while the proportion of TLR4 neurons devoid of VIP decreased. Simultaneous addition of LPS and VIP to the neuronal cultures resulted in a neuronal survival comparable to controls. CONCLUSIONS: LPS recognition by myenteric neurons is mediated via TLR4 and causes neuronal cell death. Presence of VIP rescues the neurons from LPS-induced neurodegeneration.
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| 6. |
- Chang, Jing-Yu, et al.
(författare)
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Serotonin uptake into cerebrovascular nerve fibers of rat, visualization by immunohistochemistry, disappearance following sympathectomy, and release during electrical stimulation
- 1989
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 492:1-2, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemistry as well as in vitro uptake and release of [3H]5-HT were performed on pial arteries of rat to investigate the nature of 5-HT containing nerve fibers. Immunoreactive fibers were constantly found only in the basilar, vertebral and superior cerebellar arteries, while in the other parts of the circle of Willis, 5-HT immunofluorescent fibers were absent. After systemic treatment with tryptophan following inhibition of monoamine oxidase with nialamide the immunofluorescence intensity was markedly enhanced. The 5-HT immunoreactive fibers disappeared after superior cervical ganglionectomy or intraventricular administration of 6-hydroxydopamine, but persisted after administration of 5,6-dihydroxytryptamine. When isolated vessels were incubated in low concentration of 5-HT (1 nM) together with nialamide, a very dense plexus of 5-HT immunoreactive fibers appeared in all branches of the circle of Willis. Uptake and release experiments were carried out by incubation of arterial preparations with 3 nM [3H]5-HT (together with nialamide), followed by electrical field stimulation, or by exposure to tyramine or 124 mM potassium, all of which induced a 100%-350% increase in the tritium release over prestimulation values. Preincubation with cocaine and bilateral superior cervical ganglionectomy abolished or markedly attenuated the release upon all modes of stimulation. The results suggested that the 5-HT observed by immunohistochemistry in pial arteries is located in sympathetic nerve terminals where it may serve as a neuromodulator that is released during nerve activation.
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| 7. |
- Chen, Ying, et al.
(författare)
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Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
- 2015
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Ingår i: Molecular Cancer Therapeutics. - 1538-8514. ; 14:1, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and is previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. beta-catenin was determined by immunohistochemistry, PAF levels by ELISA and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared to WT mice. While all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared to WT mice, cytosol expression of beta-catenin was significantly decreased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion lack of alk-SMase markedly increases AOM/DSS induced colonic tumorigenesis associated with decreased ceramide and increased sphingosine-1-phosphate and PAF levels.
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| 8. |
- Cheng, Xiaowen, et al.
(författare)
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A novel serotonin-containing tuft cell subpopulation in mouse intestine
- 2019
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 376:2, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a novel subset of doublecortin-like kinase 1 (DCLK1)-immunoreactive (IR) tuft cells that also contain serotonin (5-hydroxytryptamine, 5HT) is described, in terms of their number, regional distribution, possible synthesis or reuptake of 5HT and proximity to 5-HT-containing enterochromaffin (EC) cells. The small intestine from C57BL/6J mice was divided into five segments while the large intestine was kept undivided. Double immunostaining was used to estimate numbers and topographic distribution of 5HT-IR (DCLK1/5HT) tuft cells and their possible expression of tryptophan hydroxylase (TPH) and serotonin transporter (SERT). Also, possible contacts between tuft cells and 5HT-IR EC cells were studied. In the small intestine, up to 80% of all tuft cells were identified as DCLK1/5HT-IR; in the large intestine, such cells were rare. The highest number of DCLK1/5HT-IR cells was found in the upper small intestine. The numbers of DCLK1/5HT-IR cells gradually decreased distally. DCLK1-IR tuft cells were not found to contain TPH, the rate-limiting enzyme in 5HT synthesis. SERT, the selective transporter for 5HT reuptake, could not convincingly be demonstrated in tuft cells. In villi and crypts, 3% and 10%, respectively, of all DCLK1-IR cells were in close proximity to EC cells. EC cells in close proximity to DCLK1-IR cells were, in villi and crypts, 3 and 8%, respectively. We conclude that DCLK1/5HT-IR cells constitute a novel subset of tuft cells that may have unique roles in the GI tract.
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| 9. |
- Cheng, Xiaowen, et al.
(författare)
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Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum
- 2018
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Ingår i: International Journal of Experimental Pathology. - : Wiley. - 0959-9673. ; 99:1, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if enteric neuropathy occurs after cerebral ischaemia, by analysing neuronal survival and relative numbers of vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing neurons in mouse ileum after three types of cerebral ischaemia. Focal cerebral ischaemia, modelled by permanent middle cerebral artery occlusion (pMCAO) and global cerebral ischaemia, modelled with either transient occlusion of both common carotid arteries followed by reperfusion (GCIR) or chronic cerebral hypoperfusion (CCH) was performed on C56BL/6 mice. Sham-operated mice for each ischaemia model served as control. Ileum was collected after 1–17 weeks, depending on model, and analysed using morphometry and immunocytochemistry. For each group, intestinal mucosa and muscle layer thicknesses, neuronal numbers and relative proportions of neurons immunoreactive (IR) for nNOS or VIP were estimated. No alterations in mucosa or muscle layer thicknesses were noted in any of the groups. Loss of myenteric neurons and an increased number of VIP-IR submucous neurons were found in mouse ileum 7 days after pMCAO. None of the global ischaemia models showed any alterations in neuronal survival or relative numbers of VIP- and nNOS-IR neurons. We conclude that focal cerebral ischaemia and global cerebral ischaemia influence enteric neuronal survival differently. This is suggested to reflect differences in peripheral neuro-immune responses.
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| 10. |
- Cheng, Xiaowen, et al.
(författare)
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Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3 +/+, but not in galectin-3 mice. In vitro we show that serum from galectin-3 +/+, but not from galectin-3 mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4 mice were unaffected. Further purified galectin-3 (10 6 M) caused loss of cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor β-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both the purified galectin-3 and the galectin-3 +/+ pMCAO serum-induced loss in vitro. Combined we show that stroke (pMCAO) triggers central and peripheral galectin-3 release causing enteric neuronal loss through a TLR4 mediated mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment of post-stroke complications.
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