scholarly journals Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy

2021 ◽  
Author(s):  
Elisa Boschetti ◽  
Roberto D'Angelo ◽  
Maria Lucia Tardio ◽  
Roberta Costa ◽  
Carla Giordano ◽  
...  
Keyword(s):  
Protein Expression ◽  
Vascular Tissue ◽  
Vascular Endothelial Cell ◽  
Neuron Specific Enolase ◽  
Fold Increase ◽  
Muscle Layer ◽  
Enteric Neurons ◽  
Longitudinal Muscle Layer ◽  
Mitochondrial Neurogastrointestinal Encephalomyopathy ◽  
Angiogenic Potential

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. Since gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from MNGIE patients. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1a (HIF-1a) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron specific enolase was used to label enteric neurons. Compared to controls, MNGIE patients showed a decreased area of vascular tissue, but a two-fold increase of submucosal vessels/mm2 with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index and HIF-1a protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased inter-ganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of MNGIE patients. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown and ischemic abnormalities in MNGIE.

scholarly journals Localization and steroid regulation of prostaglandin E2 receptor protein expression in ovine cervix

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 743-750 ◽  
Author(s):  
Thomas Schmitz ◽  
Brian A Levine ◽  
Peter W Nathanielsz
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Longitudinal Muscle ◽  
Muscle Layer ◽  
Cervical Dilatation ◽  
Cervical Ripening ◽  
Receptor Protein ◽  
Longitudinal Muscle Layer ◽  
Ripening Process ◽  
Ep Receptor

Although prostaglandin E2(PGE2) has been identified as a central mediator of the cervical ripening process, the mechanisms responsible for PGE2ripening are still poorly understood, partly because of the lack of information concerning the precise cellular localization and regulation of PGE2(EP) receptors in the cervix. To provide new insights into the mechanisms of cervical ripening, we used indirect immunofluorescence to localize cervical EP receptor protein expression in ovariectomized ewes and examined the effect of administration of progesterone or estradiol. EP receptors were widely distributed in cervical blood vessels, epithelium of the cervical canal, circular and longitudinal muscles, and stroma. Estradiol replacement decreased EP1and EP3receptor protein in blood vessel media (by 23 and 31% respectively,P< 0.05) and decreased EP1receptor protein expression in the longitudinal muscle layer (by 27%,P< 0.05). Stromal EP1and EP3receptor protein expression was also reduced by estradiol (by 29 and 20% respectively,P< 0.05). Progesterone replacement had no significant effect on EP receptor protein expression. The arterial changes would favor PGE2-induced vasodilatation, subsequent edema and leukocyte infiltration during the cervical ripening process whereas the muscular alterations would facilitate smooth muscle relaxation and cervical dilatation. Furthermore, estradiol provoked perinuclear localization of EP3receptor protein in the longitudinal muscle layer. This latter result suggests that cellular EP receptor localization is regulated by estradiol and that PGE2may also control smooth muscle contraction and regulate ovine cervical dilatation in an intracrine manner via EP3receptors.

scholarly journals Resveratrol Stimulates Cortisol Biosynthesis by Activating SIRT-Dependent Deacetylation of P450scc

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3258-3268 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Marion B. Sewer
Keyword(s):  
Protein Expression ◽  
Fold Increase ◽  
Pyridine Nucleotide ◽  
Nucleotide Metabolism ◽  
Side Chain ◽  
Mitochondrial Enzyme ◽  
Adrenocortical Cells ◽  
Protein Levels ◽  
Chain Cleavage ◽  
Cleavage Enzyme

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450.

Patch-clamp study of neurons and glial cells in isolated myenteric ganglia

2000 ◽  
Vol 278 (4) ◽  
pp. G644-G651 ◽  
Author(s):  
M. Hanani ◽  
M. Francke ◽  
W. Härtig ◽  
J. Grosche ◽  
A. Reichenbach ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Glial Cells ◽  
Muscle Layer ◽  
Membrane Receptors ◽  
Delayed Rectifier ◽  
Longitudinal Muscle Layer ◽  
Inward Currents ◽  
Morphological Identity ◽  
Clamp Study ◽  
Myenteric Ganglia

Most of the physiological information on the enteric nervous system has been obtained from studies on preparations of the myenteric ganglia attached to the longitudinal muscle layer. This preparation has a number of disadvantages, e.g., the inability to make patch-clamp recordings and the occurrence of muscle movements. To overcome these limitations we used isolated myenteric ganglia from the guinea pig small intestine. In this preparation movement was eliminated because muscle was completely absent, gigaseals were obtained, and whole cell recordings were made from neurons and glial cells. The morphological identity of cells was verified by injecting a fluorescent dye by micropipette. Neurons displayed voltage-gated inactivating inward Na+ and Ca2+currents as well as delayed-rectifier K+ currents. Immunohistochemical staining confirmed that most neurons have Na+ channels. Neurons responded to GABA, indicating that membrane receptors were retained. Glial cells displayed hyperpolarization-induced K+ inward currents and depolarization-induced K+ outward currents. Glia showed large “passive” currents that were suppressed by octanol, consistent with coupling by gap junctions among these cells. These results demonstrate the advantages of isolated ganglia for studying myenteric neurons and glial cells.

scholarly journals First reported case of per anal endoscopic myectomy (PAEM): A novel endoscopic technique for resection of lesions with severe fibrosis in the rectum

2017 ◽  
Vol 05 (03) ◽  
pp. E146-E150 ◽  
Author(s):  
David Rahni ◽  
Takashi Toyonaga ◽  
Yoshiko Ohara ◽  
Francesco Lombardo ◽  
Shinichi Baba ◽  
...  
Keyword(s):  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Rectal Tumor ◽  
Resection Margins ◽  
Submucosal Layer ◽  
Longitudinal Muscle Layer ◽  
Circular Muscle Layer ◽  
Tunneling Method ◽  
Severe Fibrosis

Background and study aims A 54-year-old man was diagnosed with a rectal tumor extending through the submucosal layer. The patient refused surgery and therefore endoscopic submucosal dissection (ESD) was pursued. The lesion exhibited the muscle retraction sign. After dissecting circumferentially around the fibrotic area by double tunneling method, a myotomy was performed through the internal circular muscle layer, creating a plane of dissection between the internal circular muscle layer and the external longitudinal muscle layer, and a myectomy was completed.The pathologic specimen verified T1b grade 1 sprouting adenocarcinoma with 4350 µm invasion into the submucosa with negative resection margins.

Sodium nitrite, a potent relaxant of rat stomach fundus: in vitro evidence

1998 ◽  
Vol 76 (10-11) ◽  
pp. 989-999 ◽  
Author(s):  
Michal Ceregrzyn ◽  
Tsuyoshi Ozaki ◽  
Atsukazu Kuwahara ◽  
Maria Wiechetek
Keyword(s):  
Methylene Blue ◽  
Potassium Channels ◽  
Guanylate Cyclase ◽  
Sodium Nitrite ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Rat Stomach ◽  
Longitudinal Muscle Layer ◽  
Stomach Fundus

The effects of sodium nitrite (0.1, 1, 10 mM) on mechanical activity of isolated rat stomach fundus muscle and the influence of guanylate cyclase activity inhibitor (methylene blue) and channel inhibitors (tetrodotoxin, charybdotoxin, apamin) were studied. Nitrite evoked dose-dependent relaxation in the longitudinal and circular muscle layers. The lowest effective concentration of sodium nitrite was 0.1 mM, which is comparable with the NOAEL (no observed adverse effect level). Tetrodotoxin (1 µM) markedly inhibited electrically induced contraction and rebound relaxation, but did not influence the nitrite-induced relaxation. Charybdotoxin (100 nM) decreased the relaxation evoked by 10 mM nitrite to 52.3 and 65.7% of control reaction in the circular and longitudinal muscle layer, respectively. Apamin (100 nM) did not influence the nitrite-induced relaxation. Methylene blue (10 µM) decreased relaxation induced by nitrite in the longitudinal and circular muscle layer, respectively, to 66.7 and 54.3% of the response to 1 mM nitrite alone. Relaxation induced by nitrite was decreased in the presence of L-cysteine (5 mM), and in the circular and longitudinal muscle layer reached 29.6 and 23.1%, respectively, of the response to 1 mM nitrite alone. We conclude that the relaxing effect of nitrite on gastric fundus results from its direct action on smooth muscle cells and probably the enteric nervous system is not involved in this action. The nitrite-elicited relaxation depends on activation of guanylate cyclase and high conductance Ca2+-activated potassium channels; however, activation of potassium channels might be a part of or might act in parallel with the mechanism involving the cyclic GMP system. Effects of nitrite observed in the presence of L-cysteine suggest that nitrosothiols are not responsible for nitrite-evoked activation of guanylate cyclase.Key words: nitrite, gastric motility, tetrodotoxin, methylene blue, charybdotoxin, L-cysteine.

Abstract 1444: Overexpression Of Endothelial Nitric Oxide Synthase Restores Post-natal Neovascularization In Atherosclerosis.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Barend Mees ◽  
Ludovic Waeckel ◽  
Dong You ◽  
Dennie Tempel ◽  
Maria Godinho ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hind Limb ◽  
Fold Increase ◽  
Tissue Perfusion ◽  
Vessel Density ◽  
Plaque Size ◽  
Angiogenic Potential ◽  
Apoe Ko Mice ◽  
Apoe Ko

Alteration in post-ischemic neovascularization is a common complication of atherosclerotic disease. This results, at least in part, from abrogation of bone-marrow mononuclear cells (BM-MNC) pro-angiogenic potential. Overexpression of eNOS has been shown to promote vessel growth in the setting of ischemia. We hypothesized that eNOS overexpression could restore impaired neovascularization in atherosclerotic (ApoE KO) mice. Hind limb ischemia was induced in mice by right femoral artery ligation. After two weeks we evaluated tissue perfusion of the foot by Laser Doppler, vessel density in the hind limb by micro-angiography and histology, and atherosclerotic plaque size. In vitro BM-MNC cell culture assays were performed. Tissue perfusion and vessel density were 1.5-fold increased in transgenic mice overexpressing eNOS (eNOStg) as compared to wild type (WT) (P<0.001, n=10). Transplantation of 1x106 WT- or eNOStg BM-MNC in WT recipients caused a 1.5-fold increase in tissue perfusion and vessel density compared to injection of PBS (P<0.001, n=10). Next, we used ApoE KO mice and crossbreeds of eNOStg and ApoE KO mice (eNOStg*ApoE KO). Tissue perfusion and vessel density were 1.8-fold increased in eNOStg*ApoE KO mice as compared to ApoE KO mice (P<0.001, n=10). Transplantation of both WT- or eNOStg*ApoE KO BM-MNC in ApoE KO recipients caused a 1.6- to 2-fold increase in tissue perfusion and vessel density compared to PBS (P<0.01, n=10), while transplantation of ApoE KO BM-MNC had no positive effect on neovascularization. Moreover, transplantation of WT BM-MNC significantly increased plaque size, while eNOStg*ApoE KO BM-MNC had no effect on plaque size. eNOS overexpression did not affect BM-MNC apoptosis and secretion of growth factors but increased their ability to differentiate in vitro into EPC. Conclusion: eNOS overexpression in the endothelium improves post-ischemic neovascularization in both physiological as atherosclerotic settings. Furthermore, eNOS overexpression in the bone marrow restores the impaired pro-angiogenic potential of atherosclerotic BM-MNC without adverse effects on plaque size. Therefore, overexpression of eNOS could play a vital part in the development of therapeutic angiogenesis for atherosclerotic disease.

Miniature Excitatory Junction Potentials in the Somatic Muscle of the Earthworm, Pheretima Communissima, in Sodium Free Solution

1969 ◽  
Vol 51 (1) ◽  
pp. 107-118
Author(s):  
Y. ITO ◽  
H. KURIYAMA ◽  
N. TASHIRO
Keyword(s):  
Reversal Potential ◽  
Muscle Layer ◽  
Physiological Solution ◽  
Free Solution ◽  
Somatic Muscle ◽  
Longitudinal Muscle Layer ◽  
High Calcium ◽  
Excitatory Junction Potentials ◽  
External Potassium ◽  
External Calcium

1. Miniature excitatory junction potentials (m.e.j.p.s) could be recorded from the longitudinal muscle layer of earthworm in sodium-free solution. 2. The amplitude and frequency of the m.e.j.p.s indicated the diffuse innervation and random release of the chemical transmitter from the nerve terminals. 3. Generation of the m.e.j.p.s was prevented by treatment with D-tubocurarine, but not by atropine and picrotoxin. 4. Hyperpolarizations of the membrane by applications of inward current increased the frequency and amplitude of the m.e.j.p.s in sodium-free solution. 5. The reversal potential level for the m.e.j.p.s in sodium-free solution was -;20 mV., and this value was 20 mV. negative to that measured in physiological solution. Low-potassium solution shifted the reversal potential levels in a more negative and high-calcium in a less negative direction. 6. The change of the reversal potential produced by a tenfold change of the external potassium concentration was 24.5 mV., and that by change of the external calcium concentration was 17 mV.

scholarly journals A Comprehensive Review of the Cosmeceutical Benefits of Vanda Species (Orchidaceae)

2015 ◽  
Vol 10 (8) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Hazrina Hadi ◽  
Syarifah Nazira Said Razali ◽  
Ammar Ihsan Awadh
Keyword(s):  
Cytochrome C ◽  
Protein Expression ◽  
Cytochrome C Oxidase ◽  
Binding Capacity ◽  
Active Agent ◽  
Fold Increase ◽  
Skin Hydration ◽  
Water Evaporation ◽  
Structural Function ◽  
Water Binding

Orchidaceae is the largest family of flowering plants with over 35000 species and 850 genera. About 3300 species of orchids are found in Malaysia and the diversity is highest in the Main, Keledang, Bintang and Tahan Ranges. Apart from being prized for their beauty, orchids have long been used by humans for medicinal purposes. Today the uses of orchids have been expanded to the food and cosmetics industries. Many cosmeceutical companies use orchid extracts as an active ingredient in their products. Previous studies provide riveting insights into the potential uses of orchid extracts as an active agent in cosmetics. This paper describes the cosmeceutical potential of orchids as an anti-aging, and skin moisturizing agent. Orchid extracts from Vanda coerulea and V. teres delay aging caused by reactive oxygen species (ROS) following UV irradiation through their antioxidant and anti-inflammatory activity. These extracts also show anti-aging properties by stimulating cytochrome c oxidase (complex IV), which is part of the electron transport chain in mitochondria. Stimulation of cytochrome c oxidase improves the respiratory function of mitochondria in keratinocytes. The presence of mucilage in orchids enables them to maintain skin hydration. Mucilage functions as a moisturizer and emollient due to its high water binding capacity. Additionally, orchid extracts provide skin hydration by stimulating aquaporin 3 (AQP3) and LEKTI protein expression. The presence of AQP3 leads to a five-fold increase in water permeability, which subsequently increases stratum corneum hydration. Increased LEKTI protein expression mediated by orchid extracts reduces the degradation of desmoglein-1 and enhances the structural function of desmosomes, which play important roles in preventing water evaporation.

Membrane currents recorded from a fragment of rabbit intestinal smooth muscle cell

1986 ◽  
Vol 251 (3) ◽  
pp. C335-C346 ◽  
Author(s):  
Y. Ohya ◽  
K. Terada ◽  
K. Kitamura ◽  
H. Kuriyama
Keyword(s):  
Smooth Muscle ◽  
Longitudinal Muscle ◽  
Outward Current ◽  
Ionic Currents ◽  
Muscle Layer ◽  
Dependent Manner ◽  
Rabbit Ileum ◽  
Longitudinal Muscle Layer ◽  
Inward Current ◽  
K Currents

Properties of ionic currents in smooth muscle membranes of the longitudinal muscle layer of the rabbit ileum were investigated using the single electrode voltage clamp method. In the present experiments, this method was applicable only to the smooth muscle ball (fragment) and not for the dispersed whole cell, because of incompleteness of the voltage clamping. A voltage step elicited a transient inward current followed by an outward current. This outward current was partly inhibited by Mn2+ or nisoldipine or by a reduction in the extracellular [Ca2+] ([Ca2+]o). Tetraethylammonium (TEA) reduced the delayed outward current in a dose-dependent manner, but 50 mM TEA did not produce a complete block of a residual current. When the pipette contained K+-free (Cs+ with TEA+) solution, the residual outward current was abolished. The inward current was elicited at -30 mV (holding potential of -60 mV) and reached the maximal value at +10 mV; the polarity was reversed at +60 mV. This inward current depended on the [Ca2+]o and was blocked by Mn2+ or nisoldipine. Ba2+ also permeated the membrane, and the inward current evoked by Ba2+ was also blocked by Mn2+ or nisoldipine. Reduction of [Na+]o in a solution containing 2.4 mM Ca2+ neither modified the current-voltage relation nor the decay of the inward current, but when [Ca2+]o was reduced to below 1 microM, Na+ permeated the membrane and was blocked by nisoldipine. In conclusion, ionic currents were recordable from the fragmented ball of the longitudinal muscle of rabbit ileum. There were at least two K+ currents as the outward current (Ca2+-dependent K+ and delayed K+ currents) and a Ca2+ current as the inward current. The property of the Ca2+ channel was similar to that observed with other preparations.

Motility of the small intestine: a look ahead

1985 ◽  
Vol 248 (5) ◽  
pp. G495-G500 ◽  
Author(s):  
J. R. Mathias ◽  
C. A. Sninsky
Keyword(s):  
Small Intestine ◽  
Action Potential ◽  
Muscle Layer ◽  
Control Mechanisms ◽  
Muscularis Mucosa ◽  
Longitudinal Muscle Layer ◽  
Look Ahead ◽  
Health And Disease ◽  
And Function ◽  
Contraction And Relaxation

Motility of the gastrointestinal tract has become an important discipline of gastroenterology. In this paper we review important observations made during the early development of this discipline, note the current level of knowledge, and look ahead to some of the questions we believe will be addressed in the near future. Is the slow wave the action potential equivalent of the longitudinal muscle layer? How does the migrating action potential complex interrelate with the migrating myoelectric complex--are they two separate complexes under different control mechanisms? How do the myenteric plexus neurons relate to these complexes? Does the muscularis mucosa control the contraction and relaxation of the villous tips? Is there a finite area in the small intestine that can function as the pacemaker? How important are substances within the lumen in controlling motility? Finally, we emphasize the importance of structure and function of the plexus neurons in motility studies. We also stress the importance of collaboration and a multidisciplinary approach for future understanding of the mechanisms of the small intestine in health and disease.

Sign in / Sign up

Export Citation Format

Share Document