Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic mesenteric ischemia (CMI) is a serious vascular condition that if left untreated may progress to acute ischemia resulting in bowel necrosis and high surgical morbidity/mortality rates. Elective intervention has been shown to prevent this progression and relieve symptoms. Current open surgical intervention involves arterial bypass using a vein or synthetic graft conduit with the inflow originating from the aorta or iliac artery. In some circumstances, the splenic artery provides an additional treatment option for revascularization of the superior mesenteric artery. In certain cases, the splenic artery has several advantages over traditional surgical options. The splenic artery is an arterial conduit much like the internal mammary artery used in coronary artery bypass grafting. These grafts are known for their long-term patency and in selected clinical circumstances are preferred over venous grafts. Because the splenic artery has a natural inflow, only a single vascular anastomosis at the outflow vessel (the SMA) is necessary. This lessens the risk of anastomotic stenosis by decreasing the number of anastomoses created and it makes the procedure shorter in duration. The fact that the inflow is provided by the splenic artery makes cross-clamping of the aorta unnecessary, thereby lessening the risk of producing cardiac ischemia and declamping hypotension. A disadvantage is the risk of splenic ischemia with the possible need for splenectomy. The majority of individuals will have adequate collateral supply to the spleen via the short gastric arteries. The risk to the patient of splenectomy versus the benefits of a less complicated arterial reconstruction with avoidance of aortic cross-clamping must be weighed on a case-by-case basis. Preventing the progression to acute mesenteric ischemia with its increased mortality by timely restoration of adequate vascular supply is an important principle in treating patients with CMI. Controversy still exists over the best treatment option for these patients, whether it be antegrade versus retrograde bypass, single-vessel versus multivessel reconstruction, or open surgical repair versus endovascular intervention. In selected patients, the use of the splenic artery can be considered as an additional option for arterial reconstruction of the SMA.
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PMID:Splenic artery-to-superior mesenteric artery bypass for chronic mesenteric ischemia--a case report. 1549 46

Visceral artery aneurysms (VAA) can be treated by revascularization, ligation, or, most often, endovascular techniques depending on clinical presentation, hemodynamic status, and location. From 1975 to 2002 a total of 42 VAA in 34 patients were treated. The lesion involved the splenic artery (SA; 19), pancreaticoduodenal artery (PDA; 6), celiac trunk (CT; 5), superior mesenteric artery (SNA; 4), common hepatic artery (CHA; 3), gastroduodenal artery (GDA; 2), left hepatic artery (LHA; 1), a branch of the inferior mesenteric artery (BIMA; 1), and a branch of the SMA (BSMA; 1). Twenty-seven VAA in 21 patients (64%) were uncomplicated (group I) and 15 VAA in 13 patients (36%) had ruptured (group II) (PDA; 6; CT, 3; SA, 1; CHA, 1; LHA, 1; BSMA, 1; BIMA, 1). In group I VAA were treated by embolization (n = 11), splenectomy (n = 6), bypass (n = 7), ligation (n = 2), and aneurysmorraphy (n = 1). No deaths were observed. The morbidity rate associated with surgical treatment was 12% including hepatic bypass thrombosis without ischemic complications in two cases. The morbidity rate associated with endovascular treatment was 18% including cholecystitis in one case and bile duct stenosis in one case. The VAA recanalization rate following embolization was 9%. In group II, 12 VAA (80%) were treated by ligation in association with splenectomy in two cases and left hepatectomy in one case. Only one bypass procedure was performed and embolization was used to treat two VAA (1 SMA and 1 PDA). The mortality rate was 20% (3/15). The morbidity rate associated with surgical treatment was 46% (6/13) including bile duct stenosis in one case, ischemic cholecystitis in one case, duodenal fistula in one case, pancreatic fistula in one case, bile tract fistula in one case, and colonic ischemia in one case. No patient died after endovascular treatment and the morbidity rate was 50% (1/2) with duodenal stenosis occurring in one case. In sum, VAA can rupture. Emergency cases can be treated by ligation in most cases or by embolization if the hemodynamic status of the patient allows. Regardless of treatment technique, the morbidity and mortality rate remains high after rupture, especially in cases involving PDA. Embolization can be proposed as a first-line treatment for most VAA. Because of the risk of rupture, endovascular or open repair is warranted for VAA and has a favorable prognosis.
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PMID:Treatment of visceral artery aneurysms: description of a retrospective series of 42 aneurysms in 34 patients. 1559 27

Splanchnic ischemia/reperfusion (I/R) induces a systemic inflammatory response with acute lung injury. Impaired production of endothelial nitric oxide (NO) plays a key role in this process. We evaluated the effects of early treatment with inhaled NO (iNO) on lung microcirculatory inflammatory changes during splanchnic I/R. I/R was induced in rats by occlusion of the superior mesenteric artery (SMA; 40 min) and reperfusion (90 min). Four groups were studied: Control, anesthesia only; Sham, all surgical procedures without I/R, ventilated with air; Air, SMA I/R, ventilation with air; and NO, SMA I/R, ventilation with NO (20 ppm) starting 10 min before reperfusion. Intravital video microscopy was used to monitor pulmonary macromolecular flux and capillary flow velocity (CFV). Leukocyte infiltration was determined by morphometry. SMA I/R decreased mean arterial blood pressure, capillary CFV (P < 0.01), and shear rate (P < 0.01), and increased pulmonary macromolecular leak by 138% +/- 8% (P < 0.001). iNO markedly attenuated the increase in macromolecular leak (P < 0.01), blunted the decrease in capillary CFV (P < 0.05) and shear rate (P < 0.05), and prevented the increase in leukocyte infiltration of the lungs after SMA I/R (P < 0.05). The direct, real-time, in vivo data suggest that early institution of low-dose iNO therapy effectively ameliorates the acute remote pulmonary inflammatory response after splanchnic I/R.
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PMID:Effects of inhaled nitric oxide on lung injury after intestinal ischemia-reperfusion in rats. 1566 30

We assessed the prevention of hepatic fibrogenesis by water-extract of Panax notoginseng Buck F.H. Chen. (Arialiaceae) root (PNS) in Long-Evans rats with cinnamon coat color (LEC rats). LEC rats were divided into three groups A, fed on a basal diet (BD); B, fed on BD plus 1% PNS; and C), fed on BD plus 0.005% lycopene as a control. All rats were sacrificed at 26 weeks of age. The percentage of the total area involved by fibrosis was 1.46 +/- 0.47 in group A, 0.83 +/- 0.10 in B (P=0.0030, B vs A) and 0.91 +/- 0.45 in C (P=0.0035, C vs. A). The percentage of the total area that was stained for alpha-SMA was 0.56 +/- 0.34 in group A, 0.15 +/- 0.02 in B (P=0.0016, B vs. A and 0.11 +/- 0.01 in C (P=0.0025, C vs. A. In group B, malondialdehyde (MDA) in the liver was lower than in group C (P=0.007). In group C, the concentration of iron in the liver was lower than in group A (P=0.0053). Thus, PNS suppressed fibrogenesis through reduced generation of lipid peroxides. The mechanisms of this preventive effect of fibrogenesis with PNS were suggested to inhibit the stellate cell activity. Second objective of this study was to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an NO synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-alpha levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect.
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PMID:A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats. 1569 47

Several studies have shown that erythropoietin (EPO) can protect the kidneys from ischemia-reperfusion injury and can raise the hemoglobin (Hb) concentration. Recently, the EPO molecule modified by carbamylation (CEPO) has been identified and was demonstrated to be able to protect several organs without increasing the Hb concentration. We hypothesized that treatment with CEPO would protect the kidneys from tubular apoptosis and inhibit subsequent tubulointerstitial injury without erythropoiesis. The therapeutic effect of CEPO was evaluated using a rat ischemia-reperfusion injury model. Saline-treated kidneys exhibited increased tubular apoptosis with interstitial expression of alpha-smooth muscle actin (alpha-SMA), while EPO treatment inhibited tubular apoptosis and alpha-SMA expression to some extent. On the other hand, CEPO-treated kidneys showed minimal tubular apoptosis with limited expression of alpha-SMA. Moreover, CEPO significantly promoted tubular epithelial cell proliferation without erythropoiesis. In conclusion, we identified a new therapeutic approach using CEPO to protect kidneys from ischemia-reperfusion injury.
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PMID:Carbamylated erythropoietin protects the kidneys from ischemia-reperfusion injury without stimulating erythropoiesis. 1719 38

Liver fibrosis is produced by myofibroblasts of different origins. In culture models, rat myofibroblasts derived from hepatic stellate cells (HSCs) and from periductal portal mesenchymal cells, show distinct proliferative and immunophenotypic evolutive profiles, in particular regarding desmin microfilament (overexpressed vs shut-down, respectively). Here, we examined the contributions of both cell types, in two rat models of cholestatic injury, arterial liver ischemia and bile duct ligation (BDL). Serum and (immuno)histochemical hepatic analyses were performed at different time points (2 days, 1, 2 and 6 weeks) after injury induction. Cholestatic liver injury, as attested by serum biochemical tests, was moderate/resolutive in ischemia vs severe and sustained in BDL. Spatio-temporal and morphometric analyses of cytokeratin-19 and Sirius red stainings showed that in both models, fibrosis accumulated around reactive bile ductules, with a significant correlation between the progression rates of fibrosis and of the ductular reaction (both higher in BDL). After 6 weeks, fibrosis was stabilized and did not exceed F2 (METAVIR) in arterial ischemia, whereas micronodular cirrhosis (F4) was established in BDL. Immuno-analyses of alpha-smooth muscle actin and desmin expression profiles showed that intralobular HSCs underwent early phenotypic changes marked by desmin overexpression in both models and that the accumulation of fibrosis coincided with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures. With the exception of desmin-positive myofibroblasts located at the portal/septal-lobular interface at early stages, and of myofibroblastic HSCs detected together with fine lobular septa in BDL cirrhotic liver, the vast majority of myofibroblasts were desmin-negative. These findings suggest that both in resolutive and sustained cholestatic injury, fibrosis is produced by myofibroblasts that derive predominantly from portal/periportal mesenchymal cells. While HSCs massively undergo phenotypic changes marked by desmin overexpression, a minority fully converts into matrix-producing myofibroblasts, at sites, which however may be important in the healing process that circumscribes wounded hepatocytes.
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PMID:Prominent contribution of portal mesenchymal cells to liver fibrosis in ischemic and obstructive cholestatic injuries. 1726 5

There is the consensus that patients with an acute type A aortic dissection (AADA) should undergo urgent surgical treatment. However, we dared to select a two-staged repair in order to relieve the visceral ischemia first. In addition, we selected revascularization using a bypass graft without using a proximal aortic replacement or aortic fenestration, because the reason for the occlusion of the SMA was judged to be an extension of the dissection out along the proximal segment of the SMA. Consequently, we proposed that a two-staged repair of the AADA with visceral ischemia was a useful option.
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PMID:Two-staged repair for an acute type A aortic dissection with visceral ischemia after an aortic valve replacement. 1830 38

Peripheral artery disease and critical limb ischemia have become prevalent health risks in the United States due to an increasing elderly population and the prevalence of obesity and diabetes mellitus. Although highly invasive endarterectomy is the most popular method for treatment, angiogenic therapies based on growth factor administration are quickly becoming a popular alternative. Enzymatic degradation of these factors in vivo may be avoided by their incorporation in a delivery vehicle where the growth factor's release rate can be controlled by altering the vehicle's properties (i.e. cross-linking density, material selection, biodegradation, etc.). Herein, we report on the immobilization and controlled release of human recombinant basic fibroblast growth factor (FGF-2) and human recombinant granulocyte colony-stimulating factor (G-CSF) from ionic, gelatin-based hydrogel scaffolds to re-establish perfusion and induce capillary outgrowth in a murine hindlimb ischemic model. In vitro studies showed that endothelial cell proliferation was highly depended on FGF-2, whereas G-CSF stimulated migration and formation of a tubular network. When FGF-2 and G-CSF were used in combination there was an 82% increase in endothelial branch point formation compared to control groups. Leg reperfusion was assessed with laser Doppler perfusion imaging, while capillary outgrowth in the ischemic leg was evaluated using CD31(+) and alpha-SMA immunostaining. The co-delivery of G-CSF (1000 ngml(-1)) and FGF-2 (1000 ng ml(-1)) from the gelatin hydrogels resulted in a 3-fold increase in the perfusion levels and a 2-fold increase in capillary density and positive alpha-SMA vessels compared to the empty vehicle group. In conclusion, the co-delivery of FGF-2 and G-CSF was superior to bolus administration or the delivery of either factor alone in promoting reperfusion and mature vessel formation.
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PMID:Co-delivery of FGF-2 and G-CSF from gelatin-based hydrogels as angiogenic therapy in a murine critical limb ischemic model. 1871 69

The type of fluid used during resuscitation may have an important impact on tissue edema. We evaluated the impact of two different regimens of fluid resuscitation on hemodynamics and on lung and intestinal edema during splanchnic hypoperfusion in rabbits. The study included 16 female New Zealand rabbits (2.9 to 3.3 kg body weight, aged 8 to 12 months) with splanchnic ischemia induced by ligation of the superior mesenteric artery. The animals were randomized into two experimental groups: group I (N = 9) received 12 mL x kg-1 x h-1 lactated Ringer solution and 20 mL/kg 6% hydroxyethyl starch solution; group II (N = 7) received 36 mL x kg-1 x h-1 lactated Ringer solution and 20 mL/kg 0.9% saline. A segment from the ileum was isolated to be perfused. A tonometric catheter was placed in a second gut segment. Superior mesenteric artery (Q SMA) and aortic (Qaorta) flows were measured using ultrasonic flow probes. After 4 h of fluid resuscitation, tissue specimens were immediately removed for estimations of gut and lung edema. There were no differences in global and regional perfusion variables, lung wet-to-dry weight ratios and oxygenation indices between groups. Gut wet-to-dry weight ratio was significantly lower in the crystalloid/colloid-treated group (4.9 +/- 1.5) than in the crystalloid-treated group (7.3 +/- 2.4) (P < 0.05). In this model of intestinal ischemia, fluid resuscitation with crystalloids caused more gut edema than a combination of crystalloids and colloids.
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PMID:Comparison of the effects of lactated Ringer solution with and without hydroxyethyl starch fluid resuscitation on gut edema during severe splanchnic ischemia. 1871 46

Hypoxic response element (HRE) offers satisfactory control over expression of hVEGF(165) in cell levels. However, the characteristics of regenerated blood vessels induced by long-term expression of transferred hVEGF(165) under control of HRE in vivo remain unknown. This study aims to investigate the effect of HRE on control of long-term expression of rAAV-delivered hVEGF(165) gene to ischemic myocardium and evaluate characteristics of angiogenesis induced by hVEGF(165) in vivo. Rabbit ischemic heart models were established surgically, rAAV-9HRE-hVEGF(165) was transfected to ischemia hearts subjected to 12 week ischemia. Molecular biological and immunohistochemistry were employed to determine expressions of HIF-1alpha and hVEGF(165). Microvessel densities of CD31(+) and alpha-SMA(+) regenerated vessels were also evaluated. Expressions of both hVEGF(165) mRNA and protein were upregulated following over-expression of endogenous HIF-1alpha early after ischemia, peaked at 4-6 weeks post-MI, declined, and approached pre-ischemia level at the end of 12 weeks of ischemia (P < 0.01). The significantly upregulated CD31 in hVEGF(165)-treated hearts presented from 8 to 12 weeks of ischemia compared with the control (P < 0.01). However, alpha-SMA expression was rapidly downregulated after ischemia and remained lower than the control level by the end of 12 weeks post-MI (P < 0.01). Overexpression of hVEGF(165) controlled by HIF-1alpha-HRE system shows a stably regional angiogenic efficacy in vivo. But, VEGF, as an early angiogenic cytokine, is inadequate for mediating histologically mature vessels in ischemia myocardium.
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PMID:Angiogenesis induced by hVEGF165 gene controlled by hypoxic response elements in rabbit ischemia myocardium. 1993 63


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