11 research outputs found
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Butyrate Potential Role in Colon Cancer Prevention and Treatment
Butyrate is produced in the colon of mammals as a result of microbial fermentation of dietary fiber, undigested starch, and proteins (Rombeau 1990). Butyrate may be an important protective agent in colonic carcinogenesis (Young 1994, Velázquez 1996a). Trophic effects on normal colonocytes in vitro (Scheppach 1992a) and in vivo (Velázquez 1996a) are induced by butyrate. In contrast, butyrate arrests the growth of neoplastic colonocytes and inhibits the preneoplastic hyperproliferation induced by some tumor promoters in vitro (Bartram 1994). Butyrate induces differentiation of colon cancer cell lines in culture (Young 1994). It also regulates the expression of molecules involved in colonocyte growth and adhesion, and inhibits the expression of several proto-oncogenes relevant to colorectal carcinogenesis, in vitro (Young 1994). Recent studies in our laboratory show that intraluminal butyrate treatments in normal rat colon results in proliferation patterns consistent with a potential protective role for butyrate in colon carcinogenesis (Velázquez 1996a). Associated with these effects, butyrate increased c-Jun whereas the secondary bile acid and tumor promoter, deoxycholate increased c-Fos, demonstrating for the first time, that these diet by-products can specifically affect colonic proto-oncogene expression in vivo. Moreover, we have recently observed that intravenous infusion of butyrate has significant anti-tumor effects, in an in vivo murine model of colon cancer metastatic to the liver (Velázquez 1996b). Preliminary work indicates that butyrate’s growth inhibitory effects in neoplastic colonocytes may be linked to inhibition of mevalonate-mediated cell growth. Additional studies are needed to fully evaluate butyrate’s anti-neoplastic effects in vivo, and to understand its mechanism(s) of action
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The scientific rationale and clinical application of short-chain fatty acids and medium-chain triacylglycerols
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MAGNETIC RESONANCE ANGIOGRAPHY OF LOWER-EXTREMITY ARTERIAL DISEASE
The success of bypass grafting to arteries of the lower leg depends greatly on the accurate identification of suitable distal vessels. Contrast angiography has been the conventional reference standard for preoperative vascular imaging of the lower extremities. It clearly defines the anatomy of the aorta, its branches, and the peripheral arteries and thus provides an accurate map of inflow and outflow vessels to plan therapeutic interventions, such as bypass grafts and angioplasty. In the past, contrast angiography was the only nonoperative, reliable, and accurate diagnostic modality used by vascular surgeons and interventional radiologists in planning therapeutic procedures for patients with lower-extremity arterial disease. However, conventional contrast angiography has definite risks and limitations.
23
It has an overall minor and major complication rate of approximately 8%, with a risk of severe contrast reaction varying from 0.04% to 0.22%.
11,13,15,25,26
Moreover, conventional contrast angiography fails to identify all patent runoff vessels in approximately 70% of patients with severe occlusive peripheral vascular disease.
12,18,21,22
Given that 29% of our patients show evidence of baseline renal insufficiency, contrast-induced worsening of renal function
11,13
has also been an issue of serious concern.
Magnetic resonance angiography (MRA) is an alternative, noninvasive imaging modality that avoids the complications of arterial puncture, eliminates the risk of contrast-induced renal failure, and has higher sensitivity than contrast angiography in the identification of patent distal vessels in patients with severe peripheral arterial occlusive disease.
9,17
MRA is as accurate and reliable as conventional contrast angiography in the preoperative imaging of inflow vessels
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and the preoperative grading of stenosis severity in peripheral arteries.
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MRA can accurately identify patent runoff vessels not visualized by conventional contrast angiography.
7,17
More importantly, results of bypasses performed to these “angiographically occult” runoff vessels are similar to those of bypasses performed to vessels detected by conventional contrast angiography.
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The recent addition of the non-nephrotoxic contrast agent, gadolinium, has further improved the accuracy and expanded the available applications of MRA.
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Magnetic resonance angiography is a cost-effective,
6,27
outpatient, noninvasive technique that, if properly performed and interpreted,
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can be sufficient for planning peripheral bypass procedures.
2,6
Although many technical and practical limitations remain to be solved before the widespread acceptance and application of MRA, some centers have already replaced conventional contrast angiography with MRA in the preoperative evaluation of patients with peripheral arterial disease.
1,2,4,
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Magnetic Resonance Angiography in Peripheral Vascular Surgery
Abstract
This chapter reviews magnetic resonance angiography (MRA) applied to the diagnosis and preoperative planning in patients with peripheral vascular disease of the lower extremities. The advantages and disadvantages, accuracy and clinical application of MRA are compared and contrasted with the traditional preoperative imaging modality for patients with vascular disease, i.e. conventional contrast angiography
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Butyrate and the Colonocyte Production, Absorption, Metabolism, and Therapeutic Implications
Butyrate is one of the three principal short chain fatty acids (SCFA) in humans generated by colonic microbial fermentation of dietary substrates. SCFA are the C2-5 organic fatty acids, also called the volatile fatty acids (VFA), which include acetate, propionate and butyrate. Colonic intraluminal levels of butyrate may play a role in the pathogenesis of a variety of diseases of the large intestine. This chapter reviews the production, absorption, metabolism, and therapeutic implications of butyrate
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Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice
Background. The short-chain fatty acid butyrate inhibits growth of colorectal carcinoma cells in vitro. Mevalonate, a short-chain fatty acid structurally and metabolically related to butyrate, is important in signal transduction and is essential for cell growth. We investigated butyrate's effects on seeding and growth of colorectal tumor cells metastatic to the liver in vivo and hypothesized that butyrate's antiproliferative effects are associated with inhibition of mevalonate-mediated cell growth.
Methods. Hepatic metastases were induced by injecting 1×10
5 MC-26 (N-methyl-N-nitrosourea-induced murine colorectal carcinoma) cells into the spleen of BALB/c mice. Mice were treated with a continuous intravenous infusion of butyrate (2 gm/kg/day) for 7 days starting 24 hours before tumor cells were injected. Study variables included liver weight and number of hepatic surface metastases. Proliferation studies on MC-26 cells were performed in vitro to examine the effects of butyrate alone or combined with mevalonate or mevastatin (an inhibitor of mevalonate synthesis).
Results. Butyrate reduced seeding and growth of colorectal tumor cells in vivo. Mevalonate diminished butyrate's antiproliferative action in vitro, whereas mevastatin potentiated this effect.
Conclusions. These studies (1) show that butyrate inhibits seeding and growth of hepatic colorectal metastases in vivo, (2) associate butyrate's antiproliferative effects with inhibition of mevalonate-mediated cell growth, and (3) indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may have synergistic antiproliferative effects when combined with butyrate
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Butyrate inhibits deoxycholate induced increase in colonic mucosal DNA and protein synthesis In Vivo
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In Vivo Crypt Surface Hyperproliferation Is Decreased by Butyrate and Increased by Deoxycholate in Normal Rat Colon: Associated In Vivo Effects on c-Fos and c-Jun Expression
Background: Studies on colon carcinogenesis suggest that the short-chain fatty acid butyrate may be protective, whereas the secondary bile acid deoxycholate may promote tumor development. Crypt surface hyperproliferation is regarded as a biomarker of colon cancer risk and can be modulated in vitro by the differentiation inducer butyrate and the tumor promoter deoxycholate. We hypothesized that butyrate decreases and deoxycholate increases crypt surface proliferation in vivo and that these effects are mediated by changes in the expression of the protooncogenes c-Fos and c-Jun, which are known to regulate proliferation and differentiation. Methods: Twenty-five adult Sprague-Dawley rats underwent colonic isolation and 24-hour intraluminal instillation of 10 mmol/L sodium chloride, 10 mmol/ L sodium butyrate, or 10 mmol/L sodium deoxycholate. Proliferation of the whole crypt and five crypt compartments from base to surface was assessed by proliferating cell nuclear antigen immunohistochemistry. The ϕh value, an index of "premalignant" hyperproliferation, was calculated as the ratio of labeled cells in the two surface compartments divided by the labeled cells in the entire crypt. Expression of c-Fos and c-Jun was evaluated by Western blot. Results: Crypt surface proliferation and the ϕh value were significantly decreased by butyrate and increased by deoxycholate. Butyrate increased colonic expression of c-Jun, whereas deoxycholate significantly induced c-Fos. Conclusions: The in vivo effects on surface proliferation are consistent with a potential tumor-promoting role for butyrate and a promotive role for deoxycholate in colon carcinogenesis. The concurrently observed effects on colonic c-Jun and c-Fos expression represent a novel finding and suggest that direct or indirect modulation of protooncogene expression may be the mechanism by which these dietary byproducts regulate proliferation in vivo. (Journal of Parenteral and Enteral Nutrition
20:243-250, 1996