Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
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PMID:Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents. 1278 86

Although naturally occurring food-borne pathogens cause more than 76 million illnesses, 325,000 hospitalizations, and 5000 deaths annually in the United States, many more infections are unrecognized and unreported. In addition, mass production and distribution of food, on a global rather than a local scale, make it possible for localized instances of contamination to spread quickly to other states, provinces, and countries. Infectious organisms are often recovered by microbiological methods, but surgical pathologists may play a very valuable role in diagnosis. This review will focus on the diagnosis of food-borne infectious diseases of the gastrointestinal tract, including those that mimic other inflammatory conditions of the gut (such as ischemia or idiopathic inflammatory bowel disease); available diagnostic methods; and gastrointestinal infectious processes that pathologists should be aware of in terms of potential biologic weapons threats.
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PMID:Pathology of food-borne infectious diseases of the gastrointestinal tract: an update. 1458 21

The course and outcome of patients after liver transplantation (LT) for primary sclerosing cholangitis (PSC) are still debated. Our purpose is to define retrospectively, the post-LT clinicopathologic findings seen in 51 PSC patients with a follow-up of 2 to 14 years. Of the total 51 patients, 16 with native liver hilar xanthogranulomatous cholangiopathy (XGC) had median graft and patient survival of 573 and 835 days, respectively compared with 2489 and 2794 days, respectively, in 35 patients without XGC. Perioperative complications resulted in 9 early deaths (day 0 to 52). Of the remaining 42 patients, 6 had recurrent PSC (R-PSC) with typical histologic and cholangiographic findings, 12 had autoimmune liver disease-not otherwise specified with histology of autoimmune hepatitis/overlap syndrome, 3 had chronic rejection, 4 had ischemic cholangiopathy, and 17 had no recurrence. The presence of inflammatory bowel disease, total ischemia time of > or =11 hours, recipient-donor ABO and HLA Class I and II matches, and the type of immunosuppression did not affect the post-LT outcome. Recipient-donor gender mismatch was more common in R-PSC than in the nonrecurrent group (P=0.045). Post-LT malignancies were significantly more common in the nonrecurrent cases compared with all others combined (P=0.031) and caused deaths in 4. The majority of deaths (11/13) in other groups were due to sepsis complicating graft dysfunction. In conclusion, allograft autoimmune liver disease was seen in 18 (43%) of 42 long-term post-LT PSC patients, with progression in 5 of 18 patients. Features of PSC were seen in 6 (33%) of 18. Native liver XGC negatively impacted post-LT graft and patient survival. Increased incidence of malignancies in the nonrecurrent group may reflect overimmunosuppression in those patients.
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PMID:Liver transplantation for primary sclerosing cholangitis: a long-term clinicopathologic study. 1465 14

Acute diarrhea is commonly caused by an infection. Severe acute diarrhea warrants immediate medical evaluation and hospitalization. Indications for stool studies include fever; bloody diarrhea; recent travel to an endemic area; recent antibiotics; immunosuppression; and occupational risks, such as food handlers. Noninfectious causes include inflammatory bowel disease, radiation enteritis, and intestinal ischemia. Management of severe acute diarrhea includes intravenous fluid rehydration and empiric antibiotics. Use of antidiarrheal agents is controversial when invasive pathogens are suspected.
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PMID:Severe acute diarrhea. 1469 6

Glutathione plays an important cytoprotective role in the gut. Animal studies have demonstrated that the provisions of glutathione precursors are protective for different types of free-radical-mediated cellular injury. There is a need to clarify the potential role of glutathione supplementation in ischemia-reperfusion injury and inflammatory bowel disease. More speculative is whether treatment with glutathione precursors can modify the progress of colorectal cancer.
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PMID:The role of glutathione in intestinal dysfunction. 1470 30

Within a framework of dual involvement of mucosa and submucosa on the one hand, and of the muscularis propria of the bowel wall on the other, it might be valid to consider involvement of the vascular supply as the essential means in itself of not only causing the morphologic lesions in inflammatory bowel disease, but also especially in accounting for persisting patterns of inflammatory response both in ulcerative colitis and in Crohn's disease. Inflammatory bowel disease as a group constitutes a spectrum of biologic and pathobiologic manifestations in terms not only of inflammatory involvement of the bowel wall but also in terms of how the bowel in its turn deals with inflammation as a pathologic lesion in its own right. Parameters of inflammatory bowel activity transcend simple concepts of etiology and pathogenesis as applicable to category disorders such as infections or bowel ischemia. Indeed, the strictly characterized initiation of the inflammatory bowel response as a function of defective regulation of the antigenicity of the luminal contents on the one hand, and on interactions between nitric oxide and free oxygen radicals on the other, might help determine a persistence of tissue damage in inflammatory bowel disease that is either relapsing/remitting or chronic in progression. In a final analysis, perhaps, there might be involved a single central form of pathway induction of dysregulated immune reactivity arising from an early disturbance in activation patterns as induced by the onset of luminal antigenicity at an early or specific-stage, further characterized perhaps by specific forms of intestinal epithelial defects of the bowel mucosa in patients subsequently developing inflammatory bowel disease. Specific genetic markers for disease susceptibility and for therapeutic responsiveness are particularly of interest. The Nucleotide binding oligomerization Domain 2 (NOD2) would recognize microbial lipopolysaccharide or else mark systemic responses to pathogens that are pathogenic to evolving inflammatory bowel disease.
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PMID:A primary dysregulation in the immunoregulatory role of the intestinal mucosal epithelial cell in inflammatory bowel disease pathogenesis? Biology of inflammatory response as tissue pattern entities in Crohn's versus ulcerative colitis. 1499 Mar 86

The ileal pouch anal anastomosis (IPAA) procedure has become the preferred surgical option for most patients with ulcerative colitis who require surgical removal of the colorectum. The vast majority of patients with this new anatomy will either not develop pouchitis or develop a few discrete episodes of acute pouchitis. However approximately one fourth of patients will develop recurrent pouchitis, with 5% being categorized as chronic pouchitis requiring maintenance therapy or, on rare occasion, pouch excision. Factors that are associated with an increased risk of pouchitis include primary sclerosing cholangitis, extraintestinal manifestations, and nonsmokers. Controversy surrounds other risk factors such as extent of colitis, backwash ileitis, preoperative pANCA levels, and carrying a specific allele for IL-1 receptor antagonist. The etiology of pouchitis is unknown, but theories range from genetic susceptibility, bacterial overgrowth, ischemia, and fecal stasis, to a recurrence of ulcerative colitis in the pouch, a missed diagnosis of Crohn's disease, or possibly a novel third form of inflammatory bowel disease. Some patients with symptoms of pouchitis will not have inflammation of the pouch, but rather, irritable pouch syndrome. Thus, endoscopic investigation with biopsy is important for declaring whether a patient has pouchitis. Indeed, the more commonly used scores, such as the pouch disease activity index, incorporate both endoscopic and histologic criteria. Not surprisingly, treatment options for patients with pouchitis resemble that of regular inflammatory bowel disease, although there have only been a few controlled trials. Antibiotics are the mainstay of therapy, with metronidazole and ciprofloxacin demonstrating benefit in controlled trials. Probiotics are effective for maintaining remission of pouchitis. Mesalamine, corticosteroids, and immunomodulators have been used with some success. Occasionally, patients with well-documented ulcerative colitis as the indication for IPAA will develop what appears to be Crohn's disease of the pouch, on the basis of granulomatous inflammation, pre-pouch ileitis, or fistulae. The treatment is similar to Crohn's disease, including the use of infliximab. Dysplasia within the pouch mucosa itself is quite rare. Reports of dysplasia occurring in patients with IPAA are usually due to neoplastic change within the residual cuff of rectal or transition zone mucosa just below the pouch, rather than in the ileal mucosa of the pouch. With further elucidation of the genetic basis for inflammatory bowel disease, we should be able to more accurately classify patients with ulcerative colitis and Crohn's disease genotypically. Hopefully, this will also bring more clarity to the heterogeneous population of patients with pouchitis and allow for more focused therapeutic strategies.
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PMID:The diagnosis and treatment of pouchitis in inflammatory bowel disease. 1511 32

Metabolic bone disease (MBD) is abnormal bone metabolism and includes the common disorders of osteoporosis and osteomalacia, which can develop in patients receiving long-term parenteral nutrition (PN). Patients who require long-term PN have significant gastrointestinal failure and malabsorption, which is generally caused by severe inflammatory bowel disease, intestinal ischemia, or malignancy. The exact cause of MBD in long-term PN patients is unknown, but its origin is thought to be multifactorial, with factors including underlying disease, effect of medications used to treat this disease (eg, corticosteroids), and various components of the PN solution. Caring for patients on long-term PN requires routine assessment and monitoring for MBD. Appropriate adjustments of the PN solution can help reduce the risk for developing PN-associated MBD and in some instances improve bone mineral density. Recent developments in pharmacologic treatment for osteoporosis show promise for patients with MBD receiving PN.
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PMID:Metabolic bone disease and parenteral nutrition. 1524 4

We report on a 33-year-old women with ulcerative colitis, who presented with inspiratory thoracic pain due to perimyocarditis. Furthermore, postprandial abdominal pain associated with diarrhea and different blood pressure values on both arms were recorded. Computed tomography revealed embolism of the pulmonal arteries and angiography demonstrated stenoses of the subclavian and renal arteries and the celiac trunc suggesting the diagnosis of Takayasu's arteritis. A coronary or infectious etiology could be excluded. Since a coincidence of Takayasu's arteritis and ulcerative colitis has been reported in the literature, abdominal pain and diarrhea can either be explained by the inflammatory bowel disease or by chronic ischemia due to intestinal vasculitis. Differential diagnosis will be facilitated by the future course of the disease.
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PMID:[33-year old patient with thoraco-abdominal pain and differences of blood pressure]. 1537 64

Thromboembolic events are a known complication in inflammatory bowel disease (IBD). We report on 2 young women with IBD and aortic mural thrombi as a source of arterioarterial embolization to the lower limbs resulting in significant morbidity. The first case was a 36-year-old woman with severe ulcerative colitis who presented with signs of microembolism into two toes of her right foot. A thrombus in the otherwise normal infrarenal aorta with occlusion of the inferior mesenteric artery was revealed by computed tomography (CT) and intrarterial angiography. The digital ischemia resolved without sequelae. The second case was a 41-year-old woman with Crohn's disease complicated by fistulas. She developed acute ischemia of her right leg. Arteriography and CT revealed infrapopliteal embolic occlusions and a thrombus in the distal otherwise normal abdominal aorta and the left iliac artery. A primarily successful thrombectomy had to be repeated 5 times because of reocclusion. Eventually the leg was exarticulated at the knee. In both patients no further thromboembolic event occurred during follow-up of 4 1/2 years and 5 1/2 years, respectively, and aortic thrombi had resolved at follow-up CT scans. Extensive work up for hypercoagulability was negative in both patients. We consider IBD as the most likely trigger for arterioarterial embolization in the absence of thrombophilia in both patients. Finally we give an overview of the literature of similar cases with aortic mural thrombi in IBD patients.
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PMID:Aortic mural thrombi in patients with inflammatory bowel disease: report of two cases and review of the literature. 1547 53


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