The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated with vascular smooth muscle and platelet functions

Smoking affects gene expression in blood of patients with ischemic stroke.

ObjectiveThough cigarette smoking (CS) is a well-known risk factor for ischemic stroke (IS), there is no data on how CS affects the blood transcriptome in IS patients.MethodsWe recruited IS-current smokers (IS-SM), IS-never smokers (IS-NSM), control-smokers (C-SM), and control-never smokers (C-NSM). mRNA expression was assessed on HTA-2.0 microarrays and unique as well as commonly expressed genes identified for IS-SM versus IS-NSM and C-SM versus C-NSM.ResultsOne hundred and fifty-eight genes were differentially expressed in IS-SM versus IS-NSM; 100 genes were differentially expressed in C-SM versus C-NSM; and 10 genes were common to both IS-SM and C-SM (P < 0.01; |fold change| ≥ 1.2). Functional pathway analysis showed the 158 IS-SM-regulated genes were associated with T-cell receptor, cytokine-cytokine receptor, chemokine, adipocytokine, tight junction, Jak-STAT, ubiquitin-mediated proteolysis, and adherens junction signaling. IS-SM showed more altered genes and functional networks than C-SM.InterpretationWe propose some of the 10 genes that are elevated in both IS-SM and C-SM (GRP15, LRRN3, CLDND1, ICOS, GCNT4, VPS13A, DAP3, SNORA54, HIST1H1D, and SCARNA6) might contribute to increased risk of stroke in current smokers, and some genes expressed by blood leukocytes and platelets after stroke in smokers might contribute to worse stroke outcomes that occur in smokers

Scintigraphy with 99mTc(V)-DMSA in monitoring patients with inflammatory bowel disease

The clinical significance of pentavalent technetium-99m dimercaptosuccinic acid (99mTc(V)-DMSA) scintigraphy in diagnosing inflammatory bowel disease (IBD) has not yet been fully elucidated. The aim of this prospective paper was to study the above. This study included 54 patients, 22 females and 32 males (mean age: 36.68±11.49; range: 18-63 years) with IBD who came to our clinics for follow-up and were examined clinically by colonoscopy and 99mTc(V)-DMSA scintigraphy. On the follow-up studies, five patients (9.25%) relapsed, and 49 (90.74%) remained at a steady condition. There was a good correlation between the scintigraphic results and the clinical and colonoscopy data of the patients (P<0.05). In conclusion, our results indicated that 99mTc(V)DMSA scintigraphy can be complementary to colonoscopy for the diagnostic evaluation of IBD

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Lung Injury Pathways: Adenosine Receptor 2B Signaling Limits Development of Ischemic Bronchiolitis Obliterans Organizing Pneumonia

Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Materials and Methods: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague–Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. Results: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. Conclusion: Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury

Ischemic Colitis: Clinical Presentation, Localization in Relation to Risk Factors, and Long-Term Results

Background: Ischemic colitis is commonly thought to occur most often in the left hemicolon close to the splenic flexure owing to insufficient blood supply near Griffith's point. This study investigates the colorectal localization pattern, the risk factors, and the long-term outcome of histologically proven ischemic colitis. Methods: Between 1996 and 2004, a total of 49 patients with a median age of 69years (range 26-94years) with colonoscopically assessed and histologically proven ischemic colitis were identified on behalf of the pathology database. Long-term results of 43 patients were evaluated retrospectively after a median interval of 79months (range 6-163months). Results: In 27 patients (55%) more than one location was affected. We found 98 affected locations in 49 patients. The distribution of ischemic colitis in our group shows no significantly preferred location. In an exploratory analysis, the cecum, ascending colon, and right flexure were affected significantly more often if intake of a nonsteroidal antiinflammatory drug (NSAID) is documented. There was no association between the location of ischemic colitis and a history of smoking, peripheral artery occlusive disease, coronary heart disease, diabetes, or malignant tumor. Conclusions: Ischemic colitis seems not to have a predisposing site of occurrence in the colorectum, especially Griffith's point which was not afflicted significantly more often than other sites. Frequently, ischemic colitis afflicts more than one colonic location. In patients being treated with NSAIDs, ischemic colitis was observed significantly more often in the right hemicolon. Recurrence of ischemic colitis seems to be rar

Accuracy of multidetector row computed tomography for the diagnosis of acute bowel ischemia in a non-selected study population

The diagnostic accuracy of multidetector row computed tomography for the prospective diagnosis of acute bowel ischemia in the daily clinical routine was analyzed. Two hundred ninety-one consecutive patients with an acute or subacute abdomen, examined by MDCT over a time period of 5 months, were included in the study. All original CT diagnoses made during the daily routine by radiological generalists were compared to the final diagnoses made by using all available medical information from endoscopies, surgical interventions, autopsies and follow-up. Finally, all CT examinations of patients with an initial CT diagnosis or a final diagnosis of bowel ischemia were reread by a radiologist specialized in abdominal imaging in order to analyze the CT findings and the reasons for initially false negative or false positive CT readings. Twenty-four patients out of 291 (8.2%) had acute bowel ischemia. The age of affected patients ranged from 50 to 94 years (mean age: 75.7 years). Eleven patients were male, and 13 female. Reasons for acute bowel ischemia were: arterio-occlusive (n=11), non-occlusive (n=5), strangulation (n=2), over-distension (n=3) and radiation (n=3). The prospective sensitivity, specificity, PPV and NPV of MDCT for the diagnosis of acute bowel ischemia in the daily routine were 79.17, 98.51, 90.48 and 98.15%. MDCT reaches a similarly high sensitivity in diagnosing acute bowel as angiography. Furthermore, it has the advantage of being helpful in most of its clinical differential diagnoses and of being less invasive with the consecutive possibility of being used earlier in the diagnostic process with all the resulting positive effects on the patients prognosis. Therefore, nowadays MDCT should probably be used as the first step imaging modality of choice in patients with suspected acute bowel ischemi

Ischaemic colitis: Practical challenges and evidence-based recommendations for management

Ischaemic colitis (IC) is a common condition with rising incidence, and in severe cases a high mortality rate. Its presentation, severity and disease behaviour can vary widely, and there exists significant heterogeneity in treatment strategies and resultant outcomes. In this article we explore practical challenges in the management of IC, and where available make evidence-based recommendations for its management based on a comprehensive review of available literature. An optimal approach to initial management requires early recognition of the diagnosis followed by prompt and appropriate investigation. Ideally, this should involve the input of both gastroenterology and surgery. CT with intravenous contrast is the imaging modality of choice. It can support clinical diagnosis, define the severity and distribution of ischaemia, and has prognostic value. In all but fulminant cases, this should be followed (within 48 hours) by lower gastrointestinal endoscopy to reach the distal-most extent of the disease, providing endoscopic (and histological) confirmation. The mainstay of medical management is conservative/supportive treatment, with bowel rest, fluid resuscitation and antibiotics. Specific laboratory, radiological and endoscopic features are recognised to correlate with more severe disease, higher rates of surgical intervention and ultimately worse outcomes. These factors should be carefully considered when deciding on the need for and timing of surgical intervention