Plasma histamine and tumour necrosis factor-alpha levels in Crohn's disease and ulcerative colitis at various stages of disease.

Mast cells secrete numerous mediators and this study investigated plasma levels of histamine, and tumor necrosis factor alpha (TNF-α) in chronic inflammatory bowel disease (IBD). Plasma levels of histamine were determined in 68 patients with Crohn's disease (CD), 22 with ulcerative colitis (UC) and 13 controls. TNF-α levels were assessed in 29 CD patients, 11 UC patients, and in 11 controls. Plasma histamine levels in the control group were 0.25 ng (0.14 - 0.33) and showed no difference to CD (0.19 ng, 0.09 - 0.35) or UC (0.23 ng, 0.11 - 0.60). Significantly lower histamine levels were only found in CD patients on 5-aminosalicylic acid treatment (P ≤ 0.04). Plasma TNF-α levels in the control group were significantly lower 0.44 ml/m(2) (0 - 1.15) than in CD patients (4.62 ml/m(2), 1.82 - 9.22, P = 0.005) or UC (3.14 ml/m(2); 0.08 - 11.34, P = 0.01). In CD disease activity, fistula, and extraintestinal manifestations (EM) were associated with significantly higher plasma TNF-α values, but not the type of treatment. We concluded that in contrast to TNF-α, histamine levels were normal in CD and UC. There is no correlation with histamine and thus the proportion of TNF-α secreted from mast cells in the plasma in patients with IBD is less important.

Analysis of immediate ex vivo release of nitric oxide from human colonic mucosa in gastrointestinally mediated allergy, inflammatory bowel disease and controls.

Nitric oxide (NO) is a local mediator in inflammation and allergy. The aim of this study was to investigate whether live incubated colorectal mucosal tissue shows a direct NO response ex vivo to nonspecific and specific immunological stimuli and whether there are disease-specific differences between allergic and chronic inflammatory bowel disease (IBD). We took biopsies (n=188) from 17 patients with confirmed gastrointestinally mediated food allergy, six patients with inflammatory bowel disease, and six control patients. To detect NO we employed an NO probe (WPI GmbH, Berlin, Germany) that upon stimulation with nonspecific toxins (ethanol, acetic acid, lipopolysaccharides), histamine (10(-8)-10(-4)M), and immune-specific stimuli (anti-IgE, anti-IgG, known food allergens) directly determined NO production during mucosal oxygenation. Non-immune stimulation of the colorectal mucosa with calcium ionophore (A23187), acetic acid, and ethanol induced a significant NO release in all groups and all biopsies. Whereas, immune-specific stimulation with allergens or anti-human IgE or -IgG antibodies did not produce significant release of NO in controls or IBD. Incubation with anti-human IgE antibodies or allergens produced a ninefold increase in histamine release in gastrointestinally mediated allergy (p<0.001), but anti-human IgE antibodies induced NO release in only 18% of the allergy patients. Histamine release in response to allergens or anti-human IgE antibodies did not correlate with NO release (r(2)=0.11, p=0.28). These data show that nonspecific calcium-dependent and toxic mechanisms induce NO release in response to a nonspecific inflammatory signal. In contrast, mechanisms underlying immune-specific stimuli do not induce NO production immediately.

Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy.

Several adverse effects of chemotherapy treatments have been described, and most of these effects are associated with direct interactions between blood cells and indirect effects generated during the oxidative metabolism of antineoplastic drugs. In this study we evaluated the oxidative systemic status and hematological profiles of breast cancer patients with advanced ductal infiltrative carcinoma treated with doxorubicin (DOX) or paclitaxel (PTX) within 1 h after chemotherapy. Blood analyses included evaluation of hemogram, pro-oxidative markers, and antioxidant status. The results showed that advanced breast cancer diseased (AD) patients without previous chemotherapy presented anemia and high oxidative stress status characterized by elevated levels of lipid peroxidation and nitric oxide, and reduced catalase activity when compared with controls. DOX-treated patients exhibited increased anemia and reduced antioxidant status, which was revealed by decreases in reduced glutathione levels and the total antioxidant capacity of plasma; however, these changes did not lead to further increases in lipid peroxidation or carbonyl proteins when compared with the AD group. PTX-treated patients also showed increased anemia, lactate dehydrogenase leakage, and enhanced lipid peroxidation. These data reveal for the first time that patients subjected to chemotherapy with DOX or PTX present immediate systemic oxidative stress and red blood cell oxidative injury with anemia development. These findings provide a new perspective on the systemic redox state of AD and patients subjected to chemotherapy regarding oxidative stress enhancement and its possible involvement in the aggravation of chronic anemia.

Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1ß, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators.

Small-bowel capsule endoscopy in patients with gastrointestinal food allergy.

BACKGROUND: Food allergy may present with a plethora of gastrointestinal and extraintestinal symptoms such as abdominal pain, diarrhea, cardiocirculatory symptoms, cutaneous reactions, or rhinitis. Macropathological lesions like lymphofollicular hyperplasia and erosive or ulcerative lesions have seldom been described in gastroscopy and colonoscopy previously. METHODS: Fifteen patients presenting with unspecific abdominal symptoms in which food allergy was detected in due course were included. During the examination process, those patients showed various indications for small-bowel capsule endoscopy, such as weight loss and anemia. RESULTS: Fourteen (93.3%) of the 15 small-bowel capsule endoscopies could be assessed, showing nonerosive lesions such as erythema, swelling, and lymphoid hyperplasia in 8 patients (57.1%) and erosive lesions such as aphthoid lesions, erosions, and petechiae in 4 patients (28.6%) with food allergy. CONCLUSION: In 15 patients with confirmed food allergy and after exclusion of other diseases, 12 (85.7%) showed various unspecific nonerosive or erosive mucosal lesions within the small bowel, resulting, however, partially in grave consequences such as anemia. Lymphoid hyperplasia was the most prominent finding in 7 patients (50%), albeit infectious disease had been excluded. Anemia improved within 1 year after adequate antiallergic treatment.