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PubMedDate not supplied

H(2)O(2) is an important mediator of physiological and pathological healing responses.

BACKGROUND: TGF-beta1 is a pleiotropic cytokine that plays a key role in wound healing and organ fibrosis. We have recently demonstrated that, in part, some fibrogenic actions of TGF-beta1 are mediated via formation of H(2)O(2). We have also demonstrated that TGF-beta1 plays a key role in the accelerated healing response induced by a peptidoglycan derived from some strains of Staphylococcus aureus (SaPG). METHODS: To investigate further the role of H(2)O(2) in healing responses, we implemented and improved a method to measure this reactive oxygen species. Using this method, we quantified the production of H(2)O(2) by cultured hepatic stellate cells-the main cells involved in type I collagen production in the liver-and by saline- and SaPG-inoculated polyvinyl alcohol sponges that had been surgically subcutaneously implanted in the dorsum of rats. RESULTS: We show that cultured hepatic stellate cells produce significant amounts of H(2)O(2). We show also that H(2)O(2) formation by saline- and SAPG-inoculated sponges is more intense during the early inflammatory phase of the healing response and precedes collagen deposition. Moreover, the production of H(2)O(2) is much higher in SaPG-inoculated sponges than in those inoculated with saline solution. CONCLUSIONS: Based on these findings, and on the fact that H(2)O(2) is produced during TGF-beta-induced upregulation of the alpha1(I) procollagen gene, we conclude that H(2)O(2) is one of the mediators of healing responses.

Animals↗
PubMed1999

Phase II study of radiochemotherapy with UFT and low-dose oral leucovorin in patients with unresectable rectal cancer.

PURPOSE: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer. METHODS AND MATERIALS: Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m2/day UFT and 30 mg/day leucovorin on days 8-35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy. RESULTS: Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%). CONCLUSION: The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.

Adult↗
PubMed2002

Extracellular matrix proteins and chemoradiotherapy: alpha5beta1 integrin as a predictive marker in rectal cancer.

AIMS: To investigate the effects of extracellular matrix (ECM) protein expression on the rates of apoptosis and proliferation in rectal cancers and subsequent response to chemoradiotherapy (CRT). METHODS: The expression of fibronectin, collagen IV, laminin and the fibronectin receptor (FnR, alpha5beta1 integrin) were analysed in 32 pre-treatment rectal cancer biopsies by immunohistochemistry. ECM expression was correlated with tumour mitotic index (MI), apoptotic index (AI) and histopathological response to CRT. RESULTS: 18/32 cancers showed a poor response and 14/32 a good response (5/14 with complete pathological response) to CRT. Moderate to strong staining was seen in 22/32 cancers for fibronectin, 5/32 for collagen IV and 18/32 for laminin. Tumour FnR was related to stromal fibronectin content, and was significantly associated with CRT response; good responders having higher FnR expression compared to poor responders. No association was found between FnR expression and either MI or AI in pre-treatment biopsies, nor between MI or AI and CRT response. CONCLUSIONS: Tumour FnR expression is independent of MI and AI, and may serve as a useful marker for CRT response in rectal cancer.

Apoptosis↗
PubMed1996

Aerosol bolus dispersion and aerosol-derived airway morphometry: assessment of lung pathology and response to therapy, Part 1.

review discusses the potential utility of two methods using inhaled aerosols to detect and diagnose lung disease and to evaluate the efficacy of therapy. Aerosol bolus dispersion measures convective gas mixing; aerosol-derived airway morphometry assesses the calibers of airway and airspaces. These two methods are discussed in terms of their ease of use (simplicity and acceptability) and current data regarding their validity, reproducibility, specificity, sensitivity, and detection of lung improvement with therapy. Part 1 of this review focuses upon aerosol bolus dispersion; Part 2(1) focuses upon aerosol-derived airway morphometry. Aerosol bolus dispersion has many features that make it clinically attractive. It is simple to administer and patients can successfully perform the maneuvers. It detects known alterations in the lungs. It is reproducible and has high specificity and sensitivity. However, every lung disease or condition known to be detected by aerosol bolus dispersion is also detected by spirometery, maximal expiratory flow-volume curves, or another conventional lung function test. This, aerosol bolus dispersion appears best reserved as a specialized method to supplement conventional lung function tests and to characterize convective gas transport.

Aerosols↗
PubMed2004

Severe acute respiratory syndrome, a pathological immune response to the new coronavirus--implications for understanding of pathogenesis, therapy, design of vaccines, and epidemiology.

Findings coming from autopsies and serum of SARS patients suggest an important immune-inflammatory implication in the evolution to respiratory distress. Conditions such as HIV infection or treatment with immunosuppressors (in cancer or autoimmune diseases) are not among the bad prognosis factors for development of distress. To date, there have been no reported case fatalities in children, probably due to their more immature immune system. Our conclusions follow: (1) The milder form of SARS in children and the apparent protective factor that immunosupression represent rules out a significant viral cytopathic effect (they would be the most affected). (2) The evidence for immune implication in distress strongly supports immunomodulators for therapy: phosphodiesterase inhibitors (due to their down-modulating activity on proinflammatory cytokines); inhaled corticoids (aimed at producing a local immunomodulation); teophylline or nedocromil sodium (which prevents inflammatory cell recruitment into the airway wall). (3) An early immunomodulatory therapy, based on the levels of proinflammatory cytokines and clinical parameters to evaluate the respiratory function such as arterial oxygen saturation, could prevent the occurrence of distress. (4) Vaccine design should consider the immune origin of distress. (5) Physicians should be aware of mildly symptomatic patients (children, immuno-compromised hosts) to avoid transmission to immunocompetent adults.

Adult↗
PubMed1980

Response of pathological ischaemic muscle pain to analgesics.

1 Twenty-four patients suffering from severe pain due to chronic occlusive arterial disease of the legs were given oral doses of indoprofen (200 mg), ibuprofen (300 mg) and placebo. 2 Differences in pain intensity scored on a five-point scale were taken as measurement of pain relief. 3 This double-blind, cross-over trial showed that indoprofen had significantly greater analgesic effect than placebo and reference drug. 4 From a methodological point of view there are many arguments on favour of pathological ischaemic pain as a test for clinical assessment of analgesics.

Aged↗
PubMed2001

Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses.

CD100/Sema4D is a 150-kd transmembrane protein that belongs to the semaphorin family. The interaction of CD100 with CD72 is critical for the immune system. In CD100-deficient mice, the production of specific antibodies against T-cell-dependent antigens is severely impaired, but not against T-cell-independent antigens. Here, a functional soluble CD100 protein (sCD100) released from activated lymphocytes is reported. sCD100 was detected in culture supernatants of activated lymphocytes. Either affinity-purified from supernatants of activated T-cells, or produced as a recombinant sCD100 protein consisting of the extracellular region of the mouse CD100 fused to the human IgG1 Fc (CD100-Fc), sCD100 significantly enhanced CD40-induced B-cell responses. Furthermore, sCD100 was detected either in sera of mice immunized with T-cell-dependent antigens, or in sera of MRL/lpr mice, but not in sera of mice immunized with T-cell-independent antigens. A significant correlation was observed between the level of sCD100 and the titer of autoantibodies in the serum of MRL/lpr mice. This study's findings suggest a potential role for sCD100 in immune responses, including production of antibody, and autoimmune diseases. (Blood. 2001;97:3498-3504)

Animals↗