DSpace Collection:https://hdl.handle.net/10171/188462024-03-28T08:45:43Z2024-03-28T08:45:43ZMolecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loadinghttps://hdl.handle.net/10171/687492024-02-12T06:06:41Z2014-01-01T00:00:00ZTitle: Molecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loading
Abstract: High-intensity exercise induces oxidative stress and inflammatory events in muscles. Tumor necrosis factor (TNF)-α may alter muscle protein metabolism or promote muscle regeneration. We hypothesized that a program of noninvasive chronic inspiratory loading of different intensities induces a differential pattern of physiological, molecular, and cellular events within rat diaphragms. Antioxidants and TNF-α blockade may influence those events. In the diaphragm, gastrocnemius, and blood of rats exposed to high-intensity inspiratory threshold loads (2 hour every 24 hours for 14 days), with and without treatment with N-acetyl cysteine or infliximab (anti-TNF-α antibody), inflammatory cells and cytokines, superoxide anion production, myogenesis markers, and muscle structure were explored. In all animals, maximum inspiratory pressure (MIP) and body weight were determined. High-intensity inspiratory loading for 2 weeks caused a decline in MIP and body weight, and in the diaphragm induced a reduction in fast-twitch fiber proportions and sizes, whereas inflammatory cells and cytokine levels, including TNF-α immunohistochemical expression, superoxide anion, internal nuclei counts, and markers of myogenesis were increased. Blockade of TNF-α improved respiratory muscle function and structure, and animal weight, and, in the diaphragm, reduced inflammatory cell numbers and superoxide anion production drastically while inducing larger increases in protein and messenger RNA levels and immunohistochemical expression of TNF-α, internal nuclei, and markers of muscle regeneration. Blunting of TNF-α also induced a reduction in blood inflammatory cytokines and superoxide anion production. We conclude that TNF-α synthesized by inflammatory cells or myofibers could have differential effects on muscle structure and function in response to chronic, noninvasive, high-intensity inspiratory threshold loading.2014-01-01T00:00:00ZBacterial secretion of histamine within the gut influences immune responses within the lunghttps://hdl.handle.net/10171/687452024-02-12T06:06:40Z2018-01-01T00:00:00ZTitle: Bacterial secretion of histamine within the gut influences immune responses within the lung
Abstract: Background:
Histamine is an important immunomodulator influencing both the innate and adaptive immune system. Certain host cells express the histidine decarboxylase enzyme (HDC), which is responsible for catalysing the decarboxylation of histidine to histamine. We and others have shown that bacterial strains can also express HDC and secrete histamine; however, the influence of bacterial-derived histamine on the host immune responses distant to the gut is unclear.
Methods:
The Escherichia coli BL21 (E coli BL21) strain was genetically modified to express the Morganella morganii (M morganii)-derived HDC gene (E coli BL21_HTW). E coli BL21 and E coli BL21_HTW were gavaged to ovalbumin (OVA) sensitized and challenged mice to investigate the effect of bacterial-derived histamine on lung inflammatory responses.
Results:
Oral administration of E coli BL21_HTW, which is able to secrete histamine, to wild-type mice reduced lung eosinophilia and suppressed ex vivo OVA-stimulated cytokine secretion from lung cells in the OVA respiratory inflammation mouse model. In histamine receptor 2 (H2R)-deficient mice, administration of histamine-secreting bacteria also reduced inflammatory cell numbers in bronchoalveolar lavage (BAL). However, the suppressive effect of bacterial-derived histamine on BAL inflammation was lost in HDC-deficient mice. This loss of activity was associated with increased expression of histamine degrading enzymes and reduced histamine receptor expression.
Conclusion:
Histamine secretion from bacteria within the gut can have immunological consequences at distant mucosal sites, such as within the lung. These effects are influenced by host histamine receptor expression and the expression of histamine degrading enzymes.2018-01-01T00:00:00ZEfficacy and Safety of Omalizumab (Xolair) for Cholinergic Urticaria in Patients Unresponsive to a Double Dose of Antihistamines: A Randomized Mixed Double-Blind and Open-Label Placebo-Controlled Clinical Trialhttps://hdl.handle.net/10171/687432024-02-12T06:06:37Z2019-01-01T00:00:00ZTitle: Efficacy and Safety of Omalizumab (Xolair) for Cholinergic Urticaria in Patients Unresponsive to a Double Dose of Antihistamines: A Randomized Mixed Double-Blind and Open-Label Placebo-Controlled Clinical Trial
Abstract: Background:
Cholinergic urticaria (UCOL) is a highly disabling inducible urticaria triggered by an increase in core body temperature.
Objective:
To explore the safety and efficacy of omalizumab in controlling UCOL.
Methods:
We conducted a multicenter randomized mixed double-blind and open-label (first 4 months blinded followed by 8 months open-label) placebo-controlled clinical trial in 22 patients suffering from UCOL who were unresponsive to a double dose of antihistamines. We performed an exercise challenge test during each visit as our main outcome variable.
Results:
The overall rate of exercise challenge test negative at week 48 was 31.3%, with an average increase in exercise challenge test negative rate of 2.9% points (95% CI, 1.5-4.2) per visit. Statistically significant differences in the negative exercise challenge test rate between the placebo and active intervention groups were not observed during the blinded period (first 4 months of the study). However, from the fourth dose, a progressive improvement was observed. When comparing before and after treatment, statistically significant improvements in all secondary outcome measures were noted after 4 doses (UCOL score: P = .0015; visual analog scale score: P = .0108; days with symptoms: P = .0125) and after 8 doses (UCOL score: P = .0005; chronic urticaria quality of life questionnaire: P = .0105; visual analog scale score: P = .0008; and days with symptoms: P = .0144). In the follow-up visit after the cessation of treatment, the symptoms reappeared, with positive exercise challenge test result and significant increases in all variables. Only 4 of 22 patients remained asymptomatic after 3 months of no treatment. No adverse effects were reported.
Conclusions:
This randomized mixed double-blind and open-label placebo-controlled trial showed evidence of the safety and potential efficacy of omalizumab in patients with UCOL.2019-01-01T00:00:00ZQuality of Life in Patients with Allergic Reactions to Medications: Influence of a Drug Allergy Evaluationhttps://hdl.handle.net/10171/687352024-02-05T06:06:25Z2019-01-01T00:00:00ZTitle: Quality of Life in Patients with Allergic Reactions to Medications: Influence of a Drug Allergy Evaluation
Abstract: Background
Suspicion of allergic drug reaction can cause important disturbances in the patient's life.
Objective
We evaluated in a prospective multicenter study the quality of life of patients who suffered a possible allergic drug reaction, and analyzed the effect of a drug allergy evaluation.
Methods
Patients (>18 years old) answered the specific questionnaire twice: before the drug allergy evaluation, and 1 month after it was completed. Statistics were performed using STATA.
Results
A total of 360 patients (240, 66.6% female; mean age, 45.4 years; standard deviation [SD], 15.6 years) completed the first questionnaire. After the evaluation, 150 of 346 patients (43.4%) were diagnosed as allergic to the drug (115 of 150 immediate; 35 of 150 delayed) and 196 of 346 patients (56.6%) as nonallergic. The mean value of the first questionnaire was 32.14 (SD, 11.84); patients with anaphylaxis, nonanaphylactic immediate reaction, with more than 1 drug reaction, or a chronic osteoarticular disease, had a statistically significant higher score in Q0 (worse quality of life). After the allergy study, the mean of the second questionnaire was 27.27 (SD, 9.96), showing a global improvement (P < .001). No statistically significant difference was found between drug allergic and non–drug allergic patients (P = .340); however, being >40 years old (P = .030), having a chronic osteoarticular disease (P = .003) and having more than 1 reaction to drugs (P < .001) were associated with a statistically significant worse quality of life after the evaluation.
Conclusions
Having suffered anaphylaxis, more than 1 reported drug allergy or presenting a musculoskeletal disease are factors that worsen the quality of life. Quality of life improved significantly after completing a drug allergy evaluation.2019-01-01T00:00:00Z