Abstract: In inflammatory diseases, where hypochlorous acid (HOCl) is elevated, iron homeostasis is disturbed, resulting in accumulation of free iron. Free iron is toxic by virtue of its ability to generate free radicals through the Fenton reaction. HOCl is generated by myeloperoxidase, (MPO) using chloride and hydrogen peroxide as substrates. Recent studies demonstrate that HOCl binds to the heme moiety of hemoglobin (Hb), which generates a transient ferric species whose formation and decay kinetics indicate it participates in protein aggregation, heme destruction, and free iron release. Here, we show that melatonin prevents HOCl‐mediated Hb heme destruction and protein aggregation, using a combination of UV‐vis spectrophotometry, ferrozine colorimetric assay, and in‐gel heme staining. We also show that melatonin treatment prevents HOCl‐mediated loss of red blood cell (RBC) viability, indicating biologic relevance of this finding. The mechanism by which melatonin prevents HOCl‐mediated Hb heme destruction is by direct scavenging of HOCl and/or through the destabilization of the higher Hb oxidative states intermediates, ferryl porphyrin radical cation Hb‐Fe(IV)=O+π? and Hb‐Fe(IV)=O, which are formed through the reaction of HOCl with Hb. Our work establishes a direct mechanistic link between melatonin and its protective effect in chronic inflammatory diseases. Collectively, in addition to acting as an antioxidant and as a MPO inhibitor, melatonin can also exert its protective effect by inhibiting HOCl‐mediated heme destruction of hemoproteins and subsequent free iron release. 相似文献
Benign prostatic hypertrophy or hyperplasia (BPH) is a frequent urological complain particularly in old-aged individuals. Those patients usually have other risk factors (such as ischemic cardiovascular diseases) for which they might be treated with anti-thrombotic agents chronically. These medicines may induce blood thinning and raise the incidence of hemorrhage. Thus, if those patients needed operative treatment for BPH, they may be at high risk of hemorrhage or its related adverse effects with the usage of anti-thrombotic drugs during the peri-operative time. On the other hand, dis-continuation of these agents can lead to ischemic events in susceptible individuals.
Therefore, this research aims to assess the safety of the continuation of using anti-thrombotic agents throughout the peri-operative duration in patients with prostate surgery in form of Transurethral Resection of Prostate (TURP) only for Benign Prostatic Hypertrophy (BPH).
Methods
Patients’ notes were reviewed retrospectively. The entire participants were categorized into two categories. First category was on clopidogrel therapy (CTC) for prolong time and the usage of these agents was carried on throughout the peri-operative period. The second category was not on clopidogrel therapy at all (NCTC). Both of these categories had Transurethral Resection of Prostate (TURP) for Benign Prostatic Hypertrophy (BPH). A comparison had been conducted between the two categories with regards to: (i) the amount of blood lost intra-operatively (ii) the duration of operation (iii) hematocrit concentration per-operatively (iv) transfused packed red blood cells (PRBC) if needed (v) clearance of hematuria postoperatively (vi) secondary hemorrhage and clot retention after discharge. Pearson Chi-square test, Independent sample t test and test for numeric variables were used as appropriate.
Results
The study identified 329 patients. One hundred and sixty five participants in the CTC (clopidogrel therapy category) and 164 in the NCTC (non-clopidogrel therapy category). It had been revealed that there was no statistically significant difference between the CTC and NCTC regarding: (i) the amount of blood lost intra-operatively (ii) the duration of operation (iii) hematocrit concentration per-operatively (iv) transfused packed red blood cells (packed RBC) if needed (v) clearance of hematuria postoperatively (vi) secondary hemorrhage and clot retention after discharge (P?>?0.65).
Conclusion
The continuation of usage of anti-thrombotic therapy (clopidogrel) during peri-operative period in patients with TURP for BPH is a safe practice. It is not associated with high probability of hemorrhage or PRBC transfusion or other adverse effects.
Background: The effects of pneumoperitoneum (ppm) on hemodynamic parameters during bariatric surgery were investigated using
the impedance cardiography monitor. Methods: 11 patients with BMI 46.5±10 kg/m2 (range 38.9-60.8 kg/m2) underwent laparoscopic adjustable gastric banding under general anesthesia. Besides routine monitoring, the impedance cardiography
(ICG) monitor was used to monitor cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), and thoracic
fluid content (TFC). Data were recorded at three stages: A) before ppm, B) during ppm, and C) after gas deflation. One-way
analysis of variance (ANOVA) was used to analyze differences of the data before, during and after ppm, and post-hoc (Bonferoni
test) for multiple comparisons of the data obtained. For all comparisons, P<0.05 was considered significant. Results: There were significant low mean values of heart rate (HR), CO and CI at stage B
compared to stage A (P<0.05). The mean values of TFC at stages A, B, and C were 30.48 ± 4.69, 29.74 ± 2.86 and 31.72 ± 4.93 k/Ohm respectively,
with a non-significant relationship (P>0.05). The mean values of SVR during the same stages A, B and C were 1299.18 ± 374.40, 1873.64 ± 276.26 and 1669.36 ± 537.92
dynes sec cm-5 respectively, with significant high mean values at stages B and C compared to mean value at stage A (P<0.05). Conclusions: Morbid obesity and pneumoperitoneum have significant effects on hemodynamics. However, it appears that
these changes were of marginal clinical significance. 相似文献
Understanding the interplay between genes and in-utero tobacco exposure in affecting child lung development is of great significance. In this study, we tested the hypothesis that tobacco-related lung-function reduction in children differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase Mu 1 (GSTM1).
Materials and methods
Data were collected among 370 children (6–10 years old, 81.6% African-Americans) and their biological mothers visiting a large children’s hospital. Study hypotheses were tested using multiple regression method.
Results
Among the study sample, 143 mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric measures (mean±SD) included were: forced vital capacity (FVC)=1635±431 mL, forced expiratory volume in the first 1 s (FEV1)=1440 ±360 mL, percent FEV1/FVC ratio=89±12, and forced expiratory flow between the 25% and 75% of FVC (FEF25–75)=1745±603 mL. In addition to a tobacco effect on FVC (−131 mL, 95% CI: −245, −17) and FEV1/FVC ratio (42, 95% CI: 1, 83), regression analysis controlling for covariates indicated that for the subsample of children whose mothers were CYP1A1?2A homozygous, maternal daily smoking was associated with −734 mL (95% CI: −1206, −262) reductions in FEV1 and −825 mL (95% CI: −909, −795) reductions in FVC; reduced smoking was still associated with −590 mL (95% CI: −629, −551) reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with −176 mL (95% CI: −305, −47) reductions in FVC.
Discussion and conclusions
Maternal smoking during pregnancy was significantly associated with lung-function reduction in children, particularly for those whose mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion. 相似文献
The purpose of this study was to determine the prevalence of respiratory and/or physical fitness health problems in adolescent (ages 18–21) water pipe (WP) smokers (with or without cigarette smoking), cigarette-only smokers, and nonsmokers.
Methods
A comparative four-group study design was used to recruit a non–probability sample of 153 WP smokers only, 103 cigarette smokers only, and 102 cigarette+WP smokers along with 296 nonsmokers. Our hypothesis was that youth who smoked WPs and/or cigarettes would report more respiratory problems and/or poorer physical fitness than those who did not smoke.
Results
The results showed that coughs were significantly associated with smoking in all three of the smoking groups (p < .05). Cigarette-only smokers reported the most adverse outcomes with more wheezing, difficulty breathing, and less ability to exercise without shortness of breath. A dose-response analysis showed similar patterns of adverse health effects for both WP and cigarette smokers. The combined use of both products was not appreciably worse than smoking one product alone. This could be due to cigarette+WP smokers' reporting using less of the respective products when only one product was smoked.
Conclusions
Even during the adolescent years, WP and/or cigarette smoking youth experienced reportable negative health effects. 相似文献
BACKGROUND AND PURPOSE: Eosinophil peroxidase (EPO) catalyses the formation of oxidants implicated in the pathogenesis of various respiratory diseases including allergy and asthma. Mechanisms for inhibiting EPO, once released, are poorly understood. The aim of this work is to determine the mechanisms by which melatonin, a hormone produced in the brain by the pineal gland, inhibits the catalytic activity of EPO. EXPERIMENTAL APPROACH: We utilized H2O2-selective electrode and direct rapid kinetic measurements to determine the pathways by which melatonin inhibits human EPO. KEY RESULTS: In the presence of plasma levels of bromide (Br-), melatonin inactivates EPO at two different points in the classic peroxidase cycle. First, it binds to EPO and forms an inactive complex, melatonin-EPO-Br, which restricts access of H2O2 to the catalytic site of the oxidation enzyme. Second, melatonin competes with Br- and switches the reaction from a two electron (2e-) to a one electron (1e-) pathway allowing the enzyme to function with catalase-like activity. Melatonin is a bulky molecule and binds to the entrance of the EPO haem pocket (regulatory sites). Furthermore, Br- seems to enhance the affinity of this binding. In the absence of Br-, melatonin accelerated formation of EPO Compound II and its decay by serving as a 1e- substrate for EPO Compounds I and II. CONCLUSIONS AND IMPLICATIONS: The interplay between EPO and melatonin may have a broader implication in the function of several biological systems. This dual regulation by melatonin is unique and represents a new mechanism for melatonin to control EPO and its downstream inflammatory pathways. 相似文献