A case of glutathione-induced life-threatening asthma attack

Baek-ok injection (glutathione) has been widely used antioxidant therapy to whiten and has antiaging effects in Korea. Glutathione is an enzyme which synthesizes leukotriene, then it can induce asthma attack theoretically; however, there have been few case reports concerning this therapy. In this report, we described a 41-year-old woman who developed glutathione-induced life-threatening asthma attack. She has asthma history controlled by an intermittent salbutamol inhaler. She developed general weakness and dyspnea right after glutathione injection, and injection was discontinued. Dyspnea was progressively aggravated, and she lost consciousness with shock. Cardiopulmonary resuscitation was started, and she arrived at the Emergency Department with wheezing, hypoxia, severe respiratory acidosis, and nonmeasurable blood pressure. Intubation and mechanical ventilation were started with intramuscular epinephrine/intravenous methylprednisolone injection and repeated salbutamol/ipratropium/budesonide inhalation. After 5 hours, extubation and spontaneous breathing were successful without wheezing. Next day, pulmonary function test showed moderate an obstructive airway disease pattern, and she was discharged with inhaled fluticasone/salmeterol, oral methylprednisolone, and montelukast. We can exclude anaphylaxis, because serum tryptase obtained at the Emergency Department was 0.0 mg/dL and the absence of skin lesions and angioedema at arrival. Baek-ok injection (glutathione) should be carefully performed in asthma patients.ope

Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death

Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative damage caused by hydrogen peroxide (H2O2), but also to endow cancer cells with resistance to both H2O2 and cisplatin and to grant them radioresistance. In this study, we examined whether Prx II antisense could enhance cisplatin-induced cell death. When gastric cancer cells were transfected with various concentrations of Prx II antisense plasmid, pPrxII/AS, and then treated with the same concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell death. The combination index (CI) at all doses of the combination was below 1, indicating that Prx II antisense sensitized cisplatin-induced cell death. This synergism was also observed in the cells transfected with a Prx II antisense oligomer. Our present results, therefore, suggest that Prx II antisense would be a very good sensitizer for cisplatin, and that Prx II as a target for chemosensitizers constitutes a promising avenue for future research.ope

c-Myc exerts a protective function through ornithine decarboxylase against cellular insults

c-Myc is known to control cell proliferation and apoptosis, and much effort has been focused on elucidating the mechanisms by which c-Myc works. In this study, we show that c-Myc expression is induced by many cellular insults, including cisplatin, doxorubicin, paclitaxel, 5-flourouracil, H2O2, and radiation, and the enhanced expression of c-Myc protects against cell death caused by these cellular insults through ornithine decarboxylase (ODC) induction. To investigate the cellular protective role of c-Myc, we constructed a stable transfectant of ODC, one of the many transcriptional targets of c-Myc in cells, and found that enhanced expression of ODC inhibited cell death induced by cellular insults such as cisplatin, H2O2, and radiation. We also found that cisplatin activated nuclear factor-κB, and this subsequently induced c-Myc expression, resulting in the blocking of apoptosis through ODC induction. The results herein, therefore, strongly suggest another role for c-Myc in a stress-response function; that is, it promotes cell survival under stressful conditions.ope

Antisense of Human Peroxiredoxin II enhances Radiation-induced Cell Death

Human peroxiredoxin II (Prx II) has been known to function as an antioxidant enzyme in cells. Using head-and-neck cancer cell lines, we investigated whether Prx II expression is related to the resistance of cells to radiation therapy in vivo and in vitro, and whether a Prx II antisense serves as a radiosensitizer. Increased expression of Prx II was observed in tissues isolated from the patients who did not respond to radiation therapy, whereas Prx II expression was weak in tissues from the patients with regressed tumors. Enhanced expression of Prx II in UMSCC-11A (11A) cells was also observed after treatment with gamma radiation. This increased expression conferred radiation resistance to cancer cells because overexpression of Prx II protected 11A cells from radiation-induced cell death, suggesting that blocking Prx II expression could enhance radiation sensitivity. Treatment of 11A cells with a Prx II antisense decreased induction of Prx II, enhancing the radiation sensitivity. From these results, we suggest that stress-induced overexpression of Prx II increases radiation resistance via protection of cancer cells from radiation-induced oxidative cytolysis and that a Prx II antisense can be used as a radiosensitizer.ope

The imbalance between coagulation and fibrinolysis is related to the severity of the illness and the prognosis in sepsis

Abstract OBJECTIVES: The coagulation and fibrinolytic system appears to be activated by the septic process independently, leading to the syndrome of disseminated intravascular coagulation (DIC). In this study, we investigated the changes within the hemostatic system related to the severity of the illness and the prognosis in patients with sepsis. METHODS: Plasma thrombin-antithrombin III (TAT) and plasmin-alpha 2-antiplasmin (PAP) complexes were measured using ELISA methods in 32 patients with sepsis and 20 controls and were analyzed according to the APACHE III scores and survival of the patients. RESULTS: Plasma TAT and PAP in patients with sepsis were significantly higher than controls. Nonsurvivors showed greater levels of TAT (21.7 +/- 22.3 ng/mL) and lower levels of PAP (628.4 +/- 378.1 ng/mL) than survivors (TAT: 11.1 +/- 11.2 ng/mL; PAP: 857.1 +/- 364.1 ng/mL). The imbalance between coagulation and fibrinolysis described as TAT/PAP ratio was closely related with APACHE III scores in patients with sepsis (r = 0.47) and the TAT/PAP ratio in nonsurvivors was significantly higher compared with survivors (34.4 +/- 21.4 vs. 14.4 +/- 13.8). CONCLUSION: In sepsis, both coagulation and the fibrinolysis system are activated and the imbalance between coagulation and fibrinolysis predisposes to the hypercoagulation state and is closely related to the severity of the disease and the prognosis.ope

A Case of Bilateral Pulmonary Sequestration

Pulmonary sequestration is a rare congenital anomaly of the lung in which it is separately supplied from the aorta or one of its branches. Bilateral pulmonary sequestration is very rare, particularly in adults. In bilateral pulmonary sequestration, resection of both sides is usually recommended if both sides are infected and symptomatic. We report the case of a 37-year-old female patient with bilateral intralobar pulmonary sequestration treated by staged bilateral lower lobectomy.ope

Definition, Epidemiology and Pathogenesis of Chronic Obstructive Pulmonary Disease

Aworking definition of chronic obstructive pulmonary disease (COPD) is given within the GOLD Global strategy as a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. There is consensus that there has been a world-wide increase in COPD, reflecting increases in cigarette smoking, especially in developing countries. According to the Global Burden of Disease Study, in terms of lost disability-adjusted life years, COPD was ranked the 12th in 1990 and predicted to rise to the 5th ranking by 2020 and COPD was the sixth most common cause of death in the world in 1990 and will rise to the third most common by 2020. COPD is characterized by exaggeration of the normal inflammation response to irritant such as cigarette smoke. The mechanisms for this amplification of inflammation in COPD are not yet certain, but may be determined by genetic factors, latent viruses and impaired histone deacetylase activity. In addition to inflammation, extracellular matrix proteolysis. Cell death and ineffective repair are thought to be important in the pathogenesis of COPD.ope

Cyclophilin a binds to peroxiredoxins and activates its peroxidase activity

Six distinct peroxiredoxin (Prx) proteins (Prx I-VI) from distinct genes have been identified in mammalian tissues. Prxs are members of a group of peroxidases that have conserved reactive cysteine residue(s) in the active site(s). An immediate physiological electron donor for the peroxidase catalysis for five Prx proteins (Prx I-V) has been identified as thioredoxin (Trx), but that for Prx VI (1-Cys Prx) is still unclear. To identify an immediate electron donor and a binding protein for Prx VI, we performed a Prx VI protein overlay assay. A 20-kDa binding protein was identified by the Prx VI protein overlay assay with flow-through fractions from a High-Q column with rat lung crude extracts. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and MS-Fit, we identified the 20-kDa Prx VI-binding protein as a cyclophilin A (CyP-A). The binding of recombinant human CyP-A (hCyP-A) to Prx VI was confirmed by using the hCyP-A protein overlay assay and Western immunoblot analysis with hCyP-A-specific antibodies. hCyP-A enhanced the antioxidant activity of Prx VI, as well as the other known mammalian Prx isotypes. hCyP-A supported antioxidant activity of Prx II and Prx VI both against thiol (dithiothreitol)-containing metal-catalyzed oxidation (MCO) systems and ascorbate-containing MCO systems. Prx II was reduced by hCyP-A without help from any other reductant, and the reduction was cyclosporin A-independent. These results strongly suggest that CyP-A not only binds to Prx proteins but also supports its peroxidase activity as an immediate electron donor. In addition, Cys(115) and Cys(161) of hCyP-A were found to be involved in the activation and the reduction of Prx.ope

Significant predictors of medically diagnosed chronic obstructive pulmonary disease in patients with preserved ratio impaired spirometry: a 3-year cohort study.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is an incompletely understood respiratory condition. We investigated the incidence and significant predictive factors of chronic obstructive pulmonary disease (COPD) in PRISm patients. METHODS: From 11,922 subjects registered in the Korea National Health and Nutrition Examination Survey, never or light smokers, young subjects, and those already medically diagnosed with COPD (defined by ICD-10 code and prescribed medication) were excluded. The 2666 remaining subjects were categorized into PRISm (normal forced expiratory volume in the first second [FEV1]/force vital capacity [FVC] [≥ 0.7] and low FEV1 (< 80%); n = 313); normal (n = 1666); and unrevealed COPD groups (FEV1/FVC ratio <  0.7; n = 687). These groups were compared using matched Health Insurance Review and Assessment Service data over a 3-year follow-up. RESULTS: COPD incidence in PRISm patients (17/1000 person-year [PY]) was higher than that in normal subjects (4.3/1000 PY; P <  0.001), but lower than that in unrevealed COPD patients (45/1000 PY; P < 0.001). PRISm patients visited hospitals, took COPD medication, and incurred hospitalization costs more frequently than normal subjects, but less frequently than unrevealed COPD patients. In the overall sample, age, FVC, FEV1, dyspnea, and wheezing were significant predictors of COPD, but in PRISm patients, only age (OR, 1.14; P = 0.002) and wheezing (OR, 4.56; P = 0.04) were significant predictors. CONCLUSION: PRISm patients are likely to develop COPD, and should be monitored carefully, especially older patients and those with wheezing, regardless of lung function.ope

Change in Forced Vital Capacity with Postures according to Neuromuscular Disease

Objective: To evaluate the difference in forced vital capacity (FVC) between sitting and supine position in patients with amyotrophic lateral sclerosis (ALS), cervical spinal cord injury (SCI) and Duchenne muscular dystrophy (DMD). Method: FVC was measured in sitting and supine position for 32 patients with DMD, 32 patients with cervical SCI and for 28 patients with ALS. The highest value in three or more attempts in each position was chosen. Results: FVCs measured in cervical SCI and ALS patients in the sitting and supine position were 1612.8+/-291.0 ml, 1393.2+/-286.7 ml and 2054.7+/-545.8 ml, 1104.3+/-425.4 ml respectively. Cervical SCI patients showed significantly higher value in the supine position (p<0.05). And ALS patients showed significantly higher value in the sitting position (p<0.05). FVCs measured in DMD patients were 1311.6+/-260.7 ml and 1213.8+/-378.9 ml respectively. There was no statistically significant difference between the measurements in both positions. Conclusion: Difference in postural change of FVC was observed in patients with different types of neuromuscular disorders. Such difference in FVC suggest that postural change of FVC should be considered in management of neuromuscular disease with respiratory muscle weakness.ope