Heterogeneity of IgE response to TDI-HSA conjugates by ELISA in toluene diisocyanate (TDI) -induced occupational asthma (OA) patients.

Toluene diisocyanate (TDI), a low molecular weight reactive chemical, is known to be a main cause of occupational asthma (OA) in Korea. Although it is thought that inhaled TDI may act as a hapten, the precise mechanisms of TDI-induced OA are unknown. In this study, TDI-human serum albumin (HSA) conjugates (5, 10, 20 and 30 min) were prepared in the range of 1.5 to 5.0 TDI mole/HSA mole. Specific binding of serum IgE to TDI-HSA (30 min) was observed using IgE ELISA as well as ELISA inhibition assay. Around 40% of TDI-induced OA patients were positive for serum specific IgE by ELISA. Degrees of serum IgE binding were different depending on which TDI-HSA conjugate was used as an antigen. Moreover, binding patterns were different depending on the individuals. Interestingly, higher binding of IgE to TDI-HSA (5 min) than to TDI-HSA (30 min) which was more highly substituted was observed in some patients. Probably new antigenic epitopes on carrier proteins were targets of the specific IgE. The results of this study indicated that IgE responses to TDI-HSA conjugates were heterogeneous in TDI-induced OA patients and self-proteins modified by reactive chemicals can become a major target antigen of IgE in certain cases.     

A comparison of coarctation resection and subclavian flap angioplasty using ultrasonographically monitored postocclusive reactive hyperemia

The reported relatively high incidence of early restenosis at the coarctation repair site with subclavian flap angioplasty, especially in infants less than 3 months of age, prompted a physiologically oriented analysis of relief of obstruction from coarctation after subclavian flap angioplasty versus resection and end-to-end anastomosis in infancy. Twenty-one patients who had undergone repair of coarctation in infancy by either subclavian flap angioplasty (nine patients) (median age 8 years) or resection and end-to-end anastomosis (12 patients) (median age 8 years) were evaluated by Doppler spectrum analysis of the blood flow velocities in the femoral artery at rest and during reactive hyperemia. The median resting right upper to lower limb systolic pressure difference (with interquartile range) was similar in the angioplasty, resection and anastomosis, and control groups: -5 mm Hg (18 mm Hg), 0 mm Hg (12 mm Hg), and -2.5 mm Hg (10 mm Hg), respectively. Also, similar resting values for the maximum frequency of the advancing curve and the pulsatility and resistance indices were measured in the three groups. During reactive hyperemia of the leg, however, a significant hemodynamic obstruction across the repair site became clinically manifest in the angioplasty group only, as documented by a lower pulsatility index in comparison with the control group (p = 0.01, Mann-Whitney U test). Comparison of the hemodynamic results between the angioplasty and resection and anastomosis groups in subdivisions of infants operated on at an age of less or greater than 3 months, both at rest and during reactive hyperemia, showed, already at rest, a significantly lower value for the pulsatility index in the former angioplasty subdivision (p = 0.05, Student's t test), indicating a significant resistance at the coarctation repair site in the angioplasty patients operated on before the third month of life. A disadvantage of angioplasty (compared with resection and anastomosis) was noted when angioplasty was performed before the third month of life, and an unequivocal lack of advantage was noted when performed beyond that period regarding relief of obstruction from coarctation. In addition, a definite potential for adverse long-term effects on the hemodynamics of the left upper limb after subclavian flap angioplasty in infancy has been documented. For these reasons we prefer to perform resection and end-to-end anastomosis for repair of coarctation in infancy.     

Specificity of co-promoting effects of caffeine on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine

The specificity of copromotion effects of caffeine with known goitrogenic factors on thyroid carcinogenesis was examined in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 8 groups, each consisting of 10 animals, and received a single sc injection of 2,800 mg/kg DHPN. From one week after the DHPN initiation, they were given basal diet, iodine deficiency (ID) diet, 500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM) solution with or without 1,500 ppm caffeine feeding for 12 weeks. The caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further (p < 0.05 or 0.01) enhanced in combination with caffeine. SDM drastically promoted thyroid carcinogenesis in association with increased serum TSH levels regardless of the caffeine treatment. Thyroid follicular carcinomas and adenomas were more frequently observed in the additional caffeine groups than in the ID alone groups. The incidence and multiplicity of focal thyroid follicular hyperplasias in the ID-treated groups were significantly (p < 0.05 and 0.01) elevated in the case of combination with caffeine. Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine. Serum thyroid hormone levels were significantly (p < 0.01) decreased by SDM but significantly (p < 0.05 or 0.01) increased by caffeine, PB or ID. Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.     

Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine retinal pericytes

One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive alpha-dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 microM) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kappaB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kappaB are involved in the apoptotic process.     

The effect of passive smoking on asthma symptoms,atopy,and airway hyperresponsiveness in schoolchildren

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey.     

Applications of the pulsatile flow versatile ECLS: in vivo studies

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.     

新生儿缺氧、缺血性脑病血中6-keto-PGF1α,NSE水平变化的临床研究

目的:探讨HIE患者血中6-keto-PGF1α、NSE水平变化及临床意义.方法:用RIA检测89例HIE患者和32例正常新生儿血中6-keto-PGF1α、NSE水平变化.结果:HIE轻、中、重度组6-keto-PGF1α水平与正常对照组比较,均存在显著性差异(p＜0.01),HIE患者轻度组NSE水平与对照组比较无显著性差异(p＞0.05),中、重度组NSE水平与对照组比较存在显著性差异(p＜0.01),6-keto-PGF1α、NSE二组血中浓度上升与HIE程度呈正相关.结论:HIE患者中6-keto-PGF1α、NSE水平检测,对判断HIE的脑损伤程度、治疗、预后观察,具有重要临床意义和应用价值.