Jugular Venous Oxygen Saturation During Mild Hypothermic Versus Normothermic Cardiopulmonary Bypass in Elderly Patients

Purpose. Age is known to be a major risk factor for adverse postoperative cognitive dysfunction after cardiac surgery. We conducted this study to determine if jugular venous oxygen saturation (SjvO₂) differed during mild hypothermic (32°C) and normothermic cardiopulmonary bypass (CPB) in elderly patients.Methods. Sixty patients aged over 70 years who underwent elective coronary artery bypass grafting were randomly divided into two groups. Group 1 (n = 30) underwent normothermic CPB (>35°C) and group 2 (n = 30) underwent mild hypothermic CPB (32°C). For the continuous monitoring of SjvO₂, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb after the induction of anesthesia. Hemodynamic parameters, and arterial and jugular venous blood gases were measured at seven time points.Results. The SjvO₂ in the normothermic group was lower at the onset of CPB and 20min after the onset, than from the time of induction of anesthesia until the start of surgery (period 1), the respective SjvO₂ values being 50.3% ± 1.0%, 50.1% ± 1.6%, and 59.5% ± 1.9% (P < 0.05). However, in the mild hypothermic group there were no changes in the SjvO₂ value throughout the study. The cerebral desaturation time (when the SjvO₂ value was <50%) and the ratio of the cerebral desaturation time to the total CPB time in the normothermic group differed significantly from those in the hypothermic group, being 19 ± 11min and 17% ± 10%, and 9 ± 3min and 8% ± 4%, respectively (P < 0.05).Conclusions. The SjvO₂ value was better during mild hypothermic CPB than during normothermic CPB in elderly patients.     

Terpene isocyanides, isocyanates, and isothiocyanates from the Okinawan marine sponge Stylissa sp

Seven new nitrogenous terpenoids, (1R,6R,7S,10S)-10-isothiocyanatocadin-4-ene (1), (1S,2S,5S,6S,7R,8S)-13-isothiocyanatocubebane (2), (1R,3S,4R,7S,8S,12S,13S)-7-isocyanoamphilecta-10,14-diene (3), (1S,3S,4R,7S,8S,12S,13S)-8-isocyanoamphilecta-11(20),14-diene (4), (3S,4R,7S,8S,11S,13S)-8-isocyanoamphilecta-1(12),14-diene (5), 8-isocyanatocycloamphilect-10-ene (6), and 8-isothiocyanatocycloamphilect-10-ene (7), were isolated from the Okinawan sponge Stylissasp., along with 12 known related compounds. Structural determinations of these compounds were made by spectroscopic analysis, and assessment was made of their cytotoxicity toward HeLa cells.     

Cullin 3 promotes proteasomal degradation of the topoisomerase I-DNA covalent complex

DNA topoisomerase I (TOP1)-DNA covalent complexes are the initial lesions produced by antitumor camptothecins (CPTs). The TOP1-directed drugs stimulate degradation of TOP1 via the ubiquitin-proteasome pathway. We found that proteasome inhibition prevents degradation of DNA-bound TOP1 and sustains high levels of covalent complexes, thus enhancing CPT-induced cell death. Consistent with this, increased degradation of TOP1-DNA covalent complexes was seen in acquired CPT-resistant cells. We found that the resistant cells showed elevated expressions of Cul3, a member of the cullin family of E3 ubiquitin ligases. The reduction in Cul3 expression by small interfering RNA decreased degradation of TOP1-DNA covalent complexes. Conversely, Cul3 overexpression by stable transfection promoted covalent complex degradation and reduced CPT-induced cell death without affecting basal TOP1 expression levels. These results indicate that Cul3, by promoting proteasomal degradation of TOP1-DNA covalent complexes, becomes an important regulator for cellular CPT sensitivity.     

Suppressive effects of milk-derived lactoferrin on psychological stress in adult rats

Lactoferrin (LF) is known as an iron-binding glycoprotein. It has been shown that bovine LF (bLF) is transported into cerebrospinal fluid via blood although its physiological effects in the central nervous system (CNS) are still unclear. In this study, a suppressive effect of bLF on psychological distress was investigated in adult rats. Intraperitoneal injection of bLF (100 mg/kg) reduced stressful behaviors in a conditioned fear-induced freezing test and an elevated plus-maze test. Interestingly, the suppressive effect of bLF was enhanced by pretreatment with electric foot-shock (FS). This suppressive effect of bLF in the elevated plus-maze test was reversed by pretreatment with naloxone, an opioid receptor antagonist, at a dose of 1 mg/kg (ip). N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, also blocked the suppressive effect of bLF and foot-shock. In addition, combined application of a low dose of bLF (30 mg/kg, ip) and l-arginine (30 and 100 mg/kg, ip) showed significant potentiated effects on psychological stress. These results suggest that bLF has suppressive effects on psychological distress, especially under the condition of moderate stress. Furthermore, it is suggested that bLF possibly activates an endogenous opioidergic system via nitric oxide synthase activation.     

A trial of a smoking rate survey using the coming-of-age ceremony for evaluating action plans to prevent tobacco use in the young

PURPOSE: To assess a smoking rate survey using the coming-of-age ceremony to examine the practicality for estimating the under twenties' smoking rate as a baseline and a long term assessment index for action plans to prevent smoking in the young. METHODS: We undertook the survey at village A (with a population of about 6,500) and town B (with about 12,000 residents) in Niigata Prefecture. Village A started a comprehensive anti-smoking policy featuring cooperation between schools and the community. Subjects were twenty-year young adults (69 in village A and 118 in town B) who attended rural coming-of-age ceremonies in 2002. The self-rated questionnaire included smoking habits, age of first smoking experience, and age of becoming a regular smoker (only in village A). RESULTS: Smoking rates were 68.0% for men and 48.6% for women in village A. Of these, approximately 90% smoked daily and more than 70% became regular smokers before the age of 20. Smoking rates in town B were similar. The results were about 20% higher than found by a smoking rate survey performed at high schools. CONCLUSION: Smoking rate surveys at coming-of-age ceremonies offer a practical and easy approach to estimate under twenties' smoking rate and assess the effects of smoking prevention strategies among the young.     

Increased plasma concentrations of the mature form of adrenomedullin during cardiac surgery and hepatosplanchnic hypoperfusion

Adrenomedullin is a potent vasodilatory peptide. Plasma adrenomedullin (AM) concentrations increase during and after cardiopulmonary bypass (CPB). However, the cause of this increase and its site of production have not been identified. We investigated the role of the hepatosplanchnic and cerebral circulations in the increase of plasma AM and investigated whether tissue hypoxygenation is a cause of the AM increase seen during CPB. We measured plasma total AM (AM-T) and the biologically active form of AM, mature AM (AM-m), in seven patients undergoing CPB. Both plasma AM-T and AM-m concentrations increased significantly 60 min after weaning from CPB. At this time point, arterial AM-T and AM-m concentrations were 18-fold and 10-fold larger, respectively, than baseline values measured after the induction of anesthesia. The plasma AM-m concentration and the ratio of AM-m/AM-T in blood from the hepatic vein were significantly larger than those from the radial artery or jugular bulb. The AM-m/AM-T ratio decreased during CPB, suggesting that production of the intermediate form of AM, AM-glycine, is more than that of AM-m. The oxygen tension of the hepatic venous blood (PhvO2) was significantly less during CPB. Plasma AM-m concentrations sampled from the hepatic vein showed a significant negative correlation with PhvO2 at 10 min (r = 0.824; P < 0.02) and 60 min (r = 0.828; P < 0.02) after the onset of CPB. These data suggest that the hepatosplanchnic circulation is an important source of AM-m during CPB. Furthermore, hypoxygenation of the hepatosplanchnic region may be an important cause of this AM-m increase.     

Sudden increase in bispectral index during propofol anesthesia in three patients

We report 3 patients who developed a sudden unpredicted increase in bispectral index (BIS) value during propofol and fentanyl anesthesia. The patients were induced with propofol 2-mg.kg-1 and fentanyl 2-micrograms.kg-1 and muscle relaxation was obtained by vecuronium 0.12-mg.kg-1. During induction of anesthesia, BIS value went down to below 50 in all three cases, and anesthesia was maintained by continuous infusion of propofol at a rate of 5 mg.kg-1.hr-1 and intermittent administration of fentanyl. Forty to sixty min after starting the operation, BIS value increased suddenly (up to 80) and the body movement of the patients was observed. The serum concentration of propofol was approximately 2.5 micrograms.ml-1. All patients were successfully treated with increasing the infusion rate of propofol and additional administration of fentanyl. No clear recall or explicit memory during operation was observed after anesthesia, but, anesthesiologists might have to pay more attention to unpredictable changes of anesthetic depth during propofol anesthesia using target controlled infusion.     

Cellular sensitization to cisplatin and carboplatin with decreased removal of platinum-DNA adduct by glucose-regulated stress

Purpose: Stress conditions, such as glucose starvation and hypoxia, that induce glucose-regulated proteins (GRPs) in cells, are seen in most solid tumors. These conditions have been shown to cause cellular resistance to multiple anticancer drugs, such as etoposide, doxorubicin, and camptothecin. We examined the effect of the GRP-inducing conditions on cellular sensitivity to cisplatin and carboplatin, which are widely used drugs against solid tumors. Methods: We generated the GRP-inducing culture conditions by exposing cells to 2-deoxyglucose (2DG), calcium ionophore A23187 and tunicamycin, and examined cellular sensitivity to cisplatin and carboplatin under these conditions. We next measured platinum accumulation and DNA-bound platinum in 2DG-stressed cells after cisplatin exposure. Results: The GRP-inducing stress conditions led to cellular sensitization to cisplatin and carboplatin. This sensitization was reversible, as the cellular sensitivity returned to normal levels 12 h after removal of 2DG. Platinum accumulation and DNA-bound platinum that were found immediately after exposure to cisplatin for 1 h were slightly increased in 2DG-stressed cells as compared with nonstressed cells. After a drug-free recovery incubation of 8 h, the DNA-bound platinum in the nonstressed cells was reduced by 33% while the amount in the 2DG-stressed cells was sustained at the initial levels. Conclusions: These results indicated that the decreased removal of platinum-DNA adducts was associated with increased sensitivity to cisplatin and carboplatin in the stressed cells. The sensitization of cancer cells under the GRP-inducing stress conditions would explain, in part, the clinical potency of platinum drugs against solid tumors. Received: 27 May 1998 / Accepted: 20 October 1998