Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model

Purpose Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. Methods We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H₂O₂). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). Results In series 1, treatment with catalase (an H₂O₂ scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H₂O₂ may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values. Conclusion Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.     

Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis

Levels of HtrA1 protein in cartilage have been reported to elevate in joints of human osteoarthritis patients. To understand roles of HtrA1 in normal osteogenesis as well as in pathogenesis of arthritis, we examine HtrA1 expression pattern during bone and cartilage development and in articular cartilage affected by experimental arthritis. HtrA1 is not expressed in mesenchymal or cartilage condensations before initiation of ossification. When ossification begins in the condensations, the expression of HtrA1 starts in chondrocytes undergoing hypertrophic differentiation near the ossification center. Hypertrophic chondrocytes found in adult articular cartilage and epiphyseal growth plates also express HtrA1. When arthritis is induced by injection of anti-collagen antibodies and lipopolysaccharide, resting chondrocytes proceed to terminal hypertrophic differentiation and start expressing HtrA1. These data suggest that hypertrophic change induces HtrA1 expression in chondrocytes both in normal and pathological conditions. HtrA1 has been reported to inhibit TGF-beta signaling. We show that HtrA1 digests major components of cartilage, such as aggrecan, decorin, fibromodulin, and soluble type II collagen. HtrA1 may, therefore, promote degeneration of cartilage by inducing terminal hypertrophic chondrocyte differentiation and by digesting cartilage matrix though its TGF-beta inhibitory activity and protease activity, respectively. In bone, active cuboidal osteoblasts barely express HtrA1, but osteoblasts which flatten and adhere to the bone matrix and osteocytes embedded in bone are strongly positive for HtrA1 production. The bone matrix shows a high level of HtrA1 protein deposition akin to that of TGF-beta, suggesting a close functional interaction between TGF-beta and HtrA1.     

A comparison of perioperative factors with two methods of coronary artery bypass grafting (CABG): off-pump and conventional

BACKGROUND: The safety and efficiency of off-pump coronary artery bypass grafting (OPCAB) are still controversial. The purpose of this study was to evaluate this approach in comparison with the conventional cardiopulmonary bypass technique (cCABG). METHODS: A retrospective review of patients who had undergone coronary artery bypass grafting independently without other operations between January 1, 1999 and September 30, 2001 was performed. The patients were divided into two groups: those who underwent OPCAB and the remainder for cCABG. The perioperative factors of the two groups were compared. RESULTS: A total of 152 OPCAB and 142 cCABG cases were reviewed. Compared with cCABG, OPCAB significantly reduced the amount of catecholamine needed on admission to ICU, intubation time, overall hospital length of stay, and neurologic events. There were also trends for decreases in ICU length of stay, mortality, and renal failure. On the other hand, OPCAB did not affect perioperative blood loss. CONCLUSIONS: Overall OPCAB is safer and more efficient than cCABG. However, we have to note in anesthetic management that OPCAB does not reduce blood loss.     

A pharmacological study of the weekday-on/weekend-off oral UFT schedule in colorectal cancer patients

PURPOSE: The new weekday-on/weekend-off schedule for oral UFT administration consists of its administration for 5 consecutive days followed by 2 days off the drug. The intratumor 5-FU (5-fluorouracil) concentration has been reported to be correlated to the tumor response in patients treated with intravenous 5-FU. The aim of this study was to investigate the pharmacokinetics during the 2 days off the drug in cancer patients treated with the weekday-on/weekend-off schedule for oral UFT. METHODS: The subjects were 24 colorectal cancer patients. They were divided into three groups, and were all given UFT, 600 mg/day, for 5 days before surgery. Surgery was performed 2, 24, or 48 h after the final dose of UFT. The 5-FU concentrations in the serum, tumor, and in the normal mucosa were measured. RESULTS: The serum 5-FU concentrations after the final dose of UFT were: 23 +/- 12 ng/ml (mean +/- SD) at 2 h, 7 +/- 3 ng/ml at 24 h, and 6 +/- 3 ng/ml at 48 h. The intratumor 5-FU concentrations were: 113 +/- 45 ng/g at 2 h, 54 +/- 20 ng/ml at 24 h, and 54 +/- 35 ng/ml at 48 h, and the concentrations in the normal mucosa were: 36 +/- 15 ng/g (mean +/- SD) at 2 h, 17 +/- 6 ng/ml at 24 h, and 18 +/- 6 ng/ml at 48 h after the final dose. While the serum 5-FU concentration decreased to very low levels by 24 h after the final dose of UFT, the intratumor 5-FU concentrations were maintained at more than 50 ng/g at least until 48 h after the final dose. The 5-FU concentrations in the normal mucosa were maintained at about one third of the intratumor concentrations at all time points. CONCLUSION: Although the weekday-on/weekend-off schedule for UFT administration included intermittent 2-day drug-off periods, this pharmacokinetic study revealed that the 5-FU concentrations in the tumor were maintained at much higher levels than in the serum throughout these periods.     

Effect of amino acids and dipeptides on accumulation of ammonia in the medium during <Emphasis Type="Italic">in vitro</Emphasis> maturation and fertilization of porcine oocytes

Aim:  The present study was designed to investigate the effect of amino acids and their dipeptides on the accumulation of ammonia in the medium during in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes.
Methods:  The IVM and IVF media were modified North Carolina State University-37 solution and modified Tyrode's albumin lactate pyruvate, respectively. Porcine oocytes were matured in IVM medium containing 75–2400 µmol ammonia. Amino acids (1.0 mmol) or their dipeptides (2.0 mmol) related to the urea cycle were added individually to the IVM and IVF media containing 300 µmol ammonia. Oocyte maturation and fertilization were assessed using acetic–orcein staining, and the accumulation of ammonia in the media was measured using the indophenol method.
Results:  Percentages of metaphase II (MII) were adversely affected ( P <  0.05) by ≥300 µmol concentrations of ammonia in the IVM medium. In the presence of 300 µmol ammonia in the IVM and IVF media, glutamic acid, l -alanyl-L-glutamine (AlaGln), l -glycyl-L-glutamine (GlyGln) and AlaGln + GlyGln showed the highest rate ( P <  0.05) of MII, monospermic fertilization, and the lowest rate ( P <  0.05) of ammonia accumulation in the media.
Conclusion:  AlaGln and GlyGln in IVM and IVF media were more stable and effective than the individual amino acids in reducing the accumulation of ammonia, and increased the rate of porcine oocyte MII and monospermic fertilization in vitro . (Reprod Med Biol 2007; 6 : 165–170)     

Influenza vaccine with Surfacten, a modified pulmonary surfactant, induces systemic and mucosal immune responses without side effects in minipigs

Immune responses and side effects of intranasally administered flu vaccine with the commercial product Surfacten, a modified bovine pulmonary surfactant, were investigated in minipigs. The use of minipigs was based on the anatomical resemblance of nasal lymph nodes, the principal antigen uptake site of respiratory mucosal immunity, between pig and human. Intranasal instillation of HA vaccine adjuvanted with Surfacten elicited significantly higher serum hemagglutination inhibition titers than the antigen alone, with wide cross-neutralizing activities of secretory IgA in nasal washes. No significant induction of inflammatory cytokines or migration of inflammatory cells was observed at the site of immunization or serum after the first immunization. These data suggest the potential usefulness of Surfacten for mucosal vaccination.     

Time progression from the patient’s operating room entrance to incision: factors affecting anesthetic setup and surgical preparation times

Purpose  Owing to recent advances in surgical technology, substantial time is required for preparing surgical equipment before incision. The purpose of this study was to demonstrate the time progression from a patient’s operating room entrance to incision and to evaluate the duration of each anesthetic procedure and surgical preparation. Methods  We marked the following seven points on the anesthetic chart: (1) entrance; (2) IV line placement; (3) preoxygenation; (4) intubation; (5) completion of patient positioning (Anesth-Set); (6) applying antiseptic solution; and (7) incision. Afterward, we analyzed the event time periods according to anesthetic procedure, patient position, surgical service, and surgical procedure (such as the utilization of endoscopy, navigation systems, and sentinel lymph node biopsy). Results  On average, it took approximately 3 min to start IV placement, 7 min until preoxygenation, 15 min until intubation, and 30 min until Anesth-Set. Epidural, arterial, and central venous catheterization required 15, 9, and 13 min, respectively. It took 20 min from Anesth-Set to incision, on average; 22, 4, and 5 min were required to prepare the navigation system, endoscope, and sentinel lymph node biopsy, respectively. In total, it took an average of 49.8 ± 17.1 min from entrance to incision, which was significantly longer (30.4 ± 8.8 min) than it took in 1985–1986. Conclusion  The mean time taken from the patient’s operating room entrance to incision is now significantly longer than before. This may be attributed, at least in part, to the preparation of equipment associated with new surgical technologies.     

B1500, a small membrane protein, connects the two-component systems EvgS/EvgA and PhoQ/PhoP in Escherichia coli

Two-component signal-transduction systems (TCSs) of bacteria are considered to form an intricate signal network to cope with various environmental stresses. One example of such a network in Escherichia coli is the signal transduction cascade from the EvgS/EvgA system to the PhoQ/PhoP system, where activation of the EvgS/EvgA system promotes expression of PhoP-activated genes. As a factor connecting this signal transduction cascade, we have identified a small inner membrane protein (65 aa), B1500. Expression of the b1500 gene is directly regulated by the EvgS/EvgA system, and b1500 expression from a heterologous promoter simultaneously activated the expression of mgtA and other PhoP regulon genes. This activation was PhoQ/PhoP-dependent and EvgS/EvgA-independent. Furthermore, deletion of b1500 from an EvgS-activated strain suppressed mgtA expression. B1500 is localized in the inner membrane, and bacterial two-hybrid data showed that B1500 formed a complex with the sensor PhoQ. These results indicate that the small membrane protein, B1500, connected the signal transduction between EvgS/EvgA and PhoQ/PhoP systems by directly interacting with PhoQ, thus activating the PhoQ/PhoP system.