Search

A 74-year-old woman underwent replacement of the ascending aorta for acute type A aortic dissection. The patient suffered from bacteremia postoperatively and repeated computed tomography showed an increasing diameter of pseudoaneurysms at the site of the proximal anastomosis due to graft infection. Re-mechanical Bentall operation and arch replacement were therefore performed using a composite graft of a rifampicin-bonded gelatin-sealed 24-mm woven Dacron graft and a mechanical valve. The postoperative course was uneventful. We report the successful in situ reconstruction using the above-mentioned Dacron graft and describe the preparation of the rifampicin solution using a surfactant.

Objective: Despite advances in design, modern ventricular assist device placement involves median sternotomy and cardiopulmonary bypass and is associated with infectious/embolic complications. In this study, we examine the feasibility and function of a novel minimally invasive, non-blood-contacting epicardial assist device in a porcine ischemic cardiomyopathy model., Methods: Feasibility was first tested in an ex vivo thoracoscopic trainer box with slaughterhouse hearts. Five male Yorkshire swine underwent selective ligation of the circumflex artery to create a posterolateral infarct Twelve weeks after infarct, all animals underwent left minithoracotomy. A custom inflatable bladder was positioned over the epicardial surface of the infarct and firmly secured to the surrounding border zone myocardium with polypropylene mesh and minimally invasive mesh tacks. An external gas pulsation system actively inflated and deflated the bladder in synchrony with the cardiac cycle. All animals then underwent cardiac magnetic resonance imaging to assess ventricular function., Results: All subjects successfully underwent off-pump placement of the epicardial assist device via minithoracotomy. Ejection fraction significantly improved from 29.1% ± 4.8% to 39.6% ± 4.23% (P < 0.001) when compared with pretreatment. End-systolic volume decreased (76.6 ± 13.3 mL vs 62.4 ± 12.0 mL, P < 0.001) and stroke volume increased (28.6 ± 3.4 mL vs 37.9 ± 3.1 mL, P < 0.05) when assisted. No change was noted in end-diastolic volume (105.1 ± 11.4 vs 100.3 ± 12.7). On postmortem examination, mesh fixation and device position were excellent in all cases. No adverse events were encountered., Conclusions: Directed epicardial assistance improves ventricular function in a porcine ischemic cardiomyopathy model and may provide a safe alternative to currently available ventricular assist device therapies. Further, the technique used for device positioning and fixation suggests that an entirely thoracoscopic approach is possible.

Cardiac hemangiomas are extremely rare benign tumors. These tumors are usually asymptomatic but they can present symptoms such as palpitations, shortness of breath, and arrythmia. We report the case of a 73-year-old man who presented with an abnormal shadow on chest computed tomography during follow-up for lung metastatic tumor after resection of his rectal cancer. A cardiac tumor was detected, and surgical resection and right ventricular plasty were successfully performed with the patient under cardiopulmonary bypass. Histopathologic examination revealed a benign cardiac hemangioma, which was categorized as a hemangioma of the mixed cavernous and capillary type., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Transcatheter mitral valve replacement would represent a major advance in heart valve therapy. Such a device requires a specialized anchoring and sealing technology. This study was designed to test the feasibility of a novel mitral valve replacement device (the sutureless mitral valve [SMV]) designed to anchor and seal in the mitral position without need for sutures., Description: The SMV is a self-expanding device consisting of a custom-designed nitinol framework and a pericardial leaflet valve mechanism., Evaluation: Ten sheep underwent successful surgical SMV device implantation. All animals underwent cardiac catheterization 6 hours postoperatively. Hemodynamic, angiographic, echocardiographic and necroscopic data were recorded. The mean aortic cross-clamp time was 9.5 ± 3.1 minutes. Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Necropsy demonstrated that the SMV devices were anchored securely., Conclusions: This study demonstrates the feasibility and short-term success of sutureless mitral valve replacement using a novel SMV device., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure after myocardial infarction (MI) is a result of increased myocardial workload, adverse left ventricular (LV) geometric remodeling, and less efficient LV fluid movement. In this study we utilize cardiac magnetic resonance imaging to evaluate ventricular function and flow after placement of a novel directed epicardial assist device., Methods: Five swine underwent posterolateral MI and were allowed to remodel for 12 weeks. An inflatable bladder was positioned centrally within the infarct and secured with mesh. The device was connected to an external gas exchange pump, which inflated and deflated in synchrony with the cardiac cycle. Animals then underwent cardiac magnetic resonance imaging during active epicardial assistance and with no assistance., Results: Active epicardial assistance of the infarct showed immediate improvement in LV function and intraventricular flow. Ejection fraction significantly improved from 26.0% ± 4.9% to 37.3% ± 4.5% (p < 0.01). End-systolic volume (85.5 ± 12.7 mL versus 70.1 ± 11.9 mL, p < 0.01) and stroke volume (28.5 ± 4.4 mL versus 39.9 ± 3.1 mL, p = 0.03) were also improved with assistance. End-diastolic volume and regurgitant fraction did not change with treatment. Regional LV flow improved both qualitatively and quantitatively during assistance. Unassisted infarct regional flow showed highly discoordinate blood movement with very slow egress from the posterolateral wall. Large areas of stagnant flow were also identified. With assistance, posterolateral wall blood velocities improved significantly during both systole (26.4% ± 3.2% versus 12.6% ± 1.2% maximum velocity; p < 0.001) and diastole (54.3% ± 9.3% versus 24.2% ± 2.5% maximum velocity; p < 0.01)., Conclusions: Directed epicardial assistance can improve LV function and flow in ischemic cardiomyopathy. This novel device may provide a valuable alternative to currently available heart failure therapies., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The functions of MAELSTROM protein (MAEL) in spermatogenesis are gradually being identified but the precise distribution of MAEL in spermatogenic cells during spermatogenesis has not yet been mapped. We studied the expression of MAEL in rat testis by immunofluorescence and immunoelectron microscopy (IEM). Immunofluorescence staining showed that MAEL was localized in intermitochondrial cement, irregularly-shaped perinuclear granules and satellite bodies of pachytene spermatocytes, and in chromatoid bodies of spermatids. The SBs appeared exclusively in pachytene spermatocytes at stages IX-X and were stained strongly for MAEL. In step 12-19 spermatids, many granules stained for MAEL but not DDX4. These granules were confirmed to be non-nuage structures, including mitochondria-associated granules, reticulated body, granulated body by IEM. In the neck region of late spermatids and sperm, MAEL-positive small granules were found. MAEL is colocalized with MIWI in nuage and non-nuage. The results suggest that MAEL seems to function in nuage and non-nuage structures and interacts with MIWI.

Olprinone, a specific phosphodiesterase III inhibitor, and corforsin daropate, a direct adenylate cyclase activator, are now being used in critical conditions. We investigated whether their therapeutic use provides protection against septic acute lung injury (ALI) and mortality. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in BALB/c mice. Olprinone or colforsin daropate was continuously given through an osmotic pump that was implanted into the peritoneal cavity immediately following CLP. These treatments prevented the ALI development in CLP mice, as indicated by the findings that severe hypoxemia, increased pulmonary vascular permeability, and histological lung damage were strikingly remedied. Furthermore, continued administration of olprinone or colforsin daropate suppressed apoptosis induction in septic lungs and improved the survival of CLP mice. Olprinone and corforsin daropate enhanced Akt phosphorylation in septic lungs. Wortmannin, which inhibits the Akt upstream regulator phosphatidylinositol 3-kinase, abrogated the protective effects of olprinone and corforsin daropate on sepsis-associated lung inflammation and apoptosis. In vivo transfection of cyclic AMP response element binding protein (CREB) decoy oligodeoxynucleotide failed to negate the abilities of these agents to increase Akt phosphorylation and to inhibit IκBα degradation in septic lungs. These results demonstrate for the first time that CREB-independent Akt-mediated signaling is a critical mechanism contributing to the therapeutic effects of olprinone and corforsin daropate on septic ALI. Moreover, our data also suggest that these cyclic AMP-related agents, by blocking both nuclear factor-κB activation and apoptosis induction, may represent an effective therapeutic approach to the treatment of the septic syndrome.

Background: The recurrence of regurgitation after surgical mitral valve (MV) repair remains a significant clinical problem. Mitral annuloplasty rings are commonly used in MV repair procedures. The purpose of this study was to demonstrate the feasibility of transvenous valve-in-ring (VIR) implantation using the Melody valve (Medtronic, Minneapolis, MN), which is a valved-stent designed for percutaneous pulmonary valve replacement, and 4 distinct types of annuloplasty ring (AR) in an ovine model., Methods: Ten sheep underwent surgical MV annuloplasty ring placement (n=10): CE-Physio, Edwards Lifesciences, Irvine, CA [n=5]; partial ring [n=3]; flexible ring [n=1]; and saddle ring [n=1]). All animals underwent cardiac catheterization, hemodynamic assessment, and Melody VIR implantation through a transfemoral venous, transatrial septal approach 1 week after surgery. Follow-up hemodynamic, angiographic, and echocardiographic data were recorded., Results: Melody VIR implantation was technically successful in all but 1 animal. In this animal a 26-mm partial AR proved too large for secure anchoring of the Melody valve. In the remaining 9 animals, fluoroscopy showed the Melody devices securely positioned within the annuloplasty rings. Echocardiography revealed no perivalvular leak, and angiography revealed no left ventricular outflow tract obstruction, vigorous left ventricular function, and no aortic valve insufficiency. The median procedure time was 55.5 (range, 45 to 78) minutes., Conclusions: This study demonstrates the feasibility of a purely percutaneous approach to MV replacement in patients with preexisting annuloplasty rings, regardless of ring type. This approach may be of particular benefit to patients with failed repair of ischemic mitral regurgitation., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Either suprarenal or infrarenal aortic clamping markedly reduces renal blood flow. This aortic clamping may cause postoperative acute kidney injury(AKI)., Methods: Fifty-four patients undergoing open abdominal aortic aneurysm (AAA) surgery were included in a retrospective study. Postoperative AKI defined as an absolute increase in serum creatinine (Cre) of more than or equal to 0.3 mg x dl(-1) or an increase in Cre of more than or equal to 50% within 48 hours after the end of the procedure., Results: Thirteen patients developed AKI, but none of them required dialysis. The patients with AKI had higher preoperative Cre, longer operation, longer clamp time and more use of diuretics intra- and postoperatively., Conclusions: AKI occurred in 24.1% of patients undergoing AAA surgery. Risk factors for AKI were preoperative Cre, operation time, clamp time and use of diuretics.

Background: Intraoperative use of remifentanil requires much more analgesics postoperatively. Moreover, remifentanil causes intraoperative hypotension and bradycardia., Methods: The objectives are to compare intra- and post-operative drug cost between patients who received remifentanil (Group R, n = 72) and those who received fentanyl (Group F, n = 66) during laparoscopic cholecystectomy retrospectively., Results: The baseline demographics were similar between the two groups. Intraoperative drug costs were 7,782 +/- 1,579 yen in Group R and 6,235 +/- 1,037 yen in Group E Postoperative drug costs were 364 +/- 521 yen in Group R and 146 +/- 153 yen in Group E Total drug costs were 8,167 +/- 1,607 yen in Group R and 6,381 +/- 1,042 yen in Group E These reached statistical significance (P < 0.01). Length of hospital stay (days) between the two groups were comparable., Conclusions: Remifentanil anesthesia requires much more intra- and post-operative drug cost than fentanyl anesthesia for laparoscopic cholecystectomy.

The paraxial trajectory method has been generalized for the application to the cathode rays inside electron guns. The generalized method can handle rays that initially make a large angle with the optical axis with a satisfactory accuracy. The key to success of the generalization is the adoption of the trigonometric function sine for the trajectory slope specification, instead of the conventional use of the tangent. Formulas have been derived to relate the ray conditions (position and slope of the ray at reference planes) on the cathode to those at the crossover plane using third-order polynomial functions. Some of the polynomial coefficients can be used as the optical parameters in the characterization of electron sources; the electron gun focal length gives a quantitative estimate of both the crossover size and the angular current intensity. An electron gun simulation program G-optk has been developed based on the mathematical formulations presented in the article. The program calculates the principal paraxial trajectories and the relevant optical parameters from axial potentials and fields. It gives the electron-optical-column designers a clear physical picture of the electron gun in a much more faster way than the conventional ray-tracing methods.

Background and Aim: Dysregulated immune responses in the gut to luminal antigens can cause inflammatory bowel diseases (IBD). The roles played by dietary antigens in the pathogenesis or prevention of IBD are poorly understood. Soybean isoflavones are digested in large amounts and have many biological activities. The aim of this study was to determine whether isoflavones in aglycon and bioavailable forms have any effect on gut immunity and protect the host from tissue damage in a mouse model of colitis., Methods: We administered daidzein-rich isoflavone aglycones (DRIA) to mice for 1 week and then treated them with 2% dextran sodium sulfate (DSS) in drinking water for 4 days to induce colitis. The effect of DRIA was evaluated by examining the histopathology of the colon, body weight changes, and functional analysis of mesenteric lymph node cells (MLN)., Results: DRIA inhibited interleukin (IL)-6 and IL-8 production by Toll-like receptor (TLR)2, and TLR4-stimulated monocytes in a dose-dependent manner. The mice administered DRIA had less inflammation and tissue damage in the colon than the control mice. This protective effect of DRIA was associated with a decrease in interferon-gamma, IL-6, and IL-12p40 secretion, and an increase in IL-10 secretion and low cell-activation status of antigen-presenting cells (APC) in MLN., Conclusion: Ingested DRIA can downregulate the functions of APC and inhibit DSS colitis.

To study the pharmacokinetics of single increasing intravenous doses (40-160 mg) and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC-SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-dose, open-label, dose-escalation part and a multiple-dose, single-blind, placebo-controlled part. The pharmacokinetics of PC-SOD were determined using noncompartmental and compartmental methods. Pharmacokinetic data from a study with PC-SOD in Caucasians were reanalyzed using the same methodology. The mean (SD) terminal half-life of PC-SOD in Japanese subjects was 25 (4) hours for the 40-mg and 80-mg doses and 31 (15) hours for the 160-mg dose. There was nonlinearity between dose-normalized C(max) and clearance (P values .002 and .022). After multiple dosing, steady state was reached after 5 days. The observed accumulation ratio was 2.6 (0.5). The pharmacokinetics of the single 80-mg dose were similar for Japanese and Caucasians. The pharmacokinetics of PC-SOD was shown to be nonlinear with dose, which may be attributable to a saturable clearing mechanism. The relatively long half-life of PC-SOD (>24 hours) suggests that it is worthwhile to study the compound as a protective agent in clinical conditions with free radical overload.

The nitrogen (N) status of a plant determines the composition of its major components (amino acids, proteins, carbohydrates and organic acids) and, directly or indirectly, affects the quality of agricultural products in terms of their calorific value and taste. Although these effects are guided by changes in metabolic pathways, no overall metabolic analysis has previously been conducted to demonstrate such effects. Here, metabolite profiling using gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of N levels on spinach tissue, comparing two cultivars that differed in their ability to use N. Wide variation in N content was observed without any distinct inhibition of growth in either cultivar. Principal component analysis (PCA) and self-organizing mapping (SOM) were undertaken to describe changes in the metabolites of mature spinach leaves. In PCA, the first component accounted for 44.5% of the total variance, the scores of which was positively correlated with the plant's N content, and a close relationship between metabolite profiles and N status was observed. Both PCA and SOM revealed that metabolites could be broadly divided into two types, correlating either positively or negatively with plant N content. The simple and co-coordinated metabolic stream, containing both general and spinach-specific aspects of plant N content, will be useful in future research on such topics as the detection of environmental effects on spinach through comprehensive metabolic profiling.

We previously reported that continuous intravenous (IV) administration of nicorandil (NIC) inhibits QT dispersion (QTd). However, no prior study has evaluated the efficacy of NIC when administered orally to acute myocardial infarction (AMI) patients following continuous IV administration. Thirty patients with anteroseptal infarction in whom revascularization was performed successfully within 6 hours of AMI onset were included in the study and assigned to one of 3 groups: group A (continuous IV administration of NIC), group B (continuous IV and oral administration of NIC), and group C (no treatment with NIC). After 24 hours, QTd in groups A and B was significantly decreased compared to QTd in group C (P < 0.01) (group A, 58.1; group B, 58.2; and group C, 81.3). The QTd obtained 3 months later was significantly shorter in group B subjects who were orally administered NIC, and QTd before percutaneous coronary intervention (PCI) was restored in group A, in which no NIC had been administered orally [group A, 66.7; group B, 54.1; and group C, 73.9; P < 0.05 (group A versus group B) and P < 0.01 (group B versus group C)]. The effects were evaluated by comparing different routes of administration. Continuous IV and subsequent oral administration of NIC inhibited prolongation of QTd, suggesting that these effects may prevent the occurrence of cardiac events during both the acute and chronic phases of AMI.

Levels of cytokinins and abscisic acid (ABA) and the expression of senescence-related genes were investigated in two maize (Zea mays L.) cultivars of different senescence type, cv. P3845 (stay-green) and cv. Hokkou 55 (earlier senescent), in a field study. The delay in leaf senescence in P3845 was correlated with increased levels of chlorophyll and nitrogen and a higher photon-saturated photosynthetic rate (P(sat)). Compared with the earlier senescent Hokkou 55, P3845 showed enhanced contents of cytokinins (trans-zeatin riboside, t-ZR; dihydrozeatin riboside, DHZR; isopentenyladenosine, iPA) and reduced levels of ABA in its leaves. In roots, P3845 had increased levels of t-ZR, DHZR, and ABA, but decreased concentrations of iPA. It was concluded that a higher rate of cytokinin transport from roots to leaves contributes to the delay of senescence in P3845. By contrast, the translocation of ABA from roots to shoots may be blocked in the stay-green cultivar, which also results in retarded leaf senescence. P3845 ear leaves contained more malondialdehyde (MDA) and higher catalase (CAT) and superoxide dismutase (SOD) activities than Hokkou 55. Since the accumulation of the mRNAs for Rubisco small subunit (rbcS), phosphoenolpyruvate carboxylase (PEPC), and SOD peaked after Chl content and P(sat) had reached their maxima, it is speculated that when leaf senescence is initiated, Chl contents decrease first, followed by the degradation of the photosynthetic apparatus and of photosynthesis-related enzymes. See1 and See2 encode senescence-related cysteine proteases; their mRNAs were most abundant in yellowing leaves, suggesting that these proteins are involved in the process of senescence rather than its initiation. mRNAs of both genes were more abundant in Hokkou 55 than in P3845, which suggests a regulation of leaf senescence at the transcriptional level.

The isoflavones genistein and daidzein and the daidzein metabolite equol have been reported to interact with estrogen receptors (ERs). Some studies indicate that they behave clinically like estrogen in some estrogen-deficiency diseases. However, the detailed molecular mechanism used by these compounds to create beneficial effects in patients with estrogen-related diseases has not been clarified. Using histone acetyltransferase (HAT) assay, we found that equol, genistein, and AglyMax had significant effects on ERalpha-mediated histone acetylation. Although 17beta-estradiol (E2)-dependent HAT activity of steroid receptor coactivators 2 (SRC2) and p300 mediated by ERbeta could be detected, it was weaker than that mediated by ERalpha. Equol, genistein, AglyMax, and daidzein all markedly stimulated ERbeta-mediated histone acetylation. On the other hand, anti-estrogenic compounds ICI 182,780 (ICI) and tamoxifen (TA) did not have an effect on HAT activity mediated by either ERalpha or ERbeta. Our data indicate that estrogenic ligands exert their effects by elevating histone acetylation and coactivator activity of ER, and suggest that the risk of estrogen-related diseases might be reduced by a sufficient amount of genistein or AglyMax supplements.

It is well known that neonatal exposure to estrogen induces masculinization or defeminization of the brain. In this study, the effects of neonatal treatment with two kinds of soybean isoflavone aglycone, genistein (GS) and daidzein (DZ), on the estrous cycle and lordosis behavior were investigated. Female rats were injected subcutaneously with 1 mg GS, 1 mg DZ, 100 microg estradiol (E2), or oil daily for 5 days from birth. As a result, vaginal opening was advanced in GS- or E2-treated females. A vaginal smear check indicated that oil- or DZ-treated females showed a constant 4- or 5-day estrous cycle, whereas GS- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovaries in the GS- or E2-treated groups were smaller than those in the oil- and DZ-treated groups and contained no corpora lutea. In the DZ group, although corpora lutea were seen, ovaries were smaller than that of control females. Behavioral tests were carried out after implantation of E2-tubes. All of the oil- or DZ-treated females showed lordosis with a high lordosis quotient (LQ). On the other hand, as male rats, LQs were extremely low in the E2-treated group, when compared to the oil-treated group. In the GS-treated group, the mean LQ was lower than that in the oil-treated group, but higher than those in the E2-treated female or male groups. These results suggest that genistein acts as an estrogen in the sexual differentiation of the brain and causes defeminization of the brain in regulating lordosis and the estrous cycle in rats. In addition, neonatal daidzein also has some influence on ovarian function.

In the trigone (three portions) and proximal urethra isolated from castrated male pigs, transmural electrical stimulation (0.5-10 Hz) induced no or slight contractions followed by frequency-related relaxations. Atropine suppressed the contraction and potentiated the relaxation. N(G)-nitro-L-arginine methylester (L-NAME), a nitric oxide (NO) synthase inhibitor, depressed or abolished the relaxation induced by low frequency stimulation, but only slightly attenuated the response to high frequency stimulation. L-Arginine reversed the inhibitory effect. L-NAME-sensitive relaxation by 1 Hz stimulation was abolished by 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. Release of NO by nerve stimulation to trigonal strips was determined by increased formation of cyclic GMP in the incubation media containing guanylate cyclase and GTP. L-NAME-resistant relaxation by 10 Hz stimulation was not impaired by ODQ, capsaicin, chymotrypsin, K(+) channel inhibitors and beta-adrenoceptor antagonists. Similar results were obtained in the trigone and urethra from normal male and female pigs. Detrusor muscle responded to nerve stimulation with contraction followed by slight relaxation. Relaxations at 1 and 10 Hz stimulation under treatment with atropine and alpha,beta-methylene ATP were partially attenuated by L-NAME. It is concluded that there is no significant difference in the inhibitory responses, sensitive and resistant to L-NAME, to nerve stimulation in the trigone and proximal urethra from castrated and non-castrated male and female pigs. Relaxations to stimulation at 1 Hz seem to be mediated exclusively by neurogenic NO and cyclic GMP generation, whereas those to 10 Hz stimulation is mainly associated with non-NO relaxing factor(s), peptides, K(+) channel openers and beta-adrenoceptor agonist being unlikely involved.

Recent studies have reported that estrogen replacement therapy (ERT) reduces the risk of cardiovascular diseases in postmenopausal women. However, mechanisms responsible for this effect are not yet completely understood, and ERT is associated with carcinogenic side effects in women and feminizing effects in men. Because soybean isoflavones, a group of natural phytoestrogens, have only weak estrogenic activity and are not known to have side effects such as carcinogenesis and feminization, we evaluated the effects of genistein, daidzein and glycitein on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated with 0.1-30 micromol/L of genistein, daidzein or glycitein to investigate cell proliferation (cell number) and DNA synthesis (cell proliferation ELISA system), respectively. We also studied their effects on platelet-derived growth factor (PDGF)-BB (20 microg/L)-induced SMC proliferation. Soybean isoflavones inhibited proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent manner. Inhibition was significant at 3 micromol/L of genistein and 10 micromol/L of both daidzein and glycitein. For significant inhibition of PDGF-BB-induced SMC proliferation, concentrations as low as 0.1 micromol/L of each isoflavone were effective. These isoflavones, with their inhibitory effects on natural and PDGF-BB-induced SMC proliferation, may be useful in attenuatating such proliferation, a basic mechanism involved in atherosclerotic vascular change, thereby preventing atherosclerotic cardiovascular diseases.

The effect of soybean meal fermented by Aspergillus awamori on the acute lethality of acetaldehyde, pentobarbital sleeping time, and cytochrome P-450 content of the hepatic microsomes was studied in mice. Most of the daidzin and genistin in soybean meal (SBM) were converted into the respective aglycones, daidzein and genistein, by fermentation. In experiment 1, mice were fed isonitrogenic test diets with one of the following five protein sources for 28 d: casein, SBM, fermented and hot-air-dried SBM (FSBM-HD), fermented and freeze-dried SBM (FSBM-FD), or methanol-extracted FSBM-FD (FSMB-FD-R). The acute lethality of acetaldehyde in mice fed the FSBM-FD diet was significantly lower than that in mice fed the SBM, FSBM-HD, or FSBM-FD-R diet. In experiments 2 and 3, mice were fed isonitrogenic test diets with one of the following four protein sources for 28 d: casein, SBM, FSBM-FD, and FSBM-FD-R. The pentobarbital sleeping time was significantly shorter and the cytochrome P-450 content was significantly higher in the mice fed the FSBM-FD diet than the respective value in mice fed the other test diets. In experiment 4, mice were fed one of eight diets which contained different levels of aglycone obtained by varying the proportion of FSBM-FD and FSBM-FD-R, for 28 d. The cytochrome P-450 content in hepatic microsomes increased as the dietary level of isoflavonoid aglycones increased, but there was a saturation phenomenon. These results suggest that soy isoflavonoid aglycones are more potent inducers of cytochrome P-450 than isoflavonoid glycosides.

The truncated Aalpha-chain of fibrinogen Marburg is partly linked with albumin by a disulfide bond. Based on the recovery of the first six amino acid residues assigned to the subunit polypeptides of fibrinogen (the Aalpha-and gamma-chains) and albumin, 0.33 mol of albumin was estimated to be linked to 1 mol of the Marburg fibrinogen. When the Marburg fibrinogen was clotted with thrombin-factor XIIIa-Ca2+, various alpham gamman heteromultimers were produced, and part of the albumin was cross-linked to the gamma-chain. Acid-solubilized Marburg fibrin monomer failed to form large aggregates that could be detected by monitoring turbidity at A350, but it was able to enhance tissue-type plasminogen-activator-catalyzed plasmin generation, though not as avidly as the normal control, indicating that the double-stranded protofibrils had, to some extent, been constructed. This idea seems to be supported by normal factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains. However, the cross-linked Marburg fibrin, being apparently fragile and translucent, was highly resistant against plasmin, and its subunit components were considerably retained for 48 hours as noted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Although the exact mechanisms are still unclear, the albumin-incorporated factor XIIIa-cross-linked Marburg fibrin seems to have undergone a critical structural alteration(s) to acquire resistance against plasmin. This aquisition of plasmin resistance may be contributed to the postoperative pelvic vein thrombosis and recurrent pulmonary embolisms in the patient after caesarian section for her first delivery at the age of 20 years.

This paper describes a use of Monte Carlo integration for population pharmacokinetics with multivariate population distribution. In the proposed approach, a multivariate lognormal distribution is assumed for a population distribution of pharmacokinetic (PK) parameters. The maximum likelihood method is employed to estimate the population means, variances, and correlation coefficients of the multivariate lognormal distribution. Instead of a first-order Taylor series approximation to a nonlinear PK model, the proposed approach employs a Monte Carlo integration for the multiple integral in maximizing the log likelihood function. Observations below the lower limit of detection, which are usually included in Phase 1 PK data, are also incorporated into the analysis. Applications are given to a simulated data set and an actual Phase 1 trial to show how the proposed approach works in practice.

We have produced a high-affinity monoclonal antibody classified as IgG1 with kappa-type light chains that recognizes the calcium ion(Ca2+)-dependent conformation of the D-domain of human fibrinogen. Binding of fibrinogen in solution to the insolubilized antibody increased in the presence of increasing concentrations of up to 2 mM Ca2+, the half-maximal binding being reached at 130 microM Ca2+. The dissociation constant was estimated to be 1.6 x 10(-8) M at 2 mM Ca2+. The antibody was found also to be dependent on other divalent metal ions including Zn2+, Mn2+, Co2+ and Cu2+, but not Ba2+, Mg2+ or Sr2+. The synthetic Gly-Pro-Arg-Pro-amide peptide, which has recently been shown to bind to close proximity to the calcium binding site in the D-domain, was unable to elicit the conformation for the antigen to be recognized by this antibody. This antibody was found to be a suitable ligand for the immunoaffinity chromatography of normal and abnormal fibrinogens directly from citrated plasma depleted of the vitamin K-dependent proteins or heparinized plasma by eliminating the precipitation procedure widely adopted in conventional techniques of fibrinogen purification. Indeed, fibrinogen Marburg I with the A alpha chains depleted of the carboxy-terminal A alpha(461-610) residue segment has been purified by this technique, although this dysfibrinogen was difficult to purify by conventional precipitation techniques.

A number of fine bands which occur in positions between the beta- and pre-beta-lipoproteins in polyacrylamide gell electrophresis are called mid-bands (MB). In this study, the relationship between the occurrence of these MB and metabolic abnormalities or vascular complications was evaluated in 181 patients with non-insulin-dependent diabetes mellitus (NIDDM). The incidence of MB in diabetic patients was significantly higher than that in 149 healthy control subjects (35 vs. 20%, p < 0.01). Analysis according to the type of MB revealed that the incidence of the central type in diabetic patients was significantly higher than that in healthy control subject (11 vs. 5%, p < 0.05). When the values of HbAlc were elevated, the incidence of MB and its central type slightly increased. The occurrence of the lower type of MB showed no relationship with the levels of HbAlc. The incidence of MB and its central type were significantly higher in patients with type IIb hyperlipidemia (86 and 41%, respectively) and with type IV hyperlipidemia (63 and 25%) than in those with normolipidemia (21 and 5%) (p < 0.01 of all). The incidence of the lower type of MB was significantly higher in patients with type IIa hyperlipidemia (25%) and with type IIb hyperlipidemia (36%) than in those with normolipidemia (11%) (p < 0.05, p < 0.01, respectively). There was no significant difference in the occurrences of MB and of the central and lower types of MB between the normolipidemic patients and healthy control subjects. The incidence of MB and its central type were significantly higher in patients with nephropathy (54 and 23%, respectively) than in those without nephropathy (32 and 9%) (p < 0.05 of all). There was no significant difference in the incidence of lower type of MB between patients with and without nephropathy. These results indicate that the incidence of central type of MB may be high in NIDDM, and that the occurrence of central type may be associated with abnormal metabolism of glucose or lipid and with diabetic nephropathy.

Concentrated red cells (CRC) were filtered through a new leukocyte removal filter, the Imugard E, which consists of a polyvinyl alcohol porous sheet. CRC were filtered through the Imugard E with neither priming before filtration nor rinsing after filtration. Leukocyte removal was 99.1 +/- 0.6, 99.6 +/- 0.3 and 99.6 +/- 0.4% on the 1st, 5th and 10th day after blood collection, respectively. Platelet removal was 96 +/- 2, 81 +/- 6 and 85 +/- 3% on the 1st, 5th and 10th day, respectively. Red cell recovery was 86 +/- 2, 86 +/- 1 and 86 +/- 1% on the 1st 5th and 10th day, respectively. Filtration time was 3.9 +/- 0.8, 5.8 +/- 0.9 and 6.1 +/- 0.8 min on the 1st, 5th and 10th day, respectively. Direct filtration of CRC through the Imugard E resulted in no significant changes in the ATP or 2,3-DPG concentrations, and no hemolysis due to filtration was noticed. It may be concluded that the Imugard E is a good filter that is simple to use and effective in leukocyte removal.