99mTc-GSA scintigraphy for assessing the functional volume ratio of the future liver remnant in the routine practice of liver resection.

BACKGROUND: The significance of incorporating regional functional heterogeneity assessment by liver scintigraphy into the calculation of the future liver remnant has been reported. However, liver scintigraphy entails additional costs and radiation exposure. Nevertheless, studies describing when liver scintigraphy demonstrates an actual benefit over computed tomography liver volumetry are lacking. Thus, we evaluated the degree of agreement between future liver remnant % values calculated by technetium 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy (galactosyl human serum albumin-based future liver remnant %) and those by computed tomography volumetry and investigated the practical impact of performing regional functional heterogeneity assessment. METHODS: The Bland-Altman method was used to retrospectively analyze the agreement between computed tomography- and galactosyl human serum albumin-based future liver remnant % measurements in 84 patients. RESULTS: In ordinary patients with a computed tomography-based future liver remnant % greater than 50%, there was a good agreement between both measurements. However, in cases with a computed tomography-based future liver remnant % less than 40%, galactosyl human serum albumin-based measurements were significantly smaller than computed tomography-based values, with 88% of these patients exhibiting a galactosyl human serum albumin-based future liver remnant % less than 30%. After portal vein embolization, galactosyl human serum albumin-based measurements were primarily greater than or in agreement with computed tomography-based values, even in cases with a computed tomography-based future liver remnant % less than 40%. CONCLUSION: Adding 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy to computed tomography liver volumetry is advised when deciding on hepatectomy in patients with a computed tomography-based future liver remnant % less than 50%. If the computed tomography-based future liver remnant % is smaller than 40%, it is strongly recommended to check future liver remnant % by 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy. In other cases, computed tomography-based future liver remnant % calculation alone can be regarded as the gold standard of safe hepatectomy.

L-Carnitine supplementation for the prevention of postoperative atrial fibrillation in aortic valve surgery.

OBJECTIVES: L-Carnitine, a quaternary amine, improves fatty acid metabolism in the heart and has anti-inflammatory effects. Several studies have reported the efficacy of L-carnitine for the prophylaxis of arrhythmia. We assessed the clinical effectiveness of L-carnitine in preventing postoperative atrial fibrillation (POAF) in aortic valve surgery. METHODS: Thirty patients who underwent aortic valve surgery were included. Fifteen patients had no prophylaxis other than conventional measures (control), while 15 patients received oral L-carnitine for 9 days (daily dose of 3 g). The incidence of POAF during 1 week after surgery was compared between the two groups. The multivariable logistic regression analysis for POAF was performed using the pre- and intraoperative parameters. RESULTS: Preoperative characteristics and operative data were comparable between the groups. The POAF rate was significantly lower in the L-carnitine group than in the control (20% and 60%, respectively; P = 0.025). L-Carnitine use was an independently negative predictor for POAF (odds ratio 0.067; 95% confidence interval 0.006-0.768). CONCLUSIONS: L-Carnitine administration may have potential for the prevention of POAF in aortic valve surgery.

Correlation between increased atrial expression of genes related to fatty acid metabolism and autophagy in patients with chronic atrial fibrillation.

Atrial metabolic disturbance contributes to the onset and development of atrial fibrillation (AF). Autophagy plays a role in maintaining the cellular energy balance. We examined whether atrial gene expressions related to fatty acid metabolism and autophagy are altered in chronic AF and whether they are related to each other. Right atrial tissue was obtained during heart surgery from 51 patients with sinus rhythm (SR, n = 38) or chronic AF (n = 13). Preoperative fasting serum free-fatty-acid levels were significantly higher in the AF patients. The atrial gene expression of fatty acid binding protein 3 (FABP3), which is involved in the cells' fatty acid uptake and intracellular fatty acid transport, was significantly increased in AF patients compared to SR patients; in the SR patients it was positively correlated with the right atrial diameter and intra-atrial electromechanical delay (EMD), parameters of structural and electrical atrial remodeling that were evaluated by an echocardiography. In contrast, the two groups' atrial contents of diacylglycerol (DAG), a toxic fatty acid metabolite, were comparable. Importantly, the atrial gene expression of microtubule-associated protein light chain 3 (LC3) was significantly increased in AF patients, and autophagy-related genes including LC3 were positively correlated with the atrial expression of FABP3. In conclusion, in chronic AF patients, the atrial expression of FABP3 was upregulated in association with autophagy-related genes without altered atrial DAG content. Our findings may support the hypothesis that dysregulated cardiac fatty acid metabolism contributes to the progression of AF and induction of autophagy has a cardioprotective effect against cardiac lipotoxicity in chronic AF.

NRF3-POMP-20S Proteasome Assembly Axis Promotes Cancer Development via Ubiquitin-Independent Proteolysis of p53 and Retinoblastoma Protein.

Proteasomes are essential protease complexes that maintain cellular homeostasis, and aberrant proteasomal activity supports cancer development. The regulatory mechanisms and biological function of the ubiquitin-26S proteasome have been studied extensively, while those of the ubiquitin-independent 20S proteasome system remain obscure. Here, we show that the cap 'n' collar (CNC) family transcription factor NRF3 specifically enhances 20S proteasome assembly in cancer cells and that 20S proteasomes contribute to colorectal cancer development through ubiquitin-independent proteolysis of the tumor suppressor p53 and retinoblastoma (Rb) proteins. The NRF3 gene is highly expressed in many cancer tissues and cell lines and is important for cancer cell growth. In cancer cells, NRF3 upregulates the assembly of the 20S proteasome by directly inducing the gene expression of the 20S proteasome maturation protein POMP. Interestingly, NRF3 knockdown not only increases p53 and Rb protein levels but also increases p53 activities for tumor suppression, including cell cycle arrest and induction of apoptosis. Furthermore, protein stability and cell viability assays using two distinct proteasome inhibitor anticancer drugs, the 20S proteasome inhibitor bortezomib and the ubiquitin-activating enzyme E1 inhibitor TAK-243, show that the upregulation of the NRF3-POMP axis leads to ubiquitin-independent proteolysis of p53 and Rb and to impaired sensitivity to bortezomib but not TAK-243. More importantly, the NRF3-POMP axis supports tumorigenesis and metastasis, with higher NRF3/POMP expression levels correlating with poor prognoses in patients with colorectal or rectal adenocarcinoma. These results suggest that the NRF3-POMP-20S proteasome assembly axis is significant for cancer development via ubiquitin-independent proteolysis of tumor suppressor proteins.

Perioperative changes of the slope in the preload recruitable stroke work relationship by a single-beat technique after mitral valve surgery in functional mitral regurgitation with non-ischemic dilated cardiomyopathy.

OBJECTIVES: The slope in the preload recruitable stroke work relationship is a highly linear, load-insensitive contractile parameter. However, the perioperative change of the slope has not been reported before. We examined the perioperative slope from a steady-state single beat in patients with functional mitral regurgitation and assessed the correlation with brain natriuretic peptide (BNP) levels. METHODS: The study included 16 patients with non-ischemic dilated cardiomyopathy and refractory heart failure: 10 patients underwent mitral valve plasty and left ventricular plasty (MVP + LVP group) and 6 patients who underwent mitral valve replacement and papillary muscle tugging approximation (MVR + PMTA group). The left ventricular ejection fraction was assessed by the modified Simpson method; the slope was assessed by the single-beat technique using transthoracic echocardiography. BNP levels were measured by chemiluminescent immunoassay. RESULTS: The left ventricular ejection fraction and slope did not significantly change from pre- to early post-surgery in the MVP + LVP group. Both the left ventricular ejection fraction and slope significantly increased 6 months after surgery in the MVR + PMTA group. Postoperative BNP level was low in the MVR + PMTA group. While the postoperative left ventricular ejection fraction did not correlate with BNP levels, the postoperative slope significantly correlated with BNP level after surgery in the MVP + LVP group and in the total functional mitral regurgitation group. CONCLUSIONS: The change of slope was dependent on surgical procedures. In functional mitral regurgitation, the slope may be a more sensitive parameter in reflecting the left ventricular contractile function than the left ventricular ejection fraction.

Risk factors for residual mitral regurgitation after aortic valve replacement in patients with severe aortic valve stenosis and moderate mitral regurgitation.

OBJECTIVES: While it was reported that patients with residual moderate mitral regurgitation (MR) after surgical aortic valve replacement (SAVR) had a poorer prognosis than those without it, the risk factors for residual MR have not been fully elucidated. The aim of the study was to evaluate risk factors for residual MR after SAVR. METHODS: Of the 222 patients who underwent isolated SAVR from 2001 to 2018, 33 (11 men; age: 74 ± 7 years) had functional moderate MR before surgery. The risk factors for residual MR were evaluated by comparing patients with residual moderate MR (n = 11, 33%) with those who exhibited improved post-surgery MR (n = 22, 67%). RESULTS: The left atrial diameter was significantly larger in the residual MR group (51 ± 7 mm) than in the improved MR group (46 ± 5 mm; P = 0.049). The mean pressure gradient at the aortic valve was significantly smaller in the residual MR group (52 ± 18 mmHg) than in the improved MR group (69 ± 22 mmHg; P = 0.043). A ratio of left atrial diameter (mm) and mean aortic valve pressure gradient (mmHg) greater than 0.9 predicted residual MR with a sensitivity of 70% and a specificity of 74% (area under the ROC curve: 0.779; P = 0.015). CONCLUSIONS: In patients with severe aortic valve stenosis and moderate MR, a high ratio of preoperative left atrial diameter and mean aortic valve pressure gradient would be a parameter predicting residual moderate MR post-SAVR.

Re-do mitral valve replacement for a bioprosthetic valve with central transvalvular leakage in a patient with ischemic cardiomyopathy: a case report.

Transvalvular leakage (TVL) of a prosthetic heart valve is not negligible regurgitant flow in patients with critically low contractile function. Although the opening function of prosthetic valves has been reported, its closing function is not well understood. A man in his 70 s had a history of mitral valve replacement (MVR) with a Magna Mitral® valve for ischemic mitral valve regurgitation. He presented with dyspnea 2 years postoperatively. Echocardiography showed moderate TVL. The pulmonary capillary wedge pressure and cardiac index were 37 mmHg and 1.65 L/min/m2, respectively. Because we considered his TVL relevant, we performed re-do MVR with a mechanical valve and papillary muscle approximation and suspension ("papillary muscle tugging approximation"). His cardiac function improved postoperatively; he was discharged with New York Heart Association class I. For MVR in patients with critically low contractile function, prosthetic valves, such as mechanical valves, with small TVL are recommended.

Mechanical properties of a new thermally deformable mitral valve annuloplasty ring and its effects on the mitral valve.

Ideally, an annuloplasty ring's shape should be changed intraoperatively if mitral valve repair is unsuccessful because of a short coaptation length or systolic anterior motion. Several post-implantation adjustable rings have been developed, but they are not freely deformable and are unsuitable for asymmetric repair of the valvular annulus. We developed a novel thermally deformable mitral annuloplasty ring to address these problems and assessed the ring's mechanical properties and its effect on the mitral valve anatomy. This ring was made of polycaprolactone. Tensile and bending tests were performed to evaluate the ring's mechanical properties. The ratio of the transverse and septal-lateral length was determined as 4:3. Using 10 pig hearts, we measured the post-deformation coaptation length and minimum distance from the coaptation to the ventricular septum, which is a factor of abnormal systolic anterior motion of the mitral valve. In the mechanical tests, the ring's yield point was greater than the deformation force of the annulus in humans. In pigs with deformation from "4:3" to "4:2", the coaptation length was significantly increased in each mitral valve part. In pigs with deformation from "4:3" to "4:4", the minimum distance from the coaptation to the ventricular septum was significantly increased. Asymmetrical ring deformation increased the coaptation length only at the deformed area. In conclusion, this new thermally deformable mitral annuloplasty ring could be "order-made" to effectively change the coaptation length in all parts of the mitral valve and the distance from the coaptation to septum post-deformation via intraoperative heating.

Anticoagulation management during cardiopulmonary bypass in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a complex autoimmune disease often related to systemic lupus erythematosus. Although adequate anticoagulation is important for APS patients during cardiopulmonary bypass, clotting tests can be potentially misleading due to antiphospholipid antibodies. We performed cardiac surgery safely in two APS patients under anticoagulation monitoring determined using preoperative heparin titration. We performed heparin titration for activated clotting time to determine the appropriate heparin concentration during cardiac surgery. We changed the targeted heparin concentration considering each patient's thrombotic risks: 3 U/ml of heparin for a normal-risk APS patient and 5 U/ml for a high-risk APS patient with a history of antiphospholipid-antibody-associated thrombocytopenia. A higher targeted heparin concentration might be necessary for patients with high thrombotic risks.

Decreased gene expression of fatty acid binding protein 3 in the atrium of patients with new onset of atrial fibrillation in cardiac perioperative phase.

BACKGROUND: Post-operative atrial fibrillation (POAF) frequently occurs after cardiac surgery. However, the mechanisms of POAF have not been fully elucidated. We aimed to examine whether pre-operative atrial gene expression related to cardiac metabolism is changed in patients with POAF. METHODS: Right atrial tissue was obtained during surgery from 38 patients who underwent cardiac surgery from 2013 to 2015. Atrial expression levels were determined by reverse transcription polymerase chain reaction for the following genes: glucose transporter type 4, peroxisome proliferator-activated receptor-α, fatty acid translocase, carnitine palmitoyltransferase 1B, and fatty acid binding protein 3 (FABP3). To investigate fatty acid ß-oxidation and tricarboxylic acid cycle capacities in the mitochondria, ß-hydroxyacyl CoA dehydrogenase and citrate synthase activity levels were spectrophotometrically determined. RESULTS: POAF within 7 days after surgery was observed in 18 (47%) patients. POAF patients were significantly older, had a larger left atrial diameter, and had reduced expression of FABP3, a fatty acids transport gene in the cytosol, compared to those in the non-POAF group. Reduced FABP3 expression predicted POAF independent of age and atrial size. In contrast, fatty acid ß-oxidation enzymatic activity was comparable between the groups. CONCLUSIONS: FABP3 gene expression in the atrium was reduced in patients with POAF. These findings suggest a potential link between altered fatty acid transport in the atrium and increased AF onset after cardiac surgery.

Feasibility and limitations of mitral valve repair, with or without left ventricular reconstruction in non-ischemic dilated cardiomyopathy.

BACKGROUND: Although non-transplant surgical interventions for non-ischemic dilated cardiomyopathy (NIDCM) are relatively effective, their feasibility and limitations have not been fully elucidated. The aim of this study was to define the feasibility and limitations of mitral valve repair, with or without surgical ventricular reconstruction for patients with NIDCM in terms of postoperative low cardiac output syndrome (LOS). METHODS: Twenty non-transplant candidates (aged 57±13 years) with NIDCM and significant mitral regurgitation had undergone mitral valve repair combined with submitral procedures. Using a 72-mL plastic ellipsoidal sizer, left ventricular reconstruction was performed concomitantly in 14/20 (70%) patients with extremely large ventricles. Total stroke volume, deceleration time of early trans-mitral flow wave, and the slope (Mw) in the preload recruitable stroke-work relationship were assessed using transthoracic echocardiography. LOS was defined as in-hospital death due to heart failure or a cardiac index less than 2.2L/min/m2 before discharge. RESULTS: There were three in-hospital deaths and four patients with postoperative cardiac index less than 2.2L/min/m2 [n=7 (35%), LOS group]. Preoperative total stroke volume, deceleration time, and the Mw were significantly lower in the LOS group compared to those in the non-LOS group; the predicted cut-off values for LOS were 84mL/beat (p=0.008), 133ms (p=0.015), and 45ergcm-3×103 (p=0.036), respectively. Preoperative left ventricular ejection fraction and ventricular size could not predict postoperative LOS. The one-year survival rate was 0% in the LOS group and 84% in the non-LOS group (p<0.001). CONCLUSIONS: Mitral valve repair, with or without left ventricular reconstruction, could be contraindicated for NIDCM patients with low total stroke volume, deceleration time, and Mw in terms of high postoperative incidence of LOS. For high-risk patients, other therapeutic strategies might be necessary.

Multiple regulatory mechanisms of the biological function of NRF3 (NFE2L3) control cancer cell proliferation.

Accumulated evidence suggests a physiological relationship between the transcription factor NRF3 (NFE2L3) and cancers. Under physiological conditions, NRF3 is repressed by its endoplasmic reticulum (ER) sequestration. In response to unidentified signals, NRF3 enters the nucleus and modulates gene expression. However, molecular mechanisms underlying the nuclear translocation of NRF3 and its target gene in cancer cells remain poorly understood. We herein report that multiple regulation of NRF3 activities controls cell proliferation. Our analyses reveal that under physiological conditions, NRF3 is rapidly degraded by the ER-associated degradation (ERAD) ubiquitin ligase HRD1 and valosin-containing protein (VCP) in the cytoplasm. Furthermore, NRF3 is also degraded by ß-TRCP, an adaptor for the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase in the nucleus. The nuclear translocation of NRF3 from the ER requires the aspartic protease DNA-damage inducible 1 homolog 2 (DDI2) but does not require inhibition of its HRD1-VCP-mediated degradation. Finally, NRF3 mediates gene expression of the cell cycle regulator U2AF homology motif kinase 1 (UHMK1) for cell proliferation. Collectively, our study provides us many insights into the molecular regulation and biological function of NRF3 in cancer cells.

Surgical strategy for ischemic mitral regurgitation adopting subvalvular and ventricular procedures.

PURPOSE: The progression of left ventricular (LV) remodeling and subsequent mitral valve tethering impair the results of reduction annuloplasty for ischemic mitral regurgitation (MR). METHODS: We studied 90 patients who underwent surgical repair of ischemic MR between 1999 and 2013 according to our surgical strategy adding submitral and ventricular procedures to annuloplasty as follows: annuloplasty alone (stage 1, n = 30), additional papillary muscle approximation (PMA) for progression of tethering (stage 2, n = 26), and additional left ventriculoplasty with PMA for progression of LV remodeling and tethering (stage 3, n = 34). RESULTS: The preoperative New York Heart Association (NYHA) functional classes (2.5 ± 0.7, 3.1 ± 0.7 and 3.3 ± 0.7 for stages 1, 2 and 3, respectively, P <0.001), LV end-diastolic diameters (56 ± 7 mm, 66 ± 5 mm and 70 ± 7 mm, P <0.001), and LV ejection fractions (45 ± 12%, 32 ± 9% and 27 ± 9%, P <0.001) significantly differed among the stages. In contrast, the MR grades did not significantly differ (2.9 ± 0.8, 3.0 ± 1.0, and 2.9 ± 1.1, respectively; P = 0.93). Both the rates of cardiac-related survival and freedom from reoperation were comparable among the 3 groups (log-rank P = 0.92 and 0.58, respectively). CONCLUSION: Additional submitral and ventricular procedures can compensate for the possible impairment of the outcomes after annuloplasty alone for ischemic MR in patients with severe LV remodeling and tethering.

Characteristics of inoperable patients with severe aortic valve stenosis -in the era of transcatheter aortic valve replacement.

PURPOSE: Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option for severe aortic valvular stenosis (AS). To determine the indication for TAVR, it is mandatory to clarify the characteristics of the patients who were judged as inoperable for conventional aortic valve replacement (cAVR). METHODS: Of 185 patients newly diagnosed as severe AS from March 2010 to April 2011, we studied the characteristics of 61 (33%) patients (mean age, 86 ± 8 years) who were judged as inoperable. RESULTS: Younger patients (<85 years old, n = 22) had more major comorbidities and lower left ventricular ejection fraction than older patients (≥85 years old, n = 39). Mean estimated mortality for cAVR by Japan score was 7.0% ± 7.4%. Japan score did not correlate to age and was calculated relatively low in the older age group (6.2% ± 7.0%) than the younger age group (8.3% ± 8.1%). CONCLUSION: One thirds of severe AS patients were judged as inoperable. In advanced age patients, age itself and other factors, which are not included in the conventional scoring systems, might have contributed to the decision making not to perform cAVR by cardiologists. Further study is necessary to define risk factors except for age.

Role of prokaryotic type I and III pantothenate kinases in the coenzyme A biosynthetic pathway of Bacillus subtilis.

Pantothenate kinases (CoaAs) catalyze the phosphorylation of pantothenate in the first step of the coenzyme A (CoA) biosynthetic pathway. These bacterial enzymes have been categorized into 3 types, the prokaryotic type I, II, and III CoaAs. Bacteria typically carry a single CoaA gene on their genome, but Bacillus subtilis possesses 2 proteins homologous to type I and III CoaAs, known as BsCoaA and BsCoaX, respectively. Both recombinant proteins exhibited the expected kinase activity and the characteristic properties of type I and III CoaAs, i.e., regulation by CoASH and acyl-CoAs in BsCoaA and the requirement of a monovalent cation in BsCoaX. Both gene disruptants appeared to grow in a manner similar to the wild-type strain. With the BsCoaX disruptant, the BsCoaA had the ability to completely fill the intracellular CoA pool, whereas the BsCoaA disruptant did not. These findings clearly indicate that these 2 CoaAs are employed together in the CoA biosynthetic pathway in B. subtilis and that the contribution of the type I CoaA (BsCoaA) to the formation of the intracellular CoA pool is larger than that of the type III CoaA (BsCoaX).

Identification of pantoate kinase and phosphopantothenate synthetase from Methanospirillum hungatei.

Pantothenate synthetase (PanC) and pantothenate kinase which function in the canonical coenzyme A (CoA) biosynthetic pathway cannot be found in most archaea. COG1829 and COG1701 intrinsic to archaea were proposed as the candidate proteins for producing 4'-phosphopantothenate instead, and the COG1701 protein from Methanosarcina mazei was assigned as PanC. Meanwhile, the Thermococcus kodakarensis COG1829 and COG1701 proteins were biochemically identified as novel enzymes, i.e., pantoate kinase (PoK) and phosphopantothenate synthetase (PPS). In this study, the functions of Mhun_0831 (COG1829) and Mhun_0832 (COG1701) from Methanospirillum hungatei were identified, and the recombinant enzymes were partially characterized. Plasmids simultaneously possessing the two genes encoding Mhun_0831 and Mhun_0832 complemented the poor growth of the temperature-sensitive Escherichia coli pantothenate kinase mutant ts9. The recombinant Mhun_0831 and Mhun_0832 expressed in E. coli cells exhibited PoK and PPS activities, respectively, being in accord with the functions of T. kodakarensis proteins. The PoK activity was most active at pH 8.5 and 40°C, and accepted ATP and UTP as a phosphate donor. Although CoA did not affect the PoK activity, the end product considerably accelerated the PPS activity. The homologs of both proteins are widely conserved in most archaeal genomes. Taken together, our findings indicate that archaea can synthesize CoA through the unique pathway involving PoK and PPS, in addition to the canonical one that the order Thermoplasmatales employs.

Optical coherence evaluation of everolimus-eluting stents 8 months after implantation.

OBJECTIVE: The aim of this study was to evaluate detailed vessel response after everolimus-eluting stents (EES) implantation in human de novo coronary lesions by optical coherence tomography (OCT). DESIGN, SETTING AND PATIENTS: Between November 2008 and October 2009, 25 patients (14 men, 65.5±8.6 years) with de novo native coronary artery lesions were implanted with 30 EES, and OCT was performed at 8 months post-implantation. MAIN OUTCOME MEASURES: Neointimal thickness (NIT) on each strut, strut apposition to the vessel wall, the frequency of struts surrounded by low intensity area and the incidence of intra-stent thrombus were analysed. To evaluate the radial unevenness of NIT, the difference between the maximum and minimum NIT (dNT) was calculated for each cross-section. RESULTS: At 236±39 days after implantation, there were no major adverse cardiac events, nor target vessel revascularisation. A total of 5,931 struts was evaluated by OCT. The median NIT was 80 µm (25th and 75th percentile 50 µm and 140 µm) and average NIT was 100±74 µm. The number of neointima-covered struts was 5,834 (98.4%), and 31 (0.52%) struts showed malapposition without neointimal coverage. The number of struts surrounded by low intensity area was 452 (7.62%). Eleven EES (37%) showed full neointimal coverage. No intra-stent thrombus was detected. The average dNT was 108±77 µm. CONCLUSIONS: Most EES struts were covered with uniform and thin neointima. The frequency of low-intensity neointima was very low, which may be a result of promoted vessel healing. These results may support improved clinical outcomes with EES in clinical trials.

Coenzyme A and its thioester pools in fasted and fed rat tissues.

Levels of three coenzyme A (CoA) molecular species, i.e., nonesterified CoA (CoASH), acetyl-CoA, and malonyl-CoA, in fasted and fed rat tissues were analyzed by the acyl-CoA cycling method which makes detection possible at the pmol level. Malonyl-CoA in brain tissues readily increased with feeding, and inversely, acetyl-CoA decreased. This phenomenon occurred in the cerebral cortex, hippocampus, cerebellum, and medulla oblongata, as well as in the hypothalamus which controls energy balance by monitoring malonyl-CoA. In the non-brain tissues, the sizes of the acetyl-CoA, malonyl-CoA, and CoASH pools depended on the tissues. The total CoA pools consisting of the above three CoA species in the liver, heart, and brown adipose tissue were larger and those of the perirenal, epididymal, and ovarian adipose tissues were much smaller, compared with those of other tissues including brain tissues. In addition, the response of each CoA pool to feeding was not uniform, suggesting that the tissue-specific metabolism individually functions in the non-brain tissues. Thus, a comprehensive analysis of thirteen types of rat tissue revealed that CoA pools have different sizes and showed a different response to fasting and feeding depending on the tissue.

Delayed neointimalization on sirolimus-eluting stents: 6-month and 12-month follow up by optical coherence tomography.

BACKGROUND: Sirolimus-eluting stents (SES) have incomplete neointimal coverage at 6-month follow up as determined with optical coherence tomography (OCT). The long-term detailed changes of neointima in SES remains to be clarified. METHODS AND RESULTS: Serial changes in neointimal coverage of SES from 6 months to 12 months using OCT were examined. Of 21 SES in 13 patients, OCT was used to visualize 2,321 stent struts at 6 months and 2,285 stent struts at 12 months. The frequency of struts without neointimal coverage decreased from 6 months to 12 months (from 10.4 to 5.7%). The frequency of malapposed struts decreased from 6 months to 12 months (from 1.7 to 0.2%). The average thickness of the neointima increased (from 112 +/-123 to 120 +/-130 microm). The frequency of struts located at the side branch orifice without neointima decreased (from 4 out of 17 (24%) to 0 out of 17 (0%)). Complete coverage with neointima was observed in 14% (3 of 21 SES) at 6 months, and 24% (5 of 21 SES) at 12 months. CONCLUSIONS: Additional neointimal coverage was observed between 6 and 12 months, with a small increase in the neointimal thickness. The incidence of complete coverage, however, was still low at 12 months. These findings suggest delayed neointimalization on SES.

Diastolic blood pressure influences cerebrovascular reactivity measured by means of 123I-iodoamphetamine brain single photon emission computed tomography in medically treated patients with occlusive carotid or middle cerebral artery disease.

OBJECTIVE: Impaired cerebrovascular reactivity (CVR) to vasodilating agents is a predictor of the onset and prognosis of ischemic stroke. It is realized that the CVR improves or worsens when measured periodically during the clinical course in medically treated patients with occlusive cerebrovascular disease. In these patients, we investigated the possible relationship between the interval change in CVR and that in systemic blood pressure (BP). METHODS: Forty-two patients (14 females and 28 males, mean age +/- SD: 65.3 +/- 8.8 years) with severe stenosis or occlusion of the common carotid, internal carotid, or middle cerebral arteries repeatedly underwent single photon emission computed tomography (SPECT) studies using 123I-iodoamphetamine to measure cerebral blood flow (CBF) distribution and CVR at a more-than-6-month interval (mean +/- SD: 18.5 +/- 8.8 months). The CVR was separately estimated in cerebral hemispheres ipsilateral and contralateral to the most severe vascular lesion as the % increase in CBF after acetazolamide loading to CBF at rest. Systemic BP was measured four times at enrollment and the follow-up SPECT studies during resting and acetazolamide loading. Average BP at each SPECT study was an average of BP measurements during resting and acetazolamide loading. Interval changes in CVR were correlated with those in average systolic BP, average diastolic BP, and average mean arterial BP. RESULTS: The interval changes in CVR were significantly correlated with those in average diastolic BP in the ipsilateral hemisphere (y = 0.71x + 1.43, r2 = 0.11, p < 0.05) and in the contralateral hemisphere (y = 0.88x - 0.46, r2 = 0.16, p < 0.05) but not with those in average systolic BP or average mean arterial BP. CONCLUSIONS: In medically treated patients with steno-occlusive carotid artery or middle cerebral artery lesions, the interval change in CVR to acetazolamide by means of 123I-IMP SPECT was influenced by the diastolic BP at the SPECT studies. Monitoring diastolic BP is important to evaluate interval change in CVR.