[Left Main Coronary Artery-to-left Atrium Fistula with Aneurysmal Dilatation:Report of a Case].

Coronary artery fistula (CAF) is a relatively rare disease, many of which are asymptomatic and are not indicated for surgery. However, CAF's patients with angina, heart failure due to shunt, and fistula hemangiomas are usually indicated for surgical treatment. A 49-year-old woman with severe congestive heart failure was found to have a fistula from the main trunk of the left coronary artery to the left atrium, and a fistula aneurysm. This patient had heart failure due to shunt blood flow, and also had a fistula aneurysm, so surgical treatment was indicated. During surgery, the fistula aneurysm was incised and the origin and opening of the fistula were closed without any problems. The postoperative course is good, and as of three years after the operation, the patient is being followed up at an outpatient clinic without recurrence of shunt flow and heart failure.

Formulation and evaluation of bitter taste-masked orally disintegrating tablets of high memantine hydrochloride loaded granules coated with polymer via layering technique.

Orally disintegrating tablets (ODTs) improve patient adherence as they can easily disintegrate in the presence of small amount of saliva. However, the bitter taste of the active pharmaceutical ingredient in ODTs reduces patient compliance. The present study aimed to formulate bitter taste-masked ODTs containing high-dose of memantine hydrochloride (MTN) to achieve a balance between bitterness suppression and dissolution rate or disintegration time and mechanical strength. The high MTN-loaded granules were prepared using a fluidized bed granulator. Taste-masking granules coated with the selected polymer were prepared using the layering technique. Three ODTs, composed of granules coated with different polymers, were prepared. The ODT prepared using granules coated with enteric polymers showed the fastest collapse time (>20 s). Dissolution rates of ODTs composed of enteric polymers were reduced by 5 min compared with ODTs composed of non-coated or coated with water-insoluble polymer granules. X-ray computed tomography analysis revealed that low density distribution of ODTs with enteric polymer granules may result in faster disintegration time. Although ODT prepared using enteric polymers had the fastest collapse time, its change in membrane potential caused by adsorption (CPA), corresponding to aftertaste, was the lowest among formulations. This CPA value was lower than the bitterness threshold.

Quantitation of trace amorphous solifenacin succinate in pharmaceutical formulations by transmission Raman spectroscopy.

It is important to quantify amorphous solid in active pharmaceutical ingredients (API) of formulations to guarantee high-quality pharmaceutical products. In this study, we aimed to quantify amorphous solid in API by transmission Raman spectroscopy (TRS) and transmission near-infra-red spectroscopy (NIRS). To quantify the amount of trace amorphous solids contained in the API of a formulation, calibration curves of tablets containing 40% or 3% solifenacin succinate (SLFS) in the pharmaceutical formulations were prepared. The tablets varied in the ratio of amorphous solids in the API. TRS and NIRS were carried out with the calibration tablets and partial least square regression (PLSR) analysis was performed. Good results were obtained by both TRS and NIRS with the calibration model containing 40% SLFS. On the contrary, with the calibration model containing 3% SLFS, the PLSR analysis results using the TRS data were better than those using the NIRS data. The low content calibration model based on TRS showed good results with R2 of 0.999, RMSECV of 1.236, and LOD of 0.12. TRS can be used to specifically detect trace amorphous solids contained in the API of a formulation.

Minimally invasive direct coronary artery bypass surgery with right gastroepiploic artery for redo patients.

Coronary artery bypass grafting (CABG) has been widely performed for coronary artery disease. Therefore, cases requiring reoperative CABG are increasing. We performed a minimally invasive direct coronary artery bypass (MIDCAB) procedure on four patients, as reoperative CABG surgery for the right coronary artery (RCA), employing the right gastroepiploic artery (RGEA). The target sites were the distal RCA in two patients and the posterior descending (PD) branch in the other two. Complete revascularization was accomplished in all patients without sternotomy, cardiopulmonary bypass (CPB), or blood transfusion. The mean operative time was 3.0 h (range: 2.4-3.7 h). Postoperative coronary angiography showed all grafts to be patent. All patients were discharged without postoperative complications and remained free from cardiac events during a mean follow-up period of 1.5 years (range: 0.5-3.0 years). MIDCAB for the RCA, employing the RGEA via a subxiphoid incision showed, excellent revascularization in redo CABG cases. This technique is a safe and effective method for redo cases.

[Familial Annulo-aortic Ectasia without Marfan Syndrome].

Marfan syndrome is a hereditary disease that presents ocular, skeletal, and cardiovascular abnormalities. In recent years, there have been several reports of patients with familial cardiovascular disease but no physical features of Marfan syndrome. We encountered 3 cases of familial annulo-aortic ectasia (AAE). Their father had also had aortic regurgitation, and died during surgery 10 years before. No case demonstrated any physical characteristics of Marfan syndrome or any other connective tissue disease. All cases were operated successfully. One case showed cystic medial necrosis, and 2 cases showed degenerative change. The present report suggests that familial AAE may be caused by weakness of the aortic wall related to heredity. If AAE is left untreated, it can lead to aortic dissection. Thus, we recommend that patients with familial AAE should undergo screening and follow-up similar to patients with Marfan syndrome.

Bovine heart NADH-ubiquinone oxidoreductase contains one molecule of ubiquinone with ten isoprene units as one of the cofactors.

NADH-ubiquinone oxidoreductase (Complex I) is located at the entrance of the mitochondrial electron transfer chain and transfers electrons from NADH to ubiquinone with 10 isoprene units (Q(10)) coupled with proton pumping. The composition of Complex I, the largest and most complex proton pump in the mitochondrial electron transfer system, especially the contents of Q(10) and phospholipids, has not been well established. An improved purification method including solubilization of mitochondrial membrane with deoxycholate followed by sucrose gradient centrifugation and anion-exchange column chromatography provided reproducibly a heme-free preparation containing 1 Q(10), 70 phosphorus atoms of phospholipids, 1 zinc ion, 1 FMN, 30 inorganic sulfur ions, and 30 iron atoms as the intrinsic constituents. The rotenone-sensitive enzymatic activity of the Complex I preparation was comparable to that of Complex I in the mitochondrial membrane. It has been proposed that Complex I has two Q(10) binding sites, one involved in the proton pump and the other functioning as a converter between one and two electron transfer pathways [Ohnishi, T., Johnson, J. J. E., Yano, T., LoBrutto, R., and Widger, R. W. (2005) FEBS Lett. 579, 500-506]. The existence of one molecule of Q(10) in the fully oxidized Complex I suggests that the affinity of Q(10) to one of the two Q(10) sites is greatly dependent on the oxidation state and/or the membrane potential and that the Q(10) in the present preparation functions as the converter of the electron transfer pathways which should be present in any oxidation state.

Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase.

All 13 lipids, including two cardiolipins, one phosphatidylcholine, three phosphatidylethanolamines, four phosphatidylglycerols and three triglycerides, were identified in a crystalline bovine heart cytochrome c oxidase (CcO) preparation. The chain lengths and unsaturated bond positions of the fatty acid moieties determined by mass spectrometry suggest that each lipid head group identifies its specific binding site within CcOs. The X-ray structure demonstrates that the flexibility of the fatty acid tails facilitates their effective space-filling functions and that the four phospholipids stabilize the CcO dimer. Binding of dicyclohexylcarbodiimide to the O(2) transfer pathway of CcO causes two palmitate tails of phosphatidylglycerols to block the pathway, suggesting that the palmitates control the O(2) transfer process.The phosphatidylglycerol with vaccenate (cis-Delta(11)-octadecenoate) was found in CcOs of bovine and Paracoccus denitrificans, the ancestor of mitochondrion, indicating that the vaccenate is conserved in bovine CcO in spite of the abundance of oleate (cis-Delta(9)-octadecenoate). The X-ray structure indicates that the protein moiety selects cis-vaccenate near the O(2) transfer pathway against trans-vaccenate. These results suggest that vaccenate plays a critical role in the O(2) transfer mechanism.

Effect of pH on the steady state kinetics of bovine heart NADH: coenzyme Q oxidoreductase.

Complete initial steady state kinetics of NADH-decylubiquinone (DQ) oxidoreductase reaction between pH 6.5 and 9.0 show an ordered sequential mechanism in which the order of substrate bindings and product releases is NADH-DQ-DQH2-NAD+. NADH binding to the free enzyme is accelerated by protonation of an amino acid (possibly a histidine) residue. The NADH release is negligibly slow under the turnover conditions. The rate of DQ binding to the NADH-bound enzyme and the maximal rate at the saturating concentrations of the two substrates, which is determined by the rates of DQH2 formation in the active site and releases of DQH2 and NAD+ from the enzyme, are insensitive to pH, in contrast to clear pH dependencies of the maximal rates of cytochrome c oxidase and cytochrome bc1 complex. Physiological significances of these results are discussed.