[Surgical treatment with the freestyle bioprosthesis and omentopexy for prosthetic valve endocarditis after aortic root replacement].

A 60-year-old woman, who had undergone aortic root replacement with composite graft 5 months previously, suffered from anemia and slight fever. Transthoracic echocardiography showed pseudoaneurysm in the aortic root, and blood culture was positive. She was diagnosed with prosthetic valve endocarditis, and surgical intervention was planned. Intraoperatively necrotic tissue and dehiscence of the suture line in the aortic annulus were found. Re-aortic root replacement with Freestyle bioprosthesis and re-hemiarch graft replacement were performed with the omentopexy around the aortic root and the new graft. Antibiotics were administered intravenously for 6 weeks postoperatively. At 7 months after the operation, no prosthetic valve infection had recurred. Although the long-term results of Freestyle bioprosthesis have not been determined, it might be a valuable option for aortic root infection as an alternative to an aortic homograft. In addition, omentopexy might also be effective in the prevention of recurrent prosthetic valve infection.

[Aortic arch replacement with covered stent-graft as elephant trunk for a type A acute aortic dissection].

We report a case of aortic arch replacement with a covered stent-graft as an "elephant trunk". A 54-year-old woman was diagnosed with Stanford type A aortic dissection. The initial intimal tear was located in the distal aortic arch. Under deep hypothermic circulatory arrest and retrograde cerebral perfusion, the distal end of the arch graft, which was turned inside out and reinforced with a Z-stent, was inserted into the distal true lumen as an "elephant trunk". Distal anastomosis was performed between the aortic wall and the inverted external graft. Graft replacement of the aortic arch and ascending aorta was followed by proximal arch grafting. Coronary artery bypass grafting to RCA was performed concomitantly. The postoperative course was uneventful, and the distal false lumen became thrombosed. This procedure is effective for reliable distal anastomosis and prevention of blood leakage into the distal false lumen.

Endoscopic therapy with absolute ethanol for postoperative recurrent ulcers in intestinal Behçet's disease, and simple ulcers.

BACKGROUND: When examined macroscopically and histologically, there are no differences between "simple" intestinal ulcers and intestinal ulcers of Behçet's disease. The postoperative recurrence of intestinal Behçet's disease and simple ulcers was frequently. Medical treatment for postoperative recurrent ulcers is palliative, and the patient often requires surgery. We studied about an effect of absolute ethanol spraying via endoscopy for the ulcers. METHOD: The postoperative rate of recurrence was 56% (9/16). Commonly the ulcer recurred around the anastomotic region. We performed spraying for recurrent ulcers with absolute ethanol via endoscope in four patients. RESULTS: This therapy was effective for the recurrent ulcer in the 4 patients. In this study, the patients who were monitored and treated by the spraying of ethanol did not require further surgery. CONCLUSIONS: This therapy should performed for recurrent ulceration in cases of simple ulcer and intestinal Behçet's disease.

Inhibition of progression of heart failure and expression of TGF-beta 1 mRNA in rats with heart failure by the ACE inhibitor quinapril.

The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28+/-0.05 to 0.87+/-0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1+/-2.0 to 6.6+/-1.5 mmHg; p < 0.05) and central venous pressure (from 2.7+/-0.9 to 0.7+/-0.4 mmHg), and increased +/- dP/dt (from +2409+/-50 to +3569+/-169 mmHg/s, and from -2318+/-235 to -3960+/-203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6+/-3%) as compared with controls (29+/-6%; p < 0.01). Expression of transforming growth factor (TGF)-beta1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-beta1 mRNA was significantly suppressed by quinapril (from 17.1+/-6.2 to 9.00+/-2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 mRNA expression.

Aneurysm in the pulmonary trunk associated with atrial septal defect, a left coronary artery fistula to the pulmonary trunk, and valvular pulmonary stenosis.

A 78-year-old woman with an aneurysm in the pulmonary trunk associated with an atrial septal defect, left anterior descending coronary artery fistula to the pulmonary trunk and valvular pulmonary stenosis is reported. The aneurysm showed gradual dilatation over 16 years and was successfully treated using aneurysmorrhaphy. Although there has been some controversy regarding the optimum management for a pulmonary artery aneurysm, surgical correction is thought to be essential for aneurysms associated with congenital cardiac anomalies because of the high incidence of rupture.

Acute effects of endothelin-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) in rats with dilated cardiomyopathy.

The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg/kg/day (groups F0, F0.3, F3, F30 and F60; each group, n = 4) of TAK-044 using an osmotic pump subcutaneously. Age-matched normal Lewis rats (n = 26) were also randomly divided into four groups to be given 0, 0.3, 3 and 30 mg/kg/day (groups N0, N0.3, N3 and N30; each group, n = 4). ET-1 concentrations in plasma and myocardium were measured, and immunohistochemical detection of ET-1 in the left ventricle from the remaining rats (groups F and N) was performed. After administration of TAK-044 for 7 days, 2, 4, 11, 21 and 42 ng/min ET-1 every 20 min was infused using a pump, and the change in mean arterial pressure of each group during the infusion was examined. The plasma and myocardial ET-1 concentrations were significantly higher in group F than group N (12.3 +/- 1.5 vs. 5.4 +/- 0.2 pg/ml and 426 +/- 31 vs. 98 +/- 6 pg/g tissue; both p < 0.01). Strong positive signals for ET-1 were found to be widely distributed in the left ventricular myocardium of both groups of rats. Although the ET-1-induced increase in the mean arterial pressure was abolished in group N30, the maximal dose of ET-1 produced a 34% increase in the mean arterial pressure in group F30. Even in group F60, ET-1-induced hypertension was blocked incompletely. These results indicate that the heart may be a major ET-1-producing organ, and a higher dose of ET-1 antagonist is needed to block the effect of ET-1 in rats with dilated cardiomyopathy.

[Advances in endoscopic therapies for cancers of the digestive tract].

Endoscopic therapies for the treatment of cancers of the digestive tract have been improved. Today, some early cancers can be curatively treated by endoscopy (endoscopic polypectomy, endoscopic mucosal resection, heatprobe method, etc.). In addition, endoscopic local injection chemotherapy is performed for some advanced cancers as an adjuvant therapy. Recent progress in endoscopic therapies for cancer is reviewed in this paper, including their historical background. Improvements in these endoscopic treatment methods are expected to provide increased advantages for the treatment of patients with cancer in the near future.

Identification of three isoforms for the Na+-dependent phosphate cotransporter (NaPi-2) in rat kidney.

We have isolated three unique NaPi-2-related protein cDNAs (NaPi-2alpha, NaPi-2beta, and NaPi-2gamma) from a rat kidney library. NaPi-2alpha cDNA encodes 337 amino acids which have high homology to the N-terminal half of NaPi-2 containing 3 transmembrane domains. NaPi-2beta encodes 327 amino acids which are identical to the N-terminal region of NaPi-2 containing 4 transmembrane domains, whereas the 146 amino acids in the C-terminal region are completely different. In contrast, NaPi-2gamma encodes 268 amino acids which are identical to the C-terminal half of NaPi-2. An analysis of phage and cosmid clones indicated that the three related proteins were produced by alternative splicing in the NaPi-2 gene. In a rabbit reticulocyte lysate system, NaPi-2 alpha, beta, and gamma were found to be 36, 36, and 29 kDa amino acid polypeptides, respectively. NaPi-2alpha and NaPi-2gamma were glycosylated and revealed to be 45- and 35-kDa proteins, respectively. In isolated brush-border membrane vesicles, an N-terminal antibody was reacted with 45- and 40-kDa, and a C-terminal antibody was reacted with 37-kDa protein. The sizes of these proteins corresponded to those in glycosylated forms. A functional analysis demonstrated that NaPi-2gamma and -2alpha markedly inhibited NaPi-2 activity in Xenopus oocytes. The results suggest that these short isoforms may function as a dominant negative inhibitor of the full-length transporter.

Hepatic sinusoidal membrane transport of anionic drugs mediated by anion transporter Npt1.

The purpose of our study was to establish the localization of the anion transporter Npt1 in liver and the relevance of Npt1 to carrier-mediated hepatic transport of beta-lactam antibiotics. Immunocytochemical examination of mouse liver with antiserum for Npt1 showed basolateral (sinusoidal) membrane localization. Function of Npt1 was characterized in Xenopus laevis oocytes. Injection of in vitro-transcribed cRNA into oocytes resulted in an increased uptake of [14C]benzylpenicillin (PCG). The Npt1-mediated uptake was saturable with a Michaelis constant (Km) of 0.46 +/- 0.18 mM and a maximum rate (Vmax) of 46.6 +/- 8.5 pmol/60 min/oocyte, and the uptake of [14C]PCG was independent of Na+ and pH, but dependent on chloride ion. Npt1-mediated [14C]PCG uptake was inhibited by several beta-lactam antibiotics and probenecid. Oocytes injected with Npt1-cRNA demonstrated significantly enhanced transport activity for other anionic compounds such as [14C]faropenem, [14C]foscarnet and [3H]mevalonic acid, as well as [14C]PCG, compared with water-injected oocytes. In conclusion, Npt1 is suggested to participate in hepatic sinusoidal membrane transport of organic anions such as beta-lactam antibiotics as well as inorganic anions for the efflux from hepatocyte-to-blood direction.

Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in thyroparathyroidectomized rats.

Dietary Pi and parathyroid hormone (PTH) are two most important physiological and pathophysiological regulators of Pi re-absorption in the renal proximal tubule. Effects of dietary Pi on Na+/Pi co-transporter NaPi-2 were investigated in thyroparathyroidectomized (TPTX) rats. NaPi-2 protein and mRNA in the kidney cortex of TPTX rats were increased approximately 3.8- and 2.4-fold in amount respectively compared with those in the sham-operated animals. Administration of PTH to the TPTX rats resulted in a decrease in the amount of NaPi-2 protein, but not in the abundance of NaPi-2 mRNA. Deprivation of dietary Pi in the TPTX rats did not affect the amount of NaPi-2 mRNA and protein. In the Pi-deprived TPTX rats, feeding of a high-Pi diet resulted in marked decreases in Pi transport activity and the amount of NaPi-2 protein in the superficial nephrons. Immunohistochemical analysis demonstrated that administration of PTH to TPTX rats resulted in a decrease in NaPi-2 immunoreactivity from both superficial and juxtamedullary nephrons within 4 h. Switching TPTX animals from a low-Pi diet to the high-Pi diet decreased NaPi-2 immunoreactivity from superficial nephrons, but not from juxtamedullary nephrons, within 4 h. These results suggest that dietary Pi could regulate the amount of NaPi-2 protein in the superficial nephrons in a PTH-independent manner.

Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil-induced injury.

BACKGROUND & AIMS: The oligopeptide transport system of the small intestine is resistant to mucosal injury. The mechanism of this resistance was investigated by examining the activity level and expression of the peptide transporter PepT1 in the intestine of rats treated with 5-fluorouracil. METHODS: The expression and localization of PepT1 were examined by immunoblot analysis of brush border membrane vesicles and immunohistochemical analysis of intestinal sections with PepT1-specific rabbit polyclonal antibodies. Also, Northern blot analysis was used for the expression of PepT1 messenger RNA (mRNA). RESULTS: Although the amounts of sucrase and an Na+-dependent glucose transporter protein in intestinal vesicles decreased markedly after 5-fluorouracil treatment, the amount of PepT1 protein remained largely unaffected. Immunohistochemical analysis also showed that the PepT1 immunoreactivity level was preserved in the brush border membrane of the remaining villi of 5-fluorouracil-treated rats. Levels of amino acid, glucose, and phosphate transporter mRNAs were profoundly depressed in 5-fluorouracil-treated animals, whereas the level of PepT1 mRNA conversely increased. CONCLUSIONS: The resistance of intestinal peptide transport to tissue injury may be attributable to increased synthesis of PepT1 rather than to a change in the kinetic properties of the residual absorbing cells.

Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate cotransporter from rat parathyroid glands.

The extracellular concentration of inorganic phosphate (Pi) is an important determinant of parathyroid cell function. The effects of Pi may be mediated through specific molecules in the parathyroid cell membrane, one candidate molecule for which would be a Na+-dependent Pi cotransporter. A complementary DNA encoding a Na+-Pi cotransporter, termed rat PiT-1, has now been isolated from rat parathyroid. The 2890-bp complementary DNA encodes a protein of 681 amino acids that shows sequence identities of 97% and 93% with the type III Na+-Pi cotransporters mouse PiT-1 and human PiT-1, respectively. Expression of rat PiT-1 in Xenopus oocytes revealed that it possesses Na+-dependent Pi cotransport activity. PiT-1 messenger RNA (mRNA) is widely distributed in rat tissues and is most abundant in brain, bone, and small intestine. The amount of PiT-1 mRNA in the parathyroid of vitamin D-deficient rats was reduced compared with that in normal animals and increased markedly after administration of 1,25-dihydroxyvitamin D3. Furthermore, the abundance of PiT-1 mRNA in the parathyroid was much greater in rats fed a low-Pi diet than in those fed a high-Pi diet. Thus, rat PiT-1 may contribute to the effects of Pi and vitamin D on parathyroid function.

Differential effects of SH-reactive agents on [(3)H](+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate and [(3)H]glutamate binding in brain synaptic membranes treated with triton X-100.

Specific binding of [(3)H](+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), an antagonist highly selective for the N- methyl- d -aspartate (NMDA)-sensitive subclass of the brain excitatory amino acid receptors, was examined in rat brain synaptic membranes treated with a low concentration of Triton X-100 using a filtration assay method. The binding was displaced by l-glutamic acid (Glu) and its analogous amino acids in a concentration-dependent manner at a concentration range of 10 nM to 0.1 mM. Agonists as well as competitive antagonists for the subclass invariably displaced the binding, while noncompetitive antagonists were ineffective as displacers of the binding. Agonists selective for the other subclasses did not affect the binding, d-2-Amino-5-phosphonovaleric and d-2-amino-7-phosphonoheptanoic acids exhibited more potent inhibition of the binding than their respective l-isomers, with the other aminophosphonates being inactive. Preincubation of synaptic membranes with different SH-reactive agents invariably resulted in a significant reduction of [(3)H]CPP binding, without significantly affecting NMDA-sensitive [(3)H]Glu binding. These results suggest that a filtration assay method is also applicable to detecting the binding of an antagonist highly selective for the NMDA-sensitive receptors to the NMDA recognition sites, in addition to a centrifugation assay method. Heterogeneity of the NMDA recognition sites is also suggested.

High concentrations of calmodulin antagonists inhibit accumulation and binding activities of [(3)H]glutamate in rat brain.

Sodium- and energy-dependent accumulation of [(3)H]l-glutamic acid (Glu) into rat cerebral cortical slices was inhibited by relatively high concentrations (40-100 ?M) of calmodulin antagonists, such as N-(6-aminohexyl)-1-naphthalenesulfonamide and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, in concentration-dependent and noncompetitive manners. The latter antagonist not only diminished the basal binding activity of [(3)H]Glu in synaptic membranes of the rat brain, but also eliminated the activities found in the presence of Cl(?) and Cl(?)/Ca(2+) ions. However, N- methyl- d -aspartate-sensitive [(3)H]Glu binding was not affected by these antagonists. These results suggest the possible involvement of the calmodulin system in glutamatergic neurotransmission in the brain.

Actinopyrones A, B and C, new physiologically active substances. I. Producing organism, fermentation, isolation and biological properties.

A strain of Streptomyces was found to produce new physiologically active substances. The active compounds were purified and separated into three substances named actinopyrones A, B and C. Actinopyrones exhibited coronary vasodilating activities in anesthetized dogs and weakly antimicrobial activities against some Gram-positive bacteria and dermatophytes.

Actinopyrones A, B and C, new physiologically active substances. II. Physico-chemical properties and chemical structures.

The structure of physiologically active substances, actinopyrones A, B and C, produced by Streptomyces pactum S12538 were determined on the basis of their spectral and chemical character. These substances were structurally related to piericidin A1.