Exploring Novel Biomarkers for an Acute Coronary Syndrome Diagnosis Utilizing Plasma Metabolomics.

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin I and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, reaching diagnostic values for ACS may take several hours. In this study, we attempted to explore novel biomarkers for ACS with higher sensitivity than that of troponin I and CK-MB. The metabolomic profiles of 18 patients with ACS upon hospital arrival and those of the age-matched control (HC) group of 24 healthy volunteers were analyzed using liquid chromatography time-of-flight mass spectrometry. Volcano plots showed 24 metabolites whose concentrations differed significantly between the ACS and HC groups. Using these data, we developed a multiple logistic regression model for the ACS diagnosis, in which lysine, isocitrate, and tryptophan were selected as minimum-independent metabolites. The area under the receiver operating characteristic curve value for discriminating ACS from HC was 1.00 (95% confidence interval [CI]: 1.00-1.00). In contrast, those for troponin I and CK-MB were 0.917 (95% confidence interval [CI]: 0.812-1.00) and 0.988 (95% CI: 0.966-1.00), respectively. This study showed the potential for combining three plasma metabolites to discriminate ACS from HC with a higher sensitivity than troponin I and CK-MB.

[Iliopsoas muscle hematoma after anticoagulant therapy for pyogenic thrombophlebitis that spilled over from ascending colon diverticulitis:a case report].

A 79-year-old male patient presented to our hospital with chief complaints of fever, abdominal pain, and jaundice. Laboratory data revealed marked hepatobiliary enzyme and inflammatory marker elevations, and computed tomography revealed ascending colon diverticulitis, thrombophlebitis, portal vein thrombus, and intrahepatic cholangitis. Blood culture revealed the presence of Prevotella sp. The patient was treated with anticoagulant therapy in addition to antimicrobial therapy;however, activated partial thromboplastin time prolongation remained insufficient. Antithrombin therapy was combined with the current therapy because antithrombin levels were low, which resulted in iliopsoas muscle hematoma. The hematoma resolved conservatively after discontinuing anticoagulation, and the patient was discharged after 19 days of hospitalization with improved cholangitis and diverticulitis. The portal vein thrombus remained after discharge;however, anticoagulation therapy was not restarted due to adverse events. This case was presented because of its difficult treatment.

[Jejunal stromal tumor concomitant ectopic pancreas in a young man with sarcoidosis:a case report].

During a medical health check, a 29-year-old man was presented to our hospital with iron deficiency anemia. He had no significant medical history in his family. Despite being diagnosed with ocular sarcoidosis 5 years ago, he had no vision problems. Physical examination revealed normal vital signs and a nontender abdomen;however, his eyelid conjuvitis was pale, and he became aware of fatigue when moving vigorously. He had upper gastrointestinal endoscopy and colonoscopy, but there was no evidence of bleeding detected. A contrasted mass 30mm in size was discovered on abdominal contrast-enhanced computed tomography at the dorsal wall of the proximal jejunum. Positron emission tomography showed an accumulation image in the bilateral hilar lymph and upper jejunum. A 30-mm submucosal tumor with a central depression in the upper jejunum was discovered using a double-balloon enteroscopy. We performed biopsies from the depression margin and tattoo marking on the oral side of the tumor. Even though the biopsies specimen revealed granulation tissue, the patient was referred to surgery and underwent a partial jejunum resection because the tumor was diagnosed as the cause of anemia. The operation went smoothly, and the patient was discharged on the seventh postoperative day. Histological examination showed a proliferation of densely packed spindle cells with prominent nuclear palisading. The immunohistochemical examination revealed that c-kit and CD34 were highly expressed, whereas desmin and S-100 proteins were not. Ki-67 expression demonstrated a very low proliferative index (2%). We discovered gastrointestinal stromal tumors (GIST), as well as an ectopic pancreas. GIST is extremely rare in young people, and the coexistence of ectopic pancreas and sarcoidosis has never been reported.

Anion effects on Li ion transference number and dynamic ion correlations in glyme-Li salt equimolar mixtures.

To achieve single-ion conducting liquid electrolytes for the rapid charge and discharge of Li secondary batteries, improvement in the Li+ transference number of the electrolytes is integral. Few studies have established a feasible design for achieving Li+ transference numbers approaching unity in liquid electrolytes consisting of low-molecular-weight salts and solvents. Previously, we studied the effects of Li+-solvent interactions on the Li+ transference number in glyme- and sulfolane-based molten Li salt solvates and clarified the relationship between this transference number and correlated ion motions. In this study, to deepen our insight into the design principles of single-ion conducting liquid electrolytes, we focused on the effects of Li+-anion interactions on Li ion transport in glyme-Li salt equimolar mixtures with different counter anions. Interestingly, the equimolar triglyme (G3)-lithium trifluoroacetate (Li[TFA]) mixture ([Li(G3)][TFA]) demonstrated a high Li+ transference number, estimated via the potentiostatic polarization method (tPPLi = 0.90). Dynamic ion correlation studies suggested that the high tPPLi could be mainly ascribed to the strongly coupled Li+-anion motions in the electrolytes. Furthermore, high-energy X-ray total scattering measurements combined with all-atom molecular dynamics simulations showed that Li+ ions and [TFA] anions aggregated into ionic clusters with a relatively long-range ion-ordered structure. Therefore, the collective motions of the Li ions and anions in the form of highly aggregated ion clusters, which likely diminish rather than enhance ionic conductivity, play a significant role in achieving high tPPLi in liquid electrolytes. Based on the dynamic ion correlations, a potential design approach is discussed to accomplish single-ion conducting liquid electrolytes with high ionic conductivity.

A retrospective cohort study to investigate the incidence of cancer-related weight loss during chemotherapy in gastric cancer patients.

PURPOSE: This study aimed to evaluate cancer-related weight loss (WL) after the start of first-line chemotherapy as a surrogate marker for cancer cachexia in patients with advanced gastric cancer. We investigated the incidence of WL and the relationship between WL and overall survival (OS) or adverse events. METHODS: We conducted a retrospective cohort study in 131 patients with advanced gastric cancer who received first-line systemic chemotherapy between September 1, 2010, and August 31, 2016, at Kurume University Hospital and Shizuoka Cancer Center Hospital. WL was defined in this study as weight loss of > 5% or weight loss of > 2% with a body mass index of < 20 kg/m2 within the last 6 months after the start of chemotherapy. RESULTS: Median age and median Eastern Cooperative Oncology Group performance status of the patients participating in this study were 68 years old and 0, respectively. Incidence of WL was 53% at the first 12 weeks after starting first-line chemotherapy, and increased to 88% after 48 weeks. Overall survival rates were significantly associated with WL at 12, 24, and 48 weeks. Appetite loss and fatigue were more frequent and more severe in patients with WL. CONCLUSION: WL was especially observed in more than half the patients within 12 weeks after starting chemotherapy. WL appeared to relate to adverse events or reduced survival. These results suggest the importance of monitoring WL or providing nutritional support at the beginning of chemotherapy.

Lithium-ion coordination-induced conformational change of PEG chains in ionic-liquid-based electrolytes.

We report the structure of poly(ethylene glycol) (PEG) in a imidazolium-based ionic liquid (IL) electrolyte containing lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) salt, as determined using Raman spectroscopy, high-energy X-ray total scattering (HEXTS), and molecular dynamics (MD) simulations. The Raman spectral study indicated that the TFSA anions bound to Li ions are desolvated when PEG is added to the LiTFSA/IL solution to form stable Li+-PEG complexes. Via quantitative analysis of the obtained Raman spectra, the desolvation number of the TFSA [nd, per one oxygen atom of the ethylene glycol unit (Opeg)] was determined to be ∼0.4, irrespective of the shape (star or linear) and molecular weight of the polymer. On the basis of radial distribution functions obtained from the HEXTS experiments and MD simulations, we demonstrated that the Li+-PEG complexation induces a conformational change of the PEG chain from gauche/anti-conformers to a syn conformer. This Li+-coordination-induced conformation resulted in a decrease in the radius of gyration (Rg) of the PEG chain, implying a folding behavior of polymer chains through multiple OpegLi+Opeg interactions.

Diversity of γ- glutamyl peptides and oligosaccharides, the "kokumi" taste enhancers, in seeds from soybean mini core collections.

Soybeans (Glycine max (L,) Merr,) contain γ-glutamyl peptides and oligosaccharides, and these components play an important role in imparting the "kokumi" taste to foods. To gain insight into the genetic diversities and molecular mechanisms of accumulation of γ-glutamyl peptides and oligosaccharides in soybean, we measured the contents of these components using the Japan and World mini core collections. Similar to other previously reported traits, wide variations were detected among the accessions in the core collections with respect to the content of γ-glutamyl peptides and oligosaccharides. We found a positive relationship between the content of γ-glutamyl tyrosine and γ-glutamyl phenylalanine and between the content of raffinose and stachyose. Furthermore, there were unique accessions that included high levels of γ-glutamyl peptides and oligosaccharides. These accessions may be helpful in understanding the accumulation mechanism of γ-glutamyl peptides and oligosaccharides and to increase the "kokumi" taste components in soybean by performing a genetic analysis.

Isolation and characterization of key contributors to the "kokumi" taste in soybean seeds.

The water extract of soybean seeds (Glycine max (L.) Merr.) is nearly tasteless, but "kokumi" taste sensation was confirmed upon addition of a basic umami solution containing glutamic acid, inosine monophosphate, and sodium chloride. To identify the key contributors to the "kokumi" taste sensation in soybean seeds, sensory-guided fractionation, taste sensory analyses, and LC-MS/MS analyses were utilized. γ-glutamyl-tyrosine and γ-glutamyl-phenylalanine were identified as contributors to "kokumi taste"; specifically, these γ-glutamyl peptides imparted the "kokumi" taste sensation at a low taste threshold in a basic umami solution. Raffinose and stachyose, which are sufficiently present in soybean seeds, exhibited a synergistic effect in regard to the enhanced "kokumi" taste sensation of γ-glutamyl peptides. This is the first report that the combined use of γ-glutamyl peptides and oligosaccharides can increase the "kokumi" intensity, which suggests that soybean extracts or soymilk can be used to enhance the "kokumi" taste sensation in food products.

A case of IgG4-related hepatic inflammatory pseudotumor replaced by an abscess after steroid treatment.

BACKGROUND: Hepatic inflammatory pseudotumor (IPT) is a rare disease which often mimics a malignant tumor and is therefore often misdiagnosed and surgically resected. Recently, a concept of IgG4-related diseases (IgG4-RD) has been proposed that is becoming widely recognized and includes IgG4-related hepatic IPT. Corticosteroids are widely accepted as the standard treatment. CASE PRESENTATION: A 72-year-old Japanese man, who had been followed for ten years after surgery and chemotherapy for treatment of hilar and lower bile duct cancers, developed intermittent fever and abdominal pain and visited this hospital. Blood examinations revealed an inflammatory reaction, worsened glucose intolerance, and an increased level of serum IgG4 (137 mg/dL). Computed tomography (CT) revealed a 5 cm-sized mass in hepatic segment 7. Because of his cancer history, not only was a benign mass suspected, but there was also the possibility of a recurrent biliary malignancy. Liver biopsy was performed and the histology met the criteria for IgG4-related IPT. Corticosteroid therapy was initiated and his symptoms quickly resolved. However, two months later, a repeat CT demonstrated that the hepatic mass had been replaced by an abscess. The abscess was initially refractory, despite tapering corticosteroid treatment, controlling diabetes by intensive insulin therapy, administration of antibiotics, and percutaneous abscess drainage. Finally, after six months, the condition resolved. CONCLUSION: The diagnosis of hepatic IPT is sometimes difficult. To differentiate it from a malignant tumor, histological examination is necessary. Although corticosteroids are recognized as the standard therapy, unexpected and critical complications can develop in cases of IgG4-related hepatic IPT.

Stimuli-responsive folding and unfolding of a polymer bearing multiple cerium(IV) bis(porphyrinate) joints: mechano-imitation of the action of a folding ruler.

A pivotal guest role: a new porphyrin polymer, poly(PorZn⋅DD) (pink/purple), composed of a porphyrinatozinc and a porphyrin double-decker complex as a repeating unit was synthesized. In poly(PorZn⋅DD), porphyrinatozinc complexes recognize a divalent amine (tan/red) to induce an intramolecular pivoting motion through the rotation of porphyrin double-decker complexes and the polymer undergoes shortening and compaction.

Synthesis, photophysical, electrochemical, tumor-imaging, and phototherapeutic properties of purpurinimide-N-substituted cyanine dyes joined with variable lengths of linkers.

Purpurinimide methyl esters, bearing variable lengths of N-substitutions, were conjugated individually to a cyanine dye with a carboxylic acid functionality. The results obtained from in vitro and in vivo studies showed a significant impact of the linkers joining the phototherapeutic and fluorescence imaging moieties. The photosensitizer-fluorophore conjugate with a PEG linker showed the highest uptake in the liver, whereas the conjugate linked with two carbon units showed excellent tumor-imaging and PDT efficacy at 24 h postinjection. Whole body imaging and biodistribution studies at variable time points portrayed enhanced fluorescent uptake of the conjugates in the tumor compared to that in the skin. Interestingly, the conjugate with the shortest linker and the one joining with two carbon units showed faster clearance from normal organs, e.g., the liver, kidney, spleen, and lung, compared to that in tumors. Both imaging and PDT efficacy of the conjugates were performed in BALB/c mice bearing Colon26 tumors. Compared to the others, the short linker conjugate showed poor tumor fluorescent properties and as a corollary does not exhibit the dual functionality of the photosensitizer-fluorophore conjugate. For this reason, it was not evaluated for in vivo PDT efficacy. However, in Colon26 tumor cells (in vitro), the short linker was highly effective. Among the conjugates with variable linkers, the rate of energy transfer from the purpurinimide moiety to the cyanine moiety increased with deceasing linker length, as examined by femtosecond laser flash photolysis measurements. No electron transfer from the purpurinimide moiety to the singlet excited state of the cyanine moiety or from the singlet excited state of the cyanine moiety to the purpurinimide moiety occurred as indicated by a comparison of transient absorption spectra with spectra of the one-electron oxidized and one-electron reduced species of the conjugate obtained by spectroelectrochemical measurements.

Conjugation of cRGD peptide to chlorophyll a based photosensitizer (HPPH) alters its pharmacokinetics with enhanced tumor-imaging and photosensitizing (PDT) efficacy.

The α(v)ß(3) integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Cyclic Arg-Gly-Asp (cRGD) peptide represents a selective α(v)ß(3) integrin ligand that has been extensively used for research, therapy, and diagnosis of neoangiogenesis. For developing photosensitizers with enhanced PDT efficacy, we here report the synthesis of a series of bifunctional agents in which the 3-(1'-hexyloxyethyl)-3-devinylpyropheophorbide a (HPPH), a chlorophyll-based photosensitizer, was conjugated to cRGD and the related analogues. The cell uptake and in vitro PDT efficacy of the conjugates were studied in α(v)ß(3) integrin overexpressing U87 and 4T1 cell lines whereas the in vivo PDT efficacy and fluorescence-imaging potential of the conjugates were compared with the corresponding nonconjugated photosensitizer HPPH in 4T1 tumors. Compared to HPPH, the HPPH-cRGD conjugate in which the arginine and aspartic acid moieties were available for binding to two subunits of α(v)ß(3) integrin showed faster clearance, enhanced tumor imaging and enhanced PDT efficacy at 2-4 h postinjection. Molecular modeling studies also confirmed that the presence of the HPPH moiety in HPPH-cRGD conjugate does not interfere with specific recognition of cRGD by α(v)ß(3) integrin. Compared to U87 and 4T1 cells the HPPH-cRGD showed significantly low photosensitizing efficacy in A431 (α(v)ß(3) negative) tumor cells, suggesting possible target specificity of the conjugate.

A Retrospective Cohort Study to Investigate the Incidence of Cachexia During Chemotherapy in Patients with Colorectal Cancer.

INTRODUCTION: This retrospective study focused on cancer cachexia in clinical practice. We evaluated the incidence of cancer cachexia and the relationship between cancer cachexia and overall survival (OS) or toxicities in patients with advanced colorectal cancer after undergoing first-line systemic chemotherapy. METHODS: We examined 150 patients with colorectal cancer who underwent first-line systemic chemotherapy between February 1, 2010 and August 31, 2016 at Shizuoka Cancer Center Hospital and Kurume University Hospital. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m2 within the past 6 months according to the European Palliative Care Research Collaborative criteria. RESULTS: One hundred patients from Shizuoka Cancer Center and 50 from Kurume University Hospital were registered. Median age and body mass index were 65 years (range 29-85) and 21.7 kg/m2 (14.8-32.5), respectively. Cumulative incidence of cancer cachexia was 50.7% at 24 weeks, and reached 91.3% over the whole study period. OS was significantly different between patients with and without cancer cachexia within 24 weeks after starting first-line treatment, although the onset of cancer cachexia within 24 weeks could not be considered as an independent prognostic factor for OS. Severe appetite loss and fatigue tended to occur more frequently in patients with cancer cachexia within 24 weeks. CONCLUSION: Cancer cachexia appears to have an onset in approximately half of patients with advanced colorectal cancer within 24 weeks after starting first-line treatment. Although causal relationships were controversial, the onset of cancer cachexia within 24 weeks tends to be related to worse outcomes. Thus, it would be better to monitor weight loss leading to cachexia in patients with advanced colorectal cancer, especially within 24 weeks after starting first-line chemotherapy. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000035002).

Feasibility and efficacy of chemoradiotherapy with concurrent split-dose cisplatin after induction chemotherapy with docetaxel/cisplatin/5-fluorouracil for locally advanced head and neck cancer.

Chemoradiotherapy (CRT) with concurrent high-dose cisplatin (CDDP) is a standard treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Docetaxel plus CDDP and 5-fluorouracil (TPF) induction chemotherapy (ICT) prior to CRT is considered for patients at high risk of distant metastases. The purpose of the current study was to evaluate the feasibility and efficacy of CRT with split-dose CDDP after TPF-ICT for LA-SCCHN. A total of 21 LA-SCCHN patients treated with TPF-ICT followed by concurrent CRT with split-dose CDDP between January 2011 and December 2017 were retrospectively analysed. The patients' characteristics were i) median age 66 years (48-75 years); ii) male/female, 21/0; iii) performance status 0-1/2, 20/1; iv) larynx/hypopharynx/oropharynx/oral cavity, 4/8/8/1 and v) clinical stage III/IV, 3/18. The numbers of TPF-ICT cycles 1/2/3 were 2/3/16. Median cumulative doses of CDDP in TPF-ICT and CRT were 180.0 and 206.7 mg/m2, respectively. All patients completed 70 Gy RT. The complete response rate was 76.2%. At a median follow-up of 51.5 months, median PFS and OS were not reached and 65.5 months, respectively. The most common grade 3 or worse toxicities during CRT-ICT were stomatitis (48%), dysphagia (21%), anorexia (17%) and leukopenia (14%). However, no grade 2 or worse nephrotoxicity, neurotoxicity or ototoxicity was observed. The results demonstrated that concurrent CRT with split-dose CDDP after TPF-ICT is feasible and effective for LA-SCCHN.

Remarkable features of the McMurry reaction conditions in dimerization of formyl- and 2-formylvinylpurpurinimides. Electrochemistry of monomeric Ni(II) purpurinimide and the corresponding dyads.

To investigate the electrochemical properties of purpurinimide dyads and electron transfer sites for their reduction and oxidation, a series of dimers with variable C-C linkages were synthesized. For the preparation of these novel structures, the formyl and 2-formylvinyl substituents were regioselectively introduced at positions 3 and 20 of Ni(II) purpurinimides by the Vilsmeier reaction. The Ni(II) complexes were then subjected to the McMurry reaction under two different conditions with unexpected results. For example, the reaction of formyl purpurinimides with TiCl(3)(DME)(1.5) failed to produce the desired C-C dimers, and the starting compounds were recovered almost quantitatively. Under similar reaction conditions, the 20-(2-formylvinyl)purpurinimide also did not dimerize but produced instead unexpected benzoisobacteriochlorins via an intramolecular cyclization. However, treatment of the 3-formyl- and 20-formylpurpurinimides with TiCl(4)/Zn produced corresponding dimers linked with one double bond (trans) in modest yields. Under similar conditions, Ni(II) purpurinimides containing a 2-formylvinyl substituent either at position 3 or at position 20 afforded the respective C-C dimers, where the purpurinimide moieties were joined with a trans-trans-trans hexatriene linker. Molecular modeling data suggest that the nature of the conformational energy difference found in all trans vs trans-cis-trans conformers of the dimers connected by a hexatriene linker at the meso- or beta-position of the macrocycle is not because of the intrinsic conformational energy difference of the linker region, which is identical for both dimers.

Neighboring Effect of Intramolecular Chlorine Atoms on Epoxide Opening Reaction by Chloride Anions.

We investigated the diastereoselectivity of ring openings for chloro vinyl epoxides with various chlorination reagents. In the chlorinolysis reactions using vinyl epoxides having an allyl alcohol, inversion:retention ratios varied depending on the chloride sources. In limited cases, the increase in retention ratio was consistent with the intervention of chloronium ions. In contrast, all vinyl epoxides bearing an α,ß-unsaturated ester gave only the inversion products. These results suggest the electron-withdrawing property suppressed the chloronium ions.

Effects of heat treatment under low moisture conditions on the protein and oil in soybean seeds.

The effects of autoclave and microwave heating on the protein and oil in soybean seeds were investigated under low moisture conditions. The nitrogen solubility index (NSI) decreased on heating. The reduction in the NSI was accompanied by an increase in the size and deformation of the oil bodies in the cellular tissue of soybean seeds. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that lipoxygenase was susceptible to heat denaturation, but 7S and 11S globulins were only partially denatured. The partial denaturation of the proteins was confirmed by Fourier transform infrared spectroscopy measurements. The ratio of oil to protein peaks increased with increasing heating, suggesting the exudation of oil to the surface or outside of oil bodies. Microwave heating is more efficient in changing the oil distribution in soybean seeds than autoclave heating. On the other hand, the degree of protein denaturation is lower after microwave heating.

Dietary low-fat soy milk powder retards diabetic nephropathy progression via inhibition of renal fibrosis and renal inflammation.

SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein-, LFSMP-, or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 wk. Renal morphology and protein expression were evaluated by histochemical staining and western blots. Although HFSMP-based diet showed no protective effect on DN. LFSMP-fed mice exhibited lower water intake, urine output, and urinary albumin, and glucose excretion. Furthermore, strong preservation of renal structural proteins and low urinary N-acetyl-beta-d-glucosaminidase activity were observed in LFSMP-fed mice, indicating alleviation of renal injury. LFSMP-fed mice showed a lesser degree of mesangial matrix expansion, of tubulointerstitial fibrosis, and of myofibroblast differentiation. Finally, milder renal inflammation was found in LFSMP-fed mice, as evidenced by a decrease in urinary monocyte chemoattractant protein- 1 excretion and lesser macrophage infiltration into the tubulointerstitium. CONCLUSION: The present data suggests that long-term consumption of LFSMP but not HFSMP retards DN progression via suppressing renal injury, myofibroblast differentiation, and renal macrophage infiltration in diabetic condition.

Rho-kinase inhibitor suppressed restenosis in porcine coronary balloon angioplasty.

BACKGROUND: Constrictive remodeling is thought to be more important than neointimal formation in coronary restenosis after balloon angioplasty. The inhibition of Rho-kinase prevents neointimal proliferation, but now this inhibition that affects constrictive remodeling remains unknown. To explore this issue further, we investigated whether a specific Rho-kinase inhibitor, Y-27632, could suppress restenosis after coronary balloon angioplasty in a porcine model. METHODS: Balloon angioplasty with local administration of Y-27632 (Y group) or vehicle (C group) was performed at 2 and 3 weeks after overstretch injury in a porcine coronary artery. Quantitative coronary angiography (QCA) and quantitative coronary ultrasound (QCU) were performed to assess the coronary lesion segment. A morphometrical analysis was performed in a histological study. Proliferative cells and p27(Kip1)-positive cells were evaluated in the arterial wall using immunohistochemistry. RESULTS: QCA and QCU demonstrated that the minimal lumen diameter and minimal lumen area were greater, and % stenosis was less in the Y group than in the C group. The QCU analysis also revealed a significant inhibition in the increase of the intimal area and a prevention of constrictive remodeling by Y-27632. In the histological study, the intimal, adventitial and collagen areas were significantly smaller in the Y group than in the C group. The Y group also exhibited significantly less proliferative activity and a significantly higher percentage of cells expressing p27(Kip1) in the arterial wall. CONCLUSION: Local delivery of Y-27632 suppressed constrictive remodeling as well as neointimal formation after coronary balloon angioplasty in pigs.