Cardiac magnetic resonance performs better in the detection of functionally significant coronary artery stenosis compared to single-photon emission computed tomography and dobutamine stress echocardiography.

BACKGROUND: Fractional flow reserve (FFR) measured on catheterization is now widely used for the diagnosis of functional myocardial ischemia in patients with coronary artery disease (CAD). FFR, however, is invasive and carries potential procedural complications. Therefore, the aim of this study was to compare the diagnostic capability in functionally significant stenosis identified on FFR, between cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI), single-photon emission computed tomography MPI (SPECT-MPI), and dobutamine stress echocardiography (DSE) in patients with CAD. METHODS AND RESULTS: A total of 25 patients who had at least 1 angiographic stenosis ≥50% on coronary angiography was studied. CMR-MPI, SPECT-MPI and DSE were done before FFR measurement. FFR was measured in all 3 major epicardial coronary arteries. Out of 71 vascular territories excluding 4 territories due to inadequate imaging, 29 (41%) had FFR <0.80. The sensitivity of CMR-MPI was significantly higher than that of SPECT-MPI and DSE (P=0.02 and P=0.001, respectively). The area under the receiver operating characteristic curve (AUC) for CMR-MPI (AUC, 0.92) was significantly greater than for SPECT-MPI (AUC, 0.73; P=0.006) and DSE (AUC, 0.69; P<0.001). CONCLUSIONS: CMR-MPI performed well in the detection of functionally significant stenosis defined according to FFR, and had the highest diagnostic sensitivity among the 3 modalities tested in patients with CAD.

Interrelation between myocardial oxidative metabolism and diastolic function in patients undergoing surgical ventricular reconstruction.

PURPOSE: Diastolic function is impaired in patients with end-stage heart failure. Favorable structural changes by surgical ventricular reconstruction (SVR) are thought to improve diastolic function, however, previous studies reported the contradictory results. We hypothesized that cardiac oxidative metabolism and diastolic dysfunction might improve in parallel to the reduction of left ventricular chamber size after SVR. METHODS: We studied 11 patients underwent SVR associated with mitral valve repair for end-stage heart failure due to dilated cardiomyopathy. Diastolic function was assessed by echocardiography and myocardial oxidative metabolism was measured by the monoexponential clearance (k-mono) of (11)C-acetate positron emission tomography at baseline and 1 month after SVR. RESULTS: All patients had preoperative severe diastolic dysfunction [E/A 4.11 ± 1.18, deceleration time (DT) 134 ± 26 ms]. The study patients were divided into 2 groups according to the changes in diastolic function after SVR; unchanged or worsened diastolic function in 6 patients (55 %, Non-responder) and improved diastolic function in 5 (45 %, Responder). K-mono and wall stress decreased only in responder. The changes in k-mono before and after SVR correlated with those in deceleration time (r = -0.63; p < 0.05) and wall stress (r = 0.75; p < 0.01). CONCLUSIONS: Improvement of diastolic dysfunction in patients with end-stage heart failure by SVR was in parallel to that in oxidative metabolism. It suggests that SVR reduced excessive metabolism during the diastolic phase, in part, via the improvement in diastolic function and the reduction in LV wall stress.

Keigai-rengyo-to as post-exposure prophylaxis for severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Effective prevention against COVID-19 is urgently required to control vaccine breakthrough infection. Laboratory and clinical data suggested that Keigai-rengyo-to (KRT) performs biological activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated whether KRT could prevent SARS-CoV-2 in medical personnel exposed to patients with COVID-19. METHODS: We conducted an open-label controlled clinical trial of medical personnel after COVID-19 vaccination at our hospital (ClinicalTrials.gov: UMIN000048389). Participants were close contacts recently exposed (<72 h) to patients with COVID-19. We provided the participants with KRT (7.5 g/day for 5 days) or no drug as a control. The primary endpoint was nicking endonuclease amplification reaction or polymerase chain reaction confirming incident SARS-CoV-2 infection. Safety was assessed in all treated participants. RESULTS: Between January and September 2022, 38 close contacts were assigned: 20 to the KRT group and 18 to the control group. During 2 weeks of follow-up, 10/38 (26%) participants had new-onset COVID-19. The incidence of COVID-19 was significantly lower in the KRT group (2/20; 10%) than in the control group (8/18; 44%), with a medium effect size (p < 0.05; phi coefficient = -0.391; total absolute risk reduction: 34.4% points). The number needed to treat to prevent the occurrence of a COVID-19 case was 2.9. The overall relative risk was 0.23 (95% confidence interval: 0.06-0.78). No serious safety problems were detected. CONCLUSION: Post-exposure prophylaxis with KRT can prevent the onset of COVID-19 in close contacts after vaccination. More randomized clinical trials with larger samples are required to better evaluate KRT as a post-exposure prophylaxis of SARS-CoV-2.

A predictive model to estimate fever after receipt of the second dose of Pfizer-BioNTech coronavirus disease 2019 vaccine: An observational cohort study.

Background and Aims: Fever after coronavirus disease 2019 (COVID-19) vaccination is generally a mild and benign event, but can cause excessive anxiety in younger adults. This study aimed to find key factors that include allergic diseases or physique that determine fever after vaccination. Methods: We conducted an observational cohort study in our hospital to assess post-COVID-19 vaccination fever from April to June 2021. A total of 153 medical personnel aged 22-86 years of age were involved in the study to receive two doses, intramuscularly 21 days apart, of the Pfizer-BioNTech COVID-19 vaccine (30 µg per dose). Vaccination records were taken more than 72 h after vaccination. Clinical and laboratory variables (age, sex, allergy history, weight, height, serum hemoglobin concentration, and these derivatives) were examined by multivariable logistic regression analysis using the peak axillary temperature in the 4-day period after the second vaccination as a dependent variable. Results: No serious safety problems were detected. The incidence of a postsecond vaccination fever of 37.3°C or above was 29.4%. Logistic regression analysis found age, history of perennial allergic rhinitis, body surface area, body weight, percent overweight, and serum hemoglobin concentration as independent predictors of postvaccination fever. The characteristics of this individual were incorporated into the numerical model of human thermoregulation. The evaluation of this model had a sensitivity of 66.1% and a specificity of 90.7% in the detection of postvaccination fever. The multiple coefficient of determination (R 2) was 0.410. Conclusion: The COVID-19 vaccine induced higher rates of fever during the 4-day period after the second vaccination. Younger age, part of the allergy history, small and light body, and concentrated blood were associated with postvaccination fever.

Effect of early oseltamivir on outpatients without hypoxia with suspected COVID-19.

BACKGROUND: Since December 2019 coronavirus disease 2019 (COVID-19) outbreaks have occurred in China and many countries around the world. The effectiveness of oseltamivir on COVID-19 suspected outpatients without hypoxia was evaluated. METHODS: A total of 16 COVID-19 suspected medical personnel and their cohabitation families without hypoxia, who came to the adult fever clinic from March to June 2020 were studied. All patients received antiviral therapy (oseltamivir) and antibacterial therapy together. RESULTS: Most of the infected patients were female (10, 63%), 1 had diabetes (6%) and 3 hypertension (19%). The median age was 45 years (interquartile range [IQR] 31-60 years). Oseltamivir administration made the temperature fall within 24 h in part (10, 63%). Clinical data were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 24 h, and patients administered late treatment (LT), initiated after this time point. Duration of fever was shorter in the ET group than in the LT group (31 ± 21 h versus 94 ± 38 h; p < 0.001). The time from fever onset to treatment initiation correlated with duration of fever (r = 0.77; p < 0.001) and the time from peak to decline (r = 0.58; p < 0.05). CONCLUSION: These findings suggest that early oseltamivir administration may lower the duration of fever in COVID-19 suspected outpatients without hypoxia when it is used in combination with antibacterial therapy.

Myocardial oxidative metabolism is increased due to haemodynamic overload in patients with aortic valve stenosis: assessment using 11C-acetate positron emission tomography.

PURPOSE: The relationship between myocardial oxidative metabolism and pressure overload in aortic valve stenosis (AS) is not fully elucidated. We identified the determinants of myocardial oxidative metabolism by measuring its changes after aortic valve replacement (AVR) in patients with AS. METHODS: Myocardial 11C-acetate clearance rate constant (Kmono), an index of oxidative metabolism, was measured non-invasively by using positron emission tomography in 16 patients with moderate to severe AS and 7 healthy controls. The severity of AS was assessed by echocardiography. Of 16 patients, 5 were reexamined at 1 month after AVR. RESULTS: Kmono was significantly higher in patients with AS than healthy controls by 42% (0.068±0.014 vs 0.048±0.007/min, p<0.01). Kmono was significantly correlated with age (r=0.58, p<0.01), left ventricular (LV) mass index (r=0.61, p<0.01) and estimated systolic LV pressure (r=0.81, p<0.001) measured by echocardiography. By multivariate analysis, estimated LV systolic pressure was an independent predictor of Kmono (ß=0.93, p<0.01). After AVR, Kmono (from 0.075±0.012 to 0.061±0.014/min, p=0.043) and LV mass index (from 183±49 to 124±41 g/ml2, p=0.043) were significantly decreased despite no significant changes in rate-pressure product. CONCLUSION: Myocardial oxygen metabolism was increased in patients with AS, which was decreased after AVR. The increased myocardial oxidative metabolism in AS was largely attributable to the pressure overload of the LV.

Peripatric differentiation among adjacent marine lake and lagoon populations of a coastal fish, Sphaeramia orbicularis (Apogonidae, Perciformes, Teleostei).

The effect of geographical isolation on speciation, particularly within short geographical ranges, is poorly understood among marine organisms. Focusing on marine lakes of the Palau Islands, we investigated the effect of geographical isolation on Sphaeramia orbicularis, a coastal fish inhabiting marine lakes and lagoons. We collected a total of 157 individuals from three meromictic marine lakes and three lagoon sites, and analyzed the genetic diversity and differentiation of the populations based on complete sequences of the mitochondrial control region (824 bp). The analyses show that the genetic diversity of marine lake populations is much lower than that of lagoon populations. Moreover, a mismatch distribution analysis suggests that marine lake populations have experienced a decrease followed by a rapid expansion of their population size. These results reveal that marine lake populations have experienced severe founder and/or bottleneck events during the last thousand to tens of thousand years. Pairwise Phi(ST )values ranged from 0.531 to 0.848 between marine lake and lagoon populations and from 0.429 to 0.870 among marine lake populations, indicating a high degree of genetic differentiation. We speculate that such peripatric differentiation between marine lake and lagoon populations was caused by a small number of individuals colonizing the lakes from the lagoon (founder event) followed by repetitive bottleneck events, such as those generated by the El Niño-Southern Oscillation (ENSO). So far, such high genetic divergences in extremely short geographical ranges (approximately 150-250 m) have scarcely been reported for marine organisms. We suggest that the marine lake is one of the good model of geographical isolation in marine organisms and each marine lake population is in the early stages of speciation.

Comprehensive phylogeny of the family Sparidae (Perciformes: Teleostei) inferred from mitochondrial gene analyses.

Sparid fishes consist of approximately 115 species in 33 genera that are broadly distributed in tropical and temperate coastal waters. Although several phylogenetic analyses were conducted based on specific molecular markers, their classification remains unresolved. Here, we present the most comprehensive molecular phylogeny of the family Sparidae to date, based on cytochrome b (cyt-b) genes. We determined 18 sequences of sparids and conducted phylogenetic analyses among 72 individuals representing 66 sparids with 23 outgroup species. Phylogenetic trees were constructed according to partitioned Maximum Likelihood (ML) and Bayesian methods. The phylogenetic analyses were conducted on two different data sets (including all positions; RY-coding). The phylogenetic trees showed monophyly of the family Sparidae with a different taxon, centracanthid Spicara. The subfamilies in the Sparidae in all trees are non-monophyletic and do not agree with current classification of the subfamilies. The genera Acanthopagrus, Cheimerius, Dentex, Diplodus, Pagellus, Pagrus, and Spicara are also non-monophyletic and their classifications should be revised based on the phylogenetic relationships and reinvestigation of morphological characters. The sparids are divided into three major clades, A, B and C, respectively in the ML tree based on all codon positions, whereas clade C was paraphyletic in the other trees. The species in clade C are known to be present in the eastern Pacific to western Atlantic, whereas those in clades A and B are distributed in various oceanic regions. Some sub-clades in clades A and B consist of species that are distributed in defined local regions. We further investigated evolutionary patterns of 87 morphological characters by ancestral character-state reconstruction according to the parsimony criteria. The results suggested high evolutionary plasticity of the characters in sparids, indicating that it causes species-diversity and taxonomic confusion at various taxonomic levels, and that such convergent evolution may occur more frequently also in other coastal fishes.

Genetic divergence and phylogenetic independence of Far Eastern species in subfamily Leuciscinae (Pisces: Cyprinidae) inferred from mitochondrial DNA analyses.

Classification of freshwater fish in the subfamily Leuciscinae, Cyprinidae is hampered by complexity or lack of morphological diversity. In this study, analyses based on mtDNA sequences were undertaken to clarify phylogenetic relationships among Far Eastern, North American and European species in the Leuciscinae. Evolutionary rate in cytochrome b gene (Cyt-b) and D-loop sequences appear to be almost constant in Leuciscinae. The topology of phylogenetic trees generated by neighbor-joining (NJ) and maximum likelihood (ML) methods based on Cyt-b gene and D-loop sequences was similar. Five major clades, designated clades 1-5, and a minor clade were discriminated. Most of the Far Eastern, North American and European species were included in the major clades. Clade 1, comprised almost entirely of Far Eastern phoxinins, is monophyletic and greatly diverged from the other species of Leuciscinae. From the present phylogenetic relationships and the previous studies, we present the following hypotheses with respect to the evolutionary history of the Far Eastern phoxinins. The Far Eastern species should be classified into Far Eastern-specific genera, although ichthyologists have still insisted that the species should be included in the European genera. The Far Eastern clade 1 consists of two subclades, including genera Pseudaspius-Tribolodon and Far Eastern Phoxinus species. According to our phylogenetic analyses, Pseudaspius leptocephalus and Tribolodon species should be reclassified into the same genus. On the basis of evolutionary rate in Cyt-b gene in Cyprinidae, it is estimated that the Far Eastern lineage diverged approximately 10-14 million years ago (mya) from the common ancestor of Leuciscinae. It is deduced that speciation of the Far Eastern species occurred until approximately 4 mya, in relation to the formation of the Sea of Japan and the Japanese Islands.

An autopsy case showing massive fibrinoid necrosis of the portal tracts of the liver with cholangiographic findings similar to those of primary sclerosing cholangitis.

An 81-year-old Japanese man with jaundice was strongly suspected clinically of having primary sclerosing cholangitis based on clinical examinations and later died of hepatic failure. The entire course of the disease lasted about 10 mo. The autopsy revealed extensive fibrinoid necrosis in the liver, kidney, spleen, pancreas, lung, lymph nodes, and pleura. Particularly extensive fibrinoid necrosis in the portal tracts of the liver induced severe stenoses of the intrahepatic bile ducts, resulting in cholestasis in association with prominent liver injury. There were no findings indicating primary sclerosing cholangitis. The hepatic lesions in this case did not coincide with any known disease including collagen diseases. To clarify the cause of irregular stenoses of the intrahepatic biliary trees on cholangiographic findings, we postulate that some form of immunological derangement might be involved in pathogenesis of fibrinoid necrosis. However, the true etiology remains unknown.

Frequent loss of heterozygosity in two distinct regions, 8p23.1 and 8p22, in hepatocellular carcinoma.

AIM: To identify the precise location of putative tumor suppressor genes (TSGs) on the short arm of chromosome 8 in patients with hepatocellular carcinoma (HCC). METHODS: We used 16 microsatellite markers informative in Japanese patients, which were selected from 61 published markers, on 8p, to analyze the frequency of loss of heterozygosity (LOH) in each region in 33 cases (56 lesions) of HCC. RESULTS: The frequency of LOH at 8p23.2-21 with at least one marker was 63% (20/32) in the informative cases. More specifically, the frequency of LOH at 8p23.2, 8p23.1, 8p22, and 8p21 was 6%, 52%, 47%, and 13% in HCC cases. The LOH was significantly more frequent at 8p23.1 and 8p22 than the average (52% vs 22%, P = 0.0008; and 47% vs 22%, P = 0.004, respectively) or others sites, such as 8p23.2 (52% vs 6%, P = 0.003; 47% vs 22%, P = 0.004) and 8p21 (52% vs 13%, P = 0.001; 47% vs 13%, P = 0.005) in liver cancer on the basis of cases. Notably, LOH frequency was significantly higher at D8S277, D8S503, D8S1130, D8S552, D8S254 and D8S258 than at the other sites. However, no allelic loss was detected at any marker on 8p in the lesions of nontumor liver tissues. CONCLUSION: Deletion of 8p, especially the loss of 8p23.1-22, is an important event in the initiation or promotion of HCC. Our results should be useful in identifying critical genes that might lie at 8p23.1-22.

Clinical implication of reverse redistribution on 99mTc-sestamibi images for evaluating ischemic heart disease.

OBJECTIVE: The purpose of this study was to clarify the usefulness of 99mTc-sestamibi (MIBI) delayed imaging in the assessment of the severity of myocardial ischemia in patients with coronary artery stenosis. METHODS: Forty-three angina pectoris with coronary stenosis of greater than 75% were enrolled in this study. Myocardial perfusion SPECT images were obtained 1 and 6 hours after an intravenous injection of MIBI at rest. Stress myocardial perfusion SPECT images were also acquired after the injection of MIBI. And myocardial fatty acid metabolism images were obtained 30 minutes after the injection of BMIPP at rest. Myocardial perfusion SPECT images were divided into 20 segments which were semiquantitatively assessed according to a 4-level defect score scale: score 0 (normal) to score 3 (severely); then the extent score (ES) and severity score (SS) were calculated. RESULTS: The sensitivity for myocardial ischemia showed the highest rate at 88.3% with MIBI delayed SPECT. According to the coronary angiography findings, MIBI stress SPECT and MIBI delayed SPECT detected the severity and extent of ischemia with more sensitivity than MIBI early SPECT in 12 patients (group A) with stenosis of more than 75% but less than 90% (p < 0.01). Even though MIBI stress SPECT detected the severity and extent of ischemia in 31 patients (group B) with stenosis of more than 90% but less than 100%, there was no significant difference between MIBI stress SPECT and MIBI delayed SPECT. BMIPP SPECT revealed significant differences between group A and group B regarding the severity of myocardial ischemia. MIBI reverse redistribution was observed in 33 patients and no significant difference existed between groups A and B. CONCLUSIONS: Myocardial washout of MIBI was frequently observed in patients with angina pectoris and the detection accuracy for ischemia was high. MIBI imaging is considered useful for assessment not only of myocardial perfusion but also mitochondrial function. The imagings with BMIPP and delayed MIBI could serve to determine the severity of myocardial ischemia more accurately.

VEGF-mediated angiogenesis is impaired by angiotensin type 1 receptor blockade in cardiomyopathic hamster hearts.

OBJECTIVE: Coronary microcirculation plays an important role in the progression of cardiac remodeling. Among angiogenic factors, it has been reported that angiotensin II may contribute to neovascularization. However, it is unknown whether inhibition of the renin-angiotensin system suppresses angiogenesis, especially within the heart. Our aim was to evaluate the effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor type I blocker valsartan on cardiac microvasculature, function, vascular endothelial growth factor (VEGF) expression, and survival in cardiomyopathic hamsters. METHODS: Male cardiomyopathic hamsters (BIO TO2) were administered either a placebo (group C), enalapril (30 mg/kg/day) (group E), or valsartan (40 mg/kg/day) (group V), starting at the age of 6 weeks. This continued until death. Hemodynamic study, histological analysis, and northern blot analysis were performed at 39 weeks. RESULTS: Group V showed significant increases in percent fibrosis, end diastolic pressure, and LV dP/dt min, and significant decreases in percent fractional shortening, LV dP/dt max, capillary density, and the level of mRNA expression of VEGF compared with group C. Group E showed significant increases in percent fractional shortening while the capillary density and level of mRNA expression of VEGF were unchanged. The 300-day survival rate was significantly lower in group V (25.0%) but higher in group E (100%) than that of group C (66.7%). CONCLUSIONS: Therapy with valsartan may have adverse effects on survival rate concomitant with the progression of cardiac remodeling owing to impaired VEGF-mediated angiogenesis. Therapy with enalapril has a neutral effect on VEGF-mediated angiogenesis, leading to the suppression of cardiac remodeling and an increase in life expectancy.

A newly developed angiotensin II type 1 receptor antagonist, CS866, promotes regression of cardiac hypertrophy by reducing integrin beta1 expression.

Previous studies have demonstrated that integrins link the extracellular matrix to the hypertrophic response pathway of cardiac myocytes in vitro. To examine the direct relation between integrin beta1 and cardiac hypertrophy in vivo, we studied the effects of a newly developed angiotensin II type 1 (AT1) blocker, CS866 (ARB; 10 mg/kg/day), an angiotensin-converting enzyme inhibitor, temocapril (ACEI, 10 mg/kg/day), or both on modulation of integrin beta1 in the hypertrophied hearts of stroke-prone spontaneously hypertensive rats (SHRSP) 6 to 12 weeks of age. Treatments with ARB, ACEI, and combination therapy significantly reduced systolic blood pressure. However, the reduction in cardiac hypertrophy was greater in SHRSP treated with ARB or combination therapy than in those treated with ACEI. Multiplex reverse transcription-polymerase chain reaction revealed significantly higher mRNA expression of atrial natriuretic factor, AT1 receptor, and integrin beta1 in untreated SHRSP than in normotensive Wistar-Kyoto rats (WKY). The mRNA levels of ANP, AT1 receptor, and integrin B1 in SHRSP were significantly decreased by treatment with ARB, ACEI, or combination therapy. Decreased mRNA expression of ANP, AT1 receptor, and integrin beta1 in the treated SHRSP was associated with reductions in blood pressure; ARB and combination therapy produced greater decreases in expression than did ACEI. These observations suggest that CS866 has a beneficial effect on myocyte hypertrophy and that down-regulation of AT1 receptor and suppression of integrin beta1 participate in the regression of pressure-induced cardiac hypertrophy in vivo. The correlation between the expression of integrin beta1 and AT1 receptor was significant. Our results also suggest that integrin expression by myocytes might be modulated by angiotensin II via AT1 receptor.

Cardiac (18)F-FDG PET/CT with heparin detects infective vegetation in a patient with mechanical valve replacement.

We report the usefulness of F-FDG PET/CT for the detection and therapy evaluation of the infective vegetation. A 64-year-old man with history of aortic valve replacement presented with 2 months of fever without identifiable cause. Echocardiogram showed no inflammation vegetation or abnormality of mechanical valve function. FDG PET/CT with 50 IU/kg IV heparin revealed focal uptakes near the mechanical aortic valve. After antibiotics therapy, fever was ameliorated, and FDG PET/CT findings showed markedly decreased uptake of the lesions. FDG PET/CT is a powerful tool to detect endocarditis even in patients with no anatomical abnormalities.

Transcriptome analysis of the duodenum, pancreas, liver, and muscle from diabetic Goto-Kakizaki rats fed a trypsin inhibitor derived from squid viscera.

Trypsin inhibitors (TIs) have various nutritional effects. However, a detailed mechanism for their effects, especially on the gene expression patterns in various tissues, remains unknown. Here, we used transcriptome techniques and gene ontology (GO) analysis to examine the effects of squid TI (sqTI), a biochemically stable peptide, on diabetic Goto-Kakizaki rats after feeding for 10 weeks. We demonstrated that downregulation of SREBP1c in the liver via duodenal/pancreatic hormones suppresses the blood cholesterol level. Consistently, in GO analysis, the term "cholesterol biosynthetic process" was enriched among downregulated genes. No hypoglycemic or insulinotropic effects were observed, in contrast to the results from our previous studies (single stimulation with the same dose of TI), which can be partly ascribed to the inactive responses of the duodenum and pancreas in this condition.

Transcriptome analysis of the duodenum in Wistar rats fed a trypsin inhibitor derived from squid viscera.

To investigate the effects of oral administration of a trypsin inhibitor (TI), normal Wistar rats were fed a TI derived from squid (Todarodes pacificus) for 10 weeks and gene expression profiles in the duodenum, pancreas, liver, and muscle were then analyzed using DNA microarrays. Although no significant changes could be observed in growth, food intake, tissue weight, or blood tests among the tissues tested, the duodenum showed the most remarkable changes in the global gene expression profile. Significant up-regulation of mRNAs encoding gastrin, gastrokine, cholecystokinin and somatostatin in the duodenum was validated by qPCR analysis. In gene ontology (GO) analysis of the up-regulated differentially expressed genes (DEGs), GO terms related to keratinization and innate mucosal defense were enriched (p < 0.001) in the category of biological processes in addition to assumable terms such as regulation of secretion and response to nutrients, vesicle-mediated transport, and so forth. In the same analysis, calcium ion binding was listed at the deepest hierarchy in the category of molecular function. These results indicate that the duodenum responds to TI treatment by a wider range of physiological processes than previously assumed such as keratinocyte differentiation and innate mucosal defense, in which calcium plays a crucial role.

Population genetic structure of the striped silverside, Atherinomorus endrachtensis (Atherinidae, Atheriniformes, Teleostei), inhabiting marine lakes and adjacent lagoons in Palau: marine lakes are "Islands" for marine species.

Although evidence for the evolution of terrestrial species on islands continues to rapidly accumulate, little is known about the evolution of marine species in geographically isolated environments such as islands as ocean currents often facilitate gene flow among populations. In this study, we focused on marine lakes of the Palau Islands, which are considered to be true analogues of terrestrial islands for marine species. To examine evolutionary processes in marine lakes, we conducted population genetic analyses on marine lake and lagoon populations of the striped silverside, Atherinomorus endrachtensis, using two mitochondrial DNA markers differing in evolutionary rate, the cytochrome b gene and the control region. The analyses revealed that the amount of genetic diversity of marine lake populations is much lower than that of lagoon populations and high levels of genetic differentiation occur among marine lake and lagoon populations. The present study has shown that marine lake populations have been completely isolated and have differentiated from lagoon populations, and each marine lake population is experiencing different evolutionary processes. These findings clearly demonstrate that marine lakes are excellent environments for the evolutionary study of marine species.

Effects of surgical ventricular reconstruction and mitral complex reconstruction on cardiac oxidative metabolism and efficiency in nonischemic and ischemic dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to investigate the effects of surgical ventricular reconstruction (SVR) on cardiac efficiency as a surrogate marker for cardiac function and oxidative metabolism in patients with severe heart failure. BACKGROUND: Our new integrated overlapping left ventriculoplasty, modified SVR, combined with mitral complex reconstruction, reduce left ventricular (LV) volume associated with improvement of symptoms of heart failure. METHODS: Twelve consecutive patients with end-stage heart failure due to nonischemic dilated cardiomyopathy (DCM) (n = 6) and ischemic dilated cardiomyopathy (ICM) (n = 6) who underwent SVR were studied. Myocardial oxidative metabolism per gram of tissue was estimated by monoexponential clearance of (11)C-acetate positron emission tomography (K(mono)). Forward stroke volume at the LV outflow tract was measured by echocardiography. Cardiac efficiency was estimated by the ratio of external work (stroke volume at the LV outflow tract index × systolic blood pressure × heart rate) to K(mono) before and 1 month after SVR. RESULTS: After SVR, medians of New York Heart Association functional class significantly improved from 3 to 1.5 (p < 0.01) in both DCM and ICM patients. End-systolic and end-diastolic volume and LV mass significantly decreased in both groups. Stroke volume at the LV outflow tract increased from 43 ± 8 ml to 52 ± 11 ml (p = 0.028) in DCM patients, but not in ICM patients (49 ± 21 ml to 59 ± 26 ml, p = 0.12). K(mono) × LV mass, as an index of global LV oxidative metabolism, decreased in DCM patients (13.6 ± 1.9 g/min vs. 8.6 ± 1.5 g/min, p = 0.03) and ICM patients (12.0 ± 3.4 g/min vs. 9.2 ± 1.0 g/min, p = 0.06). As a result, cardiac efficiency increased in all patients with DCM (3.34 ± 0.46 × 10E6 vs. 4.74 ± 0.88 × 10E6 mm Hg·ml·min/m(2), p = 0.03) and in 5 of 6 patients with ICM (4.54 ± 1.66 × 10E6 vs. 5.99 ± 2.11 × 10E6 mm Hg·ml·min/m(2), p = 0.12). CONCLUSIONS: Combined surgery with SVR and mitral complex reconstruction reduced LV volume in association with improvement of cardiac efficiency in patients with severe heart failure.

Acute coronary syndrome due to coronary artery compression by a metastatic cardiac tumor.

A 60-year-old female without coronary risk factors was admitted to the hospital with ST-elevation acute coronary syndrome (ACS). She had previously suffered breast cancer and received radical mastectomy followed by chemotherapy and radiation. Emergent coronary angiography showed an occlusion of the proximal left anterior descending coronary artery (LAD) and coronary angioplasty was performed. Coronary computed tomography (CT) angiography (CTA) disclosed a tumor invading the left ventricular anterior wall and surrounding the coronary artery. Myocardial single-photon-emission CT (SPECT) using 123I-BMIPP showed a defect in the same portion. A fusion image of the CTA and the SPECT delineated a tumor surrounding the coronary artery. She finally died two months later from a terminal condition. Autopsy demonstrated a tumor involving the left ventricular anterior wall and surrounding the LAD. Pathology of the affected LAD showed only fibrous plaque without vulnerable plaque, thrombus, or tumor invasion to the coronary wall. Thus, compression of the coronary artery by the metastatic tumor was the most likely mechanism of ACS.