Association between J-CTO score and long-term target lesion revascularization rate after successful chronic total coronary occlusion angioplasty (from the J-CTO Registry).

OBJECTIVES: The aim of this study was to evaluate the impact of the J-CTO score on long-term target lesion revascularization (TLR) after successful native chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). BACKGROUND: We previously reported that the J-CTO score could be used to stratify the lesion complexity and procedural success rate in CTO lesions. METHODS: We evaluated the prognostic significance of a high J-CTO score for long-term TLR rate in the J-CTO Registry. RESULTS: In the 425 lesions of 408 patients who underwent successful CTO-PCI during a median follow-up of 63.0 (interquartile range: 21.2-72.9) months in the J-CTO Registry, the cumulative incidence of TLR of lesions with a J-CTO score ≥ 2 (n = 216) was significantly higher than in those with a J-CTO score ≤ 1 (n = 209) (27.0 versus 19.4% at 5 years, respectively, P = 0.04). Among 323 lesions of 309 patients with a complete 5-year follow-up, the rate of TLR was 28% (n = 91). A J-CTO score ≥ 2 was independently associated with a higher risk of TLR (odds ratio, 1.73; 95% confidence interval, 1.01-2.99, P = 0.048) even after adjustment for clinically relevant baseline factors. CONCLUSIONS: Patients with high J-CTO score lesions had a higher 5-year risk of TLR.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Intrauterine insemination with fresh semen in Amur leopard cat (Pionailurus bengalensis eutilura) during non-breeding season.

Equine and human chorionic gonadotropins were administered to two female Amur leopard cats to induce estrus and ovulation during non-breeding season. Fresh semen collected from male cats was surgically inseminated into the uterine horn of the females. In one animal, two fetal sacs without heartbeats were observed on abdominal ultrasonography 31 days after insemination, which indicated that embryo death had occurred. In the other animal, fetal heartbeats were detected in two fetal sacs 29 days after insemination, which confirmed as pregnancy. This animal delivered two newborns 68 days after insemination; the one of the kittens was assumed to be stillbirth, and the other grew normally. In this study, we successfully obtained a kitten from an Amur leopard cat by artificial breeding for the first time in Japan.

Puberty, ovarian cycle, pregnancy, and postpartum ovulation in captive Sichuan golden monkeys (Rhinopithecus roxellana) based on changes in urinary and fecal gonadal steroid metabolites.

The purpose of this study was to evaluate the reproductive status and clarify the reproductive physiology of captive Sichuan golden monkeys. The concentrations of urinary estradiol-3-glucuronide (E2G) and pregnanediol-glucuronide (PdG) or fecal estradiol-17ß (E2) and PdG in two females, and fecal testosterone concentrations in a male, were measured continuously using enzyme immunoassays. On the basis of these hormone profiles, the follicular phase, luteal phase, and ovarian cycle were calculated to be 14.7 ± 4.8, 10.4 ± 2.8, and 25.1 ± 3.3 days, respectively. The first ovulation (puberty) in a female monkey was observed at 5.1 years old, and the first pregnancy was diagnosed at 6.4 years old. For the first 2 months of pregnancy (204 days), fecal E2 and PdG maintained constant high values and then increased until parturition. These profiles were similar to urinary E2G and PdG changes. During the last trimester of a twin pregnancy, fecal PdG was up to approximately three times higher compared with a single pregnancy. Therefore, fecal PdG levels in late pregnancy may be effective for the detection of a twin pregnancy. The first postpartum ovulation occurred 66 (fetal death and artificial rearing), 143 (fetal death), and 189 (natural suckling) days after parturition. The anovulation period of the natural suckling case was longer than the others. Conception and postpartum ovulation were detected between September and January. Fecal testosterone levels of the male were correlated with the fecal E2 level of the nonpregnancy period in exhibited together female. Our results reported that urinary (E2G and PdG) and fecal (E2 and PdG) hormone measurement is effective for monitoring the reproductive status, thereby expanding knowledge of the reproductive endocrinology of this endangered species.

Impact of J-CTO score on procedural outcome and target lesion revascularisation after percutaneous coronary intervention for chronic total occlusion: a substudy of the J-CTO Registry (Multicentre CTO Registry in Japan).

AIMS: We investigated the impact of the J-CTO score, a pre-procedural risk score for successful guidewire crossing within 30 minutes through chronic total occlusion (CTO) lesions, on procedural and midterm clinical outcomes in terms of target lesion revascularisation (TLR) after CTO recanalisation. METHODS AND RESULTS: The primary endpoint of this substudy was midterm TLR. The net midterm success rate was calculated by multiplying the lesion success rate by the TLR-free survival rate. The initial lesion success rates according to the J-CTO score categories of 0, 1, 2, and ≥3 were 97.0%, 92.1%, 86.5%, and 73.6%, respectively (p<0.001). The TLR rates at one year according to the J-CTO score categories of 0, 1, 2, and ≥3 were 5.3%, 11.1%, 16.7%, and 13.4%, respectively (p=0.082). The net midterm success rates according to the J-CTO score categories of 0, 1, 2, and ≥3 were 91.9%, 81.9%, 72.1%, and 63.7%, respectively (p<0.001). CONCLUSIONS: Patients with CTO lesions with lower J-CTO scores are expected to achieve a high procedural success rate and an increased TLR-free survival rate. Patients with high J-CTO scores still remain an issue.

Successful interventional revascularization utilizing hybrid procedural steps of rotational atherectomy and retrograde approach via an ipsilateral collateral.

Here, we report a case of successful interventional revascularization of the left anterior descending artery (LAD) in two heavy calcified chronic total occlusion (CTO) lesions, which were uncrossable utilizing hybrid procedural steps of local rotational atherectomy and a retrograde approach by reverse controlled antegrade and retrograde tracking (CART) technique via an ipsilateral intraseptal collateral. A-76-year-old man that had undergone previous coronary artery bypass surgery was admitted for ischemic heart failure. Coronary angiography showed that the left internal thoracic artery graft that was anastomosed to the first diagonal branch was patent. However, his native LAD had two CTOs as if the open vessel had sandwiched them. Moreover, there were no interventional collaterals. The antegrade guidewire was successfully passed through both CTOs. However, devices were uncrossable at the entry of the distal LAD-CTO. After stent deployment at the proximal CTO, local rotational atherectomy with a 1.5 mm burr was performed as plaque modification from the protruding calcified plaque at the bifurcation of the first septal branch to the distal CTO entry for the following procedure, although the dedicated guidewire was unable to pass completely through the distal CTO segment. Staged PCI to the distal LAD-CTO was performed using a retrograde approach via an ipsilateral intraseptal collateral, which had grown due to recanalization of the proximal LAD-CTO. Due to plaque modification by rotablation at the first attempt, successful interventional revascularization to the distal LAD-CTO was accomplished using the reverse CART technique.

Effects of 13 developmentally toxic chemicals on the migration of rat cephalic neural crest cells in vitro.

The inhibition of neural crest cell (NCC) migration has been considered as a possible pathogenic mechanism underlying chemical developmental toxicity. In this study, we examined the effects of 13 developmentally toxic chemicals on the migration of rat cephalic NCCs (cNCCs) by using a simple in vitro assay. cNCCs were cultured for 48 h as emigrants from rhombencephalic neural tubes explanted from rat embryos at day 10.5 of gestation. The chemicals were added to the culture medium at 24 h of culture. Migration of cNCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of cNCCs between 24 and 48 h of culture. Of the chemicals examined, 13-cis-retinoic acid, ethanol, ibuprofen, lead acetate, salicylic acid, and selenate inhibited the migration of cNCCs at their embryotoxic concentrations; no effects were observed for acetaminophen, caffeine, indium, phenytoin, selenite, tributyltin, and valproic acid. In a cNCC proliferation assay, ethanol, ibuprofen, salicylic acid, selenate, and tributyltin inhibited cell proliferation, suggesting the contribution of the reduced cell number to the inhibited migration of cNCCs. It was determined that several developmentally toxic chemicals inhibited the migration of cNCCs, the effects of which were manifested as various craniofacial abnormalities.

Influence of Sex on Long-Term Outcomes After Implantation of Bare-Metal Stent: A Multicenter Report From the Coronary Revascularization Demonstrating Outcome Study-Kyoto (CREDO-Kyoto) Registry Cohort-1.

BACKGROUND: Female sex was reported to be associated with lower risk for midterm restenosis and repeat revascularization after bare-metal stent implantation. However, the influence of sex on very long-term outcomes after bare-metal stent implantation has not been yet reported. METHODS AND RESULTS: Among the 9877 patients in the multicenter Coronary Revascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto) registry cohort-1, bare-metal stent implantation was performed in 5313 patients (men, n=3742 and women, n=1571). Follow-up was completed in 4515 patients (85.0%) at 10 years (duration, 10.3 ± 3.1 [0.0-14.1] years). The cumulative incidence of target-lesion revascularization (TLR) was 27% at 1 year and 34% at 10 years (0.8%/y beyond 1 year). Non-target-lesion revascularization (non-TLR) was the dominant coronary revascularization beyond 1 year (13% at 1 year and 31% at 10 years [2.0%/y beyond 1 year]). Cumulative incidence of stent thrombosis was low (1.2% at 1 year and 1.9% at 10 years). Women were older and had greater prevalence of cardiovascular risk factors than men. The cumulative 10-year incidences of and adjusted risk for TLR were significantly higher in men than in women (36% versus 30%, P<0.001; adjusted hazard ratio, 1.29; 95% confidence interval, 1.15-1.46; P<0.001). The higher risk of men relative to women for TLR was consistent regardless of age (<75 years and ≥ 75 years). Men in comparison with women were also associated with significantly higher adjusted risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR. CONCLUSIONS: TLR and stent thrombosis continued to occur without attenuation up to 10 years after bare-metal stent implantation. Men in comparison with women were associated with higher adjusted 10-year risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR.

Colloidal submicron-particle curcumin exhibits high absorption efficiency-a double-blind, 3-way crossover study.

Curcumin is a major constituent of the spice turmeric and has various biological activities, including anticancer, antioxidant, and anti-inflammatory properties, as well as alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to exert its bioactivities. To overcome this problem, several curcumin preparations with a drug-delivery system (DDS) have been developed to increase the bioavailability of curcumin after oral administration, and tested as functional foods and potential medical agents in humans. We have also produced capsules containing Theracurmin, curcumin dispersed with colloidal submicron-particles. To evaluate the absorption efficiency of three types of DDS curcumin, we performed a double-blind, 3-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin and 2 other capsule types of curcumin with DDS, BCM-95 (micronized curcumin with turmeric essential oils) and Meriva (curcumin-phospholipid). Nine healthy subjects (male/female=5/4, age: 24-32 y old) were administered these 3 preparations of DDS curcumin, at commonly used dosages. Six capsules of Theracurmin, 1 capsule of BCM-95, and 2 capsules of Meriva contain 182.4 ± 1.0, 279.3 ± 10.7, and 152.5 ± 20.3 mg of curcumin, respectively. The maximal plasma curcumin concentration (0-24 h) of Theracurmin was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively. Moreover, the area under the blood concentration-time curve at 0-24 h was found to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva, respectively. These data indicate that Theracurmin exhibits a much higher absorption efficiency than other curcumin DDS preparations.

Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2.

Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.

Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence.

Simple in vitro migration assay for neural crest cells and the opposite effects of all-trans-retinoic acid on cephalic- and trunk-derived cells.

Here, we describe a simple in vitro neural crest cell (NCC) migration assay and the effects of all-trans-retinoic acid (RA) on NCCs. Neural tubes excised from the rhombencephalic or trunk region of day 10.5 rat embryos were cultured for 48 h to allow emigration and migration of NCCs. Migration of NCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of NCCs between 24 and 48 h of culture. RA was added to the culture medium after 24 h at embryotoxic concentrations determined by rat whole embryo culture. RA (10 µM) reduced the migration of cephalic NCCs, whereas it enhanced the migration of trunk NCCs, indicating that RA has opposite effects on these two types of NCCs.

Proteomic analysis of ethanol-induced embryotoxicity in cultured post-implantation rat embryos.

Protein expression changes were examined in day 10.5 rat embryos cultured for 24 hr in the presence of ethanol by using two-dimensional electrophoresis and mass spectrometry. Exposure to ethanol resulted in quantitative changes in many embryonic protein spots (16 decreased and 28 increased) at in vitro embryotoxic concentrations (130 and 195 mM); most changes occurred in a concentration-dependent manner. For these protein spots, 17 proteins were identified, including protein disulfide isomerase A3, alpha-fetoprotein, phosphorylated cofilin-1, and serum albumin. From the gene ontology classification and pathway mapping of the identified proteins, it was found that ethanol affected several biological processes involving oxidative stress and retinoid metabolism.

Late adverse events after implantation of sirolimus-eluting stent and bare-metal stent: long-term (5-7 years) follow-up of the Coronary Revascularization Demonstrating Outcome study-Kyoto registry Cohort-2.

BACKGROUND: Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. METHODS AND RESULTS: Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). CONCLUSIONS: Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

Drinkable preparation of Theracurmin exhibits high absorption efficiency--a single-dose, double-blind, 4-way crossover study.

Curcumin has various biological activities including antioxidant and antiinflammatory actions, and alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to realize its bioactivities. We have generated capsules and tablets containing Theracurmin, a highly absorptive curcumin. In addition, we recently created a drinkable preparation of Theracurmin. To evaluate the absorption efficiency of this type of curcumin, we performed a single-dose, double-blind, 4-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin beverage and 3 other drinkable types of curcumin sold in Japan. Twenty-four healthy subjects (male/female=13/11, age: 23-32) were administered with these 4 drinkable preparations of curcumin. The area under the blood concentration-time curve at 0-8 h was found to be 1.5 to 4.0-fold higher with Theracurmin than with the other 3 kinds of curcumin beverage. Moreover, maximal plasma curcumin concentrations (0-8 h) of Theracurmin were 1.8 to 3.8 times higher than those of the other 3 curcumin beverages. These data indicate that our newly prepared Theracurmin beverage exhibits a much better absorption efficiency than other kinds of curcumin beverage sold in Japan.

Long-term outcomes after percutaneous coronary intervention for chronic total occlusion (from the CREDO-Kyoto registry cohort-2).

Despite improving success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions, the clinical benefit of recanalization of CTO is still a matter of debate. Of 13,087 patients who underwent PCI in the CREDO-Kyoto registry cohort-2, 1,524 patients received PCI for CTO (CTO-PCI). Clinical outcomes were compared between 1,192 patients with successful CTO-PCI and 332 patients with failed CTO-PCI. In-hospital death tended to occur less frequently in the successful CTO-PCI group than in the failed CTO-PCI group (1.4% vs 3.0%, p = 0.053). Through 3-year follow-up, the cumulative incidence of all-cause death was not significantly different between the successful and failed CTO-PCI groups (9.0% vs 13.1%, p = 0.18), whereas the cumulative incidence of cardiac death was significantly less in the successful CTO-PCI group than in the failed CTO-PCI group (4.5% vs 8.4%, p = 0.03). However, after adjusting confounders, successful CTO-PCI was associated with lesser risk for neither all-cause death (hazard ratio 0.93, 95% confidence interval 0.64 to 1.37, p = 0.69) nor cardiac death (hazard ratio 0.71, 95% confidence interval 0.44 to 1.16, p = 0.16). The cumulative incidence of coronary artery bypass grafting (CABG) was remarkably less in patients with successful PCI compared with those with failed PCI (1.8% vs 19.6%, p <0.0001). In conclusion, successful CTO-PCI compared with failed PCI was not associated with lesser risk for 3-year mortality. However, successful CTO-PCI was associated with significantly less subsequent CABG.

Diversity in the matrix structure of eggshells in the Testudines (Reptilia).

The eggshells of 56 chelonians were examined by electron microscopy and X-ray diffractometry. They were classified into six types in terms of the matrix structure of their calcareous layer; type I was composed of a thin calcareous layer with minerals in an amorphous structure; type II with shell units composed of mammillary cores calcified with aragonite crystals; type III with shell units composed of mammillary cores, plus a single palisade layer also calcified with aragonite crystals, and with each shell unit separated; type IV with shell units the same as type III, but tightly packed together; type V with shell units composed of mammillary cores plus two palisade layers; and type VI with a cuticle layer calcified with calcite crystals over the same structure as that of type V. X-ray diffraction analyses at the outer surface of eggshells showed a gradual change in crystal disposition from the random disposition of type II to the single direction-oriented disposition of type V. The shell height was approximately parallel to the development of the palisade-layer matrix. The limiting membrane of all eggshell types was perforated with canals and that of type I was partially missing. Type I had a parchment shell, types II and III had a pliable shell (some were rigid) and types IV to VI had rigid shells. The present study showed that the hardness of eggshells can be determined by the composition of the shell matrices, as shell matrices are the framework for mineralization.

Season- and age-related reproductive changes based on fecal androgen concentrations in male koalas, Phascolarctos cinereus.

The purposes of the present study were to clarify age- and season- related androgen patterns, and to compare the reproductive physiology between Japanese captive koala populations and Australian populations. To measure fecal androgens, feces were collected from male koalas (4.2 to 13.8 years of age) kept in Japanese zoos. Fecal androgens were extracted with methanol from the lyophilized samples and determined by enzyme immunoassay using 4-androstene-3,17-dione antibody. Fecal androgen concentration in male koalas increased after sexual maturation and remained relatively high until old age. In the survey with the Japanese zoo studbook of koalas, copulation (conception) month showed a pyramid shape with a peak in March to June (60.7%) in koalas born and reared in Japanese zoos and from July to April with the highest concentration in September to January (69.7%) in Australian institutes. Japanese zoo koala populations have a characteristic physiological cycle adapted to Japan's seasonal changes. The suitable month of year for copulation or conception in Japan is diametrically opposed to that in Australia. Mean fecal androgen concentrations by month in the males born and reared in Japan indicated annual changes with the highest concentration in May and the lowest value in November. Fecal androgen analysis may be a noninvasive alternative tool to monitor circulating testosterone and may be helpful in understanding reproductive activity and physiology in male koalas.

Reproductive characteristics of female lesser mouse deers (Tragulus javanicus) based on fecal progestagens and breeding records.

Information about breeding and the reproductive biology of mouse deer is limited in the wild and captivity. No reports on reproductive endocrinology are available. The objective of the present study was to observe the reproductive biology based on breeding records, to validate the utility of the non-invasive endocrine monitoring technique using feces of the female lesser mouse deer (Tragulus javanicus), and thus to clarify the reproductive physiology. Breeding records from 2 females were investigated and the fecal progestagen profile was monitored in captivity. Fecal progestagens were extracted using methanol and measured by enzyme immunoassay. From the breeding records, many births occurred in May (spring) and November-December (winter); however, fecal progestagen profile showed cyclical changes throughout the year in a female mouse deer. Most mounting and mating behaviors were observed 2-3 days after the peak of progestagen concentration during luteal phase. The ovarian cycle length based on the fecal progestagen profile averaged 14.5±0.3 days. The fecal progestagen concentration remained high during pregnancy. Fecal progestagen monitoring is useful for evaluating ovarian activity and pregnancy in the lesser mouse deer.

Antiplatelet therapy and long-term clinical outcome after sirolimus-eluting stent implantation: 5-year outcome of the j-Cypher registry.

Due to serious concerns on very late stent thrombosis (VLST), extended use of dual antiplatelet therapy (DAPT) beyond 1 year after DES implantation has become a common clinical practice despite apparent lack of evidence suggesting its efficacy in reducing VLST. The study population consisted of 12812 patients in the j-Cypher registry who were treated with at least one sirolimus-eluting stent (SES). We assessed the relation between duration of thienopyridine therapy and clinical outcomes with a landmark analysis at 1 year after SES implantation. Among 11713 patients without myocardial infarction (MI), stent thrombosis and stroke at 1 year who were eligible for the landmark analysis, 7414 patients (63 %) were maintained on thienopyridine at 1-year landmark point, while 4299 patients (37 %) had discontinued thienopyridine before 1-year landmark point. Patients in the on-thienopyridine group had more complex characteristics than patients in the off-thienopyridine group. Cumulative incidence of and the risk for definite VLST in the on-thienopyridine group relative to the off-thienopyridine group favored prolonged DAPT, but were not significant [0.9 and 1.2 %, P = 0.1, and adjusted HR (95 % CI): 0.71 (0.47-1.06), P = 0.11]. Cumulative incidence of and the risk for a composite of death, MI, or stroke in the on-thienopyridine group relative to the off-thienopyridine group were also not significant [15.3 and 14.3 %, P = 0.15, and adjusted HR (95 % CI): 0.99 (0.89-1.11), P = 0.89]. Prolonged use of thienopyridine beyond 1 year after SES implantation was not associated with significant decrease in the risks for VLST or for serious cardiovascular events including death, MI or stroke.