The trophotaenial placenta is a branching, ribbon-like structure that extends from the perianal region of the embryo in viviparous teleost fishes belonging to the family Goodeidae. It is a hindgut-derived pseudoplacenta, which contributes to absorbing maternal nutrients during the prenatal stage. The trophotaeniae are known to reduce at birth; however, no previous study has evaluated the removal mechanisms. We report here the analysis of the trophotaeniae using the goodeid fish species Xenotoca eiseni. The X. eiseni trophotaenia consists of an epidermal cell layer, mesenchyme, vasculature, and circulating erythrocytes. The trophotaeniae had preliminary regressed when the embryo was born. Immunohistochemistry indicated that caspase3-activated cells with fragmented nuclei are present in the regressed processes of the fry immediately after birth, but not in the vasculature and blood cells. This finding suggests that the trophotaenia is rapidly resorbed by apoptosis in the last phase of the pregnancy and that its circulatory pathway is maintained. Such prenatal regression of pseudoplacentae has not been reported in other viviparous vertebrates. On the other hand, similar apoptotic remodeling in the gut has been reported in amphibians, which is regulated by thyroid hormone. Thus, apoptotic regression of the trophotaeniae might occur in a manner similar to amphibian metamorphosis.
We investigated the incidence of prostaglandin-associated periorbitopathy (PAP) in subjects with glaucoma treated with latanoprost ophthalmic solution.
Subjects and methods
One eye and the forehead in 22 subjects were evaluated. All patients had used latanoprost for more than 1 year (range, 12 to 45 months; mean, 26.0 months) and were prostaglandin F2α analogue treatment-naïve. Digital photographs of the subjects obtained before latanoprost therapy and at the last examination were compared retrospectively. Four signs of PAP (deepening of the upper eyelid sulcus (DUES), upper eyelid ptosis, flattening of the lower eyelid bags, and inferior scleral show) and supplemental side effects around the eyelids (eyelash growth, poliosis, and eyelid pigmentation) were judged to be negative or positive by three independent observers. If the observers unanimously rated a sign as positive, the result was defined as positive.
Twelve subjects (54.5%) had no apparent signs. Three subjects were judged to have DUES (13.6%), and two subjects each were judged to have flattening of the lower eyelid bags and eyelid pigmentation (9.0%). The other signs were judged as positive in only one subject each, respectively (4.5%). A univariate logistic regression analysis showed no significant associations between any of the signs and age, sex, or the duration of therapy.
Latanoprost induced DUES, upper eyelid ptosis, flattening of the lower eyelid bags, inferior scleral show, and supplemental side effects around the eyelids; however, the rates of such occurrence might be relatively low.
glaucoma; prostaglandin F2α; deepening of the upper eyelid sulcus
Bifidobacterium longum 105-A shows high transformation efficiency and allows for the generation of gene knockout mutants through homologous recombination. Here, we report the complete genome sequence of strain 105-A. Genes encoding at least four putative restriction-modification systems were found in this genome, which might contribute to its transformation efficiency.
Both circuit and single-cell properties contribute to network rhythms. In vitro, pyramidal cells exhibit theta-band membrane potential (subthreshold) resonance, but whether and how sub-threshold resonance translates into spiking resonance in behaving animals is unknown. Here, we used optogenetic activation to trigger spiking in pyramidal cells or parvalbumin immunoreactive interneurons (PV) in the hippocampus and neocortex of freely-behaving rodents. Individual directly-activated pyramidal cells exhibited narrow-band spiking centered on a wide range of frequencies. In contrast, PV photoactivation indirectly induced theta band-limited, excess post-inhibitory spiking in pyramidal cells (resonance). PV-inhibited pyramidal cells and interneurons spiked at PV-inhibition troughs, similar to CA1 cells during spontaneous theta oscillations. Pharmacological blockade of hyperpolarization-activated (Ih) currents abolished theta resonance. Inhibition-induced theta-band spiking was replicated in a pyramidal cell-interneuron model that included Ih. Thus, PV interneurons mediate pyramidal cell spiking resonance in intact cortical networks, favoring transmission at theta frequency.
Accumulated signal noise will cause the integrated values to drift from the true value when measuring orientation angles of wearable sensors. This work proposes a novel method to reduce the effect of this drift to accurately measure human gait using wearable sensors. Firstly, an infinite impulse response (IIR) digital 4th order Butterworth filter was implemented to remove the noise from the raw gyro sensor data. Secondly, the mode value of the static state gyro sensor data was subtracted from the measured data to remove offset values. Thirdly, a robust double derivative and integration method was introduced to remove any remaining drift error from the data. Lastly, sensor attachment errors were minimized by establishing the gravitational acceleration vector from the acceleration data at standing upright and sitting posture. These improvements proposed allowed for removing the drift effect, and showed an average of 2.1°, 33.3°, 15.6° difference for the hip knee and ankle joint flexion/extension angle, when compared to without implementation. Kinematic and spatio-temporal gait parameters were also calculated from the heel-contact and toe-off timing of the foot. The data provided in this work showed potential of using wearable sensors in clinical evaluation of patients with gait-related diseases.
gait analysis; biomechanics; wearable sensors; drift effect; Lower Limb Kinematics; spatio-temporal gait parameter
Seborrheic dermatitis is an inflammatory eruption that tends to distribute on the sebaceous areas of the body and is rarely described as a paraneoplasia. Here we report a case with a responsive seborrheic dermatitis-like eruption of the head which resulted in generalized erythroderma. Intensive examinations detected concurrent malignant lymphoma.
Seborrheic dermatitis; Paraneoplastic syndrome; Peripheral T cell lymphoma
The hydroxylation of aromatic substrates catalyzed by coupled binuclear copper enzymes has been observed with side-on-peroxo-dicopper(II) (P) and bis-μ-oxo-dicopper(III) (O) model complexes. The substrate-bound-O intermediate in [Cu(II)2(DBED)2(O)2]2+ (DBED=N,N′-di-tert-butyl-ethylenediamine) was shown to perform aromatic hydroxylation. For the [Cu(II)2(NO2-XYL)(O2)]2+ complex, only a P species was spectroscopically observed. However, it was not clear whether this O-O bond cleaves to proceed through an O-type structure along the reaction coordinate for hydroxylation of the aromatic xylyl linker. Accurate evaluation of these reaction coordinates requires reasonable quantitative descriptions of the electronic structures of the P and O species. We have performed Cu L-edge XAS on two well-characterized P and O species to experimentally quantify the Cu 3d character in their ground state wavefunctions. The lower per-hole Cu character (40±6%) corresponding to higher covalency in the O species compared to the P species (52±4%) reflects a stronger bonding interaction of the bis-μ-oxo core with the Cu(III) centers. DFT calculations show that 10-20% Hartree-Fock (HF) mixing for P and ~38% for O species are required to reproduce the Cu-O bonding; for the P species this HF mixing is also required for an antiferromagnetically coupled description of the two Cu(II) centers. B3LYP (with 20% HF) was, therefore, used to calculate the hydroxylation reaction coordinate of P in [Cu(II)2(NO2-XYL)(O2)]2+. These experimentally calibrated calculations indicate that the electrophilic attack on the aromatic ring does not involve formation of a Cu(III)2(O2−)2 species. Rather, there is direct electron donation from the aromatic ring into the peroxo σ* orbital of the Cu(II)2(O22−) species, leading to concerted C-O bond formation with O-O bond cleavage. Thus, species P is capable of direct hydroxylation of aromatic substrates without the intermediacy of an O-type species.
Recent studies have demonstrated that immune cells play an important role in the pathogenesis of many neurological conditions. Immune cells constantly survey the brain microvasculature for irregularities in levels of factors that signal homeostasis. Immune responses are initiated when necessary, resulting in mobilisation of the microglial cells resident in the central nervous system (CNS) and/or of infiltrating peripheral cells. However, little is known about the kinetics of immune cells in healthy and diseased CNS, because it is difficult to perform long-term visualisation of cell motility in live tissue with minimal invasion. Here, we describe highly sensitive in vivo MRI techniques for sequential monitoring of cell migration in the CNS at the single-cell level. We show that MRI combined with intravenous administration of super-paramagnetic particles of iron oxide (SPIO) can be used to monitor the transmigration of peripheral phagocytes into healthy or LPS-treated mouse brains. We also demonstrate dynamic cell migration in live animal brains with time-lapse MRI videos. Time-lapse MRI was used to visualise and track cells with low motility in a control mouse brain. High-sensitivity MRI cell tracking using SPIO offers new insights into immune cell kinetics in the brain and the mechanisms of CNS homeostasis.
The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection.
This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children.
Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0–44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model.
Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.
Hepatitis B virus; Single-nucleotide polymorphism; Human leukocyte antigen; IL28B; IL10; HBeAg; Seroconversion; Children; HLA-DP
Previous research on American football injuries in Japan has focused on incidence proportion in terms of the number of injuries divided by the number of players. This is the first study to examine injury rates over several seasons.
To conduct a prospective study of injuries in a Japanese Division I collegiate American football team over the 2007 through 2009 seasons.
Collegiate football team at Doshisha University, Kyoto, Japan.
Patients or Other Participants:
All 289 athletes who played on the collegiate Division I football team during the 2007 through 2009 seasons.
Main Outcome Measure(s):
A certified athletic trainer kept a daily record of all practice and game injuries. Injury rates were calculated according to season, injury type, body part, severity, and mechanism. Injuries were also analyzed according to position of player, school year, and playing experience.
The game injury rate (GIR; 32.7 injuries/1000 athlete-exposures) was higher than the practice injury rate (PIR; 10.9 injuries/1000 athlete-exposures) over the 3 seasons (P < .05). The PIR was higher among Japanese players than the comparable United States collegiate football injury rates (5.8–7.0 injuries/1000 athlete-exposures). Ankle and foot injuries occurred more frequently during games, whereas thigh and gluteal injuries occurred more frequently during practices.
Our data show differences between games and practices in terms of injury rates, body parts injured, and positions of players injured. The high PIR in Japan may be due to the increased contact during practices and length of practices compared with the United States. Further research involving multiple teams is recommended to validate the trends noted in this study. The expanded data set could assist in the development of safety regulations and preventive interventions for Japanese football.
Japanese football; American football; college football; injury rates
Several recent studies have reported the involvement of bladder dysfunction in the delayed recovery of urinary continence following radical prostatectomy (RP). The objective of this study was to investigate the significance of detrusor overactivity (DO) as a predictor of the early continence status following robot-assisted RP (RARP). This study included 84 consecutive patients with prostate cancer undergoing RARP. Urodynamic studies, including filling cystometry, pressure flow study, electromyogram of the external urethral sphincter and urethral pressure profile, were performed in these patients before surgery. Urinary continence was defined as the use of either no or one pad per day as a precaution only. DO was preoperatively observed in 30 patients (35.7%), and 55 (65.5%) and 34 (40.5%) were judged to be incontinent 1 and 3 months after RARP, respectively. At both 1 and 3 months after RARP, the incidences of incontinence in patients with DO were significantly higher than in those without DO. Of several demographic and urodynamic parameters, univariate analyses identified DO and maximal urethral closure pressure (MUCP) as significant predictors of the continence status at both 1 and 3 months after RARP. Furthermore, DO and MUCP appeared to be independently associated with the continence at both 1 and 3 months after RARP on multivariate analysis. These findings suggest that preoperatively observed DO could be a significant predictor of urinary incontinence early after RARP; therefore, it is recommended to perform urodynamic studies for patients who are scheduled to undergo RARP in order to comprehensively evaluate their preoperative vesicourethral functions.
detrusor overactivity; robot-assisted radical prostatectomy; urinary incontinence
Erectile dysfunction (ED) is a major complication after radical prostatectomy (RP); however, debate continues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function (EF). This study included a total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 (46.6%) of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation (60.0%) was significantly greater than that in those without penile rehabilitation (38.2%). Of several parameters examined, the preoperative International Index of Erectile Function-5 (IIEF-5) score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP.
erectile function; nerve-sparing radical prostatectomy; penile rehabilitation; vardenafil
The objective of this study was to characterise the mechanism underlying acquired resistance to temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), in renal cell carcinoma (RCC).
A parental human RCC cell line, ACHN (ACHN/P), was continuously exposed to increasing doses of up to 20 μM of temsirolimus, and a cell line resistant to temsirolimus (ACHN/R), showing a sixfold higher IC50 than that of ACHN/P, was developed.
Following treatment with temsirolimus, phosphorylation of S6 kinase in ACHN/P was markedly inhibited, whereas there was no detectable expression of phosphorylated S6 in ACHN/R before and after temsirolimus treatment. However, AKT and p44/42 mitogen-activated protein kinase (MAPK) were constitutively phosphorylated even after temsirolimus treatment in ACHN/R, but not in ACHN/P. There was no significant difference between the sensitivities of ACHN/P and ACHN/R to KU0063794, a dual inhibitor of mTOR complex 1 (mTORC1) and mTORC2. Similar sensitivities to temsirolimus in ACHN/P and ACHN/R could be achieved by additional treatment with specific inhibitors of AKT- and MAPK-signaling pathways.
The activation of signal transduction pathways via mTORC2, but not via mTORC1, may have an important role in the acquisition of a resistant phenotype to temsirolimus in RCC.
renal cell carcinoma; temsirolimus; mTORC1; mTORC2
Major depression is a serious mental disorder that causes substantial distress and impairment in individuals and places an enormous burden on society. Although antidepressant treatment is the most common therapy provided in routine practice, there is little evidence to guide second-line therapy for patients who have failed to respond to antidepressants. The aim of this paper is to describe the study protocol for a randomised controlled trial that measures the clinical effectiveness of cognitive behavioural therapy (CBT) as an augmentation strategy to treat patients with non-psychotic major depression identified as suboptimal responders to usual depression care.
Methods and analysis
The current study is a 16-week assessor-blinded randomised, parallel-groups superiority trial with 12-month follow-up at an outpatient clinic as part of usual depression care. Patients aged 20–65 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Major Depressive Disorder who have experienced at least one failed trial of antidepressants as part of usual depression care, will be randomly assigned to receive CBT plus treatment as usual, or treatment as usual alone. The primary outcome is the change in clinician-rated 17-item GRID-Hamilton Depression Rating Scale (GRID-HAMD) score at 16 weeks, and secondary outcomes include severity and change in scores of subjective depression symptoms, proportion of responders and remitters, safety and quality of life. The primary population will be the intention-to-treat patients.
Ethics and dissemination
All protocols and the informed consent form comply with the Ethics Guideline for Clinical Research (Japanese Ministry of Health, Labour and Welfare). Ethics review committees at the Keio University School of Medicine and the Sakuragaoka Memorial Hospital approved the study protocol. The results of the study will be disseminated at several research conferences and as published articles in peer-reviewed journals. The study will be implemented and reported in line with the CONSORT statement.
Trial registration number
UMIN Clinical Trials Registry: UMIN000001218.
major depressive disorder; cognitive behavior therapy; randomized controlled trial; clinical protocols
Ascaris lumbricoides infection is rare among children in developed countries. Although large numbers of adult Ascaris in the small intestine can cause various abdominal symptoms, this infection remains asymptomatic until the number of worms in the intestine considerably increases in most cases. Ascaris causing bilious vomiting suggesting ileus is rare, especially in developed countries. A 6-year-old boy who lived in Japan, presented with abdominal colic, bilious vomiting at the pediatric emergency room. He appeared pale, and had no abdominal distention, tenderness, palpable abdominal mass, or findings of dehydration. He experienced bilious vomiting again during a physical examination. Laboratory tests showed mild elevation of white blood cells and C-reactive protein levels. Antigens of adenovirus, rotavirus, and norovirus were not detected from his stool, and stool culture showed normal flora. Ultrasonography showed multiple, round-shaped structures within the small intestine, and a tubular structure in a longitudinal scan of the small intestine. Capsule endoscopy showed a moving worm of Ascaris in the jejunum. Intestinal ascariasis should be considered as a cause of bilious vomiting in children, even at the emergency room in industrial countries. Ultrasound examination and capsule endoscopy are useful for diagnosis of pediatric intestinal ascariasis.
Ascaris lumbricoides; Paralytic ileus; Capsule endoscopy; Ultrasound; Bilious vomiting
The American Academy of Dermatology published a new guideline regarding topical therapy in atopic dermatitis in May 2014. Although topical steroid addiction or red burning skin syndrome had been mentioned as possible side effects of topical steroids in a 2006 review article in the Journal of the American Academy of Dermatology, no statement was made regarding this illness in the new guidelines. This suggests that there are still controversies regarding this illness. Here, we describe the clinical features of topical steroid addiction or red burning skin syndrome, based on the treatment of many cases of the illness. Because there have been few articles in the medical literature regarding this illness, the description in this article will be of some benefit to better understand the illness and to spur discussion regarding topical steroid addiction or red burning skin syndrome.
topical steroid addiction; atopic dermatitis; red burning skin syndrome; rebound; corticosteroid; eczema
The relationship between mortality and impaired cognitive function has not been thoroughly investigated in a very elderly community-dwelling population, and little is known about the association of disease-specific mortality with Mini-Mental State Examination (MMSE) subscale scores. Here we evaluated these data in Japanese community-dwelling elderly. In 2003, 85 year-olds (n=207) were enrolled; 205 completed the MMSE for cognitive function and were followed-up for 10 years, during which time 120 participants died, 70 survived, and 17 were lost to follow-up. Thirty-eight deaths were due to cardiovascular disease, 22 to senility, 21 to respiratory disease, and 16 to cancer. All-cause mortality decreased by 4.3% with a 1-point increase in the global MMSE score without adjustment, and it decreased by 6.3% with adjustment for both sex and length of education. Cardiovascular mortality decreased by 7.6% and senility mortality decreased by 9.2% with a 1-point increase in the global MMSE score with adjustment for sex and education. No association was found between respiratory diseases or cancer mortality and global MMSE score. All-cause mortality also decreased with increases in MMSE subscale scores for time orientation, place orientation, delayed recall, naming objects, and listening and obeying. Cardiovascular mortality was also associated with the MMSE subscale of naming objects, and senility mortality was associated with the subscales of time orientation and place orientation. Thus, we found that impaired cognitive function determined by global MMSE score and some MMSE subscale scores were independent predictors of all-cause mortality or mortality due to cardiovascular disease or senility in 85 year-olds.
cognition; elderly; mortality; community-dwelling; MMSE
The influence of size on the effectiveness of nasobiliary catheters has not yet been studied. We compared biliary drainage effectiveness and procedure-related discomfort and adverse events in 5 French (Fr) and 7 Fr nasobiliary catheters.
We prospectively studied 100 patients undergoing endoscopic biliary drainage for obstructive jaundice, who were randomly allocated to a 5 Fr or 7 Fr nasobiliary catheter group. As the primary endpoint, the effectiveness was evaluated by the serum total bilirubin decreasing rate and the success rate of jaundice relief. As the secondary endpoint, the degree of discomfort was investigated using a questionnaire survey after catheter removal.
The bilirubin decrease rate was significantly higher in the 7 Fr catheter group than in the 5 Fr group (53.0 ± 21.4% vs 40.5 ± 29.9%, respectively; P = 0.019). The success rate of jaundice relief tended to be higher in the 7 Fr catheter group, although the difference was not statistically significant (98% vs 88%, respectively; P = 0.056). The questionnaire survey demonstrated that total discomfort was significantly greater in the 7 Fr group (3.9 ± 1.5 vs 3.2 ± 1.4, respectively; P = 0.018). Larger-diameter catheters tended to increase difficulty in eating, although the difference between the groups was not statistically significant.
7 Fr nasobiliary catheters are recommended for patients requiring rapid and reliable relief of obstructive jaundice. However, because they can cause greater discomfort, 5 Fr nasobiliary catheters are preferred in other settings.
On July 1, 2012; UMIN000008288 (Japan Primary Registries Network).
Electronic supplementary material
The online version of this article (doi:10.1186/1471-230X-14-161) contains supplementary material, which is available to authorized users.
Nasobiliary catheter; Obstructive jaundice; Endoscopic biliary drainage; Questionnaire survey; Catheter size
Uterine leiomyoma, commonly known as fibroids, is a benign neoplasm of smooth muscle in women. The incidence of clinically symptomatic fibroids in reproductive-age women is approximately 20 %, with nearly 80 % of black women suffering from this condition. Symptoms include severe pain and hemorrhage; fibroids are also a major cause of infertility or sub-fertility in women. Uterine leiomyoma consist of hyperplastic smooth muscle cells and an excess deposition of extracellular matrix, specifically collagen, fibronectin, and sulfated proteoglycans. Extracellular matrix components interact and signal through integrin-β1 on the surface of uterine leiomyoma smooth muscle cells, provide growth factor storage, and act as co-receptors for growth factor-receptor binding. ECM and growth factor signaling through integrin-β1 and growth factor receptors significantly increases cell proliferation and ECM deposition in uterine leiomyoma. Growth factors TGF-β, IGF, PDGF, FGF and EGF are all shown to promote uterine leiomyoma progression and signal through multiple pathways to increase the expression of genes encoding matrix or matrix-modifying proteins. Decreasing integrin expression, reducing growth factor action and inhibiting ECM action on uterine leiomyoma smooth muscle cells are important opportunities to treat uterine leiomyoma without use of the current surgical procedures. Both natural compounds and chemicals are shown to decrease fibrosis and uterine leiomyoma progression, but further analysis is needed to make inroads in treating this common women’s health issue.
Fibroids; Infertility; Myometrium; Reproductive biology; Smooth muscle
The aim of the present study was to examine the short‐ and long‐term effect of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin in poorly controlled type 2 diabetic patients.
Materials and Methods
We consecutively enrolled a total of 30 type 2 diabetic patients whose glycated hemoglobin levels (National Glycohemoglobin Standardization Program) were ≥7.4%, stopped all oral antidiabetic drugs and started insulin therapy. When fasting plasma glucose levels became <140 mg/dL, we carried out the first oral glucose tolerance test (OGTT). After 1‐week sitagliptin treatment (50 mg/day), the second OGTT was carried out. Furthermore, we evaluated the long‐term efficacy of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin.
After 1‐week sitagliptin treatment, the area under the curve of insulin was markedly increased, and the area under the curve of glucagon and glucose was markedly decreased. Duration of diabetes and insulin secretory capacity were correlated with the effect of sitagliptin. Furthermore, interestingly, near normalization of glycemic control with insulin therapy for 1–2 weeks brought out the long‐term effectiveness of sitagliptin on glucose tolerance for 24 weeks, which was not observed with other antidiabetic drugs.
These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.
Dipeptidyl peptidase‐4 inhibitor; Insulin therapy; Sitagliptin
A susceptibility locus, Nidd2n, for type 2 diabetes has been mapped to mouse chromosome 14 (Chr 14) and confirmed using the consomic strain (C3H-Chr 14NSY) of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes. The aim of this study was to localize and characterize Nidd2n.
We constructed two novel congenic strains homozygous for different segments of NSY-Chr 14 on the control C3H/HeNcrj (C3H) background: R1 (C3H.NSY-(D14Mit206-D14Mit5)) possesses the proximal and middle segment, and R2 (C3H.NSY-(D14Mit206-D14Mit186)) possesses the most proximal segment of NSY-Chr 14. Diabetes-related phenotypes were studied in comparison with those of consomic C3H-Chr 14NSY (R0) and parental NSY and C3H strains. Congenic R1 and R2 showed significantly higher post-challenge glucose than that in C3H mice. Fasting glucose, in contrast, was significantly lower in R1 and R2 than in C3H mice. Insulin sensitivity was significantly impaired in R1 and R2 compared to C3H mice. R2 showed significantly higher body weight and fat-pad weight than those in C3H and R1. Leptin level was significantly higher in R0, R1 and R2 than in C3H mice, with R2 showing the highest level, similar to that in NSY mice. Serum adiponectin level was significantly lower in R0, R1 and R2 than in C3H mice, while it was significantly higher in NSY than in C3H mice.
These data indicate that Chr 14 harbors multiple genes for diabetes-related phenotypes. The original Nidd2n, which is located in the middle region of Chr 14, was divided into two segments; Nidd2.1n in proximal Chr 14 and Nidd2.2n in distal Chr 14. Nidd2.1n contributes to post-challenge hyperglycemia, insulin resistance and adiposity. Nidd2.2n contributes to fasting as well as post-challenge hyperglycemia and insulin resistance. Adp1n, which contributes to decreased adiposity and increased insulin sensitivity, rather than a diabetogenic gene, was mapped in the middle segment.
Adiposity; Animal model; Complex trait; Consomic strain; Insulin resistance
We report the 1.86-Mb draft genome and annotation of Lactobacillus oryzae SG293T isolated from fermented rice grains. This genome information may provide further insights into the mechanisms underlying the fermentation of rice grains.
Weissella oryzae was originally isolated from fermented rice grains. Here we report the draft genome sequence of the type strain of W. oryzae. This first report on the genomic sequence of this species may help identify the mechanisms underlying bacterial adaptation to the ecological niche of fermented rice grains.