Dietary instructions focusing on meal-sequence and nutritional balance for prediabetes subjects: An exploratory,cluster-randomized,prospective, open-label,clinical trial

BackgroundAlthough lifestyle modifications are known to be effective in type 2 diabetes (T2D) as well as in prediabetes, adherence to a healthy diet is difficult for some, and interventions of lifestyle modifications need to be revised occasionally. Meal sequence has been gaining attention as a part of a healthy diet among T2D individuals to improve glycemia and body weight. In addition, a dietary instruction program, SMART Washoku®, which can help individuals to consume a more nutritionally balanced diet, has been developed.MethodsThe current exploratory trial was designed to examine the effects of dietary instructions focusing on meal sequence and nutritional balance in individuals with prediabetes in the Japanese national health check-up and guidance program. Participants were cluster-randomized into three groups: Group A, receiving a conventional health guidance program (n = 11); Group B, receiving health guidance with dietary instructions focusing on meal sequence (n = 18); and Group C, receiving health guidance with dietary instructions focusing on nutritional balance (n = 13). Participants received health guidance education and various measurements before and 6 months after the instructions.ResultsBody weight in Group B was significantly reduced compared to that in Group A, with similar adherence, while the effects on glycemia were similar between the two Groups. Body weight reduction was greater in Group C compared to that in Group A, although adherence in Group C was significantly lower than that in Group A.ConclusionThe group receiving health guidance with dietary instructions focusing on meal sequence exhibited similar adherence and greater reduction in body weight than the group receiving conventional health guidance.     

Novel non‐alcoholic steatohepatitis model with histopathological and insulin‐resistant features

Although several non‐alcoholic steatohepatitis (NASH) models have been reported to date, few of these models fully reflect the histopathology and pathophysiology of human NASH. The aim of this study was to establish a novel NASH model by feeding a high‐fat (HF) diet and administering both carbon tetrachloride (CCl₄) and the Liver X receptor agonist T0901317. Male C57BL/6J mice were divided into four groups (each n = 5): HF, HF + CCl₄, HF + T0901317, and the novel NASH model (HF + CCl₄ + T0901317). CCl₄ (0.1 mL/kg) and T0901317 (2.5 mg/kg) were intraperitoneally administered four times and five times, respectively. The livers of the novel NASH model group presented a whitish colour. The serum levels of TNF‐α and IL‐6 were significantly increased in the novel NASH model group, and mice in this group exhibited histopathological features and insulin resistance reflective of NASH, i.e., macrovesicular hepatic steatosis, ballooning hepatocytes, Mallory‐Denk bodies, lobular inflammation and fibrosis. The novel NASH model group presented significantly upregulated expression levels of mRNAs related to lipogenesis, oxidative stress, fibrosis and steatosis and significantly downregulated expression levels of mRNAs related to triglyceride export. We successfully established a novel experimental NASH model that exhibits similar histopathology and pathophysiology to human NASH.     

Cortical hemoglobin-concentration changes under the coil induced by single-pulse TMS in humans: a simultaneous recording with near-infrared spectroscopy

We measured cortical hemoglobin-concentration changes under the coil induced by single-pulse transcranial magnetic stimulation (TMS) using a technique of simultaneous recording with near-infrared spectroscopy (NIRS). Single-pulse TMS was delivered over the hand area of the left primary motor cortex at an intensity of 100, 120, or 140% of the active motor threshold (AMT). NIRS recordings were also made during sham stimulation. These four different stimulation sessions (TMS at three intensities and sham stimulation) were performed both when the subject slightly contracted the right first dorsal interosseous muscle and when relaxed it (active and resting conditions). Under the active condition with TMS at 100% AMT, we observed a transient increase in oxy-hemoglobin (oxy-Hb), which was significantly larger than sham stimulation. Under the resting conditions with TMS at 120 and 140% AMT, we observed significant decreases in both deoxy-hemoglobin (deoxyHb) and total-hemoglobin (total-Hb) as compared to sham stimulation. We suggest that the increase of oxy-Hb concentration at 100% AMT under the active condition reflects an add-on effect by TMS to the active baseline and that decrease of deoxy-Hb and total-Hb concentrations at 120 and 140% AMT under the resting condition are due to reduced baseline firings of the corticospinal tract neurons induced by a lasting inhibition provoked by a higher intensity TMS.     

Damage to DNA purified from the radioresistant prokaryote, Deinococcus radiodurans, by acid heating

Using a highly radioresistant bacterium, Deinococcus radiodurans, the mechanism of degradation of the purified DNA molecules by heating was examined under acidic conditions. Setting the treatment temperature at 55?C with a duration of 0 to 20 min and adjusting the pH of the cell suspension to 3, 5 or 7, cell viabilities after the treatment were compared. The survival rate decreased in proportion to the reduction of pH. DNA purified from D. radiodurans was then damaged by irradiation with gamma-rays at 0.22 kGy or 1 kGy. It was considered that the radioresistance of D. radiodurans was due to its high repair capability, rather than any specificity of DNA structure. Purified D. radiodurans DNA was resistant to heating up to 90?C at neutral pH. However, marked DNA damage occurred when it was heated at pH values below 5.0. Then, DNA labeled with [3H]adenine was examined. Treatment at lower pH and higher temperature resulted in release of more adenine base, i.e., the purine ring, from the DNA molecules. Therefore, we assumed that the decrease in survival of D. radiodurans in vivo and damage to its DNA in vitro by acid heating were due to the release of adenine and guanine from the DNA, i.e., depurination.     

Evidence of the extrathymic development of tyrosinase-related protein-2-recognizing CD8+ T cells with low avidity

The majority of the human tumour‐associated antigens characterized to date are derived from non–mutated self‐proteins. However, nothing is known about the development of autoreactive and tumour‐associated antigen‐recognizing T cells. Tyrosinase‐related protein (TRP)‐2 is a non‐mutated melanocyte differentiation antigen and TRP‐2‐recognizing CD8⁺ T cells are known to show responses to melanoma both in humans and mice. In addition, TRP‐2‐reactive T cells with low avidity have been suggested to be readily induced from the spleen cells of naïve mice. On the other hand, recent reports suggest that self antigen‐reactive CD8⁺ T cells can be positively selected in the periphery. In this study, we tested the possibility that TRP‐2‐reactive CD8⁺ T cells in naïve mice could develop via the extrathymic pathway. As a consequence, TRP‐2‐reactive CD8⁺ T cell precursors in naïve C57BL/6 mice were suggested to express both interleukin‐2 (IL‐2) receptor β chain (IL‐2Rβ) and CD44 molecules, in a manner similar to that of extrathymically developed T cells. Furthermore, IL‐2Rβ⁺ CD44⁺ CD8⁺ T cells were detected in the adult thymectomized and bone marrow‐reconstituted mice, and functional TRP‐2‐reactive T cells were generated from their spleen cells. Overall, these results suggest that low avidity CD8⁺ T cells recognizing TRP‐2 can be developed extrathymically.     

Reduced α-adrenoceptor responsiveness and enhanced baroreflex sensitivity in Cry-deficient mice lacking a biological clock

To reveal the role of clock genes in generating the circadian rhythm of baroreflexes, we continuously measured mean arterial pressure and baroreflex sensitivity in free-moving normal wild-type mice, and in Cry -deficient mice which lack a circadian rhythm, in constant darkness for 24 h. In wild-type mice the mean arterial pressure was higher at night than during the day, and was accompanied by a significantly enhanced baroreflex sensitivity of −13.6 ± 0.8 at night compared with −9.7 ± 0.7 beats min⁻¹ mmHg⁻¹ during the day ( P < 0.001). On the other hand, diurnal changes in arterial pressure disappeared in Cry -deficient mice with remarkably enhanced baroreflex sensitivity compared with wild-type mice ( P < 0.001): −21.9 ± 1.6 at night and −23.1 ± 2.1 beats min⁻¹ mmHg⁻¹ during the day. Moreover, the mean arterial pressure response to 10 μg kg⁻¹ of phenylephrine, an α₁-adrenoceptor agonist, was severely suppressed in Cry -deficient mice regardless of time, while that for the wild-type mice was 10.1 ± 1.9 mmHg in the night, significantly lower than 22.0 ± 3.5 mmHg in the day ( P < 0.01). These results suggest that CRY genes are involved in generating the circadian rhythm of baroreflex sensitivity, partially by regulating α₁-adrenoceptor-mediated vasoconstriction in peripheral vessels.     

Vascular flow patterns of hepatic tumors in contrast-enhanced 3-dimensional fusion ultrasonography using plane shift and opacity control modes.

OBJECTIVE: This study was conducted to determine whether contrast-enhanced 3-dimensional (3D) fusion ultrasonography with combined use of the plane shift and opacity control modes can serve as a useful tool for identifying the vascular characteristics of hepatic tumors in 3D perspective. METHODS: Contrast-enhanced 3D fusion ultrasonography was performed in 31 patients with hepatic tumors after the intravenous injection of contrast media. The shapes, courses, and distributions of tumor vessels, displayed in 3D perspective, were examined to identify the characteristic vascular flow patterns of various tumors. Images before and after contrast media administration were compared for evaluation of the effectiveness of contrast enhancement with regard to tumor diameter for various types of tumors. The images were interpreted in a blinded manner by 3 physicians specializing in abdominal ultrasonography, and vascular flow patterns were determined on the basis of consensus. RESULTS: The characteristic vascular flow patterns observed in hepatocellular carcinomas are reticular flow within the tumor and flow showing a ringlike distribution surrounding the tumor. Metastatic tumors show a vascular flow pattern running between adjacent tumor nodules, and hemangiomas show localized nodular flow at the tumor margins. Contrast enhancement was found to be useful for showing the vascular flow patterns in small hepatocellular carcinomas and hemangiomas. CONCLUSIONS: Contrast-enhanced 3D fusion ultrasonography makes it possible to display images combining the plane shift and opacity control modes to show tumor vessels, including minute vascular flow within hepatic tumors, in 3D perspective and to identify tumor-specific vascular flow patterns.     

Tensile bond strengths and adhesive interfaces of ten dentin bonding systems

Tensile bond strength measurements and scanning electron microscopic observations have been performed to evaluate the adhesive properties of new dentin bonding systems. To date, however, it was impossible to compare previously reported data among researchers, because there was no standardization of in vitro test methods. There have also been few reports about the correlation among tensile bond strengths (TBS) and morphological features of the adhesive interfaces of recent systems. Therefore, the purpose of this study was to investigate the relationship between TBS to bovine dentin, following the guidelines documented by the International Organization for Standardization (ISO), and the morphology of resin/dentin interfaces of nine commercially available and one experimental bonding systems. The nine recent bonding systems used in this study showed significantly higher mean TBS (ranging from 25.0 to 14.8 MPa) than did a system (PhB) marketed ten years ago (9.3 MPa). However, morphological features of the resin/dentin interface varied among the systems, and no statistically significant correlation was found between TBS and width of the hybrid layer (p = 0.62). In order to evaluate the quality of the resin/dentin interface, quantitative analyses are needed to clarify the saturation and polymerization of resin in the hybrid layer.     

Peptide vaccination for patients with melanoma and other types of cancer based on pre-existing peptide-specific ctotoxic T-lymphocyte precursors in the periphery

Identification of antigenic peptides expressed on cancer cells enables us to treat cancer patients with peptide-based immunotherapy. Although optimal protocols for peptide-based vaccines have not yet been elucidated, boosting the immune system could be a better approach than priming the immune system to elicit prompt and potent peptide-specific T-cell responses in cancer patients. With this possibility in mind, the authors undertook a clinical trial in which cancer patients were vaccinated with peptides (maximum 4) after confirmation of pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the periphery. Fourteen patients (seven with melanoma and seven with other types of cancer) positive for either HLA-A24 or HLA-A2 were enrolled in this study. Fourteen and 16 peptides were used to screen for HLA-A24+ and HLA-A2+ patients, respectively. The vaccination was well tolerated, and the only adverse effects were local pain and fever. Kinetic analysis revealed that peptide-reactive CTLs increased after peptide vaccination in 7 of 14 patients. Immunoglobulin G (IgG) reactive to the administered peptides was detected in 2 patients before vaccination, although it became detectable in 8 of the other 12 patients after the peptide vaccination. Stable disease for more than 6 months was observed in five patients (one with melanoma and four with other types of cancer); all of these patients showed increased levels of peptide-specific IgG. These results indicate that peptide vaccination of patients showing evidence of pre-existing peptide-specific CTL precursors can be applied in further clinical trials aimed at the treatment of melanoma and other types of cancer.     

Bactericidal activity of middle ear effusion on a single isolate of non-typable Haemophilus influenzae

Bactericidal activity of middle ear effusion (MEE) from children with otitis media with effusion (OME) on one strain of non-typable Haemophilus influenzae was measured and was compared with that of normal human serum. H. influenzae culture negative MEEs had a bactericidal activity on one strain of non-typable H. influenzae (P less than 0.01), and the activity of serous effusions was significantly stronger than that of mucoid ones (P less than 0.01). The bactericidal activity of 20% pooled MEE was almost equal to that of 4% normal human serum. Heat treatment (56 degrees C, 30 min) abolished this activity of both pooled MEE and normal human serum. Addition of fresh guinea pig serum (GPS) as a complement source to the heat-treated pooled MEE restored this activity, while its addition to the heat-treated normal human serum failed to do so. These results suggest that complement factor is important in the bactericidal activity of MEE.