Rapid Efficacy of Low Carbohydrate Diet for Diabetic Patient by Use of FreeStyle Libre

In recent years, continuous glucose monitoring (CGM) has been introduced and used in clinical diabetic research. Authors have investigated research about Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) and developed medical and social LCD movement through Japan LCD Promotion Association (JLCDPA). In this study, a case with remarkable improving effect for change from CR to LCD is presented using CGM. The case is 41 years-old female with type 2 diabetes mellitus (T2DM). She was newly diagnosed as T2DM with HbA1c 11.0%, glucose >400 mg/dL, BMI 26.0, AST 30 IU/mL, Hb 16.3 g/dL. She was given CR meal with 60% carbohydrate on day 1 to 4, and LCD meal with 12% carbohydrate on day 5 to 7. Daily profile of blood glucose showed 200-400 mg/dL in day 1-4, 160-240 mg/dL on day 5 and 110-150 mg/dL on day 7. FreeStyle Libre (Abbott, USA) has been valid and useful medical apparatus for monitoring the the detailed fluctuation of blood glucose. Blood glucose value was immediately decreased just after starting LCD, and the short-term effect of the LCD was found. These results would become basal and reference data and contribute to the development of future research

Fasting period after Rybelsus administration influences clinical benefit

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been attracted attention for various beneficial effects. Among them, oral semaglutide (Rybelsus) was developed using the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). The relationship between the bioavailability and post-dose fasting time period was analyzed. The results showed that i) its bioavailability with drinking 50mL and 120mL of water together was almost similar, ii) bioavailability for 240mL intake was about 2/3 of 50-120mL, iii) general availability would be about 1.4% for 50-120ml water, and 0.8% for 240mL of water. Tolerability and safety of Rybelsus showed similar results for healthy subjects, patients with renal and/or hepatic impairment. From mentioned above, Rybelsus has been one of the topic agents with characteristic mechanism of SNAC and clinical benefit of GLP-1RA. It will be expected to be applied widely in actual diabetic practice

In Vivo Roles of Fatty Acid Biosynthesis Enzymes in Biosynthesis of Biotin and alpha-Lipoic Acid in Corynebacterium glutamicum

For fatty acid biosynthesis, Corynebacterium glutamicum uses two type I fatty acid synthases (FAS-I), FasA and FasB, in addition to acetyl-coenzyme A (CoA) carboxylase (ACC) consisting of AccBC, AccD1, and AccE. The in vivo roles of the enzymes in supplying precursors for biotin and alpha-lipoic acid remain unclear. Here, we report genetic evidence demonstrating that the biosynthesis of these cofactors is linked to fatty acid biosynthesis through the FAS-I pathway. For this study, we used wild-type C. glutamicum and its derived biotin vitamer producer BFI-5, which was engineered to express Escherichia coli bioBF and Bacillus subtilis bioI. Disruption of either fasA or fasB in strain BFI-5 led to decreased production of biotin vitamers, whereas its amplification contributed to increased production, with a larger impact of fasA in both cases. Double disruptions of fasA and fasB resulted in no biotin vitamer production. The acc genes showed a positive effect on production when amplified simultaneously. Augmented fatty acid biosynthesis was also reflected in pimelic acid production when carbon flow was blocked at the BioF reaction. These results indicate that carbon flow down the FAS-I pathway is destined for channeling into the biotin biosynthesis pathway, and that FasA in particular has a significant impact on precursor supply. In contrast, fasB disruption resulted in auxotrophy for lipoic acid or its precursor octanoic acid in both wild-type and BFI-5 strains. The phenotypes were fully complemented by plasmid-mediated expression of fasB but not fasA. These results reveal that FasB plays a specific physiological role in lipoic acid biosynthesis in C. glutamicum. IMPORTANCE For the de novo biosynthesis of fatty acids, C. glutamicum exceptionally uses a eukaryotic multifunctional type I fatty acid synthase (FAS-I) system comprising FasA and FasB, in contrast to most bacteria, such as E. coli and B. subtilis, which use an individual nonaggregating type II fatty acid synthase (FAS-II) system. In this study, we reported genetic evidence demonstrating that the FAS-I system is the source of the biotin precursor in vivo in the engineered biotin-prototrophic C. glutamicum strain. This study also uncovered the important physiological role of FasB in lipoic acid biosynthesis. Here, we present an FAS-I enzyme that functions in supplying the lipoic acid precursor, although its biosynthesis has been believed to exclusively depend on FAS-II in organisms. The findings obtained here provide new insights into the metabolic engineering of this industrially important microorganism to produce these compounds effectively.ArticleAPPLIED AND ENVIRONMENTAL MICROBIOLOGY. 83(19):UNSP e01322-17 (2017)journal articl

Suppression of Vortex Precession in a Non-Contact Handling Device by a Circular Column

Vortex levitation attains non-contact handling by injecting air through a tangential nozzle into a cylindrical cup generating the swirling flow. The precessing of the swirling flow causes pressure fluctuation. This phenomenon becomes apparent as the gap between the cup and workpiece increases, which significantly disturbs the stability of conveyance. In this paper, suppression of pressure fluctuation by a cylindrical column that stabilizes the vortex levitation is described and its mechanism is mentioned. According to the experimental set up, the pressure was measured at the center of the workpiece and the wall of the cup; velocity field under the work piece was visualized by PIV. The result suggested that the larger diameter column denoted the effect on suppression of the fluctuation because the precessing of the swirling flow became stable. On the other hand, variation of the column thickness had insignificant effect on suppressing the fluctuation, but sucking force became weakened since the swirling velocity decreased.ArticleJournal of Flow Control, Measurement & Visualization. 4:70-78 (2016)journal articl

The role of snare proteins in cortical development

Neural communication in the adult nervous system is mediated primarily through chemical synapses, where action potentials elicit Ca2+ signals, which trigger vesicular fusion and neurotransmitter release in the presynaptic compartment. At early stages of development, the brain is shaped by communication via trophic factors and other extracellular signaling, and by contact-mediated cell–cell interactions including chemical synapses. The patterns of early neuronal impulses and spontaneous and regulated neurotransmitter release guide the precise topography of axonal projections and contribute to determining cell survival. The study of the role of specific proteins of the synaptic vesicle release machinery in the establishment, plasticity, and maintenance of neuronal connections during development has only recently become possible, with the advent of mouse models where various members of the N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex have been genetically manipulated. We provide an overview of these models, focusing on the role of regulated vesicular release and/or cellular excitability in synaptic assembly, development and maintenance of cortical circuits, cell survival, circuit level excitation–inhibition balance, myelination, refinement, and plasticity of key axonal projections from the cerebral cortex. These models are important for understanding various developmental and psychiatric conditions, and neurodegenerative diseases

Clinical effect for diabetic pregnant female by Low Carbohydrate Diet (LCD) and Continuous Glucose Monitoring (CGM)

In the diabetic medical practice, continuous glucose monitoring (CGM) has been recently used with beneficial efficacy. Authors have continued women’s medical care and research on Calorie Restriction (CR) and Low Carbohydrate Diet (LCD), and developed medical and social LCD movement by Japan LCD Promotion Association (JLCDPA). In this study, a diabetic female case with remarkable improving effect is shown using CGM and LCD. The case is 27 years-old female with type 2 diabetes mellitus (T2DM). She has been pregnant and on multiple daily insulin injection (MDI) with insulin 48 units/day in the university hospital. She was on this treatment until 28th weeks with no preeclampsia symptoms, and hoped to change the treatment of LCD. She came to our women’s clinic with the current data of weight 101kg, BMI 37.1 and HbA1c 7.0%. By application of FreeStyle Libre (Abbott, USA), her glucose variability showed around 160mg/dL with some episodes of hyperglycemia. The meal was changed from CR to LCD after 29th week, then insulin administration could be discontinued in 10 days. This glucose variability showed remarkable efficacy for combination of LCD and CGM. These results would become basal and reference data and contribute to the development of future research

An analysis of intestinal morphology and incretin-producing cells using tissue optical clearing and 3-D imaging

Tissue optical clearing permits detailed evaluation of organ three-dimensional (3-D) structure as well as that of individual cells by tissue staining and autofluorescence. In this study, we evaluated intestinal morphology, intestinal epithelial cells (IECs), and enteroendocrine cells, such as incretin-producing cells, in reporter mice by intestinal 3-D imaging. 3-D intestinal imaging of reporter mice using optical tissue clearing enabled us to evaluate both detailed intestinal morphologies and cell numbers, villus length and crypt depth in the same samples. In disease mouse model of lipopolysaccharide (LPS)-injected mice, the results of 3-D imaging using tissue optical clearing in this study was consistent with those of 2-D imaging in previous reports and could added the new data of intestinal morphology. In analysis of incretin-producing cells of reporter mice, we could elucidate the number, the percentage, and the localization of incretin-producing cells in intestine and the difference of those between L cells and K cells. Thus, we established a novel method of intestinal analysis using tissue optical clearing and 3-D imaging. 3-D evaluation of intestine enabled us to clarify not only detailed intestinal morphology but also the precise number and localization of IECs and incretin-producing cells in the same samples

Suppression of Vortex Precession in a Non-Contact Handling Device by a Circular Column

Vortex levitation attains non-contact handling by injecting air through a tangential nozzle into a cylindrical cup generating the swirling flow. The precessing of the swirling flow causes pressure fluctuation. This phenomenon becomes apparent as the gap between the cup and workpiece increases, which significantly disturbs the stability of conveyance. In this paper, suppression of pressure fluctuation by a cylindrical column that stabilizes the vortex levitation is described and its mechanism is mentioned. According to the experimental set up, the pressure was measured at the center of the workpiece and the wall of the cup; velocity field under the work piece was visualized by PIV. The result suggested that the larger diameter column denoted the effect on suppression of the fluctuation because the precessing of the swirling flow became stable. On the other hand, variation of the column thickness had insignificant effect on suppressing the fluctuation, but sucking force became weakened since the swirling velocity decreased

Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study

Background The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). Methods In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. Results The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). Conclusion As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN