Publications by authors named "Akihiro Mori"

78 Publications

Comparison of cholesterol levels among lipoprotein fractions separated by anion-exchange high-performance liquid chromatography in periparturient Holstein-Friesian dairy cows.

J Vet Med Sci 2020 Dec 7. Epub 2020 Dec 7.

Kenhoku Veterinary Clinical Center, Miyagi Prefectural Agricultural Mutual Aid Association.

Changes in lipoprotein profiles occur in dairy cows during the periparturient period and in cows with transition cow disease. Here, the lipoprotein profiles of Holstein-Friesian dairy cows during the periparturient period were obtained by anion-exchange, high-performance liquid chromatography to evaluate the usefulness of lipoprotein profile evaluation during the periparturient period and in cows with fatty liver and milk fever. Lipoprotein levels (including total and high- (HDL-C) and low-density lipoprotein (LDL-C) cholesterol) in 10 healthy cows were low 4 weeks prepartum, with the lowest values at calving or within 1 week of calving; the values increased at 8 weeks postpartum. The lipoprotein levels were measured in 16 cows diagnosed with fatty liver (n=10) or milk fever (n=6) and compared to 10 healthy dairy cows. A significant difference was observed in HDL-C between healthy cows (at calving and 1 week postpartum), and the fatty liver and milk fever cows. Cows with fatty liver and milk fever had a lower mean HDL-C than the 10 healthy dairy cows at calving and 1 week postpartum. HDL-C might be a good indicator of energy balance for differentiating healthy cows from those with transition cow disease.
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http://dx.doi.org/10.1292/jvms.20-0361DOI Listing
December 2020

Investigation of Clinical Safety of Human iPS Cell-Derived Liver Organoid Transplantation to Infantile Patients in Porcine Model.

Cell Transplant 2020 Jan-Dec;29:963689720964384

Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Transplantation of liver organoids has been investigated as a treatment alternative to liver transplantation for chronic liver disease. Transportal approach can be considered as a method of delivering organoids to the liver. It is important to set the allowable organoid amount and verify translocation by intraportal transplantation. We first examined the transplantation tolerance and translocation of porcine fetal liver-derived allogeneic organoids using piglets. Fetal liver-derived organoids generated from the Kusabira Orange-transduced pig were transplanted to the 10-day-old piglet liver through the left branch of the portal vein. All recipients survived without any observable adverse events. In contrast, both local and main portal pressures increased transiently during transplantation. In necropsy samples, Kusabira Orange-positive donor cells were detected primarily in the target lobe of the liver and partly in other areas, including the lungs and brain. As we confirmed the transplantation allowance by porcine fetal liver-derived organoids, we performed intraportal transplantation of human-induced pluripotent stem cell (iPSC)-derived liver organoid, which we plan to use in clinical trials, and portal pressure and translocation were investigated. Human iPSC-derived liver organoids were transplanted into the same 10-day-old piglet. Portal hypertension and translocation of human iPSC-derived liver organoids to the lungs were observed in one of two transplanted animals. Translocation occurred in the piglet in which patent ductus venosus (PDV) was observed. Therefore, a 28-day-old piglet capable of surgically ligating PDV was used, and after the PDV was ligated, human iPSC-derived liver organoids with the amount of which is scheduled in clinical trials were transplanted. This procedure inhibited the translocation of human iPSC-derived liver organoids to extrahepatic sites without no portal hypertension. In conclusion, human iPSC-derived liver organoids can be safely transplanted through the portal vein. Ligation of the ductus venosus prior to transplantation was effective in inhibiting extrahepatic translocation in newborns and infants.
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http://dx.doi.org/10.1177/0963689720964384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784600PMC
October 2020

Effect of postprandial moderate-intensity walking for 15-min on glucose homeostasis in type 2 diabetes mellitus patients.

Diabetol Int 2020 Oct 3;11(4):383-387. Epub 2020 Apr 3.

The Graduate Center of Human Sciences, Aichi Mizuho College, 2-13, Shunko-cho, Mizuho-ku, Nagoya, Aichi 467-0867 Japan.

Aim: Diabetes patients usually have a low activity level and complain about lack of time. Therefore, we investigated the effect of short time, postprandial moderate-intensity exercise on glucose homeostasis in type 2 diabetes patients.

Methods: Eleven patients with type 2 diabetes were recruited. Patients spent the first day of the study without exercise (non-exercise day; NE day). In the second day, they walked at moderate-intensity (40% of the maximum heart rate reserve) for 15 min, 30 min after each meal (exercise day; E day). Glucose homeostasis was estimated by a continuous glucose monitor (CGM). All meals during the study were of standard composition. We compared NE day and E day concerning 24-h glucose homeostasis and 3 h postprandial glucose levels by the incremental area under the curve (iAUC) method. Medications were not changed during the study.

Results: The number of patients under basal supported oral therapy, intensive insulin therapy and oral hypoglycemic agents (OHA) were 5, 4 and 2, respectively. The blood glucose standard deviation over 24 h and the iAUC for the 24-h glycemic variability (NE day vs. E day; 34,765 [21,424-56,014] vs. 23,205 [15,323-39,779]) were smaller in E day than in NE day.

Conclusion: These results suggest that postprandial moderate-intensity walking, easily performable in daily life activities, was effective for improving glucose homeostasis. Further study should be performed to clarify the relationship between postprandial walk and drug therapy (insulin and OHA), including insulin secretory ability.
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http://dx.doi.org/10.1007/s13340-020-00433-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538501PMC
October 2020

The effect of Insulin Degludec on glycemic control in diabetic cats over a 12-month period.

J Vet Med Sci 2020 Jun 20;82(6):695-698. Epub 2020 Apr 20.

School of Veterinary Nursing & Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8602, Japan.

Insulin degludec (IDeg) is a long-acting basal insulin recently developed for use in humans. This study aimed to investigate the effects of IDeg on glycemic control in diabetic cats. Changes in body weight, IDeg dosage, and glycated albumin (GA) were evaluated at 0, 1, 3, 6, 9, and 12 months following initiation of IDeg. A significant decrease in GA was observed and a mean GA level below 25% was achieved between 3 and 12 months. Furthermore, a significant increase in body weight was observed between 3 and 12 months. The mean IDeg dose was 0.75 ± 0.68 IU/kg/day at 12 months. Taken together, long-term glycemic control was successfully achieved in diabetic cats using IDeg.
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http://dx.doi.org/10.1292/jvms.19-0309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324837PMC
June 2020

SPECC1L regulates palate development downstream of IRF6.

Hum Mol Genet 2020 03;29(5):845-858

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.
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http://dx.doi.org/10.1093/hmg/ddaa002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104672PMC
March 2020

The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats.

Int J Mol Sci 2019 Dec 26;21(1). Epub 2019 Dec 26.

Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

In this study, we reveal that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage. The liver organoids significantly reconstituted the hepatocytes; hence, the liver was significantly enlarged in this group, compared to the monolayer cell transplantation group in the retrorsine/partial hepatectomy (RS/PH) model. In the liver organoid transplantation group, the bile ducts were located in the donor area and connected to the recipient bile ducts. Thus, the rate of bile reconstruction in the liver was significantly higher compared to that in the monolayer group. By transplanting liver organoids, we saw a level of 70% replacement of the damaged liver. Consequently, in the transplantation group, diminished ductular reaction and a decrease of placental glutathione S-transferase (GST-p) precancerous lesions were observed. After trans-portal injection, the human induced pluripotent stem cell (hiPSC)-derived liver organoids revealed no translocation outside the liver; in contrast, the monolayer cells had spread to the lungs. The hiPSC-derived liver organoids were attached to the liver in the immunodeficient RS/PH rats. This study clearly demonstrates that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage in rats.
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http://dx.doi.org/10.3390/ijms21010178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981799PMC
December 2019

Comparison of the effects of four commercially available prescription diet regimens on the fecal microbiome in healthy dogs.

J Vet Med Sci 2019 Dec 15;81(12):1783-1790. Epub 2019 Oct 15.

School of Veterinary Nursing & Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan, Musashino, Tokyo 180-8602, Japan.

The effects of prescription diets on canine intestinal microbiota are unknown. In this study, we used next generation sequencing to investigate the impact of four commercially available prescription diet regimens on the fecal microbiome in six healthy dogs. The diet regimens used were as follows: weight-loss diet, low-fat diet, renal diet, and anallergenic diet. We found a significantly decreased proportion of phylum Actinobacteria with the weight-loss diet compared to the anallergenic diet. There were no significant differences in the proportion of phylum Bacteroidetes between the four diets. The proportion of phylum Firmicutes was significantly decreased with the weight-loss diet compared to the anallergenic diet. The proportion of phylum Fusobacteria was significantly increased with the weight-loss diet compared to the anallergenic diet. There were no significant differences in the proportion of phylum Proteobacteria after consumption of the four diets. We therefore demonstrated that commercial prescription diet influences the fecal microbiome in healthy dogs. These results might be useful when choosing a prescription diet for targeting a disease.
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http://dx.doi.org/10.1292/jvms.19-0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943313PMC
December 2019

Dulaglutide-combined basal plus correction insulin therapy contributes to ideal glycemic control in non-critical hospitalized patients.

J Diabetes Investig 2020 Jan 28;11(1):125-131. Epub 2019 Jun 28.

Department of Endocrinology and Diabetes, Ichinomiyanishi Hospital, Aichi, Japan.

Aims/introduction: We investigated whether dulaglutide (DU)-combined conventional insulin therapy is beneficial for glycemic control in non-critically ill hospitalized patients with type 2 diabetes.

Materials And Methods: This study was a prospective, randomized controlled pilot study. Participants were randomized to either basal-plus (BP) therapy, where basal insulin and corrective doses of regular insulin were administered before meals, or BP + DU therapy, where BP therapy was combined with DU. Blood glucose (BG) levels before and after every meal were measured for 7 days after assignment to groups. Because we consider the ideal BG during hospitalization to be within 100-180 mg/dL, we defined this range as the hospitalized ideal glucose range (hIGR). We compared the percentage of BG measurements within the hIGR among all BG measurements (%hIGR), mean BG, glucose variability and insulin dose between the two groups.

Results: Of 54 patients, 27 were assigned to the BP group and 27 to the BP + DU group. The %hIGR was significantly higher (44% vs 56%, P < 0.001), and the frequency of BG >240 mg/dL and BG <70 mg/dL was significantly lower in the BP + DU group than in the BP group (both P < 0.001). The mean BG (183 ± 29 vs 162 ± 30 mg/dL, P < 0.05), standard deviation (P < 0.01), coefficient of variation (P < 0.01) and total regular insulin dose (P < 0.05) in the BP + DU group were significantly lower than those in the BP group. No significant side-effects were observed in either group.

Conclusions: BP + DU therapy reduced the frequency of hyperglycemia and hypoglycemia, and resulted in a lower glucose variability.
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http://dx.doi.org/10.1111/jdi.13093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944833PMC
January 2020

Genetic relatedness of a new Japanese isolates of Alexandrium ostenfeldii bloom population with global isolates.

Harmful Algae 2019 04 18;84:64-74. Epub 2019 Mar 18.

National Research Institute of Fisheries Science, Yokohama, Kanagawa, 236-8648, Japan. Electronic address:

In recent years, blooms of toxic Alexandrium ostenfeldii strains have been reported from around the world. In 2013, the species formed a red tide in a shallow lagoon in western Japan, which was the first report of the species in the area. To investigate the genetic relatedness of Japanese A. ostenfeldii and global isolates, the full-length SSU, ITS and LSU sequences were determined, and phylogenetic analyses were conducted for isolates from western and northern Japan and from the Baltic Sea. Genotyping and microsatellite sequence comparison were performed to estimate the divergence and connectivity between the populations from western Japan and the Baltic Sea. In all phylogenetic analyses, the isolates from western Japan grouped together with global isolates from shallow and low saline areas, such as the Baltic Sea, estuaries on the east coast of U.S.A. and from the Bohai Sea, China. In contrast, the isolates from northern Japan formed a well-supported separate group in the ITS and LSU phylogenies, indicating differentiation between the Japanese populations. This was further supported by the notable differentiation between the sequences of western and northern Japanese isolates, whereas the lowest differentiation was found between the western Japanese and Chinese isolates. Microsatellite genotyping revealed low genetic diversity in the western Japanese population, possibly explained by a recent introduction to the lagoon from where it was detected. The red tide recorded in the shallow lagoon followed notable changes in the salinity of the waterbody and phytoplankton composition, potentially facilitating the bloom of A. ostenfeldii.
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http://dx.doi.org/10.1016/j.hal.2019.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540814PMC
April 2019

Long-term management and postmortem examination in a diabetic cat with acromegaly treated with two courses of radiation therapy.

J Vet Med Sci 2019 Jan 16;81(1):71-76. Epub 2018 Nov 16.

School of Veterinary Nursing & Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8602, Japan.

A 12-year-old, castrated male cat with diabetes mellitus was diagnosed with acromegaly and examined with magnetic resonance imaging (enlarged pituitary gland, 8 mm); serum hormone concentrations were measured. After the first course of radiation therapy (4 Gy, 12 fractions), insulin administration was not required from day 420 after diagnosis. Enlarged pituitary tumor (8 mm) recurred, and insulin dosage amount of the cat was increased on day 1,065. The second course of radiation therapy (6 Gy, 4 fractions) was performed on day 1,201 and insulin administration was again discontinued. However, the cat died from lymphoma on day 1,397. Postmortem examination revealed pituitary adenoma. Most tumor cells were positive for chromogranin A, synaptophysin, and growth hormone immunohistochemistry. The pancreatic islet cells revealed diffuse hyperplasia. We achieved long-term successful management of an acromegalic cat with two courses of RT. However, a protocol for a second course of RT for feline recurrent pituitary tumor should be further discussed.
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http://dx.doi.org/10.1292/jvms.17-0289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361652PMC
January 2019

Time-action profiles of insulin degludec in healthy dogs and its effects on glycemic control in diabetic dogs.

J Vet Med Sci 2018 Nov 11;80(11):1720-1723. Epub 2018 Oct 11.

School of Veterinary Nursing & Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8602, Japan.

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0-13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.
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http://dx.doi.org/10.1292/jvms.17-0714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261804PMC
November 2018

Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease.

J Vet Med Sci 2018 Apr 8;80(4):672-675. Epub 2018 Mar 8.

Department of Veterinary Nursing, School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan.

A 12-year-old female Shih-Tzu with hyperadrenocorticism and hypothyroidism developed concurrent refractory generalized demodicosis that did not respond to doramectin treatment. Although amitraz treatment was effective, the dog developed severe diabetes, which resulted in the cessation of amitraz and trilostane. Attempts to control the diabetes were unsuccessful, and its hyperadrenocorticism was left untreated, leading to the recurrence of demodicosis. However, demodicosis went into complete remission with a single dose of fluralaner. Transient erythematous papules appeared on the trunk three days after the administration of fluralaner, but no other adverse reactions were noted. We demonstrated that fluralaner is a potent treatment for demodicosis, and skin eruptions are possible after the first dose of the drug.
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http://dx.doi.org/10.1292/jvms.17-0274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938199PMC
April 2018

Zipbodyzyme: Development of new antibody-enzyme fusion proteins.

J Biosci Bioeng 2018 Jun 3;125(6):637-643. Epub 2018 Feb 3.

Laboratory of Molecular Biotechnology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Electronic address:

A new antibody-enzyme fusion protein, named Zipbodyzyme, composed of a Fab antibody (i.e., an antigen-binding fragment of an antibody) and an enzyme, has been successfully produced in the cytoplasm of Escherichia coli. Zipbodyzymes have a leucine zipper (LZ) pair at the C-termini of the heavy chain (Hc) and the light chain (Lc) of Fab, to promote the association of the Hc and the Lc in E. coli cytoplasm, adjoining a fused enzyme. A Zipbodyzyme containing mouse-derived anti-E. coli O157 Fab and a luciferase or a green fluorescent protein retained both the antigen-binding and an enzymatic activity/fluorescence. The bifunctional proteins were applicable in direct enzyme-linked immunosorbent assay (ELISA) without the need for a secondary antibody, indicating that the utility of the antibody enzyme bifunctional fusion protein will be expanded.
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http://dx.doi.org/10.1016/j.jbiosc.2017.12.021DOI Listing
June 2018

Development of an external-to-internal convertible endoscopic biliary drainage device - a preliminary prospective feasibility study.

Endosc Int Open 2018 Jan 16;6(1):E123-E126. Epub 2018 Jan 16.

Department of Gastroenterology, Ichinomiya Nishi Hospital, Aichi, Japan.

Background And Study Aims:  Endoscopic nasobiliary drainage (ENBD) for a malignant stricture in the bile duct has some advantages over endoscopic biliary stenting (EBS). However, ENBD may cause nasopharyngeal discomfort. We developed an external-to-internal convertible endoscopic biliary drainage (ETI-EBD) device that enables both internal and external drainage to occur during a single endoscopy.

Patients And Methods : This device consists of three parts, comprising a 5-Fr ENBD tube (250 cm) (ENBD-t), an 8.5-Fr EBS tube (7 cm) (EBS-t), and an 8-Fr pusher tube for EBS (230 cm) (P-t). The EBS-t is mounted over the ENBD-t at the distal end of the ENBD-t. The P-t is also placed over the ENBD-t. After an endoscopic sphincterotomy, the EBS-t of the device is inserted into the papilla, then the duodenal endoscope is withdrawn, leaving the device in place. After ENBD, only the ENBD-t was withdrawn from the P-t. At this point, the EBS-t was isolated and left without endoscopy or radiography.

Results : ETI-EBD was successfully placed in all consecutive 21 patients (100 %). The release of EBS-t from ENBD-t wit was successfully completed in 19 patients (90.5 %). There were 4 patients with kink of P-t when exchanging this device from the mouth to the nose. It was difficult for 2 patients to withdraw the ENBD-t because of poor lubrication performance. There were no significant complications associated with the use of the device.

Conclusion : This device allows for both external and internal biliary drainage with a single endoscopy.
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http://dx.doi.org/10.1055/s-0043-123934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770265PMC
January 2018

Pituitary size alteration and adverse effects of radiation therapy performed in 9 dogs with pituitary-dependent hypercortisolism.

Res Vet Sci 2018 Jun 10;118:19-26. Epub 2018 Jan 10.

School of Veterinary Nursing & Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8602, Japan. Electronic address:

The purpose of this study was to determine the therapeutic and/or adverse effects of radiation therapy (RT) against pituitary tumors in dogs with pituitary-dependent hypercortisolism, as monitored by frequent post-RT detailed MRI examinations, clinical signs, and changes in hormone concentrations. Nine dogs with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH stimulation test) and adverse effects of RT were evaluated before and post-RT. The P/B value was significantly lower in all nine dogs post-RT. One dog lacking any neurological signs demonstrated no change in clinical signs pre and post-RT. Out of 8 dogs which exhibited neurological signs pre-RT, half of them demonstrated complete resolution of their signs, whereas the other half showed transient resolution. In all animals with recurrence of neurological signs, pituitary tumor regrowth was not observed; however, MRI revealed moderate to severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was observed in three of nine dogs post-RT. RT did not induce any significant changes in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum cortisol concentrations. In conclusion, RT is effective to reduce pituitary size and the mass effect, but does not appear to affect blood hormone concentrations, necessitating additional medical treatment against hypercortisolism. Periodic MRI imaging post-RT enables early detection of adverse effects of RT.
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http://dx.doi.org/10.1016/j.rvsc.2018.01.001DOI Listing
June 2018

Association of MEOX2 polymorphism with nonsyndromic cleft palate only in a Vietnamese population.

Congenit Anom (Kyoto) 2018 Jul 28;58(4):124-129. Epub 2017 Nov 28.

Division of Research and Treatment for Oral Maxillofacial Congenital Anomalies, Aichi Gakuin University, Nagoya, Japan.

To evaluate the association between the single nucleotide polymorphism (SNP) rs227493 in the MEOX2 gene and nonsyndromic cleft palate only, this research was conducted as a case-control study by comparing a nonsyndromic cleft palate only group with an independent, healthy, and unaffected control group who were both examined by specialists. Based on clinical examination and medical records, we analyzed a total of 570 DNA samples, including 277 cases and 293 controls, which were extracted from dry blood spot samples collected from both the Odonto and Maxillofacial Hospital in Ho Chi Minh City and Nguyen Dinh Chieu Hospital in Ben Tre province, respectively. The standard procedures of genotyping the specific SNP (rs2237493) for MEOX2 were performed on a StepOne Realtime PCR system with TaqMan SNP Genotyping Assays. Significant statistical differences were observed in allelic frequencies (allele T and allele G) between the non-syndromic cleft palate only and control groups in female subjects, with an allelic odds ratio of 1.455 (95% confidence interval: 1.026-2.064) and P < 0.05. These study findings suggest that nonsyndromic isolated cleft palate might be influenced by variation of MEOX2, especially SNP rs2237493 in Vietnamese females.
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http://dx.doi.org/10.1111/cga.12259DOI Listing
July 2018

Evaluation of newly developed veterinary portable blood glucose meter with hematocrit correction in dogs and cats.

J Vet Med Sci 2017 Oct 18;79(10):1690-1693. Epub 2017 Aug 18.

School of Veterinary Nursing & Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.

This study evaluated the accuracy of a newly developed veterinary portable blood glucose meter (PBGM) with hematocrit correction in dogs and cats. Sixty-one dogs and 31 cats were used for the current study. Blood samples were obtained from each dog and cat one to six times. Acceptable results were obtained in error grid analysis between PBGM and reference method values (glucose oxidation methods) in both dogs and cats. Bland-Altman plot analysis revealed a mean difference between the PBGM value and reference method value of -1.975 mg/dl (bias) in dogs and 1.339 mg/dl (bias) in cats. Hematocrit values did not affect the results of the veterinary PBGM. Therefore, this veterinary PBGM is clinically useful in dogs and cats.
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http://dx.doi.org/10.1292/jvms.17-0184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658561PMC
October 2017

Many transcription factors contribute to C. elegans growth and fat storage.

Genes Cells 2017 Sep 8;22(9):770-784. Epub 2017 Aug 8.

Program in Systems Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Reverse genetic screens by RNA interference (RNAi) in model organisms such as the nematode Caenorhabditis elegans have provided numerous insights into gene function, thereby connecting genotype to phenotype. However, genes that contribute only subtly are often missed because relatively large numbers of measurements and reliable quantification are required to overcome experimental and biological noise that may mask subtle phenotypic effects. Here, we address this challenge by focusing on two phenotypes in C. elegans: growth and fat storage. We carried out comprehensive RNAi knockdown of transcription factors (TFs), as these are known important regulators of biological processes during development and the maintenance of homeostasis. Microscopy images of TF knockdown animals stained with Oil Red O (ORO) were captured, and body size (proxy for growth) and ORO staining intensity (proxy for fat storage) were precisely quantified using a newly developed imaging tool we named IPPOME (Image Processing for Precise and Objective MEasurement). We found that a surprisingly large proportion of TFs contribute to growth and fat storage, but that most TFs have only subtle, yet significant effects. This study provides a blueprint for studies of other genes and phenotypes in C. elegans.
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http://dx.doi.org/10.1111/gtc.12516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495572PMC
September 2017

Development of a rapid immunoassay system: Luminescent detection of antigen-associated antibody-luciferase in the presence of a dye that absorbs light from free antibody-luciferase.

J Biosci Bioeng 2017 Dec 22;124(6):694-699. Epub 2017 Jul 22.

Laboratory of Molecular Biotechnology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Electronic address:

In this report, we developed a rapid immunoassay system, designated the bioluminescent interference gathering optical (BINGO) assay, which required no time-consuming washing steps for removal of unbound antibodies. This system employed a luciferase (Luc)-conjugated antibody (LucAb) and a dye that absorbed light from the LucAb. The antigen-associated LucAb was localized by transfer of an antigen to the detector-side of a chamber where a detector photomultiplier tube (PMT) was installed. In contrast, the free LucAb was distributed throughout the solution, and the light emitted by the free LucAb was absorbed by the dye. Therefore, only light from LucAb associated with antigen could be detected by the PMT. The new system could be used to rapidly detect the amount of antigen-antibody-Luc complex by collecting steps, such as centrifugation or magnetic collection of antibody-coated magnetic beads. Proof-of-principle experiments were performed using a model system with streptavidin beads and biotinylated Luc. The feasibility of the system was demonstrated using magnetic beads coated with anti-Escherichia coli O157 antibody, enabling detection of 4 × 10 cells in only 15 min. Thus, this system may have applications in a variety of biomedical fields.
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http://dx.doi.org/10.1016/j.jbiosc.2017.06.016DOI Listing
December 2017

Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study.

Diabetes Obes Metab 2018 02 22;20(2):438-442. Epub 2017 Aug 22.

Internal Medicine, Ichinomiya Nishi Hospital, Ichinomiya, Japan.

This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD). Thirty-two T2D patients with NAFLD diagnosed by computed tomography or abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administered) or metformin (1500 mg, newly or additionally administrated). Data on the liver-to-spleen attenuation ratio (L/S), visceral fat area, body mass index, glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), fasting plasma glucose, C-peptide immunoreactivity (CPR), and CPR index were collected at baseline and after 6 months. The change in L/S was significantly greater in the luseogliflozin group than in the metformin group. Similarly, the changes in the visceral fat area, HbA1c, and body mass index were significantly greater in the luseogliflozin group than in the metformin group. The changes in ALT, fasting glucose, CPR, and CPR index were not significant in both groups. In conclusion, luseogliflozin significantly reduced liver fat deposition as compared to metformin, which may indicate clinical relevant benefits for NAFLD.
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http://dx.doi.org/10.1111/dom.13061DOI Listing
February 2018

Effects of two different glutamine-containing enteral supplements on stool frequency and density in elderly patients recovering from acute critical illness.

Geriatr Gerontol Int 2017 Dec 4;17(12):2514-2519. Epub 2017 Jul 4.

Department of Endocrinology and Diabetes, Ichinomiyanishi Hospital, Aichi, Japan.

Aim: Glutamine has various beneficial functions in the gastrointestinal tract. The present study was designed to investigate the effect of two different glutamine supplements on bowel movement at the start of enteral feeding in elderly inpatients.

Methods: This was a double-blind, prospective, randomized comparison study. A total of 25 patients aged >75 years recovering from a critical illness in a non-intensive care unit and scheduled for tube feeding were recruited. Of them, 22 consenting patients were randomly assigned to two groups: glutamine-fiber-oligosaccharide treatment group (n = 11) and glutamine F treatment group (n = 11). They were given glutamine three times daily at a dosage of 9 g/day. Enteral nutrition was given at the same dosage to both groups for the duration of the study. The end-points were stool frequency, Bristol Scale Form Score, bowel function index (Bristol Scale Form Score × stool frequency), the percentage of patients with stool frequency over three per day and those with a BSFS of 6 or 7 in each group.

Results: There were no significant differences between the two groups in terms of patient characteristics before the study. All the end-points in the glutamine F group were significantly lower than those in the glutamine-fiber-oligosaccharide group.

Conclusions: Compared with glutamine-fiber-oligosaccharide, glutamine F administration resulted in stool hardening and reduced stool frequency in elderly inpatients recovering from acute critical illness in non-intensive care units. The effects might be caused by the different additive components of glutamine supplements. Geriatr Gerontol Int 2017; 17: 2514-2519.
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http://dx.doi.org/10.1111/ggi.13121DOI Listing
December 2017

Investigating the Relationship between Morning Glycemic Variability and Patient Characteristics Using Continuous Glucose Monitoring Data in Patients with Type 2 Diabetes.

Intern Med 2017 15;56(12):1467-1473. Epub 2017 Jun 15.

Department of Endocrinology and Diabetes, Ichinomiyanishi Hospital, Japan.

Objective To investigate the relationship between patient characteristics and morning glycemic variability. Methods We retrospectively evaluated 106 patients with type 2 diabetes who underwent continuous glucose monitoring during admission. The highest postprandial glucose level (within 3 hours after breakfast; 'highest level'), the time from the start of breakfast to the highest postprandial glucose level ('highest time'), the difference between the pre-breakfast and highest postprandial breakfast glucose level ('increase'), the area under the curve (AUC; ≥180 mg/dL) for the glycemic variability within 3 hours after breakfast ('morning AUC'), and the post-breakfast glucose gradient ('gradient') were calculated. We analyzed the associations between these factors and nocturnal hypoglycemia and the patients' characteristics by using a regression analysis. Results After stepwise multivariate adjustment, significant independent associations were found between 'highest level' and high age, low BMI, and high HbA1c; 'highest time' and high HbA1c, low C-peptide immunoreactivity (CPR), and low fasting plasma glucose (FPG); the 'increase' and high age, low BMI, high HbA1c, low FPG and hypoglycemia; 'morning AUC' and high age, high HbA1c and hypoglycemia; and 'gradient' and long duration of diabetes and low BMI. Conclusion Higher age and lower BMI are associated with higher 'highest' and 'increase' levels. Higher HbA1c levels were linked to a longer 'highest time', and longer durations of the diabetes, while lower BMI values were related to a higher 'gradient'.
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http://dx.doi.org/10.2169/internalmedicine.56.7971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505900PMC
December 2017

The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and Its Implication in Human Prostate Cancer Cell Growth Inhibition.

Acta Med Okayama 2017 Apr;71(2):135-142

Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key molecule that promotes cancer progression. We previously developed an adenoviral vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene therapy. The therapeutic effects are based on suppressing the growth of cancer cells, but, the underlying molecular mechanism has not been fully clarified. To elucidate this mechanism, we investigated the effects of Ad-REIC on the expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC also suppressed the cell growth of LNCaP cells. Since other researchers have demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c-Myc protein positively regulate the expression of CD147, we investigated the correlation between the CD147 level and the activation of MAPK and c-Myc expression. Unexpectedly, no positive correlation was observed between CD147 and its possible regulators, suggesting that another signaling pathway was involved in the downregulation of CD147. This is the first study to show the downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the therapeutic effects of Ad-REIC may be due to the downregulation of the cancer-progression factor, CD147.
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http://dx.doi.org/10.18926/AMO/54982DOI Listing
April 2017

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

Res Vet Sci 2017 Oct 8;114:163-169. Epub 2017 Apr 8.

School of Veterinary Nursing & Technology, Nippon Veterinary and Life Science University, Tokyo, Japan.

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs.
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http://dx.doi.org/10.1016/j.rvsc.2017.04.004DOI Listing
October 2017

Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E.

Cancer Res 2017 02 22;77(3):613-622. Epub 2016 Nov 22.

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Small molecules and antisense oligonucleotides that inhibit the translation initiation factors eIF4A1 and eIF4E have been explored as broad-based therapeutic agents for cancer treatment, based on the frequent upregulation of these two subunits of the eIF4F cap-binding complex in many cancer cells. Here, we provide support for these therapeutic approaches with mechanistic studies of eIF4F-driven tumor progression in a preclinical model of melanoma. Silencing eIF4A1 or eIF4E decreases melanoma proliferation and invasion. There were common effects on the level of cell-cycle proteins that could explain the antiproliferative effects in vitro Using clinical specimens, we correlate the common cell-cycle targets of eIF4A1 and eIF4E with patient survival. Finally, comparative proteomic and transcriptomic analyses reveal extensive mechanistic divergence in response to eIF4A1 or eIF4E silencing. Current models indicate that eIF4A1 and eIF4E function together through the 5'UTR to increase translation of oncogenes. In contrast, our data demonstrate that the common effects of eIF4A1 and eIF4E on translation are mediated by the coding region and 3'UTR. Moreover, their divergent effects occur through the 5'UTR. Overall, our work shows that it will be important to evaluate subunit-specific inhibitors of eIF4F in different disease contexts to fully understand their anticancer actions. Cancer Res; 77(3); 613-22. ©2016 AACR.
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http://dx.doi.org/10.1158/0008-5472.CAN-16-1298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362820PMC
February 2017

A gene-centered C. elegans protein-DNA interaction network provides a framework for functional predictions.

Mol Syst Biol 2016 Oct 24;12(10):884. Epub 2016 Oct 24.

Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90% of C. elegans TFs and 15% of gene promoters. We used this network as a backbone to predict TF binding sites for 77 TFs, two-thirds of which are novel, as well as integrate gene expression, protein-protein interaction, and phenotypic data to predict regulatory and biological functions for multiple genes and TFs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081483PMC
http://dx.doi.org/10.15252/msb.20167131DOI Listing
October 2016

Major Increases between Pre- and Post-breakfast Glucose Levels May Predict Nocturnal Hypoglycemia in Type 2 Diabetes.

Intern Med 2016;55(20):2933-2938. Epub 2016 Oct 15.

Department of Endocrinology and Diabetes, Ichinomiyanishi Hospital, Japan.

Objective The aim of this study was to determine whether nocturnal hypoglycemia may be predicted according to morning glucose levels. Methods We retrospectively evaluated 106 patients with type 2 diabetes who underwent continuous glucose monitoring during admission. The pre-breakfast glucose level (Pre-breakfast level), highest postprandial glucose level within 3 hours after breakfast (Highest level), time from the start of breakfast to the highest postprandial glucose level (Highest time), difference between the pre-breakfast and highest postprandial breakfast glucose levels (Increase), area under the glucose curve (≥180 mg/dL) within 3 hours after breakfast (Morning AUC), post-breakfast glucose gradient (Gradient), and the increase-to-pre-breakfast ratio (Increase/Pre-breakfast) were calculated. The subjects were divided into hypoglycemic and non-hypoglycemic patients and compared for the above parameters using the t-test. A receiver operating characteristic analysis was used to determine the optimal cut-off values to predict nocturnal hypoglycemia (Hypoglycemia). Results Twenty-eight patients (26.4%) had hypoglycemia. The Pre-breakfast levels were significantly lower in patients with hypoglycemia than those without (p=0.03). The Increases were significantly higher in patients with hypoglycemia than those without (p=0.047). The Increase/Pre-breakfast ratio were significantly larger in patients with hypoglycemia than those without (p=0.0002). Their cut-off values were as follows (level, sensitivity, specificity, and area under the curve): 123 mg/dL, 0.89, 0.55, and 0.78 (p<0.0001); 90.5 mg/dL, 0.75, 0.64, and 0.76 (p<0.0001); and 90.2%, 0.75, 0.76, and 0.78 (p<0.0001), respectively. Conclusion Major increases between the pre- and post-breakfast glucose levels may predict nocturnal hypoglycemia in patients with type 2 diabetes.
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http://dx.doi.org/10.2169/internalmedicine.55.7085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109558PMC
February 2017

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans.

Elife 2016 07 6;5. Epub 2016 Jul 6.

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.
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http://dx.doi.org/10.7554/eLife.17670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951191PMC
July 2016

Hypoglycemia and glycemic variability are associated with mortality in non-intensive care unit hospitalized infectious disease patients with diabetes mellitus.

J Diabetes Investig 2016 May 17;7(3):429-35. Epub 2015 Nov 17.

Department of Endocrinology and Diabetes Ichinomiyanishi Hospital Ichinomiya Japan.

Aims/introduction: We aimed to identify factors - glycemic control, reactive inflammatory biomarkers or vital signs - associated with mortality in diabetic patients admitted to hospital for various infections (non-intensive care unit).

Materials And Methods: We retrospectively analyzed the cases of 620 diabetic patients admitted to hospital for various infections (non-intensive care unit) who underwent glucose monitoring >3 times per day. We extracted data regarding reactive inflammatory biomarkers and vital signs recorded on day 1 of hospital stay, and data on bacteremia and hypoglycemia status, glycemic variability (GV; coefficient of variation and standard deviation) and mean glucose concentrations during the entire hospital stay. Univariate and stepwise multivariate logistic regression analyses were carried out to determine the association between these factors and mortality.

Results: The mortality rate was 10.1%. Reactive inflammatory biomarkers, vital signs and bacteremia were not associated with mortality. According to the results of the adjusted analysis, hypoglycemia showed a significant positive association with mortality, increasing death risk by 266% (odds ratio [OR] 2.66, 95% confidence interval [95% CI] 1.22-5.83; P = 0.0006). High coefficient of variation and standard deviation values were significantly associated with increased mortality, increasing death risk by 18% (OR 1.18, 95% CI 1.01-1.38; P = 0.03) and 9% (OR 1.09, 95% CI 1.01-1.18; P = 0.03), respectively. Mean glucose concentrations were also significantly associated with mortality, increasing death risk by 5% (OR 1.05, 95% CI 1.02-1.08; P = 0.0008).

Conclusions: Glycemic indices (especially hypoglycemia and GV), rather than reactive inflammatory biomarkers or vital signs, were associated with mortality in non-intensive care unit diabetes mellitus patients with infections.
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http://dx.doi.org/10.1111/jdi.12436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847899PMC
May 2016

Evaluation of safety of insulin degludec on undergoing total colonoscopy using continuous glucose monitoring.

J Diabetes Investig 2016 May 6;7(3):374-80. Epub 2015 Sep 6.

Department of Endocrinology and Diabetes Ichinomiyanishi Hospital Aichi Japan.

Aims/introduction: There is little information regarding how to use insulin degludec (D) when diabetic patients are preparing for total colonoscopy (TCS).

Materials And Methods: A total of 12 patients with type 2 diabetes treated with insulin D and scheduled to undergo TCS were enrolled in the present study. A continuous glucose monitoring device was attached to each patient for 4 days, from two evenings before TCS to the morning after the procedure. The patients fasted for 24 h, starting after 18.00 h the day before TCS. Insulin D was only discontinued the morning of the day TCS was carried out.

Results: No patients experienced hypoglycemia during the daytime fasting period (08.00-18.00 h the day of TCS); the hypoglycemic index, mean glucose level, and standard deviation were 0, 141.3 ± 31.5 mg/dL and 15.6 ± 6.5 mg/dL. The mean glucose level and standard deviation during the daytime fasting period were significantly lower than during the daytime control period (08.00-18.00 h the day before TCS; P = 0.003, P = 0.001, respectively). The mean fasting glucose and fasting plasma glucose levels were significantly correlated (r = 0.78, P = 0.002), as were both the mean glucose level and standard deviation during the daytime control period, and the change in the mean glucose level (fasting period minus control period; r = -0.79, P = 0.002, and r = -0.69, P = 0.01, respectively).

Conclusions: Patients can safely undergo TCS when insulin D is discontinued only once on the day of the procedure.
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http://dx.doi.org/10.1111/jdi.12409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847892PMC
May 2016