Efficacy and safety of switching from basal insulin to once‐daily insulin degludec/insulin aspart in Japanese patients with inadequately controlled type 2 diabetes: A 4‐week,randomized, open‐label,treat‐to‐target study

Aims/Introduction

A prospective, 4‐week, single‐center, randomized, open‐label, parallel‐group, treat‐to‐target study was carried out to develop an algorithm for safe and effective switching from basal insulin to once‐daily insulin degludec/insulin aspart (IDegAsp) in patients with inadequately controlled type 2 diabetes.

Materials and Methods

Patients were randomly assigned to continue their current basal insulin therapy (n = 10) or to switch to IDegAsp on a 1:1 unit basis (n = 10). The insulin dose could be titrated once weekly, targeting a self‐measured blood glucose of 80–100 mg/dL before breakfast. A mixed meal test was carried out at baseline and after 4 weeks.

Results

After 4 weeks, the mean daily dose of insulin was similarly increased by 60% in both groups, and there was a significant decrease of mean plasma glucose and glucose area under the glucose concentration vs time curve for 2 h in the meal test. The mean estimated treatment difference (IDegAsp group ? basal insulin group) of the mean plasma glucose level was ?28 mg/dL (95% confidence interval ?47 to ?8, P = 0.008) after 4 weeks and that of the area under the glucose concentration vs time curve for 2 h was ?2,800 mg/min/dL (95% confidence interval ?5,300 to ?350, P = 0.028), confirming the superiority of IDegAsp to basal insulin. In the IDegAsp group, the 2‐h postprandial plasma glucose level was significantly decreased to the fasting plasma glucose range. There were no confirmed hypoglycemic episodes in either group during the 4‐week study period.

Conclusions

After switching from basal insulin, the IDegAsp dose can be uptitrated by 60% based on fasting plasma glucose data. However, monitoring of postprandial glucose should be considered before further uptitration of IDegAsp.

     

A case of psittacosis showing a localized peripheral air-space consolidation]

A 29-year-old man was admitted with fever and anorexia. Radiographic examinations of the chest showed a localized peripheral non-segmental air-space consolidation in the right lower lobe. He had a history of exposure to parakeets, and psittacosis was diagnosed based on the elevated serum complement fixation titer against Chlamydia psittaci. The common radiographic finding of psittacosis is ground-glass attenuation radiating from the hilar areas. We report a rare case of psittacosis presenting a localized consolidation, clearly limited to the subpleural region of the lung.     

An effective strategy to reduce blood pressure after forest walking in middle-aged and aged people

[Purpose] Forest walking may be effective for human health, but little information is available about effects of energy expenditure on blood pressure responses after forest walking. The aim of this study was to investigate the relationship between the activity energy expenditure and changes in blood pressure in individuals after forest walking. [Subjects] The subjects were 54 middle-aged and elderly people. [Methods] All subjects walked in the forest for approximately 90 min. Blood pressure, salivary amylase, and the Profile of Mood States were evaluated before and after forest walking, and activity energy expenditure was monitored throughout forest walking. Subjects were divided into two groups according to mean arterial pressure changes: a responder group (>5% decreases) and a nonresponder group (<5%). [Results] Forest walking significantly reduced the mean arterial pressure and improved the Profile of Mood States in both groups. Activity energy expenditure was related to changes in mean arterial pressure in the responder group, while this relation was not observed in the nonresponder group. Differential activity energy expenditure did not strongly affect improvement of the Profile of Mood States. [Conclusion] Greater walking-related greater activity energy expenditure might be required to accentuate physiological beneficial effects on in middle-aged and aged people. Furthermore, the forest environment per se can attenuate psychological stress.Key words: Hypertension, Profile of Mood States, Responder and nonresponder     

Temperature changes caused by the difference in the distance between the ultrasound transducer and bone during 1?mhz and 3?mhz continuous ultrasound: a phantom study

[Purpose] This study aimed to use a thermograph to observe temperature changes caused by different distances between an ultrasound transducer and bone during 1 MHz and 3 MHz continuous ultrasound emission on a phantom. [Materials and Methods] We observed the distribution of temperature elevations on a phantom consisting of pig ribs and tissue-mimicking material. One megahertz and 3 MHz ultrasound were delivered at 2.0 W/cm² for 5 minutes. To record the temperature changes on the phantom, we took a screenshot of the thermograph with a digital camera every 20 seconds. [Results] With 1 MHz ultrasound at the distances of 2 and 3 cm, the temperature elevation near the bone was higher than that near the transducer. However, with 3 MHz ultrasound, the temperature elevation was higher near the transducer rather than near the bone. At this point, we consider that there is a possibility of heat injury to internal organs in spite of there being no elevation of skin temperature. [Conclusion] When performing ultrasonic therapy, not only should the frequency be taken into consideration, but also the influence of the absorption coefficient and the reflection of the tissue. We visually confirmed the thermal ultrasound effect by thermography. Special attention to the temperature elevation of the internal organs is necessary to avoid injuries.Key words: Ultrasound, Thermal effect, Thermography     

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na⁺-Cl⁻ cotransporter (NCC) and Na⁺-K⁺-2Cl⁻ cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.     

Cytomegalovirus cholangitis and pancreatitis in an immunocompetent patient

Cholangitis and pancreatitis associated with cytomegalovirus (CMV) infection in an immunocompetent patient is reported. Endoscopic retrograde cholangiography performed on a 55-year-old man for evaluation of the cause of jaundice and liver dysfunction revealed a distal focal irregular narrowing of the common bile duct. Microscopic findings of the resected specimen showed chronic cholangitis and CMV pancreatitis. Immunohistochemistry disclosed that epithelial cells in the inflamed bile duct were positive for CMV antigen, which was compatible with CMV cholangitis. Inflammation of the biliary tract or pancreas by CMV has been commonly reported as a complication in immunocompromised patients. Our report appears to be a rare case, but suggests that CMV cholangitis or pancreatitis should be considered in the differential diagnoses of common bile duct stenosis or pancreatitis even in immunocompetent individuals.     

18F-FDG PET/CT imaging for a gastrointestinal mantle cell lymphoma with multiple lymphomatous polyposis

Multiple lymphomatous polyposis(MLP)is an uncommon type of gastrointestinal lymphoma characterized by the presence of multiple polyps along the gastrointestinal tract.Most of this entity is in fact considered the counterpart of gastrointestinal tract involvement for mantle cell lymphoma(MCL).To our knowledge,there have been no reports on[fluorine-18]-fluorodeoxy-glucose(18F-FDG)-positron emission tomography(PET)/computed tomography(CT)imaging for gastrointestinal MCL with MLP.We present the results of 18F-FDG PET/CT imaging in a patient with gastrointestinal tract involvement of MCL showing continuous MLP from the stomach to the rectum and intestinal intussusception.FDG-PET/CT findings were false negative in typical MLP spreading widely over the gastrointestinal tract,but uptake was noted in large lesions with deep infiltration considered atypical as MLP.On FDG-PET/CT imaging,the Ki-67proliferative index,which is a cell proliferation marker,showed neither correlation with the presence of uptake nor the maximum standardized uptake value.     

First report of Kudoa species in the somatic muscle of the Japanese parrotfish Calotomus japonicus (Scaridae) and a description of Kudoa igami,n. sp. (Myxozoa: Multivalvulida)

Three species of the Kudoid parasite (Myxozoa: Multivalvulida) were observed in the somatic muscle of Japanese parrotfish Calotomus japonicus caught off the coast of western Japan. All three species formed pseudocysts in myofibers and caused subclinical infections. The three Kudoa species were distinguished by spore morphology, as well as their 18S and 28S rDNA sequences. We identified a previously undescribed taxa Kudoa igami n. sp. with spores that were stellate with rounded peripheral edges and five to six polar capsules (prevalence 29.3 %). Kudoa igami n. sp. were morphologically most similar to Kudoa neothunni but were distinguishable by a more rounded shape in the apical view. Molecular analyses demonstrated that the K. igami n. sp. is closely related to Kudoa thalassomi; however, the similarity in the 28S rDNA sequence was <96 % and the spore morphology was different. We found Kudoa thalassomi in one sample (prevalence 2.4 %), which is a new host and geographical record for this species. Kudoa lateolabracis, which causes postmortem myoliquefaction in Chinese sea bass Lateolabrax sp. and olive flounder Paralichthys olivaceus was found in Japanese parrotfish (prevalence 41.5 %) for the first time, but did not cause myoliquefaction. We also expanded the host record for the brain-infecting Kudoa yasunagai (prevalence 94.1 %). In addition, an unidentified microsporidia was observed in the somatic muscle (prevalence 23.3 %).