Effect of baseline urinary glucose levels on the relationship between sodium-glucose cotransporter 2 inhibitors and serum uric acid in Japanese patients with type 2 diabetes mellitus.

In patients with type 2 diabetes mellitus (T2DM), controlling serum uric acid (SUA) and blood glucose levels is important. Moreover, sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease SUA levels by accelerating urinary uric acid excretion. We investigated the effect of baseline urinary glucose levels on the relationship between SGLT2 inhibitors and SUA levels. We conducted a retrospective observational study using the electronic medical records of patients with T2DM of Kindai University Nara Hospital (April 2013 to March 2022). We divided the patients into two groups according to their baseline urinary glucose levels: the N-UG group, which included patients with negative urinary glucose strip test results (-), and the P-UG group, which included patients with positive urinary glucose strip test results (± or more). The changes in SUA levels before and after SGLT2 inhibitor administration were investigated. For comparison, the changes in SUA levels before and after the prescription of antidiabetic agents, excluding SGLT2 inhibitors, were also investigated. Our results revealed that SGLT2 inhibitors significantly decreased the SUA levels in patients in the N-UG group but tended to decrease its levels in those in the P-UG group. Regardless of the urinary glucose status at baseline, the administration of SGLT2 inhibitors may be useful for patients with T2DM to prevent the complications of hyperuricemia.

Lead-free MCP to improve coincidence time resolution and reduce MCP direct interactions.

Achieving direct imaging of the annihilation position of a positron on an event-by-event basis using an ultrafast detector would have a great impact on the field of nuclear medicine. Cherenkov emission is the most attractive physical phenomenon for realizing such an ultrafast timing performance. Moreover, a microchannel-plate photomultiplier tube (MCP-PMT) is one of the most promising photodetectors for fully exploiting the fast timing properties of Cherenkov emission owing to its excellent single photon time resolution of 25 ps full width at half maximum (FWHM). However, as the MCP structure generally contains a lead compound, the gamma rays frequently and directly interact with the MCP, resulting in the degradation of its timing performance and generation of undesirable side peaks in its coincidence timing histogram. To overcome this problem, we have developed a new MCP-PMT based on an MCP consisting of borosilicate glass, thus drastically reducing the probability of the photoelectric effect occurring in the MCP. To evaluate its insensitivity to gamma rays and its timing performance, a coincidence experiment was performed and showed that the probability of direct interactions was reduced by a factor of 3.4. Moreover, a coincidence time resolution of 35.4 ± 0.4 ps FWHM, which is equivalent to a position resolution of 5.31 mm, was obtained without any pulse height/area cut, improving to 28.7 ± 3.0 ps when selecting on the highest amplitude events by careful optimization of the voltage divider circuit of the new MCP-PMT. The timing performance of this new MCP-PMT presents an important step toward making direct imaging possible.

Time-dependent changes in serum magnesium levels in patients receiving cetuximab with low baseline serum sodium levels.

Cetuximab causes electrolyte abnormalities, such as hypomagnesemia, hypokalemia, and hypocalcemia. However, little is known about the relationships between the onset of hypomagnesemia, patient background before administration, and time-dependent changes in serum magnesium levels. Therefore, we examined the patient backgrounds that influenced the onset of hypomagnesemia and the time-dependent changes in serum magnesium levels in patients receiving cetuximab. A retrospective study was performed to investigate patients with advanced or recurrent colorectal cancer or head and neck cancer, treated with a cetuximab regimen from 2012 to 2020 at Kindai University Nara Hospital. In total, 52 patients who met the inclusion criteria were enrolled in this study. The serum magnesium level was significantly lower in the hyponatremia before the administration group than in the non-hyponatremia group (p < 0.001). Univariate logistic regression analysis revealed that the baseline serum sodium levels (odds ratio [OR]: 0.741, 95% confidence interval [CI]: 0.588-0.934) and the combination of magnesium oxide tablet (OR: 0.997, 95% CI: 0.995-0.999) were one of the independent factors for hypomagnesemia. These results indicated that hyponatremia before administration may be an indicator of serum magnesium levels after administration of cetuximab. Cetuximab-induced hypomagnesemia may be predicted using baseline serum sodium levels, and hypomagnesemia may be prevented by administration of magnesium oxide tablets. Our findings provided new evidence for the management of serum magnesium levels in patients receiving cetuximab.

Precise analysis of the timing performance of Cherenkov-radiator-integrated MCP-PMTs: analytical deconvolution of MCP direct interactions.

In order to achieve the ultimate goal of reducing coincidence time resolution (CTR) to 10 ps, thus enabling reconstruction-less positron emission tomography, a Cherenkov-radiator-integrated microchannel plate photomultiplier tube (CRI) reaching CTR of sub-50 ps full width at half maximum (FWHM) has been developed. However, a histogram of time differences between a pair of the CRIs shows undesirable side peaks, which are caused by gamma rays directly interacting with the micro channel plates (MCPs). Such direct interaction events are detrimental to the timing performance of the CRI. In this paper, we demonstrate an analytical method of deconvolving MCP direct interaction events from the timing histogram. Considering the information of the main and the two side peaks, the timing uncertainty caused by the MCP direct interaction events is deconvolved and the CTR of the CRI is analytically investigated. Consequently, the CTR is improved from 41.7 to 40.5 ps FWHM by the deconvolution. It means that a mixture of the Cherenkov radiator events and the MCP direct interaction events contribute to the CTR by a factor of 10 ps. The timing performance of the MCP direct interaction events are also evaluated. The CTR between the two MCPs is found to be 66.2 ps FWHM. This indicates that a photocathode-free radiation detector with high timing performance is possible. Elimination of the photocathode from the detector would make detector construction easier and more robust.

Coincidence time resolution of 30 ps FWHM using a pair of Cherenkov-radiator-integrated MCP-PMTs.

Radiation detectors dedicated to time-of-flight positron emission tomography (PET) have been developed, and coincidence time resolution (CTR) of sub-100 ps full width at half maximum (FWHM) has been achieved by carefully optimizing scintillators and photodetectors. Achieving a CTR of 30 ps FWHM by using a pair of annihilation γ-rays would allow us to directly localize the annihilation point within an accuracy of 4.5 mm. Such direct localization can potentially eliminate the requirement of image reconstruction processes in clinical PET systems, which would have a huge impact on clinical protocols and molecular imaging. To obtain such a high CTR, researchers have investigated the use of prompt emissions such as Cherenkov radiation and hot-intra band luminescence. Although it is still challenging to achieve a CTR of 30 ps FWHM even with a Cherenkov-based detector, the experimentally measured CTR is approaching the goal. In this work, we developed a Cherenkov-radiator-integrated micro-channel plate photomultiplier tube (CRI-MCP-PMT), where there are no optical boundaries between the radiator and photocathode, and its timing performance was investigated. By removing the optical boundaries, reflections are eliminated and transmission to the photocathode is improved, resulting in high timing capability. As a result, a CTR of 30.1 ± 2.4 ps FWHM, which is equivalent to a position resolution of 4.5 ± 0.3 mm along a line of response (LOR), was obtained by using a pair of CRI-MCP-PMTs.

Useful laboratory markers for the diagnosis of bone marrow involvement by malignant lymphoma.

INTRODUCTION: This study aimed to investigate the effect of bone marrow involvement by malignant lymphoma (BMI) on laboratory data and to determine the useful laboratory markers for diagnosing BMI. METHODS: We compared laboratory data between patients with and without BMI. We performed multivariate logistic regression and receiver operating characteristic (ROC) analyses to evaluate the diagnostic values of independent predictors. RESULTS: In the BMI group, platelets in peripheral blood (PLT) and megakaryocyte count in bone marrow (MgK) were significantly lower than those in the non-BMI group (PLT, P < .0001; MgK, P = .0384). The rate of peripheral blood involvement by malignant lymphoma (PBI), red blood cell distribution width (RDW), D-dimer (DD), soluble interleukin-2 receptor (sIL2R), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) was significantly higher in the BMI group than in the non-BMI group (PBI, P < .0001; RDW, P = .0190; DD, P = .0006; sIL2R, P < .0001; AST, P = .0256; LDH, P = .0002). In multivariate analysis, PBI, PLT, sIL2R, and MgK levels were independent predictors of BMI. CONCLUSION: PBI, PLT, sIL2R, and MgK may be the useful laboratory markers for BMI diagnosis.

Wash or wipe? A comparative study of skin physiological changes between water washing and wiping after skin cleaning.

BACKGROUND/PURPOSE: Presently, skin-cleaning agents that claim to be removed by water or wiping alone are commercially available and have been used for the purpose of bed baths. However, there is a lack of knowledge on how water washing and wiping differently affect skin physiological functions or ceramide content. The aim of this study was to compare the effects of water washing and wiping on skin physiological functions and ceramide content. METHODS: Three kinds of the cleaning agents with different removal techniques (ie, water washing and wiping) were used in this study. Skin physiological functions (ie, transepidermal water loss, skin hydration, and skin pH) and skin ceramide content were measured before and after seven consecutive days of the application of each cleaning agent. RESULTS: No significant differences in skin physiological functions or ceramide content were observed between water washing and wiping. CONCLUSION: Cleaning agents that claim to be removed by water washing or wiping do not affect skin physiological functions or ceramide content by either removal method.

Contribution of the lateral lemniscus to the control of swallowing in decerebrate cats.

Lateral lemniscus, a relay nucleus of auditory sensation, is involved in the control of phonatory movements such as human speech and vocalization of animals. The present study was designed to test whether neurons in the lateral lemniscus contributed to the control of swallowing, one of non-phonic oro-pharyngolaryngeal movements. In acutely decerebrated cats (n=15), swallowing was induced by electrical stimulation (20-80µA at 10Hz for 20s with rectangular pulses of 0.2ms duration) delivered to the superior laryngeal nerve (SLN). Repetitive electrical stimulation (30-50µA at 50Hz for 10-20s) applied to the dorsal nucleus of the lateral lemniscus (LLD) increased the number and reduced the latency to the onset of the SLN-induced swallowing. On the other hand, stimulation of the ventral nucleus of the lateral lemniscus and the paralemniscal area, corresponding to the ventrolateral part of the parabrachial nucleus and the Kölliker-Fuse nucleus, often suppressed the SLN-induced swallowing. Microinjection of NMDA (0.1-0.15µl, 5.0-10mM) into the LLD through a stereotaxically placed glass micropipette facilitated the SLN-induced swallowing, i.e., the number was increased and the latency of swallowing was reduced. We also injected muscimol (a gamma amino-butyric acid (GABA)A receptor agonist), bicuculline (a GABAA receptor antagonist) and baclofen (a GABAB receptor agonist) into the LLD (0.1-0.15µl and 5.0mM for each substance). It was observed that an injection of muscimol suppressed the SLN-induced swallowing. However, an injection of bicuculline facilitated the swallowing. An injection of baclofen did not alter the swallowing. These results suggest the presence of functional topography in the lateral lemniscus and the paralemniscal area in relation to the control of swallowing. The facilitatory LLD-effects on swallowing are modulated by glutamatergic and GABAergic receptors on neurons in the LLD.

A phylogenetic foundation for comparative mammalian genomics.

A major effort is being undertaken to sequence an array of mammalian genomes. Coincidentally, the evolutionary relationships of the 18 presently recognized orders of placental mammals are only just being resolved. In this work we construct and analyse the largest alignments of amino acid sequence data to date. Our findings allow us to set up a series of superordinal groups (clades) to act as prior hypotheses for further testing. Important findings include strong evidence for a clade of Euarchonta+Glires (=Supraprimates) comprised of primates, flying lemurs, tree shrews, lagomorphs and rodents. In addition, there is good evidence for a clade of all placental mammals except Xenarthra and Afrotheria (=Boreotheria) and for the previously recognised clades Laurasiatheria, Scrotifera, Fereuungulata, Ferae, Afrotheria, Euarchonta, Glires, and Eulipotyphla. Accordingly, a revised classification of the placental mammals is put forward. Using this and molecular divergence-time methods, the ages of the superordinal splits are estimated. While results are strongly consistent with the earliest superordinal divergences all being >65 mybp (Cretaceous period), they suffer from greater uncertainty than presently appreciated. The early primate split of tarsiers from the anthropoid lineage at ~55 mybp is seen to be an especially informative fossil calibration point. A statistical framework for testing clades using SINE data is presented and reveals significant support for the tarsier/anthropoid clade, as well as the clades Cetruminantia and Whippomorpha. Results also underline our thesis that while sequence analysis can help set up hypothesised clades, SINEs obtainable from sequencing 1-2 MB regions of placental genomes are essential to testing them. In contrast, derivations suggest that empirical Bayesian methods for sequence data may not be robust estimators of clades. Our findings, including the study of genes such as TP53, make a good case for the tree shrew as a closer relative of primates than rodents, while also showing a slower rate of evolution in key cell cycle genes. Tree shrews are consequently high value experimental animals and a strong candidate for a genome sequencing initiative.

Appropriate likelihood ratio tests and marginal distributions for evolutionary tree models with constraints on parameters.

We show how to make appropriate likelihood ratio tests for evolutionary tree models when parameters such as edge (internodes or branches) lengths have nonnegativity constraints. In such cases, under the null model of an edge length being zero, the marginal distribution of this parameter is proven to be a "half-normal", that is, 50% zero values and 50% the positive half of a normal distribution. Other constrained parameters, such as the proportion of invariant sites, give similar results. To make likelihood ratio tests between nested models, e.g., H(0): homogeneous site rates, and H(1): site rates follow a gamma distribution with variance 1/k, then asymptotically as sequence length increases, the distribution under H(0) becomes a mixture of chi distributions, in this case 50% chi(0), and 50% chi(1) (where the subscript denotes degrees of freedom, i.e. , not the usually assumed 100% chi(1); which leads to a conservative test). Such mixtures are sometimes called distributions. Simulations show that even with sequences as short as 125 sites, some parameters, including the proportion of invariant sites, fit asymptotic distributions closely.

Intra-operative hyaluronic acid clearance predicts postoperative graft function in living related liver transplantation.

Although intra-operative hyaluronic acid (HA) clearance has been reported to be a predictive parameter for early graft function after the implantation of a cadaveric hepatic graft, it has yet to be evaluated as a parameter in assessing graft function in living related liver transplantation. The aim of this study was to evaluate whether intra-operative HA clearance can be a predictive parameter of early graft function in living related liver transplant patients. Eight consecutive patients, who underwent a living related liver transplantation, were entered into the study. The HA clearance 180 min after reperfusion of the graft was evaluated. Significantly higher serum HA levels were found in the patients with fulminant hepatitis than in the patients with non-fulminant hepatitis before operation (P < 0.01), just before reperfusion (P < 0.01), and 180 min after reperfusion (P < 0.05). The HA clearance correlated with the peak total bilirubin within 5 postoperative days (P < 0.05) and the lactic acid one day after operation (P < 0.01). The intra-operative HA clearance serves as a sensitive parameter for assessing the postoperative graft function after the implantation of the new liver. Based on our findings, measuring the HA clearance was thus found to be clinically useful in the assessment of graft function in living related liver transplantation.

Oxidative stress induced by environmental tobacco smoke in the workplace is mitigated by antioxidant supplementation.

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Previous studies by this laboratory have shown that exposure to workplace ETS results in increased oxidative stress and damage, as measured by increased levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. 8-Hydroxy-2-deoxyguanosine, a marker of oxidative DNA damage, was also 63% greater in the exposed group compared with controls. Subjects in the previous study who reported workplace exposure to ETS were given a 60-day supply of an over-the-counter antioxidant formulation consisting of 3000 microg of beta-carotene, 60 mg of vitamin C, 30 I.U. of alpha-tocopherol, 40 mg of zinc, 40 microg of selenium, and 2 mg of copper. After the 60-day supplementation period, blood samples were again drawn, and the results were compared with the presupplementation values. A 62% decrease in 8-hydroxy-2-deoxyguanosine was observed after supplementation. Lipid peroxidation levels were also decreased, as were the antioxidant enzyme activities. The biochemical evidence suggests that exposure to ETS in the workplace increases oxidative stress and that antioxidant supplementation may provide some protection.

Environmental tobacco smoke in the workplace induces oxidative stress in employees, including increased production of 8-hydroxy-2'-deoxyguanosine.

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Our objective was to determine the oxidative stress effects of ETS on employees who are exposed. The results provide information that is useful to the resolution of risk assessment questions associated with ETS. We analyzed two blood draws from volunteers in our control and exposed groups. The level of exposure to ETS was determined through plasma cotinine measurements, which showed a 65% increase from the control group to the exposed group. Exposure to ETS resulted in a statistically significant increase of 63% of the oxidative DNA mutagen 8-hydroxy-2'-deoxyguanosine in the blood of exposed subjects. This oxidative DNA damage has been linked to an increased risk of developing several degenerative chronic diseases, including coronary heart disease and cancer. The exposed subjects also had increased levels of superoxide dismutase, catalase, glutathione peroxidase (GPOX), and glutathione reductase. However, these increases were only statistically significant in catalase and GPOX. Catalase levels were 13% higher in the exposed group, and GPOX levels were 37% higher in exposed volunteers. The biochemical evidence suggests that exposure to ETS causes oxidative stress, resulting in DNA damage that may increase the risk of certain diseases.

Kinetics of selenium incorporation into tissues of female mallard ducks.

Selenium is essential for both mammalian and avian species, although its metabolism in birds has been less thoroughly studied. Little information has been available on the kinetics of selenium in birds, especially as it relates to the teratogenicity seen in waterfowl consuming excessive amounts. This study describes the pharmacokinetics of small amounts of 75Se as selenious acid injected into female mallard ducks. Labeled selenium was injected into a wing vein of restrained animals and tissues taken at five different time points up to 24 h post-injection. Selenium levels as percent of injected dose were determined in liver, kidney, heart, lung, adrenals, thyroid, spleen, pancreas, ovaries, intestine, muscle and plasma. Estimates of kinetic parameters (uptake and elimination rates, time of maximum concentration and maximum concentration) were obtained with a non-linear kinetics computer program (PCNONLIN, SCI Software, Lexington, KY). Results showed four basic patterns of distribution, uptake and elimination. Visceral tissues exhibited a triphasic pattern with a rapid rise, a decline followed by a distinctive increase in levels between the last two time points. Brain uptake was continuous over the 24 h. Plasma rose rapidly and then declined to a constant level. The ovaries as a tissue of interest relating to the teratogenic effects of selenium showed the greatest relative increase at 24 h, suggesting kinetic mechanisms consistent with a pathway that might lead to accumulation of toxic levels and teratogenic effects during embryo development.

Blood antioxidants changes in young women following beta-carotene depletion and repletion.

OBJECTIVE: This study was undertaken to investigate the relationship between beta-carotene intake and biochemical indices of antioxidant status in the blood of nine premenopausal women ages 18 to 42. METHODS: Nine healthy adult women were fed a low beta-carotene diet for 68 days. They were repleted with the same diet supplemented with beta-carotene (15 mg beta-carotene) for 28 days. During the last week of the study, they received an additional mixed carotenoid supplement. Indices of blood antioxidant status were measured on days 1, 29, 36, 43, 50, 64, 71, 92, and 99. RESULTS: We found significant increases of erythrocyte conjugated dienes between the 71st and 99th day of the study; increases of glutathione (GSH) peroxidase (GP) on day 43 and day 92 compared to a decrease on day 29; and decreases of GSH reductase throughout the treatment period. Erythrocyte catalase activities seemed to parallel GP activities. Erythrocyte oxidized glutathione (GSSG) levels were depressed both after beta-carotene depletion and repletion. beta-Carotene depletion/repletion had no effect on plasma vitamin E or GSH levels. Platelet GSH levels were depressed after beta-carotene depletion followed by elevated GSH levels after beta-carotene repletion. CONCLUSION: A diet low in beta-carotene and adequate in all other nutrients, including vitamin A, resulted in altered erythrocyte and platelet antioxidant indices; however, it had little impact on plasma GSH or vitamin E levels in young healthy women. Our results are consistent with the suggestion that carotenes may be important in the prevention of oxidative damage.

[Effects of anticoagulant therapy on retinal vein occlusion].

The combined effect of prostaglandin E1, stellate ganglion block, warfarin potassium and photocoagulation on 66 cases (eyes) of retinal vein occlusion was investigated immediately after, and 3 months and 6 months after final treatment. The time between onset and treatment was 2 months or less. Macular hemorrhage and edema were observed in all cases. The effectiveness rate 6 months after treatment was 35% in hemorrhagic central retinal vein occlusion and 63% in branch retinal vein occlusion. Visual acuity increased gradually with time from immediately after to 6 months after treatment. The effectiveness of treatment including warfarin potassium was lower than that of treatment without warfarin potassium in branch retinal vein occlusion, and many cases showed a marked decrease of visual acuity which might be related to the prolonged hemorrhage. These results suggest that combining prostaglandin E1, stellate ganglion block and photocoagulation in retinal vein occlusion produces better effects on visual acuity than ordinary treatment or spontaneous regression.

MRI changes and deficits of higher brain functions in preterm diplegia.

Forty-one preterm children (29 with spastic diplegia and 12 without motor deficits) who had a normal verbal IQ were studied to clarify the clinical significance of neuroanatomical abnormalities disclosed by T1-weighted and T2-weighted magnetic resonance imaging (MRI). Both types of images clearly showed abnormalities in the frontal corona radiata of the children with spastic diplegia, while there were no abnormalities in the children without motor deficits. We compared the T1-weighted imaging findings with deficits of higher brain functions, evaluated by the performance subtests of the Wechsler Intelligence Scale. Thinning of the parietal and/or occipital white matter was noted in children with visuospatial cognitive deficits. Thus, MRI may be helpful in confirming early clinical suspicions of visuospatial cognitive deficits as well as motor deficits in preterm children, especially those with spastic diplegia.

Isolation and identification of a cardioactive peptide from Tenebrio molitor and Spodoptera eridania.

We isolated several cardioactive peptides from extracts of whole heads of the mealworm, Tenebrio molitor, and the southern armyworm, Spodoptera eridania, using a semi-isolated heart of Manduca sexta for bioassay. We have now isolated from each species the peptide with the strongest effect on rate of contraction of the heart. The peptides were identified using micro Edman sequencing and mass spectrometric methods. This cardioactive peptide has the same primary structure from both species: Pro-Phe-Cys-Asn-Ala-Phe-Thr-Gly-Cys-NH2, a cyclic nonapeptide which is identical to crustacean cardioactive peptide (CCAP) originally isolated from the shore crab, Carcinus maenas, and subsequently isolated from Locusta migratoria and Manduca sexta. This is additional evidence that CCAP has widespread occurrence in arthropoda.