An infantile traumatic brain injury with a bright tree appearance detected before the late seizure.

INDRODUCTION: Infantile traumatic brain injury (TBI) rarely follows a biphasic clinical course and exhibits a bright tree appearance (BTA) on magnetic resonance imaging (MRI). This is termed infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD). TBIRD has clinical features similar to those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). It remains to be clarified which patients with infantile TBI will develop TBIRD and the prevention and treatment of TBIRD. CASE AND REVIEW: We report a case of TBIRD that exhibited BTA 1 day before the late seizure and review 12 cases of TBIRD. All patients developed a subdural hematoma (SDH), were younger than 2 years, and presented with a biphasic phase within 3-6 days. The median interval between BTA and TBI was 5 days. Of the 5 cases examined with MRI before the biphasic phase, only our case was detected with BTA 4 days after TBI. CONCLUSION: Predicting the biphasic clinical course may be possible by examining MRI after TBI in patients under 2 years of age who develop SDH with unconsciousness, seizure, or hemiplegia, and these patients should be strictly followed up for 1 week.

Clarithromycin Suppresses Chloride Channel Accessory 1 and Inhibits Interleukin-13-Induced Goblet Cell Hyperplasia in Human Bronchial Epithelial Cells.

Activation of the interleukin-13 (IL-13) receptor leads to signal transducer and activator of transcription 6 (STAT6) activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF) and chloride channel accessory 1 (CLCA1), increasing secretion of the gel-forming mucin MUC5AC. Activation of the epidermal growth factor receptor (EGFR) also leads to MUC5AC production via extracellular signal-regulated kinase (ERK1/2). We examined the effect of clarithromycin IL-13 signaling leading to production. Normal human bronchial epithelial (NHBE) cells were grown for 14 days at an air-liquid interface (ALI) with IL-13 and/or clarithromycin. Histochemical analysis was performed using hematoxylin and eosin (HE) staining and MUC5AC immunostaining. MUC5AC, SPDEF, and CLCA1 mRNA expression were evaluated by real-time PCR. Western analysis was used to assess phosphorylation of STAT6 and ERK1/2. Clarithromycin decreased IL-13-induced goblet cell hyperplasia and MUC5AC mRNA expression in a dose-dependent manner. Clarithromycin decreased IL-13-stimulated SPDEF and CLCA1 mRNA expression in a dose-dependent manner, and at 32 µg/ml CLCA1 was profoundly decreased (P < 0.001). Although clarithromycin had no effect on STAT6 phosphorylation induced by IL-13, it decreased constitutive phosphorylation of ERK1/2 (P < 0.05).

Stability of Adrenaline in Irrigating Solution for Intraocular Surgery.

Intraocular irrigating solution containing 1 µg/mL adrenaline is widely used during cataract surgery to maintain pupil dilation. Prepared intraocular irrigating solutions are recommended for use within 6 h. After the irrigating solution is admistered for dilution, the adrenaline may become oxidized, and this may result in a decrease in its biological activity. However, the stability of adrenaline in intraocular irrigating solution is not fully understood. The aim of this study was to evaluate the stability of adrenaline in clinically used irrigating solutions of varying pH. Six hours after mixing, the adrenaline percentages remaining were 90.6%±3.7 (pH 7.2), 91.1%±2.2 (pH 7.5), and 65.2%±2.8 (pH 8.0) of the initial concentration. One hour after mixing, the percentages remaining were 97.6%±2.0 (pH 7.2), 97.4%±2.7 (pH 7.5), and 95.6%±3.3 (pH 8.0). The degradation was especially remarkable and time dependent in the solution at pH 8.0. These results indicate that the concentration of adrenaline is decreased after preparation. Moreover, we investigated the influence of sodium bisulfite on adrenaline stability in irrigating solution. The percentage adrenaline remaining at 6 h after mixing in irrigating solution (pH 8.0) containing sodium bisulfite at 0.5 µg/mL (concentration in irrigating solution) or at 500 µg/mL (concentration in the undiluted adrenaline preparation) were 57.5 and 97.3%, respectively. Therefore, the low concentration of sodium bisulfite in the irrigating solution may be a cause of the adrenaline loss. In conclusion, intraocular irrigation solution with adrenaline should be prepared just prior to its use in surgery.

Rho-kinase inhibitor targeting the liver prevents ischemia/reperfusion injury in the steatotic liver without major systemic adversity in rats.

Rho-kinase (ROCK) inhibitors improve liver blood flow after ischemia/reperfusion (IR) injury, especially in the setting of steatosis, by decreasing the resistance of intrahepatic microcirculation through hepatic stellate cell (HSC) relaxation. However, the systemic administration of ROCK inhibitors causes severe hypotension; therefore, liver-specific ROCK inhibition is required. Here, we tested vitamin A (VA)-coupled liposomes carrying the ROCK inhibitor Y-27632 for targeted HSCs in steatotic rats. Rat livers with steatosis induced by a choline-deficient diet were subjected to IR injury. The delivery site and effect of the ROCK inhibitor were investigated. After liposomal Y-27632 injection, the survival rate after IR, the liver blood flow, the portal perfused pressure, and the hemodynamics were investigated. Immunohistochemical studies showed VA-coupled liposome accumulation in livers. Liposomal Y-27632 was 100-fold more effective in inhibiting HSC activation than free Y-27632. Liposomal Y-27632 improved the survival rate after IR injury, the liver blood flow, and the portal perfusion pressure without severe hypotension. In contrast, untargeted Y-27632 elicited severe systemic hypotension. We conclude that VA-coupled liposomes carrying the ROCK inhibitor yield enhanced drug accumulation in the liver and thus mitigate IR injury in the steatotic liver and reduce major systemic adversity.

Growth of metal nanowire forests controlled through stress fields induced by grain gradients.

Pure metal nanowires (NWs) are one-dimensional nanomaterials with distinctive properties for various applications. Nevertheless, mass-growth forests have not been developed because of vapor pressure limitations, chemical reduction problems, or both. We succeeded in the mass growth of aluminum (Al) NW forests at desired locations by controlling atomic diffusion within the solid film. Whereas prior attention has focused only on how to increase the driving force, we show that focused ion beam irradiation created localized regions of high stress, which provided pathways for atomic diffusion as well as nuclei and driving forces for vertical NW growth. The underlying growth process could in principle be extended to other metals.

Micromachined structures decoupling Joule heating and electron wind force.

Microstructural changes in conductive materials induced by electric current treatments, such as electromigration and electroplasticity, are critical in semiconductor and metal processing. However, owing to the inevitable thermal effect (Joule heating), the athermal effect on microstructural modifications remains obscure. This paper presents an approach of utilizing pre-micromachined structures, which obstruct current flow but maintain a thermal history similar to that of the matrix, effectively disentangling the thermal and athermal effects. A duplex stainless-steel material is selected to validate the feasibility of this method. Microstructural characterizations show that the athermal effect, especially the electron wind force (EWF), primarily governs the element diffusion and phase transformation in this study. Moreover, many σ phases (Cr-enriched) are precipitated in the micromachined structures, whereas no precipitation occurred in the matrix, suggesting that the directional EWF disrupts the Cr aggregation caused by Joule heating. Furthermore, we present a critical formula for determining the dimensions of micromachined structures of commonly used metallic materials. The proposed method may serve as an effective and powerful tool for unveiling the athermal effect on microstructural alterations.

Effectiveness of Unguided Internet-Based Cognitive Behavioral Therapy for Subthreshold Social Anxiety Disorder in Adolescents and Young Adults: Multicenter Randomized Controlled Trial.

BACKGROUND: Social anxiety disorder (SAD) is a common mental disorder in adolescents and young adults. Early intervention and support could help prevent the development of full-blown SAD. Considering that adolescents with social anxiety symptoms do not prefer face-to-face sessions due to their fear of communicating with therapists, internet-based cognitive behavioral therapy (ICBT) was implemented. OBJECTIVE: This study aimed to examine the effectiveness of complete self-help ICBT for subthreshold SAD in high school and college students with no history of mental disorders. METHODS: A multicenter randomized controlled trial designed to demonstrate the objective was conducted from December 2022 to October 2023. Participants were students enrolled at 6 universities and 1 high school. The intervention was a complete self-help ICBT and consisted of 10 text-based sessions that taught cognitive behavioral therapy techniques for social anxiety in youths and young adults. The comparison was a no-treatment condition (control group), which was randomly assigned in a 1:1 ratio by a computer program. A total of 2 psychological scales were used to assess the severity of social anxiety, and 1 psychological scale each was used to measure symptoms of depression, general anxiety, and quality of life. RESULTS: In total, 77 students were enrolled as study participants. Through the randomization procedure, 38 participants were included in the intervention group, and 39 patients were included in the control group. Results from the analysis of covariance with depression as covariates showed that the participants in the intervention group had significantly reduced symptoms of social anxiety, depression, and general anxiety compared to the control group. The response rate was 61% (19/31) in the intervention group and 24% (9/38) in the control group: odds ratio (OR) 4.97 (95% CI 1.61-16.53; P=.003) in the Fisher exact test. The recovery rate was 68% (21/31) in the intervention group and 34% (13/38) in the control group: OR 3.95 (95% CI 1.32-12.56; P=.008). The OR for the remission ratio was 2.01 (95% CI 0.64-6.60; P=.20) and for the risk of worsening was 0.23 (95% CI 0.002-1.33; P=.10), but no significant difference was observed. CONCLUSIONS: The results of this randomized controlled trial show that fully unguided ICBT improves subthreshold SAD in adolescents and young adults. Interpretation of the effectiveness in preventing SAD that meets the diagnostic criteria is limited by sample size and the follow-up period. Future studies should include more extended observations and larger sample sizes in high-risk populations. TRIAL REGISTRATION: UMIN-CTR UMIN000050064; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057035.

The mechanisms of insulin secretion and calcium signaling in pancreatic ß-cells exposed to fluoroquinolones.

Fluoroquinolones reportedly induce hypoglycemia through stimulation of insulin secretion from pancreatic ß-cells via inhibition of K(ATP) channels and activation of L-type voltage-dependent Ca(2+) channels. In physiological condition, the cytosolic Ca(2+) concentration ([Ca(2+)](c)) is also regulated by release of Ca(2+) from intracellular Ca(2+) stores. In this study, we investigated the mechanism of insulin secretion induced by fluoroquinolones, with respect to intracellular Ca(2+) stores. Even where the absence of supplemental extracellular Ca(2+), insulin secretion and [Ca(2+)](c) were increased by gatifloxacin, levofloxacin or tolbutamide. Insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones were reduced by depleting of Ca(2+) in endoplasmic reticumum (ER) by thapsigargin, and inhibiting ryanodine receptor of ER by dantrolene. Inhibition of inositol 1,4,5-triphosphate receptor of ER by xestospongin C suppressed insulin secretion induced by fluoroquinolones, whereas it did not affect [Ca(2+)](c). Destruction of acidic Ca(2+) stores such as lysosome and lysosome-related organelles by glycyl-L-phenylalanine-2-nephthylamide (GPN) did not affect insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones. The increase in insulin and [Ca(2+)](c) induced by tolbutamide were reduced by thapsigargin, dantrolene, and GPN but not by xestospongin C. In conclusion, fluoroquinolones induces Ca(2+) release from ER mediated by the ryanodine receptor, and the reaction might involve in insulin secretion. Sulfonylureas induce Ca(2+) release from GPN-sensitive acidic Ca(2+) stores, but fluoroquinolones did not.

The valproate serum level in maintenance therapy for bipolar disorder in Japan.

The appropriate therapeutic serum valproate level in maintenance therapy for bipolar disorder is not well known. We studied the serum valproate levels in seventeen bipolar I and twenty-four bipolar II disorder outpatients who had been treated with stable doses of valproate successfully for at least 12 months as prophylactic therapy. The trough serum valproate levels were 52.2 +/- 20.4 microg/ml in bipolar I, and 41.0 +/- 18.3 microg/ml in bipolar II disorder patients, respectively. A greater trend towards a higher trough level (p = 0.07) was indicated in the bipolar I disorder group. We speculate that these valproate levels may be an approximation to the appropriate valproate levels in maintenance therapy and that there may be a correlation between the level of valproate required for stabilization and the subtype of the bipolar disorder. However, when interpreting these findings, certain limitations to this study? Need to be taken into account as follows. The sample size was small. We could not look at a group on valproate that had relapsed and a group that had dropped out of maintenance therapy. Further studies are needed.

Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells.

Solithromycin is a novel fluoroketolide antibiotic belonging to the class of macrolide antibiotics. Activation of the interleukin (IL)-13 receptor leads to STAT6 activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF), chloride channel accessory 1 (CLCA1), and anoctamin-1 (ANO1), all of which are associated with the induction of MUC5AC. We examined the effects of solithromycin on mucin production led by IL-13 signaling. Normal human bronchial epithelial cells were grown at the air-liquid interface with IL-13 with/without solithromycin for 14 days. Histochemical analysis was performed using hematoxylin and eosin staining and MUC5AC immunostaining. MUC5AC, SPDEF, CLCA1, and ANO1 mRNA expressions were examined using real-time polymerase chain reaction. Western blot analysis was performed to assess CLCA1 and ANO1 proteins, and phosphorylation of STAT6 and ERK. Solithromycin attenuated IL-13 induction of goblet cell hyperplasia and MUC5AC, CLCA1 and ANO1 mRNA and protein expression induced by IL-13, but had no effect on the phosphorylation of STAT6 and ERK. Our results indicate that solithromycin could attenuate goblet cell hyperplasia and MUC5AC induced by IL-13 through inhibition of CLCA1 and ANO1 mRNA and protein expression. However, much more information is required to clarify the molecular mechanisms underlying the inhibition of CLCA1 and ANO1 by solithromycin.

Thermal stress-assisted formation of submicron pillars from a thin film of CoCrCuFeNi high entropy alloy: experiments and simulations.

In this work, for the first time, the thermal stress-assisted formation of submicron pillars (SPs) from a high entropy alloy (HEA) thin film is made possible, and novel molecular dynamics (MD) simulations are proposed to assess the underlying mechanisms. In a series of experiments, the growth of quasi-equiatomic HEA SPs from CoCrCuFeNi HEA thin films was demonstrated under different heating and cooling conditions. Atomistic simulations are performed to probe possible formation mechanisms in two ways. One is to first obtain surface elastic constants and then conduct surface stability analysis with the consideration of size-dependent surface stress. The other is to effectively apply large compressive stress while simplifying the molecular dynamics (MD) model by using the Stoney equation to perform long-term MD simulations. From the former, it is suggested that surface diffusion is likely not the dominant cause for the observed pillar formation. From the latter, it is revealed that the level of compressive stress plays a much greater role than the crystalline structure of the film sample. Light has been shed on the stress-assisted formation of submicron pillars from CoCrCuFeNi HEA films by both experimental and simulation approaches.

Metabolic dependency of non-small cell lung cancer cells affected by three-dimensional scaffold and its stiffness.

Three-dimensional (3D) extracellular matrix (ECM) microenvironment is an important regulator of the stiffness of the tumors. Cancer cells require heterogeneous metabolic phenotypes to cope with resistance in the malignant process. However, how the stiffness of the matrix affects the metabolic phenotypes of cancer cells, is lacking. In this study, the young's modulus of the synthesized collagen-chitosan scaffolds was adjusted according to the percentage ratio of collagen to chitosan. We cultured non-small cell lung cancer (NSCLC) cells in four different microenvironments (two-dimensional (2D) plates, stiffest 0.5-0.5 porous collagen-chitosan scaffolds, middle stiff 0.5-1 porous collagen-chitosan scaffolds, and softest 0.5-2 porous collagen-chitosan scaffolds) to investigate the influence of the difference of 2D and 3D cultures as well as the 3D scaffolds with different stiffnesses on the metabolic dependency of NSCLC cells. The results revealed that NSCLC cells cultured in 3D collagen-chitosan scaffolds displayed higher capacity of mitochondrial metabolism and fatty acid metabolism than that cultured in 2D culture. The metabolic response of NSCLC cells is differential for 3D scaffolds with different stiffnesses. The cells cultured in middle stiff 0.5-1 scaffolds displayed a higher potential of mitochondrial metabolism than that of stiffer 0.5-0.5 scaffolds and softer 0.5-2 scaffolds. Furthermore, NSCLC cells culture in 3D scaffolds displayed drug resistance compared with that in 2D culture which maybe via the hyperactivation of the mTOR pathway. Moreover, the cells cultured in 0.5-1 scaffolds showed higher ROS levels, which were counterbalanced by an equally high expression of antioxidant enzymes when compared to the cells grown in 2D culture, which may be regulated by the increased expression of PGC-1α. Together, these results demonstrate that differences in the microenvironments of cancer cells profoundly impact their metabolic dependencies.

Stiffer-Matrix-Induced PGC-1α Upregulation Enhanced Mitochondrial Biogenesis and Oxidative Stress Resistance in Non-small Cell Lung Cancer.

Introduction: Metabolic strategies in different microenvironments can affect cancer metabolic adaptation, ultimately influencing the therapeutic response. Understanding the metabolic alterations of cancer cells in different microenvironments is critical for therapeutic success. Methods: In this study, we cultured non-small cell lung cancer cells in three different microenvironments (two-dimensional (2D) plates, soft elastic three-dimensional (3D) porous 2 wt% scaffolds, and stiff elastic 3D porous 4 wt% scaffolds) to investigate the effects of different matrix elasticity as well as 2D and 3D culture settings on the metabolic adaptation of cancer cells. Results: The results revealed that PGC-1α expression is sensitive to the elasticity of the 3D scaffold. PGC-1α expression was markedly increased in cancer cells cultured in stiff elastic 3D porous 4 wt% scaffolds compared with cells cultured in soft elastic 3D porous 2 wt% scaffolds or 2D plates, enhancing mitochondrial biogenesis and oxidative stress resistance of non-small cell lung cancer through increased reactive oxygen species (ROS) detoxification capacity. However, phosphofructokinase-1 (PFK-1) expression, a key rate-limiting enzyme in glycolysis, did not change significantly in the three microenvironments, indicating that microenvironments may not affect the early stage of glycolysis. Conversely, monocarboxylate transporter 1 (MCT1) expression in 3D culture was significantly reduced compared to 2D culture but without significant difference between soft and stiff scaffolds, indicating that MCT1 expression is more sensitive to the shape of the different cultures of 2D and 3D microenvironment surrounding cells but is unaffected by the scaffold elasticity. Conclusions: Together, these results demonstrate that differences in the microenvironment of cancer cells profoundly impact their metabolic response.

Effect of Arginine Vasopressin on Intraoperative Hypotension Caused by Oral Administration of 5-Aminolevulinic Acid.

5-Aminolevulinic acid (5-ALA) is used for the photodynamic diagnosis of malignant tumors and has been effectively utilized to improve the complete resection rate and reduce the risk of tumor recurrence. However, intraoperative hypotension is a common adverse effect of oral 5-ALA, and it occasionally progresses to severe prolonged hypotension requiring high-dose catecholamine administration. We report a case of intraoperative hypotension due to oral 5-ALA in which arginine vasopressin (AVP) administration was effective for increasing the blood pressure. A 77-year-old man scheduled for a craniotomy for glioma was administered 5-ALA orally before surgery. After the induction of anesthesia, his blood pressure decreased substantially. Although we administered various vasopressor agents, hypotension was prolonged. However, after starting a continuous administration of AVP, the systolic blood pressure increased, and the hemodynamic parameters remained stable during the remainder of the operation. 5-ALA administration may lower blood pressure by inducing nitric oxide production, and AVP inhibits inducible nitric oxide synthase messenger RNA expression and interleukin-1ß-stimulated nitric oxide production. In light of these mechanisms, AVP may be a reasonable treatment agent for hypotension induced by 5-ALA.

Propensity-Score Matched Analysis of the Effectiveness of Baricitinib in Patients With Coronavirus Disease 2019 (COVID-19) Using Nationwide Real-World Data: An Observational Matched Cohort Study From the Japan COVID-19 Task Force.

Background: To determine the effectiveness of baricitinib in patients with coronavirus disease 2019 (COVID-19), investigate whether baricitinib prevents the need for invasive mechanical ventilation and identify patient subgroups that would benefit from baricitinib. Methods: This observational matched-cohort study was conducted by the Japan COVID-19 Task Force, a nationwide multicenter consortium. Patients with COVID-19 aged ≥18 years were identified from 70 hospitals in Japan. Among patients with confirmed COVID-19 from February 2020 to September 2021, those receiving baricitinib were propensity-score matched with controls. Results: Among 3309 patients, 144 propensity score-matched pairs were identified. Thirteen (9.0%) patients in the baricitinib group and 27 (18.8%) in the control group required invasive mechanical ventilation during the disease course (odds ratio, 0.43). Although the baricitinib group had more severe disease, there were no significant differences in the intensive care unit admission rates (odds ratio, 1.16) and mortality rates (odds ratio, 0.74) between groups. In subgroup analyses, baricitinib was associated with a significant reduction in the need for invasive mechanical ventilation in patients requiring oxygen support (odds ratio, 0.28), with rapid shadow spread on chest radiography (odds ratio, 0.11), or treated with remdesivir (odds ratio, 0.27), systemic corticosteroids (odds ratio, 0.31), or anticoagulants (odds ratio, 0.17). Conclusions: Baricitinib is effective at preventing the need for invasive mechanical ventilation in patients with COVID-19.

Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats.

It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson's disease (PD) patients receiving long term L-DOPA therapy. However, the physiological role of 3-OMD has not been well understood. Therefore, in order to clarify the effects of 3-OMD on physiological function, we examined the behavioral alteration in rats based on locomotor activity, and measured dopamine (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic administration. The study results showed that repeated administrations of 3-OMD increased its blood and the striatum tissue levels in those rats, and decreased locomotor activity in a dose dependent manner. Although 3-OMD subchronic administration showed no significant change in DA level in the striatum, DA metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased. After 3-OMD washout period (7 d), locomotor activity and DA turnover in those rats returned to normal levels. Furthermore, locomotor activity and DA turnover decreased by 3-OMD administration were recovered to normal level by acute L-DOPA administration. These results suggested that 3-OMD affect to locomotor activity via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD patients receiving L-DOPA therapy.

Influences of pyrexia and age on theophylline clearance in young children with asthma.

Fifty hospitalized children with asthmatic bronchitis and bronchial asthma were treated with a continuous intravenous drip infusion of aminophylline. To investigate the pharmacokinetics of theophylline in the presence of pyrexia, patients were divided into two groups based on body temperature: a pyrexia group (> or = 38 degrees C) and a non-pyrexia group (< 38 degrees C). Theophylline clearance was 0.064 +/- 0.017 liters/kg/hr in the non-pyrexia group and 0.049 +/- 0.010 liters/kg/hr in the pyrexia group. Theophylline clearance in the non-pyrexia and pyrexia groups was 0.044 +/- 0.007 liters/kg/hr and 0.030 +/- 0.009 liters/kg/hr (< or = 6 months), 0.071 +/- 0.011 liters/kg/hr and 0.047 +/- 0.008 liters/kg/hr (6 to < or = 12 months), 0.084 +/- 0.012 liters/kg/hr and 0.055 +/- 0.006 liters/ kg/hr (1 to < or = 2 years), and 0.065 +/- 0.007 liters/kg/hr and 0.051 +/- 0.001 liters/kg/hr (2 to < or = 3 years), respectively. In all age groups, theophylline clearance of the pyrexia group was significantly less than that of the non-pyrexia group (p < 0.01), showing that there was a significant pharmacokinetic difference in theophylline clearance between the groups. Multivariate statistical analysis showed that theophylline clearance was affected by pyrexia and age. This study showed that the presence of pyrexia decreases theophylline clearance, and that it affects theophylline clearance in an age-dependent manner. Based on the results of this study, dosages should be designed based on the clearance at the time of pyrexia.

Bioengineered PLEKHA7 nanodelivery regularly induces behavior alteration and growth retardation of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most lethal leukemia with an extremely poor prognosis and high relapse rates. In leukemogenesis, adhesion abnormalities can readily guide an imbalance between hematopoietic progenitor cells and bone marrow stromal cells, altering the normal hematopoietic bone marrow microenvironment into leukemic transformation that enhances leukemic proliferation. Here, we have firstly studied the PLEKHA7 expression in leukemic cells to assess their growth capability affected by the restoration of PLEKHA7 in the cells. The efficacy of PLEKHA7-loaded cRGD-mediated PEGylated cationic lipid nanoparticles for efficient PLEKHA7 delivery in leukemic cells as well as the effect of PLEKHA7 on the regulated induction of AML behavior and growth alterations were investigated. PLEKHA7 re-expression diminished colony-forming ability and reinforced the incidence of growth retardation without apoptosis in AML cell lines. PLEKHA7 regulated the restoration of cell surface adhesion and integrity during normal homeostasis. Our findings revealed that PLEKHA7 functions as a behavior and growth modulator in AML. To our knowledge, the role of PLEKHA7 in AML had not been studied previously and our data could be exploited for further mechanistic studies and insights into altering human AML behavior and growth.

Nanocarriers for drug-delivery systems using a ureido-derivatized polymer gatekeeper for temperature-controlled spatiotemporal on-off drug release.

Accidental chemotherapy extravasation exacerbates the side effects of anticancer drugs. Therefore, drug-delivery nanocarriers should be designed to avoid persistent drug release at off-target sites and promote burst drug release at on-target. Considering these requirements, poly(allylamine)-co-poly(allylurea) (PAU), a ureido-derivatized temperature responsive polymer with upper critical solution temperature (UCSTs), is an ideal material. This report describes the fabrication, characterization, and in vitro cellular toxicity of PAU polymer-grafted magnetic mesoporous silica nanoparticles as drug-delivery nanocarriers. A UCST of 43 °C and an ultranarrow transition temperature range of 39-43 °C was realized, ensuring that the nanocarriers suppressed undesirable leakage to below 10 % of the drug loading for 8 h in the absence of a thermal stimulus. A drug release burst of up to 75 % of the drug loading was achieved within 30 min after the stimulus, reducing the viability of the in vitro cancer cells to 12 %. Therefore, the ureido-derivatized polymer is one of the most suitable gatekeepers for drug-delivery nanocarriers.

Relationship between 3-O-methyldopa and the clinical effects of entacapone in advanced Parkinson's disease.

The aim of this study is to clarify the relationship between serum 3-O-methyldopa (3-OMD) and the clinical effects of entacapone. The 3-OMD and maximum serum concentration (Cmax) of levodopa were measured in 21 Parkinson's Disease patients who took 100 mg levodopa / dopa decarboxylase inhibitor. After the administration of entacapone, the 3-OMD concentration and percentage of "on" time during waking hours (% of "on" time) were studied for 8 weeks. The 3-OMD concentration was reduced by 34%, and the increase in % of "on" time was 28% at the 8th week compared with baseline. We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. The COMT-index was significantly correlated with the increase in % of "on" time at the 8th week. In conclusion, the measurement of baseline 3-OMD and levodopa pharmacokinetics is useful for predicting the clinical effects of entacapone.