Clinical Characteristics of Hyponatremia

Background & aims : We investigated the contributing factors of hyponatremia in patients on nutrition support using bioelectrical impedance analysis (BIA). Methods : Thirty patients administered enteral or parenteral nutrition support for at least 72 hours were studied. We collected nutritional and electrolyte intake, serum biochemical parameters, and body composition measured by BIA. Patients were classified into two groups according to their serum sodium levels : (1) Normanatremia group, 135–145 mEq / L (n = 18) and (2) Hyponatremia group, less than 135 mEq / L (n = 12), and their characteristics were analyzed. Results : There were no significant differences between the Normonatremia and Hyponatremia groups in terms of energy, protein, and sodium intake. Serum biochemical parameters other than serum sodium and chloride levels were comparable between the two groups. On the other hand, the ratio of extracellular water to total body water (ECW / TBW) obtained by BIA was significantly higher in the Hyponatremia group than in the Normonatremia group. Further, an elevated ECW / TBW significantly and negatively correlated with serum albumin level. Conclusions : Regardless of sodium intake, higher ECW / TBW was associated with hyponatremia in patients on nutrition support. ECW / TBW may be an important clinical parameter relevant to the nutritional care of hyponatremia

Identification of targets of tumor suppressor microRNA-34a using a reporter library system

miRNAs play critical roles in various biological processes by targeting specific mRNAs. Current approaches to identifying miRNA targets are insufficient for elucidation of a miRNA regulatory network. Here, we created a cell-based screening system using a luciferase reporter library composed of 4,891 full-length cDNAs, each of which was integrated into the 3′ UTR of a luciferase gene. Using this reporter library system, we conducted a screening for targets of miR-34a, a tumor-suppressor miRNA. We identified both previously characterized and previously uncharacterized targets. miR-34a overexpression in MDA-MB-231 breast cancer cells repressed the expression of these previously unrecognized targets. Among these targets, GFRA3 is crucial for MDA-MB-231 cell growth, and its expression correlated with the overall survival of patients with breast cancer. Furthermore, GFRA3 was found to be directly regulated by miR-34a via its coding region. These data show that this system is useful for elucidating miRNA functions and networks

Microglial re-modeling contributes to recovery from ischemic injury of rat brain: A study using a cytokine mixture containing granulocyte-macrophage colony-stimulating factor and interleukin-3

Ischemic stroke is a leading cause of mortality and permanent disability. Chronic stroke lesions increase gradually due to the secondary neuroinflammation that occurs following acute ischemic neuronal degeneration. In this study, the ameliorating effect of a cytokine mixture consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 was evaluated on ischemic brain injury using a rat stroke model prepared by transient middle cerebral artery occlusion (tMCAO). The mixture reduced infarct volume and ameliorated ischemia-induced motor and cognitive dysfunctions. Sorted microglia cells from the ischemic hemisphere of rats administered the mixture showed reduced mRNA expression of tumor necrosis factor (TNF)-α and IL-1β at 3 days post-reperfusion. On flow cytometric analysis, the expression of CD86, a marker of pro-inflammatory type microglia, was suppressed, and the expression of CD163, a marker of tissue-repairing type microglia, was increased by the cytokine treatment. Immunoblotting and immunohistochemistry data showed that the cytokines increased the expression of the anti-apoptotic protein Bcl-xL in neurons in the ischemic lesion. Thus, the present study demonstrated that cytokine treatment markedly suppressed neurodegeneration during the chronic phase in the rat stroke model. The neuroprotective effects may be mediated by phenotypic changes of microglia that presumably lead to increased expression of Bcl-xL in ischemic lesions, while enhancing neuronal survival

Tumor size and proliferative marker geminin levels associated with SUVmax levels on PET for breast cancers

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67- high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Comparison of one-year results of photodynamic therapy combined with ranibizumab or aflibercept for treating polypoidal choroidal vasculopathy.

PurposeTo compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV).MethodsWe retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated.ResultsForty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P ConclusionsPDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up

Incidence of elevated intraocular pressure after intravitreal injection in Japanese patients with age-related macular degeneration

Abstract The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP

Sensitivity and specificity of high-resolution wide field fundus imaging for detecting neovascular age-related macular degeneration.

PurposeEarly detection and treatment are important management strategies for neovascular age-related macular degeneration (AMD). The purpose of this study was to determine the sensitivity and specificity in detecting neovascular AMD using two wide-field imaging systems: ClarusTM (CLARUS 500™, Carl Zeiss Meditec AG, Jena, Germany) and Optos®(Optos California®, Optos PLC, Dunfermline, United Kingdom), compared to conventional digital fundus photographs.MethodsWe retrospectively analyzed 109 eyes of 73 consecutive patients with neovascular AMD, who underwent standard examination and multimodal imaging, including fundus photography, and optical coherence tomography (OCT). Unmasked graders utilized slit-lamp biomicroscopy and OCT to diagnose neovascular AMD. Masked graders evaluated ClarusTM, Optos®, and digital fundus photograph methods to determine the presence of choroidal neovascularization associated with AMD. Sensitivity and specificity analyses were performed using combined fundoscopy and OCT as the reference standard.ResultsNinety eyes were diagnosed with neovascular AMD and the remaining 19 eyes were normal based on the reference standard. Of these, neovascular AMD was detected using ClarusTM in 94.4% (85/90). The sensitivities of Optos® and digital fundus photographs were 81.1% (73/90) and 87.8% (79/90), respectively. The specificities using ClarusTM, Optos®, and digital fundus photographs were 89.5% (17/19), 94.7% (18/19), and 89.5% (17/19), respectively.ConclusionClarusTM, with its ability to image high-resolution wide field fundus, was considered superior for diagnosing neovascular AMD with high sensitivity and specificity. It may be a useful screening tool for early detection of neovascular AMD, facilitating prompt referral and treatment

Evaluation of formulation properties and skin penetration in the same additive-containing formulation

The aim of this study is to examine the physicochemical properties of the external preparation, the effect on the skin permeability and the human senses. Miconazole nitrate cream formulation (MCZ-A: bland name and MCZ-B, −C, −D: generics) to measure the physicochemical properties, was performed by the skin permeation test and human sensory test. The flattening, viscoelasticity, and water content of each cream were measured and each cream was subjected to near-infrared (NIR) absorption spectroscopy and human sensory testing. The yield value was calculated based on measured flattening and was 734.8 dynes/cm2 for MCZ-A, 1198.9 dynes/cm2 for MCZ-B, 461.3 dynes/cm2 for MCZ-C and 3112.3 dynes/cm2 for MCZ-D. Measurement of viscoelasticity and viscosity revealed that MCZ-C had a smaller tanδ than the other 3 creams at 25 °C. NIR absorption spectroscopy revealed that MCZ-A had the highest absorption peak due to hydroxyl groups, followed by MCZ-C, −B, and then −D. Measurement of water content revealed that MCZ-A had a water content of 65.9%, MCZ-B, −C, and −D had a water content of around 56.3%. Human sensory testing revealed differences between MCZ-A and MCZ-C and between MCZ-B and MCZ-D in terms of spreadability and feel. These findings indicate that differences in water and oil content and emulsification resulted in the creams having different physical properties, such as flattening, internal structure, and dynamic viscoelasticity. NIR absorption spectroscopy, which allows non-destructive measurement of a sample’s physicochemical properties, and measurement of viscoelasticity and viscosity, which allows measurement of a sample’s dynamic viscoelasticity, revealed differences in the physical properties of creams. The skin permeation test, skin MCZ amount was 7.48 µg/cm2 for MCZ-A, 5.11 µg/cm2 for MCZ-B, 12.08 µg/cm2 for MCZ-C and 3.75 µg/cm2 for MCZ-D. In addition, since the drug spread is good about the skin migration, spreadability is affecting the potential dermal transfer