The Role of Potassium in Fluid Therapy

For general practitioners, who handle more than 85 per cent of all pediatric care, POSTGRADUATE MEDICINE here presents authoritative, up-to-date summaries by specialists in pediatric problems.     

Toxicity of triphenyltin chloride to the rotifer Brachionus koreanus across different levels of biological organization

Although triphenyltin (TPT) compounds are ubiquitous pollutants in urbanised coastal environments in Asian regions, their toxicities to marine organisms are still poorly known. This study was designed to investigate the toxicity of triphenyltin chloride (TPTCl) on the rotifer Brachionus koreanus across different levels of biological organisation. Firstly, we concurrently performed a 24 h static‐acute toxicity test and a 6‐day semi‐static multigenerational life‐cycle test using the rotifer. Our results demonstrated that the 24‐h median lethal concentration of TPTCl for the rotifer was 29.6 μg/L and the 6‐day median effect concentration, based on the population growth inhibition, was 3.31 μg/L. Secondly, we examined the expression of 12 heat shock protein (hsp) genes, four glutathione S‐transferase (GST) genes, one retinoid X receptor (RXR) gene and 13 cytochrome P450 (CYP) genes in the rotifers after exposure to 20 µg/L TPTCl for 24 h. Among these studied genes, hsp90α2, GST‐O and CYP3045C1 were the most significantly up‐regulated genes with a relative expression level up to 32.9, 4.4 and 62.6 folds, respectively. The expression of these three genes in the rotifers showed an increasing trend in the first few hours of TPTCl exposure, peaked at 3 h (hsp90α2 and GST‐O) and 12 h (CYP3045C1) respectively, and then gradually returned to a lower level at 24 h. Such up‐regulations of hsp and GST genes probably offer cellular protection against the TPT‐mediated oxidative stress while the accelerated induction of CYP genes possibly facilitates the detoxification of this toxicant in the rotifer. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 13–23, 2016.     

Associations of intra-renal arterial resistance index with chronic kidney disease and carotid intima-media thickness in type 2 diabetes mellitus

Renal dysfunction can be evaluated by increased intra-renal arterial resistance index (RI). We evaluated 113 Chinese men with type 2 diabetes on their RI. Results suggest that RI is associated with chronic kidney disease and subclinical arteriosclerosis. RI may help monitoring the deterioration of intra-renal hemodynamics.     

Immune-mediated complications of the graft in interferon-treated hepatitis C positive liver transplant recipients

Hepatitis C virus (HCV) re-infection of the graft is universal and interferon based antiviral therapy remains at present the treatment of choice in HCV liver transplant recipients. Apart from the antiviral effects, interferon and ribavirin have both potent immunomodulatory properties resulting in a broad range of immune-related disorders including acute cellular rejection and chronic ductopenic rejection as well as de novo autoimmune hepatitis. Further complicating the picture, HCV infection per se is associated with a variety of autoimmune phenomena. We discuss here the immune-mediated complications and their relationship to chronic HCV and interferon based antiviral therapy.     

Insights into the diagnosis and pathogenesis of the antiphospholipid syndrome

The Antiphospholipid syndrome (APS), formerly known as Anticardiolipin or Hughes syndrome, is a systemic autoimmune disorder characterized by obstetrical complications and thrombotic events affecting almost every organ-system in patients persistently testing positive for antiphospholipid antibodies (aPL). The contribution of the extra-criteria aPL to the pathogenesis of APS have exceeded the expectations of a simple, direct pathologic ‘hit’ leading to thrombogenesis or obstetrical complications, and more pathologic pathways are being linked directly or indirectly to aPL. The value of extra-criteria aPL is on the rise, and these antibodies are nowadays evaluated as markers for risk assessment in the diagnostic approach to APS. A diagnosis of APS should be considered in pediatric patients with suggestive clinical and laboratory picture. Management of APS remains mostly based on anticoagulation, while other drugs are being tested for efficacy and side effects. Low-dose aspirin may have a role in the management of thrombotic and obstetric APS. Due to the high variability in disease severity and complication recurrence outcomes, new tools are being developed and validated to assess the damage index and quality of life of APS patients.     

Development of a novel, physiologically relevant cytotoxicity model: Application to the study of chemotherapeutic damage to mesenchymal stromal cells

There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. Conversely, the vast majority of agents are detoxified by the liver, consequently toxicity from such agents may be overestimated.In this study we describe the development of a novel in-vitro model, which could be adapted for any toxicology setting. The model utilises HepG2 liver spheroids as a source of metabolic enzymes, which have been shown to more closely resemble human liver than traditional monolayer cultures. A co-culture model has been developed enabling the effect of any metabolised agent on another cell type to be assessed. This has been optimised to enable the study of damaging effects of chemotherapy on mesenchymal stem cells (MSC), the supportive stem cells of the bone marrow. Several optimisation steps were undertaken, including determining optimal culture conditions, confirmation of hepatic P450 enzyme activity and ensuring physiologically relevant doses of chemotherapeutic agents were appropriate for use within the model. The developed model was subsequently validated using several chemotherapeutic agents, both prodrugs and active drugs, with resulting MSC damage closely resembling effects seen in patients following chemotherapy.Minimal modifications would enable this novel co-culture model to be utilised as a general toxicity model, contributing to the drive to reduce animal safety testing and enabling physiologically relevant in-vitro study.     

Incremental value of real-time ultrasound elastography in differentiating breast masses

Aim of the work

To evaluate the value of real-time ultrasound elastography (RTE) in differentiating benign from malignant breast masses.

Materials and methods

This study included, whether palpable or non-palpable, 145 sonographically proven breast masses in 121 patients, imaged by conventional B-mode US, color-flow Doppler US and RTE with histopathological analysis considered as the golden standard reference.

Results

Lesions were differentiated into benign and malignant by conventional B-mode US (79; 45.5% and 66; 54.5%, respectively), RTE (80; 55.2% and 65; 44.8% respectively), and histopathology (82; 56.6% and 63; 43.4%, respectively). The mean difference in the mass size was significant between B-mode US and RTE in malignant masses (P = 0.002), while not significant among benign masses (P = 0.153). The B-mode US depicted sensitivity of 92.06%, specificity of 90.24%, PPV of 87.88%, NPV of 93.67% and accuracy of 91.03%, while the RTE showed sensitivity of 98.41%, specificity of 96.34%, PPV of 95.38%, NPV of 98.75% and accuracy of 97.24%.

Conclusion

Combined use of RTE can complement conventional B-mode US with improving its diagnostic performance in differentiating breast lesions with subsequent reduction in the rate of unnecessary biopsies in benign lesions.     

The dopaminergic stabilizer ASP2314/ACR16 selectively interacts with D2High receptors

Dopaminergic stabilizers are recognized as compounds that can either enhance or antagonize dopamine (DA)‐dependent behaviors depending on the prevailing dopaminergic tone. The dopaminergic stabilizer ASP2314 is being tested clinically and has been reported to have antipsychotic effects in a clinical trial as an add on medication. To elucidate the mechanisms of action of this dopaminergic stabilizer, its potency on the functional dopamine D2^High receptors was examined. In competition with D2 receptors selectively labeled by [³H]domperidone, ASP2314 had a dissociation constant, Ki^High, of 1.62 μM for D2^High in human cloned D2Long receptors and 0.83 μM for rat homogenized striata. Using the D2 agonist ligand [³H](+)‐4‐propyl‐3,4,4a,5,6,10b‐hexahydro‐2H‐naphtho[1,2‐b][1,4]oxazin‐9‐ol ((+)PHNO), ASP2314 had a high‐affinity K_i of 32 nM for D2^High for rat homogenized striata. ASP2314 stimulated the incorporation of [³⁵S]GTP‐γ‐S into rat striata by 50% at 43 nM, and into the cloned D2Long membranes by 50% at 3.2 μM (compared to 100% stimulation by 10 μM dopamine). With similar concentrations of ASP2314 inhibiting the binding of ligands at D2^High and stimulating [³⁵S]GTP‐γ‐S incorporation, the data indicate that the dopaminergic stabilizing action of ASP2314 may be related to the selectivity for the D2^high state of the D2 receptor. Synapse 63:930–934, 2009. © 2009 Wiley‐Liss, Inc.