New Tubulocentric Insights for Diabetic Nephropathy: From Pathophysiology to Treatment

The prevalence of diabetes is increasing worldwide, and one of the most important complications, diabetic nephropathy, constitutes a significant global health care and socioeconomic burden. Glomerular dysfunction is a major factor in the development and progression of diabetic nephropathy. However, emerging evidence suggests that tubular damage also plays an important role in the pathogenesis of diabetic nephropathy. This tubulocentric view shifts the focus markedly from glomeruli to proximal tubules, which might have an important role as a trigger or a driver in the early development and progression of diabetic nephropathy. Accordingly, numerous studies have focused on several different tubular damage markers that are clinically indicated as potential biomarkers for the early detection of diabetic nephropathy. Furthermore, these findings are relevant for identifying therapeutics for diabetic nephropathy that target the proximal tubules. This review outlines new tubulocentric insights into diabetic nephropathy, from pathophysiological mechanisms to diagnostic and therapeutic approaches

Development of thermal switch using liquid column

Paper presented at the 6th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, South Africa, 30 June - 2 July, 2008.This paper presents the thermal switch which is composed of several switching channels, breathing grooves, reservoirs and actuators to control the liquid column. In the “on” state, a switching channel is filled with liquid supplied by an actuator, which decreases the thermal resistance. In the “off” state, the air fills in the gap of two plates instead of the liquid column and the thermal resistance is increased. Through this switch operation, temperature of the designated hot spot can be controlled locally. In order to realize the desired switch operation, the liquid column should be precisely controlled based on channel design. The switching channel is composed of burst area and path area to achieve the smooth operation. The burst area was geometrically designed to provide the hydrophilic surface geometrically by taking into account of burst area. Experiments were performed on a designed switch for the liquid column control and the heat flow regulation. The results showed that this thermal switch is able to make the “on” and “off” state by controlling liquid column well. Also, the temperature distribution and thermal resistance has been changed according to channel state.vk201

Epidermal Cysts in a Tacrolimus Treated Renal Transplant Recipient

Tacrolimus, a calcineurin inhibitor, formerly also known as FK506, is a macrolactam drug isolated from Streptomyces tsukubaensis. Its mode of action closely parallels the action of cyclosprorin A (CsA) and can be used for the treatment of inflammatory and autoimmune skin diseases in which systemic CsA has proved effective against psoriasis, pyoderma gangrenosum, atopic dermatitis, lupus erythematosus and graft versus host disease (GVHD). Although several cases of epidermal cysts have been reported in patients using cyclosporine and other immunosuppressants after organ transplantation; such types of cases have yet not been reported after administration of tacrolimus. However, we report herein a case of presence of multiple, various sized epidermal cysts in a renal transplant recipient receiving tacrolimus

Patients with systemic lupus erythematosus have abnormally elevated Epstein–Barr virus load in blood

Various genetic and environmental factors appear to be involved in systemic lupus erythematosus (SLE). Epstein–Barr virus (EBV) is among the environmental factors that are suspected of predisposing to SLE, based on the characteristics of EBV itself and on sequence homologies between autoantigens and EBV antigens. In addition, higher titers of anti-EBV antibodies and increased EBV seroconversion rates have been observed in SLE patients as compared with healthy control individuals. Serologic responses do not directly reflect EBV status within the body. Clarification of the precise status of EBV infection in SLE patients would help to improve our understanding of the role played by EBV in this disease. In the present study we determined EBV types in SLE patients (n = 66) and normal control individual (n = 63) by direct PCR analysis of mouthwash samples. We also compared EBV load in blood between SLE patients (n = 24) and healthy control individuals (n = 29) using semiquantitative PCR assay. The number of infections and EBV type distribution were similar between adult SLE patients and healthy control individuals (98.5% versus 94%). Interestingly, the EBV burden in peripheral blood mononuclear cells (PBMCs) was over 15-fold greater in SLE patients than in healthy control individuals (mean ± standard deviation: 463 ± 570 EBV genome copies/3 μg PBMC DNA versus 30 ± 29 EBV genome copies/3 μg PBMC DNA; P = 0.001), suggesting that EBV infection is abnormally regulated in SLE. The abnormally increased proportion of EBV-infected B cells in the SLE patients may contribute to enhanced autoantibody production in this disease

Effect of volatile fatty acid concentration on anaerobic degradation rate from field anaerobic digestion facilities treating food waste leachate in

The purpose of this study was to investigate the effect of volatile fatty acid concentration on anaerobic degradation rate of food waste leachate in the anaerobic digestion facilities. The anaerobic digestion facilities treating food waste leachate (FWL), codigestion with food leachate and animal manure (A-MIX), and codigestion with food waste leachate and sewage sludge (S-MIX) were selected for this study. In accordance with the regulation under Wastes Control Act in South Korea, the guideline of volatile solid removal rate for anaerobic digestion facility is set as 65% for anaerobic degradation efficiency. Highest volatile solids removal rates were achieved from FWL (63.5%) than A-MIX (56.4%) and S-MIX (41.2%). Four out of eight FWLs met the guidelines. The concentration of volatile fatty acids, therefore, was analyzed to determine the relationship with volatile solid removal rate. The results showed that, in order to meet the Korean guideline of 65% volatile solid removal rate, volatile fatty acid concentrations should remain below 4,000 mg/L on the field anaerobic digestion facilities treating FWL. Volatile fatty acid concentrations should be used along with others as an operational parameter to control and manage the anaerobic digestion process

Early Growth Response 1-Dependent Downregulation of Matrix Metalloproteinase 9 and Mouse Double Minute 2 Attenuates Head and Neck Squamous Cell Carcinoma Metastasis

Background/Aims: The functional relevance of early growth response-1 (EGR1) on cancer invasion remains controversial. The effect of EGR1 on the expression of MMP9, which is important for HNSCC invasion, is still disputed. There is no previous data showing the effect of EGR1 on mouse double minute 2 (MDM2), an enhancer of matrix metalloproteinase 9 (MMP9) expression. Our aim is to clarify the negative correlation between EGR1 expression and head and neck squamous cell carcinoma (HNSCC) metastasis. Methods: EGR1 mRNA and protein expressions were compared in normal and HNSCC tissues using The Cancer Genome Atlas (TCGA) dataset analysis or immunohistochemistry (IHC), respectively. In vitro cell invasion was evaluated Matrigel invasion assay. EGR1-dependent inhibition of MDM2 transcription was assessed by promoter–luciferase assay and chromatin immunoprecipitation (ChIP). Results: TCGA data showed that EGR1 mRNA levels are significantly higher in normal oral tissues as compared with HNSCC tumor tissues (adjusted P = 1.64x10-16). In addition, nonmetastatic HNSCC tissues showed significantly higher EGR1 mRNA levels as compared with metastatic tissues (adjusted P = 0.023). IHC analysis showed that primary tumor tissues expressed significantly higher levels of nuclear EGR1 compared with paired metastatic lymph node tissues (P < 0.05). EGR1 overexpression downregulated MMP9 and MDM2 protein expression. Consistent with these observations, TCGA data analysis found significantly fewer metastatic patients among a subgroup of population presenting higher EGR1 expressions with lower MMP9 and/or MDM2. Conclusion: Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis

NMDA Receptor in Vasopressin 1b Neurons Is Not Required for Short-Term Social Memory, Object Memory or Aggression

This work is licensed under a Creative Commons Attribution 4.0 International License.The arginine vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including aggression, social learning and memory. Genetic removal of Avpr1b from mouse models results in deficits in aggression and short-term social recognition in adults. Avpr1b gene expression is highly enriched in the pyramidal neurons of the hippocampal cornu ammonis 2 (CA2) region. Activity of the hippocampal CA2 has been shown to be required for normal short-term social recognition and aggressive behaviors. Vasopressin acts to enhance synaptic responses of CA2 neurons through a NMDA-receptor dependent mechanism. Genetic removal of the obligatory subunit of the NMDA receptor (Grin1) within distinct hippocampal regions impairs non-social learning and memory. However, the question of a direct role for NMDA receptor activity in Avpr1b neurons to modulate social behavior remains unclear. To answer this question, we first created a novel transgenic mouse line with Cre recombinase knocked into the Avpr1b coding region to genetically target Avpr1b neurons. We confirmed this line has dense Cre expression throughout the dorsal and ventral CA2 regions of the hippocampus, along with scattered expression within the caudate-putamen and olfactory bulb (OB). Conditional removal of the NMDA receptor was achieved by crossing our line to an available floxed Grin1 line. The resulting mice were measured on a battery of social and memory behavioral tests. Surprisingly, we did not observe any differences between Avpr1b-Grin1 knockout mice and their wildtype siblings. We conclude that mice without typical NMDA receptor function in Avpr1b neurons can develop normal aggression as well as short-term social and object memory performance

Acute Kidney Injury due to Menstruation-related Disseminated Intravascular Coagulation in an Adenomyosis Patient: A Case Report

The authors report a case of acute kidney injury (AKI) resulting from menstruation-related disseminated intravascular coagulation (DIC) in an adenomyosis patient. A 40-yr-old woman who had received gonadotropin for ovulation induction therapy presented with anuria and an elevated serum creatinine level. Her medical history showed primary infertility with diffuse adenomyosis. On admission, her pregnancy test was negative and her menstrual cycle had started 1 day previously. Laboratory data were consistent with DIC, and it was believed to be related to myometrial injury resulting from heavy intramyometrial menstrual flow. Gonadotropin is considered to play an important role in the development of fulminant DIC. This rare case suggests that physicians should be aware that gonadotropin may provoke fulminant DIC in women with adenomyosis

A novel β-glucan produced by Paenibacillus polymyxa JB115 induces nitric oxide production in RAW264.7 macrophages

The effect of extracellular β-(1→3), (1→6)-glucan, produced by Paenibacillus polymyxa JB115, on nitric oxide (NO) production in RAW264.7 macrophages was investigated. β-glucan induced the production of NO by RAW264.7 macrophages in a concentration- and time-dependent manner. Moreover, β-glucan stimulation increased the mRNA expression of iNOS, COX-2 and IL-6 in RAW264.7 macrophages in a concentration-dependent manner

Polymer Micelle Formulation for the Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy and Pharmacokinetic Studies in Mice

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitroperformances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers