Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis

Summary

Background and objectives

Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic utility of newer biomarkers or traditional markers (fractional excretion of sodium [FeNa] and urea [FeUrea] and microscopy) over clinical assessment alone.

Design, setting, participants, & measurements

This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death.

Results

In 249 recipients, 57% were ≥65 years old, 48% were from intensive care, and mean baseline GFR was 69 ± 30 ml/min per 1.73 m². AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and “other” in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values <0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful.

Conclusions

On the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.     

Ceramicines J–L, new limonoids from Chisocheton ceramicus

Three new limonoids, ceramicines J (1), K (2), and L (3), were isolated from the hexane layer of Chisocheton ceramicus bark extract. Their structures were elucidated from 1D and 2D NMR data. Ceramicines J-L (1-3) exhibited dose-dependent moderate cytotoxicity against the HL-60 cell line.     

Thematic information content assessment of the ASTER GDEM: a case study of watershed delineation in West Java,Indonesia

This study assesses the thematic information content using subwatershed boundaries mapped using advanced spaceborne thermal emission and reflection (ASTER) global digital elevation model (GDEM), shuttle radar topography mission (SRTM) DEM and a topographic map (Topo-DEM), and verifies the absolute elevation accuracy by the use of a real-time kinematic differential global positioning system (RTK-DGPS) survey. Subwatershed boundaries extracted from the three different DEMs exhibit a high degree of congruency especially in upstream areas. In these areas, SRTM exhibits lower root mean square errors (RMSEs) than the ASTER GDEM. The discrepancies were larger at lower altitudes. The vertical accuracy assessment using the RTK-DGPS data showed strong correlation with the three DEMs at some stations but the accuracy varied from one area to another. The ASTER GDEM and SRTM had lower accuracy than the Topo-DEM due to the influence of artefacts as shown by their total average RMSE (4.42, 3.30 and 3.13 m, respectively). The average RMSE values also indicate that SRTM is comparatively more accurate than ASTER GDEM.     

Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer cells

AIM:To investigate the events associated with the apoptotic effect of p-Coumaric acid,one of the phenolic components of honey,in human colorectal carcinoma(HCT-15)cells.METHODS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertazolium-bromide assay was performed to determine the antiproliferative effect of p-Coumaric acid against colon cancer cells.Colony forming assay was conducted to quantify the colony inhibition in HCT15 and HT 29 colon cancer cells after p-Coumaric acid treatment.Propidium Iodide staining of the HCT15 cells using flow cytometry was done to study the changes in the cell cycle of treated cells.Identification of apoptosis was done using scanning electron microscope and photomicrograph evaluation of HCT 15cells after exposing to p-Coumaric acid.Levels of reactive oxygen species(ROS)of HCT 15 cells exposed to p-Coumaric acid was evaluated using 2’,7’-dichlorfluorescein-diacetate.Mitochondrial membrane potential of HCT-15 was assessed using rhodamine-123 with the help of flow cytometry.Lipid layer breaks associated with p-Coumaric acid treatment was quantified using the dye merocyanine 540.Apoptosis was confirmed and quantified using flow cytometric analysis of HCT15 cells subjected to p-Coumaric acid treatment after staining with YO-PRO-1.RESULTS:Antiproliferative test showed p-Coumaric acid has an inhibitory effect on HCT 15 and HT 29 cells with an IC50(concentration for 50%inhibition)value of 1400 and 1600μmol/L respectively.Colony forming assay revealed the time-dependent inhibition of HCT 15 and HT 29 cells subjected to p-Coumaric acid treatment.Propidium iodide staining of treated HCT 15cells showed increasing accumulation of apoptotic cells(37.45±1.98 vs 1.07±1.01)at sub-G1phase of the cell cycle after p-Coumaric acid treatment.HCT-15 cells observed with photomicrograph and scanning electron microscope showed the signs of apoptosis like blebbing and shrinkage after p-Coumaric acid exposure.Evaluation of the lipid layer showed increasing lipid layer breaks was associated with the growth i     

Induction of immune memory by a multisubunit chlamydial vaccine

We tested the hypothesis that intramuscular immunization with a multisubunit chlamydial vaccine candidate will induce long lasting immune responses in mice. Accordingly, groups of female C57BL/6 mice were immunized intramuscularly with Vibrio cholerae ghosts (VCG) expressing the Poring B and polymorphic membrane protein-D proteins of Chlamydia trachomatis or a control antigen. Humoral and cell-mediated immune responses were evaluated following immunization and after live chlamydial infection. Immunization induced an anamnestic response characterized by chlamydial-specific IgG2a and IgA antibodies in sera and vaginal lavage as well as specific genital and splenic T cell responses. The results also revealed that the local mucosal and systemic cellular and humoral immune effectors induced in mice following immunization with the vaccine candidate are long lasting. Vaccinated mice cleared intravaginal challenge with 10⁵ chlamydial inclusion forming units within 12 days compared to control mice, which shed up to 2 × 10³ IFUs at this time point. Moreover, rechallenge of mice 98 days after resolution of the primary infection resulted in the recall and retention of a relatively high frequency of chlamydial-specific Th1 cells and IgG2a in the genital mucosa. These results provide the first evidence that a VCG-based multisubunit chlamydial vaccine is capable of effectively stimulating anamnestic systemic and mucosal immune responses in mice. The data support further vaccine evaluation and testing for induction of long-term protective immunity.     

Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

Objective

To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma.

Methods

Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations.

Results

Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities.

Conclusions

The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.     

Preliminary In Vitro Antisickilng Properties of Crude Juice Extracts of Persia Americana,Citrus Sinensis,Carica Papaya and Ciklavit?

The antisickling properties of crude juice extracts of the edible portions of three commonly consumed tropical fruits namely Persia americana, Citrus sinensis, and Carica papaya were investigated in vitro alongside a new drug preparation called Ciklavit® that has antisickling activity. Four different solvent extracts of the crude juice of each fruit including aqueous, acidic, alkaline and alcoholic extracts were prepared and their antisickling effects on sickle cell trait (HbAS) and sickle cell disease (HbSS) blood samples checked alongside Ciklavit®. Blood samples were stabilized using normal saline and the antisickling effects were checked by counting the number of sickle cells remaining after incubation of the blood samples with the crude fruit extracts and Ciklavit® for twenty-four hours. The results showed that Ciklavit® produced a sustained reduction in the number of sickle cells in both HbAS and HbSS blood samples. Also the alkaline and alcoholic extracts of P. americana and C. papaya produced significant reduction in the number of sickle cells.     

Is the Glycoprotein Responsible for the Differences in Dispersal Rates between Lettuce Necrotic Yellows Virus Subgroups?

Lettuce necrotic yellows virus is a type of species in the Cytorhabdovirus genus and appears to be endemic to Australia and Aotearoa New Zealand (NZ). The population of lettuce necrotic yellows virus (LNYV) is made up of two subgroups, SI and SII. Previous studies demonstrated that SII appears to be outcompeting SI and suggested that SII may have greater vector transmission efficiency and/or higher replication rate in its host plant or insect vector. Rhabdovirus glycoproteins are important for virus–insect interactions. Here, we present an analysis of LNYV glycoprotein sequences to identify key features and variations that may cause SII to interact with its aphid vector with greater efficiency than SI. Phylogenetic analysis of glycoprotein sequences from NZ isolates confirmed the existence of two subgroups within the NZ LNYV population, while predicted 3D structures revealed the LNYV glycoproteins have domain architectures similar to Vesicular Stomatitis Virus (VSV). Importantly, changing amino acids at positions 244 and 247 of the post-fusion form of the LNYV glycoprotein altered the predicted structure of Domain III, glycosylation at N248 and the overall stability of the protein. These data support the glycoprotein as having a role in the population differences of LNYV observed between Australia and New Zealand.