Antibodies Against M-Type Phospholipase A2 Receptor (PLA2R) in Patients with Primary Membranous Nephropathy and Lupus Nephritis Class V: A Review

Membranous nephropathy (MN) is a very common disease of male adults with nephrotic syndrome. The disease can be primary, when the cause is not known, or secondary associated with infections, drugs, neoplasias and autoimmune systemic diseases, such as systemic lupus erythematosus (SLE). The primary form accounts for 70–80% of the cases. SLE is a common cause of secondary MN affecting young women. The differential diagnosis from primary and lupus MN by clinical and morphological findings can be difficult. The search for autoantibodies against podocyte antigen M-type phospholipase A2 receptor (PLA2R) has demonstrated high positivity in the serum and renal biopsies in the primary MN and negativity in lupus MN (WHO class V). There is a large literature on the role of anti-PLA2R antibody in the diagnosis and follow-up of patients with membranous nephropathy. The aim of this review is to summarize the literature data on the etiopathogenesis of MN and the value of anti-PLA2R antibody screening for the diagnosis and management of patients

Adjuvant requirement for successful immunization with recombinant derivatives of Plasmodium vivax merozoite surface protein-1 delivered via the intranasal route

Recently, we generated two bacterial recombinant proteins expressing 89 amino acids of the C-terminal domain of the Plasmodium vivax merozoite surface protein-1 and the hexa-histidine tag (His6MSP1(19)). One of these recombinant proteins contained also the amino acid sequence of the universal pan allelic T-cell epitope (His(6)MSP1(19)-PADRE). in the present study, we evaluated the immunogenic properties of these antigens when administered via the intra-nasal route in the presence of distinct adjuvant formulations. We found that C57BL/6 mice immunized with either recombinant proteins in the presence of the adjuvants cholera toxin (CT) or the Escherichia coli heat labile toxin ( LT) developed high and long lasting titers of specific serum antibodies. the induced immune responses reached maximum levels after three immunizing doses with a prevailing IgG1 subclass response. in contrast, mice immunized by intranasal route with His(6)MSP1(19)-PADRE in the presence of the synthetic oligonucleotides adjuvant CpG ODN 1826 developed lower antibody titers but when combined to CT, CpG addition resulted in enhanced IgG responses characterized by lower IgG1 levels. Considering the limitations of antigens formulations that can be used in humans, mucosal adjuvants can be a reliable alternative for the development of new strategies of immunization using recombinant proteins of P. vivax.Universidade Federal de São Paulo, Dept Microbiol Imunol Parasitol, Escola Paulista Med, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Interdisciplinar Terapia Genica, Escola Paulista Med, BR-04044010 São Paulo, BrazilUniv São Paulo, Dept Microbiol, Inst Ciencias Biomed, São Paulo, BrazilUniv São Paulo, Dept Anal Clin & Toxicol, Fac Ciencias Farmaceut, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol Parasitol, Escola Paulista Med, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Interdisciplinar Terapia Genica, Escola Paulista Med, BR-04044010 São Paulo, BrazilWeb of Scienc

Laparoscopy versus laparotomy for benign ovarian tumour

Background: Over the last 10 years laparoscopy and minilaparotomy have become increasingly common approaches for the surgical removal of benign ovarian tumours. However, in the event that a tumour is found to be malignant, laparotomy is the appropriate procedure. Careful preoperative assessment including transvaginal ultrasound with morphological scoring, colour doppler assessment of vascular quality, and serum cancer antigen 125 (CA 125) level is desirable. Objectives: To determine the benefits, harms, and cost of laparoscopy orminilaparotomy compared with laparotomy in women with benign ovarian tumours. Search methods: We searched electronic databases, trial registers, and reference lists of published trial reports. Reference lists from trials and review articles were searched. Selection criteria: All randomised controlled trials comparing either laparoscopy or minilaparotomy with laparotomy for benign ovarian tumours. Data collection and analysis: Eight review authors independently assessed the eligibility and quality of each study and extracted the data Main results: The results of nine randomised controlled trials (N = 482 women) showed that laparoscopic surgery was associated with fewer adverse events of surgery (surgical injury or postoperative complications including fever or infection) (OR 0.3, 95% CI 0.2 to 0.5), less postoperative pain (VAS score WMD -2.4, 95% CI -2.7 to -2.0), greater likelihood of being pain free after two days (OR 7.42, 95% CI 4.86 to 11.33), and fewer days in hospital (WMD -2.88, 95% CI -3.1 to -2.7) than with laparotomy. In one study that reported costs, laparoscopy was associated with a significant reduction in costs compared to laparotomy (WMD - USD 1045, 95% CI -1348 to -742) in 1993. Very high levels of heterogeneity made it inappropriate to pool data on duration of surgery. Three RCTs compared laparoscopy versus minilaparotomy and found that laparoscopy was associated with reduced odds of any adverse event (surgical injury or postoperative complications) (OR 0.10, 95% CI 0 to 0.8) and lower VAS scores for pain (WMD -1.0, 95% CI -1.6 to -0.45). Duration of hospital stay ranged between 1 and 2.2 days, with substantial heterogeneity. Authors’ conclusions: In women undergoing surgery for benign ovarian tumours, laparoscopy was associated with a reduction in fever, urinary tract infection, postoperative complications, postoperative pain, number of days in hospital, and total cost. These findings should be interpreted with caution since only a small number of studies were identified. These included a total of only 769 women and not all of the important outcomes were reported in each study

Can water remediated by manganese spinel ferrite nanoparticles be safe for marine bivalves?

In the last few years the use of nanoparticles (NPs) such as the manganese spinel ferrite (MnFe2O4) has been increasing, with a vast variety of applications including water remediation from pollutants as metal(oid)s. Although an increasing number of studies already demonstrated the potential toxicity of NPs towards aquatic systems and inhabiting organisms, there is still scarce information on the potential hazard of the remediated water using NPs. The present study aimed to evaluate the ecotoxicological safety of Pb contaminated seawater remediated with MnFe2O4, NPs, assessing the toxicity induced in mussels Mytilus galloprovincialis exposed to contaminated seawater and to water that was remediated using MnFe2O4, NPs. The results obtained demonstrated that seawater contaminated with Pb, NPs or the mixture of both (Pb + NPs) induced higher toxicity in mussels compared to organisms exposed to Pb, NPs and Pb + NPs after the remediation process. In particular, higher metabolic depression, oxidative stress and neurotoxicity were observed in mussels exposed to contaminated seawater in comparison to mussels exposed to remediated seawater.publishe

Mutations in blind cavefish target the light-regulated circadian clock gene, period 2

Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors.Universidad de Ferrara | Ref. FAR2014-201

Evolution shapes the responsiveness of the D-box enhancer element to light and reactive oxygen species in vertebrates

The circadian clock is a highly conserved cell-autonomous mechanism that directs daily rhythms in most aspects of biology. Daily entrainment by environmental signals, notably light, is essential for its function. However, our understanding of the mechanisms and the evolution of photic entrainment remains incomplete. Fish represent attractive models for exploring how light regulates the circadian clock due to the direct light sensitivity of their peripheral clocks. Central to this property is the light induced expression of clock genes that is mediated by D-box enhancer elements. Here, using zebrafish cells, we reveal that the light responsive D-box enhancer serves as a nuclear target for reactive oxygen species (ROS). We demonstrate that exposure to short wavelengths of visible light triggers increases in ROS levels via NADPH oxidase activity. Elevated ROS activates the JNK and p38 MAP kinases and in turn, induces clock gene expression via the D-box. In blind cavefish and mammals, where peripheral clocks are no longer entrained by direct illumination, ROS levels are still increased upon light exposure. However, in these species ROS no longer induces D-box driven clock gene transcription. Thus, during evolution, alterations in ROS-responsive signal transduction pathways underlie fundamental changes in peripheral clock photoentrainment.Universidad de Ferrara | Ref. FAR2014–201

Remediation of Arsenic from contaminated seawater using manganese spinel ferrite nanoparticles: ecotoxicological evaluation in Mytilus galloprovincialis

In the last decade different approaches have been applied for water remediation purposes, including the use of nanoparticles (NPs) to remove metals and metalloids from water. Although studies have been done on the toxic impacts of such NPs, very scarce information is available on the impacts of water after decontamination when discharged into aquatic environments. As such, in the present study we aimed to evaluate the ecotoxicological safety of seawater previously contaminated with arsenic (As) and remediated by using manganese-ferrite (MnFe2O4-NPs) NPs. For this, mussels Mytilus galloprovincialis were exposed for 28 days to different conditions, including clean seawater (control), As (1000 μg L−1) contaminated and remediated (As 70 μg L−1) seawater, water containing MnFe2O4- NPs (50 mg L−1) with and without the presence of As. At the end of exposure, concentrations of As in mussels tissues were quantified and biomarkers related to mussels’ metabolism and oxidative stress status were evaluated. Results revealed that mussels exposed to water contaminated with As and to As + NPs accumulated significantly more As (between 62% and 76% more) than those exposed to remediated seawater. Regarding biomarkers, our findings demonstrated that in comparison to remediated seawater (conditions a, b, c) mussels exposed to contaminated seawater (conditions A, B, C) presented significantly lower metabolic activity, lower expenditure of energy reserves, activation of antioxidant and biotransformation defences, higher lipids and protein damages and greater AChE inhibition. Furthermore, organisms exposed to As, NPs or As + NPs revealed similar biochemical effects, both before and after water decontamination. In conclusion, the present study suggests that seawater previously contaminated with As and remediated by MnFe2O4-NPs presented significantly lower toxicity than As contaminated water, evidencing the potential use of these NPs to remediate seawater contaminated with As and its safety towards marine systems after discharges to these environments.publishe

Preliminary management strategy evaluation for blue shark in the Indian Ocean using a data-limited approach

In tuna-RFMOs there has been an effort to move to quantitative stock assessments for pelagic sharks, especially for the main species such as blue shark Prionace glauca. In IOTC, blue shark was last assessed in 2017 with the use of an integrated length-based age-structured model (SS3). This paper now presents a preliminary exercise with data-limited Management Strategy Evaluation (MSE) to test options for different potential management procedures (MPs), using the data-limited methods toolkit (DLMtool). Reference points have not yet been adopted for sharks in IOTC, so for this exercise we set some tentative reference points noting that those can be updated in the future as needed. Eighty-nine MPs were evaluated with 9 considered potentially acceptable. Options and tradeoffs between those MPs are shown and described in the paper. We have focused mainly on trade-offs between biomass and yield, but according to the management objectives agreed other performance metrics can be applied. Even thought this is a preliminary exercise at this point, we hope that it provides initial thoughts and opens the discussion for the advancement of the blue shark management and conservation in the Indian Ocean

Conjugated Linoleic Acid: good or bad nutrient

Conjugated linoleic acid (CLA) is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia

Proteasome function is required for activation of programmed cell death in heat shocked tobacco Bright-Yellow 2 cells

AbstractTo find out whether and how proteasome is involved in plant programmed cell death (PCD) we measured proteasome function in tobacco cells undergoing PCD as a result of heat shock (HS-PCD). Reactive oxygen species (ROS) production, cytochrome c levels and caspase-3-like protease activation were also measured in the absence or presence of MG132, a proteasome inhibitor. We show that proteasome activation occurs in early phase of HS-PCD upstream of the caspase-like proteases activation; moreover inhibition of proteasome function by MG132 results in prevention of PCD perhaps due to the prevention of ROS production, cytochrome c release and caspase-3-like protease activation