Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies

Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine < 500 µmol/liter (N = 17), or > 500 µmol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow-up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases

Long-term progestin contraceptives (LTPOC) induce aberrant angiogenesis, oxidative stress and apoptosis in the guinea pig uterus: A model for abnormal uterine bleeding in humans

BACKGROUND: Irregular uterine bleeding is the major side effect of, and cause for, discontinuation of long-term progestin-only contraceptives (LTPOCs). The endometria of LTPOC-treated women display abnormally enlarged, fragile blood vessels (BV), decreased endometrial blood flow and oxidative stress. However, obtaining sufficient, good quality tissues have precluded elucidation of the mechanisms underlying these morphological and functional vascular changes. METHODS: The current study assessed the suitability of the guinea pig (GP) as a model for evaluating the uterine effects of LTPOC administration. Thus GPs were treated with a transdermal pellet for 21 days and examined for endometrial histology, angiogenic markers as well as markers of oxidative stress and apoptosis. RESULTS AND DISCUSSION: We now demonstrate that GP uteri were enlarged by both estradiol (E2) and medroxyprogesterone acetate (MPA) (p < 0.001). Effects of MPA on uterine weight differed significantly depending on E2 levels (p < 0.001), where MPA opposed the E2 effect in combined treatments. Angiogenesis parameters were similarly impacted upon: MPA alone increased BV density (p = 0.036) and BV average area (p = 0.002). The presence of E2 significantly decreased these parameters. These changes were associated with highly elevated of the lipid peroxidation product, 8-isoprostane (8-isoP) content in E2+MPA-treated and by nuclear 8-OH-deoxyguanosine (8oxoG) staining compared to all other groups (p < 0.001). Abnormalities in the E2+MPA group were consistent with chromatin redistribution, nuclear pyknosis, karyolysis and increased apoptosis as observed by a marked increase in TUNEL labeling. CONCLUSIONS: LTPOC exposure alters endometrial vascular and tissue morphology consistent with oxidative stress and apoptosis in a complex interplay with endogenous estrogens. These findings are remarkably similar to in vivo change observed in the human uterus following LTPOC administration. Hence, the GP is an excellent model for the study of LTPOC effects on the uterus and will be extremely useful in determining the mechanistic pathways involved in this process which cannot be conducted on humans

Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception

BACKGROUND: Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle. METHODS: Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant). The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1. RESULTS: The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining. CONCLUSION: The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants

Abnormal Uterine Bleeding during Progestin-Only Contraception May Result from Free Radical-Induced Alterations in Angiopoietin Expression

Abnormal uterine bleeding is the leading indication for discontinuation of long-term progestin-only contraceptives (LTPOCs). Histological sections of endometria from LTPOC-treated patients display abnormally enlarged blood vessels at bleeding sites. Paradoxically, a trend toward reduced endometrial perfusion in LTPOC users has been reported in these patients. We hypothesized that hypoxia/reperfusion-induced free radical production inhibits the expression of angiopoietin-1 (Ang-1), a vessel stabilizing factor, leaving unopposed the effects of endothelial Ang-2, a vessel-branching and permeability factor. Immunohistochemical studies confirmed selective decreases in stromal cell Ang-1 in LTPOC-exposed endometrium. To indirectly assess whether LTPOC enhances endometrial free radical production, immunostaining was conducted for the phosphorylated form of the stress-activated kinases SAPK/JNK and p38. These kinases were greatly increased in endometria from LTPOC-treated patients. Interestingly, the endothelial cells but not the stromal cells displayed enhanced immunostaining for the phosphorylated mitogen-activated kinase (pMAPK) after LTPOC treatment. To further examine the effects of progestin, hypoxia, and reactive oxygen species (ROS) on the regulation of Ang-1 and Ang-2 as well as the activation of MAPK, SAPK/JNK, and p38 by the relevant cell types, we conducted in vitro studies with cultured human endometrial stromal cells (HESCs) and human endometrial endothelial cells (HEECs). Cultures of HESCs were treated with vehicle control, estradiol (E(2)), or with medroxyprogesterone acetate ± E(2) under hypoxic and normoxic conditions. Although medroxyprogesterone acetate but not E(2) increased Ang-1 expression, hypoxia greatly decreased Ang-1 protein and mRNA expression. In contrast, HESCs did not appear to express Ang-2 protein or mRNA. Conversely, cultured HEECs did not appear to express Ang-1, but expressed Ang-2, the levels of which were significantly increased by hypoxia. Hypoxia also induced the phosphorylation of SAPK/JNK and p38 in both cultured HESCs and HEECs. Moreover, ROS such as that observed after hypoxia/reperfusion resulted in the activation of SAPK/JNK and p38 in HESCs and HEECs and inhibited Ang-1 in cultured HESCs. These effects could be blocked by oxygen radical scavengers. Consistent with the in vivo studies, MAPK was activated after ROS treatment in HEECs but not in HESCs. Our findings suggest that LTPOC-induced endometrial bleeding occurs as a result of hypoxia/reperfusion-induced free radicals that directly damage vessels and alter the balance of Ang-1 and Ang-2 to produce the characteristic enlarged and permeable vessels that are prone to bleeding

Consultancy-Based Projects

This chapter will:; ; ; Show how consultancy work can inform business discourse teaching;; ; ; Discuss how needs analysis and communication audits can be used to generate recommendations for teaching and training;; ; ; Profile a number of consultancy-based business discourse projects and show how they have informed training and course development;; ; ; Provide a case study, together with a set of tasks appropriate for the business discourse classroom, and a set of further readings

RESEARCH Open Access

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rat

Assessing Biofuel Crop Invasiveness: A Case Study

BACKGROUND: There is widespread interest in biofuel crops as a solution to the world's energy needs, particularly in light of concerns over greenhouse-gas emissions. Despite reservations about their adverse environmental impacts, no attempt has been made to quantify actual, relative or potential invasiveness of terrestrial biofuel crops at an appropriate regional or international scale, and their planting continues to be largely unregulated. METHODOLOGY/PRINCIPAL FINDINGS: Using a widely accepted weed risk assessment system, we analyzed a comprehensive list of regionally suitable biofuel crops to show that seventy percent have a high risk of becoming invasive versus one-quarter of non-biofuel plant species and are two to four times more likely to establish wild populations locally or be invasive in Hawaii or in other locations with a similar climate. CONCLUSIONS/SIGNIFICANCE: Because of climatic and ecological similarities, predictions of biofuel crop invasiveness in Hawaii are applicable to other vulnerable island and subtropical ecosystems worldwide. We demonstrate the utility of an accessible and scientifically proven risk assessment protocol that allows users to predict if introduced species will become invasive in their region of interest. Other evidence supports the contention that propagule pressure created by extensive plantings will exacerbate invasions, a scenario expected with large-scale biofuel crop cultivation. Proactive measures, such as risk assessments, should be employed to predict invasion risks, which could then be mitigated via implementation of appropriate planting policies and adoption of the "polluter-pays" principle

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics