Protein level expression of Toll-like receptors 2, 4 and 9 in renal disease

Background. Toll-like receptors (TLR) recognize a variety of ligands, including pathogen-associated molecular patterns and link innate and adaptive immunity. Individual receptors can be up-regulated during infection and inflammation. We examined the expression of selected TLRs at the protein level in various types of renal disease. Methods. Frozen sections of renal biopsies were stained with monoclonal antibodies to TLR-2, -4 and -9. Results. Up-regulation of the three TLRs studied was seen, although the extent was modest. TLR-2- and -4-positive cells belonged to the population of infiltrating inflammatory cells; only in the case of TLR-9 were intrinsic glomerular cells positive in polyoma virus infection and haemolytic uraemic syndrome (HUS). Conclusions. Evidence for the involvement of the three TLRs tested in a variety of human renal diseases was found. These findings add to our understanding of the role of the innate immune system in kidney diseas

Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands

The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1 month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0.25 weight % (wt%), n 186) to a moderately organic diet (50–90 % organic dairy/meat, 0·29 wt%, n 33, P=0.02) and to a strict organic diet (> 90 % organic dairy/meat, 0.34 wt%, n 37, P<=0.001). The levels of TVA were augmented among the participants with a moderately organic diet (0·54 wt%) and those with a strict organic diet (0.59 wt%, P<=0.001), in comparison with the conventional group (0·48 wt%). After adjusting for covariables (recruitment group, maternal age, maternal education, use of supplements and season), statistical significance was retained in the group of the strict organic dairy users (P<0.001 for rumenic acid). Hence, the levels of CLA and TVA in human milk can be modulated if breastfeeding mothers replace conventional dairy and/or meat products by organic ones. A potential contribution of CLA and TVA to health improvement is briefly discussed

Postpartum urinary retention: what are the sequelae? A long-term study and review of the literature.

INTRODUCTION AND HYPOTHESIS Postpartum urinary retention (PUR) may cause long-term urogenital tract morbidity. The incidence ranges from 0.18 to 14.6%, but the importance of prompt diagnosis and appropriate management is often underappreciated. The paucity of data on long-term outcome after PUR contributes to these drawbacks. The aim of this study was to assess long-term persistence of elevated PVR (post-void residual urine) volume after PUR. Pathophysiology, risk factors and management of PUR are reviewed. METHODS In our tertiary referral urogynecology unit in the University Women's Hospital of Bern, Switzerland, all patients who were referred for PUR were asked to participate in this study. PVR was measured sonographically every 2 days until day 15, then after 6, 12, 24 and 36 months and, if increased, the patients were instructed to perform clean intermittent self-catheterization. If retention persisted longer than the lactation period, multichannel urodynamics was performed. RESULTS Sixty-two patients were included. The median PVR normalized at day 7. Long-term voiding disorders were found in 8.2%, 6.7%, and 4.9% after 1, 2, and 3 years respectively. Multichannel urodynamics confirmed in all patients with persisting retention an acontractile detrusor and de novo stress urinary incontinence in 4 cases. Quantile regression did not reveal any factor contributing to earlier recovery. Eighty-nine percent of the patients with PUR had operative vaginal deliveries, emphasizing the importance of this risk factor for PUR. CONCLUSIONS In most cases PUR resolves early, but voiding difficulties persist more often than previously thought, and for these patients the consequences are devastating. Obstetric awareness, early active management, and developing management strategies in the postpartum period might preclude lower urinary tract morbidity

Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands

The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0·25 weight % (wt%), n 186) to a moderately organic diet (50-90% organic dairy/meat, 0·29wt%, n 33, P=0·02) and to a strict organic diet (>90% organic dairy/meat, 0·34wt%, n 37, P≤0·001). The levels of TVA were augmented among the participants with a moderately organic diet (0·54wt%) and those with a strict organic diet (0·59wt%, P≤0·001), in comparison with the conventional group (0·48wt%). After adjusting for covariables (recruitment group, maternal age, maternal education, use of supplements and season), statistical significance was retained in the group of the strict organic dairy users (P<0·001 for rumenic acid). Hence, the levels of CLA and TVA in human milk can be modulated if breastfeeding mothers replace conventional dairy and/or meat products by organic ones. A potential contribution of CLA and TVA to health improvement is briefly discusse

Synergy between CD26/DPP-IV Inhibition and G-CSF Improves Cardiac Function after Acute Myocardial Infarction

SummaryIschemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1α is the major chemokine attracting stem cells to the heart. Since SDF-1α is cleaved and inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), we established a therapeutic concept—applicable to ischemic disorders in general—by combining genetic and pharmacologic inhibition of DPP-IV with G-CSF-mediated stem cell mobilization after myocardial infarction in mice. This approach leads to (1) decreased myocardial DPP-IV activity, (2) increased myocardial homing of circulating CXCR-4+ stem cells, (3) reduced cardiac remodeling, and (4) improved heart function and survival. Indeed, CD26 depletion promoted posttranslational stabilization of active SDF-1α in heart lysates and preserved the cardiac SDF-1-CXCR4 homing axis. Therefore, we propose pharmacological DPP-IV inhibition and G-CSF-based stem cell mobilization as a therapeutic concept for future stem cell trials after myocardial infarction

Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda

BACKGROUND Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. INTERVENTION Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. LESSONS LEARNT Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. RECOMMENDATIONS Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries

Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases

Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information

Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study.

OBJECTIVE To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty