Endothelin system expression in the kidney following cisplatin-induced acute kidney injury in male and female mice.

The chemotherapeutic agent cisplatin accumulates in the kidney and induces acute kidney injury (AKI). Preclinical and clinical studies suggest that young female mice and women show greater recovery from cisplatin-AKI compared to young male mice and men. The endothelin (ET) and ET receptors are enriched in the kidney and may be dysfunctional in cisplatin-AKI; however, there is a gap in our knowledge about the putative effects of sex and cisplatin on the renal ET system. We hypothesized that cisplatin-AKI male and female mice will have increased expression of the renal ET system. As expected, all cisplatin-AKI mice had kidney damage and body weight loss greater than control mice. Cisplatin-AKI mice had greater cortical Edn1, Edn3, Ednra, and Ednrb, while outer medullary Ednra was significantly suppressed in both sexes. Of the ∼25 000 genes sequenced from the inner medulla, only 91 genes (comparing saline mice) and 134 genes (comparing cisplatin-AKI mice) were differentially expressed and they were unrelated to the ET system. However, Edn1 was significantly greater in the inner medulla of male and female cisplatin-AKI mice. Thus, RNA profiles of the ET system were significantly affected by cisplatin-AKI throughout the kidney regardless of sex and this may help determine the therapeutic potential of targeting the ET receptors in cisplatin-AKI.

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system.

We tested the hypothesis that ethanol would aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) sepsis in the cardiorenal system and that inhibition of inducible nitric oxide synthase (iNOS) would prevent such response. Male C57BL/6 mice were treated with ethanol for 12 weeks. One hour before SL-CLP surgery, mice were treated with N6-(1-iminoethyl)-lysine (L-NIL, 5 mg/kg, i.p.), a selective inhibitor of iNOS. A second dose of L-NIL was administered 24 h after SL-CLP surgery. Mice were killed 48 h post surgery and the blood, the renal cortex, and the left ventricle (LV) were collected for biochemical analysis. L-NIL attenuated the increase in serum creatinine levels induced by ethanol, but not by SL-CLP. Ethanol, but not SL-CLP, increased creatine kinase (CK)-MB activity and L-NIL did not prevent this response. In the renal cortex, L-NIL prevented the redox imbalance induced by ethanol and SL-CLP. Inhibition of iNOS also decreased lipoperoxidation induced by ethanol and SL-CLP in the LV. L-NIL prevented the increase of pro-inflammatory cytokines and reactive oxygen species induced by ethanol and (or) SL-CLP in the cardiorenal system, suggesting that iNOS modulated some of the molecular mechanisms that underlie the deleterious effects of both conditions in the cardiorenal system.

Renal expression and urinary excretion of aquaporin-2 in postobstructive uropathy in rats.

This work assessed the time course of water renal management together with aquaporin-2 (AQP2) kidney expression and urinary AQP2 levels (AQP2u) in obstructive nephropathy. Adult male Wistar rats were monitored after 1, 2, and 7 days of bilateral ureteral release (bilateral ureteral obstruction (BUO); BUO-1, BUO-2 and BUO-7). Renal water handling was evaluated using conventional clearance techniques. AQP2 levels were assessed by immunoblotting and immunohistochemical techniques. AQP2 expression in apical membranes was downregulated in BUO-1 rats and upregulated both in BUO-2 and BUO-7 animals. AQP2 protein expression in whole cell lysate fraction from kidney cortex and medulla were significantly decreased in all the experimental groups. Concomitantly, mRNA levels of AQP2 decreased in renal medulla of all groups and in renal cortex from BUO-1; however, in renal cortex from BUO-2 and BUO-7 a recovery and an increase in the level of AQP2 mRNA were, respectively, observed. BUO-7 group showed a significant increase in AQP2u. The alterations observed in apical membranes AQP2 expression could explain, at least in part, the evolution time of water kidney management in the postobstructive phase of BUO. Additionally, the AQP2u increase after 7 days of ureteral release may be postulated as a biomarker of improvement in the kidney function.

Erythropoietin alters the pharmacokinetics of organic anions mainly eliminated by the kidney in rats.

Erythropoietin (EPO) is a cytokine originally used for its effects on the hematopoietic system, and is widely prescribed around the world. In the present study, the effects of EPO administration on p-aminohippurate (PAH, a prototype organic anion) pharmacokinetics and on the renal expression of PAH transporters were evaluated. Male Wistar rats were treated with EPO or saline (control group). After 42 h, PAH was administered, and plasma samples were obtained at different time points to determine PAH levels. PAH levels in renal tissue and urine were also assessed. The renal expression of PAH transporters was evaluated by Western blotting. EPO-treated rats showed an increase in PAH systemic clearance, in its elimination rate constant, and in urinary PAH levels, while PAH in renal tissue was decreased. Moreover, EPO administration increased the expression of the transporters of the organic anions evaluated. The EPO-induced increase in PAH clearance is accounted for by the increase in its renal secretion mediated by the organic anion transporters. The goal of this study is to add important information to the wide knowledge gap that exists regarding drug-drug interactions. Owing to the global use of EPO, these results are useful in terms of translation into clinical practice.

Ethanol consumption increases renal dysfunction and mortality in a mice model of sub-lethal sepsis.

Chronic ethanol consumption and sepsis cause oxidative stress and renal dysfunction. This study aimed to examine whether chronic ethanol consumption sensitizes the mouse kidney to sub-lethal cecal ligation and puncture (SL-CLP) sepsis, leading to impairment of renal function by tissue oxidative and inflammatory damage. Male C57BL/6J mice were treated for 9 weeks with ethanol (20%, v/v) before SL-CLP was induced. Systolic blood pressure (SBP), survival rate, creatinine plasma, oxidative stress, and inflammatory parameters, inducible nitric oxide synthase (iNOS), cytokines, and metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) levels were evaluated. Chronic ethanol consumption increased SBP, plasma creatinine, O2.-, H2O2, lipid peroxidation, catalase activity, Nox4, IL-6, and TNF-α levels, and MMP-9/TIMP-1 ratio. SL-CLP decreased SBP, increased creatinine, lipid peroxidation, IL-6, TNF-α, nitrate/nitrite (NOx), and iNOS levels, and MMP-2/TIMP-2 ratio, and decreased catalase activity. SL-CLP mice previously treated with ethanol showed a similar decrease in SBP but higher mortality and creatinine levels than SL-CLP alone. These responses were mediated by increased O2-, lipid peroxidation, IL-6, TNF-α, NOx, iNOS, MMP-2, and MMP-9 levels, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios. Our findings demonstrated that previous oxidative stress and inflammatory damage caused by ethanol consumption sensitizes the kidney to SL-CLP injury, resulting in impaired kidney function and sepsis prognosis.

Race, Kidney Transplants, Immunosuppression Research, and White Supremacy under Apartheid, 1960-80.

This paper uses the history of kidney transplantation in South Africa as a lens through which to write a racialized, micro history that illustrates the politics of medical discoveries and medical research at one of South Africa's most prestigious medical research universities, the University of the Witwatersrand (Wits) in Johannesburg. Between 1966 and the 1980s, the Wits team became the most advanced and prolific kidney transplant unit in the country. Yet the racist, oppressive Apartheid system fundamentally shaped these developments. Transplantation, as this paper shows, became an elite medical procedure, performed by a select group of white doctors on mostly white patients. For these doctors, transplantation showed their medical prowess and displayed the technical advancements they were able to make in research and clinical practice as they strove to position South Africa as a significant international player in medical research, despite academic boycotts and increasing sanctions. Transplantation became a symbol of white supremacy in a country where the black majority were excluded from anything but the most basic health care.

Preconditioning with atorvastatin against renal ischemia-reperfusion injury in nondiabetic versus diabetic rats.

Acute renal failure complicates renal ischemia-reperfusion (I/R) owing to reactive oxygen species production. Atorvastatin (ATO) has anti-inflammatory and antioxidant properties. The current study investigated whether ATO alleviated damage induced by renal I/R injury in nondiabetic versus diabetic rat models. Thirty-six rats were equally divided into 6 groups: group A1 (nondiabetic sham), group A2 (nondiabetic I/R), group A3 (nondiabetic ATO + I/R), group B1 (diabetic sham), group B2 (diabetic I/R), and group B3 (diabetic ATO + I/R). All groups experienced 45 min of bilateral renal ischemia followed by 24 h of reperfusion. Groups A3 and B3 were treated with single intraperitoneal doses of ATO (10 mg/kg) 30 min before ischemia. Histological analysis of kidney tissues, kidney function tests, and analyses of caspase-3 and CD44 expression and oxidative stress markers were performed to assess tubular injury. Histological analysis revealed marked tubular damage in groups A2 and B2 but improvement in groups A3 and B3. Improvements were also found in groups A3 and B3 for caspase-3 and CD44 expression, kidney function tests, and oxidative stress markers. Our results suggest ATO may ameliorate renal I/R injury differently between nondiabetic and diabetic rats.

The contribution of muscle, kidney, and splanchnic tissues to leucine transamination in humans.

The first steps of leucine utilization are reversible deamination to α-ketoisocaproic acid (α-KIC) and irreversible oxidation. Recently, the regulatory role of leucine deamination over oxidation was underlined in rodents. Our aim was to measure leucine deamination and reamination in the whole body, in respect to previously determined rates across individual organs, in humans. By leucine and KIC isotope kinetics, we determined whole-body leucine deamination and reamination, and we compared these rates with those already reported across the sampled organs. As an in vivo counterpart of the "metabolon" concept, we analysed ratios between oxidation and either deamination or reamination. Leucine deamination to KIC was greater than KIC reamination to leucine in the whole body (p = 0.005), muscles (p = 0.005), and the splanchnic area (p = 0.025). These rates were not significantly different in the kidneys. Muscle accounted for ≈60% and ≈78%, the splanchnic bed for ≈15% and ≈15%, and the kidney for ≈12% and ≈18%, of whole-body leucine deamination and reamination rates, respectively. In the kidney, percent leucine oxidation over either deamination or reamination was >3-fold greater than muscle and the splanchnic bed. Skeletal muscle contributes by the largest fraction of leucine deamination, reamination, and oxidation. However, in relative terms, the kidney plays a key role in leucine oxidation.

Chronic intermittent hypobaric hypoxia provides vascular protection in the aorta of the 2-kidney, 1-clip rat model of hypertension.

Many studies have demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can reduce blood pressure in spontaneously hypertensive rats and renovascular hypertensive (RVH) rats in which endothelial dysfunction is determined as a critical factor. However, whether CIHH can regulate vasodilation of the aorta in RVH rats remains unknown. The purpose of this study was to investigate the effect of CIHH on impaired relaxation of the aorta in the 2-kidney, 1-clip (2K1C) RVH rat model. The results showed CIHH improved the impaired endothelium-dependent relaxation in the 2K1C rat aorta. The endothelial dysfunction was prevented by the p38 antagonist SB203580, but not by the ERK1/2 antagonist PD98059 or JNK antagonist SP600125. Furthermore, the expression of p-eNOS, HIF-1α, and HIF-2α increased while that of p-p38 and BMP-4 decreased in CIHH-treated aortas from 2K1C rats. Finally, the p-eNOS expression was upregulated and the p-p38 expression was downregulated by pre-incubation of SB203580 or the BMP-4 antagonist Noggin with the aorta. CIHH ameliorated the impairment of endothelium-dependent relaxation through upregulating the expression of p-eNOS, which may be mediated by the inhibition of BMP-4/p-p38 MAPK, and upregulating the expression of HIFs in the 2K1C rat aorta.

Protective effects of kolaviron and gallic acid against cobalt-chloride-induced cardiorenal dysfunction via suppression of oxidative stress and activation of the ERK signaling pathway.

Cobalt (Co) toxicity is a potential public health problem due to recent renewed use of Co in orthopedic implants, dietary supplements, and blood doping in athletes and horses. We investigated the protective roles of kolaviron (KV), a bi-flavonoid of Garcinia kola, and gallic acid (GA) on cobalt chloride (CoCl2)-induced cardiorenal damage in rats. CoCl2 caused significant increases (p < 0.05) in serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), xanthine oxidase (XO), urea, creatinine, malondialdehyde, H2O2, nitric oxide, as well as C-reactive protein expression, along with significant (p < 0.05) reduction in cardiac and renal expression of extracellular signal regulated kinase (ERK) and the activities of superoxide dismutase, catalase, and glutathione S-transferase. KV and GA prevented the toxic effects of CoCl2 by stimulating ERK expression and reversing Co-induced biochemical changes. Administration of CoCl2 alone did not significantly alter ECG patterns in the rats, although co-treatment with KV (200 mg/kg) produced QT-segment prolongation and also appeared to potentiate Co hypotension. Histopathology of the heart and kidneys of rats treated with KV and GA confirmed the biochemical data. KV and GA thus protected against cardiac and renal damage in Co intoxication via antioxidant and (or) cell survival mechanisms, possibly involving ERK activation.

Antihypertensive effects of fargesin in vitro and in vivo via attenuating oxidative stress and promoting nitric oxide release.

Fargesin, a bioactive neolignan isolated from magnolia plants, is widely used in the treatment of managing rhinitis, inflammation, histamine, sinusitis, and headache. To provide more biological information about fargesin, we investigated the effects of fargesin on rat aortic rings and 2-kidney, 1-clip (2K1C) hypertensive rats. In vitro, fargesin caused concentration-dependent vasorelaxation in rat isolated aortic rings induced by KCl and norepinephrine. The effect was weakened by endothelium denudation and nitric oxide (NO) synthesis inhibition. In vivo, the evolution of systolic blood pressure (SBP) was followed by weekly measurements. Angiotensin II (Ang II) and endothelin (ET) levels, NO and nitric oxide synthase (NOS), and plasma and liver oxidative stress markers were determined at the end of the experimental period. After 5 weeks of fargesin treatment, we found that fargesin treatment reduced SBP, cardiac hypertrophy, and Ang II and ET levels of hypertensive rats. Increased NOS activity and NO level were observed in fargesin-treated rats. Normalisation of plasma MDA concentrations and improvement of the antioxidant defence system in plasma and liver accompanied the antihypertensive effect of fargesin. Taken together, these results provided substantial evidences that fargesin has antihypertensive effect in 2K1C hypertensive rats via inhibiting oxidative stress and promoting NO release.

[Polycystic kidney disease and kidney transplantation]. / Prise en charge de la polykystose rénale autosomique dominante avant transplantation rénale.

OBJECTIVES: To perform a state of the art about autosomal dominant polykystic kidney disease (ADPKD), management of its urological complications and end stage renal disease treatment modalities. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): "autosomal dominant polykystic kidney disease", "complications", "native nephrectomy", "kidney transplantation". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 3779 articles. After reading titles and abstracts, 52 were included in the text, based on their relevance. RESULTS: ADPKD is the most inherited renal disease, leading to end stage renal disease requiring dialysis or renal transplantation in about 50% of the patients. Many urological complications (gross hematuria, cysts infection, renal pain, lithiasis) of ADPKD required urological management. The pretransplant evaluation will ask the challenging question of native nephrectomy only in case of recurrent kidney complications or large kidney not allowing graft implantation. The optimum timing for native nephrectomy will depend on many factors (dialysis or preemptive transplantation, complication severity, anuria, easy access to transplantation, potential living donor). CONCLUSION: Pretransplant management of ADPKD is challenging. A conservative strategy should be promoted to avoid anuria (and its metabolic complications) and to preserve a functioning low urinary tract and quality of life. When native nephrectomy should be performed, surgery remains the gold standard but renal arterial embolization may be a safe option due to its low morbidity.

Automatic segmentation of kidneys in computed tomography images using U-Net.

PURPOSE: Accurate segmentation of target volumes and organs at risk from computed tomography (CT) images is essential for treatment planning in radiation therapy. The segmentation task is often done manually making it time-consuming. Besides, it is biased to the clinician experience and subject to inter-observer variability. Therefore, and due to the development of artificial intelligence tools and particularly deep learning (DL) algorithms, automatic segmentation has been proposed as an alternative. The purpose of this work is to use a DL-based method to segment the kidneys on CT images for radiotherapy treatment planning. MATERIALS AND METHODS: In this contribution, we used the CT scans of 20 patients. Segmentation of the kidneys was performed using the U-Net model. The Dice similarity coefficient (DSC), the Matthews correlation coefficient (MCC), the Hausdorff distance (HD), the sensitivity and the specificity were used to quantitatively evaluate this delineation. RESULTS: This model was able to segment the organs with a good accuracy. The obtained values of the used metrics for the kidneys segmentation, were presented. Our results were also compared to those obtained recently by other authors. CONCLUSION: Fully automated DL-based segmentation of CT images has the potential to improve both the speed and the accuracy of radiotherapy organs contouring.

Effects of saddle tilt and stirrup length on the kinetics of horseback riders.

Background: How the modification of saddle fitting parameters in horse riding affects rider's kinetics is very uncertain. The aim of this study is to describe how manipulating the two main adjustments that an end-user is likely to perform (saddle tilt and stirrup length) affects the biomechanics of a horse rider on a living horse. Methods: Eleven showjumpers volunteered to take part in this study. Each participant performed a 120-strides standardization trial at trot and canter, with 0° saddle tilt and stirrup length that would position the rider's knee at 90°. Following the standardization trial, four interventions were performed, which consisted of 60 strides with 60 mm shorter stirrups, 60 mm longer stirrups, 4° forward tilted saddle and 4° backward tilted saddle. Stirrup and rein tension forces were measured with tension loadcells. A symmetry index was calculated. Acceleration was measured with inertial measuring units at the helmet and back of the rider and shock attenuation was calculated. Results: Shortening the stirrups and adjusting saddle tilt significantly enhanced shock attenuation at canter and increased force on the stirrups at trot and canter (p < 0.05). Lowering the stirrups reduced rein tension forces (p = 0.01). At trot, adjusting saddle tilt and stirrup length enhanced symmetry index on the bit (p < 0.05). These results allowed for general guidelines to be proposed, although individualization became an evident part of any saddle setup design due to a high inter-subject variability.

Evaluating Horse Owner Expertise and Professional Use of Auxiliary Reins during Horse Riding.

Auxiliary reins are commonly used for the training of riders and horses as well as in daily training. They are often criticized when used incorrectly, as they will not help and can harm the horse by causing overwork, accidents, and injuries, which harm the horse in the long term. They also often conceal causal rider problems while trying to achieve quick success. The aim of this paper was to investigate, with an online horse-owner questionnaire, which and how often auxiliary reins were used and whether they were used appropriately. Only participants who were currently using auxiliary reins were selected. Consequently, 823 participants were questioned, of which 362 were currently using auxiliary reins at least every two weeks. Auxiliary reins were mainly used according to their discipline: the running side rein was the most popular when working from the ground and the sliding ring martingale was the most popular for ridden equestrian activities. Most of the test subjects only attached the auxiliary reins after the warm-up phase, but half of the participants did not change them during the entire training session. Most participants (75%) could at least identify what the correct head position of the horse should look like. However, there were still too many (50%) who adjusted their horse too tightly and did not change anything at that time despite the related breathing problems. The study found that most participants used the reins responsibly, but there is still a need for clarification and information relating to the functions of the different auxiliary reins among horse owners.

Overexpression of the Severe Acute Respiratory Syndrome Coronavirus-2 Receptor, Angiotensin-Converting Enzyme 2, in Diabetic Kidney Disease: Implications for Kidney Injury in Novel Coronavirus Disease 2019.

OBJECTIVES: Diabetes is associated with adverse outcomes, including death, after coronavirus disease 19 (COVID-19) infection. Beyond the lungs, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, can infect a range of other tissues, including the kidney, potentially contributing to acute kidney injury in those with severe disease. We hypothesized that the renal abundance of angiotensin-converting enzyme (ACE) 2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS). METHODS: The expression of ACE 2 was examined in 49 archival kidney biopsies from patients with diabetic kidney disease and from 12 healthy, potential living allograft donors using next-generation sequencing technology (RNA Seq). RESULTS: Mean ACE 2 messenger RNA was increased approximately 2-fold in diabetes when compared with healthy control subjects (mean ± SD, 13.2±7.9 vs 7.7±3.6 reads per million reads, respectively; p=0.001). No difference in transcript abundance was noted between recipients and nonrecipients of agents that block the RAAS (12.2±6.7 vs 16.2±10.7 reads per million reads, respectively; p=0.25). CONCLUSIONS: Increased ACE 2 messenger RNA in the diabetic kidney may increase the risk and/or severity of kidney infection with SARS-CoV-2 in the setting of COVID-19 disease. Further studies are needed to ascertain whether this diabetes-related overexpression is generalizable to other tissues, most notably the lungs.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): An Emerging Relationship With Pregestational Diabetes Mellitus Among First Nations and Non-First Nations People in Saskatchewan-Results From the DIP: ORRIIGENSS Project.

OBJECTIVES: Because congenital anomalies of the kidneys and urinary tract (CAKUT) represent a frequent cause of end stage renal disease (ESRD) in the young, we explored the epidemiology of CAKUT and the role of diabetes in pregnancy. METHODS: This was a retrospective cohort study of CAKUT, by maternal diabetes status, from among all 1980‒2009 births in Saskatchewan First Nations (FN) and non-First Nations (non-FN) people. We determined frequencies, predictors and complications of CAKUT, as well as cumulative survival (to 2014) of affected persons until ESRD and death. RESULTS: Of the 411,055 babies (204,167 mothers) in the Saskatchewan maternal-infant database, 2,540 had CAKUT (391 FN and 2,149 non-FN). Overall annual CAKUT incidence was 0.63% for non-FN and 0.57% for FN (p=0.082), but 5-year CAKUT incidence only increased among FN (0.40% in 1980‒1984 and 0.76% in 2005‒2009, p<0.0001) and was highest among offspring of FN mothers with pregestational diabetes (pre-G/DM) (0% before 1995, 2.51% in 2000‒2004 and 1.66% in 2005-2009). Pre-G/DM, but not gestational diabetes mellitus (GDM), was an independent predictor of CAKUT in non-FN (odds ratio, 1.79; 95% confidence interval, 1.20 to 2.69), and in FN interacting with maternal history of stillbirth (odds ratio, 7.90; 95% confidence interval, 1.14 to 54.6). ESRD was >100-fold more likely among offspring with CAKUT compared with all other offspring and was responsible for 40% of ESRD cases in young FN and non-FN people. CONCLUSIONS: In Saskatchewan, pre-G/DM is an emerging cause of CAKUT, accounting for 40% of ESRD cases in FN/non-FN children and young adults. Because pre-G/DM‒related CAKUT is potentially preventable with optimal glycemic management, increased recognition of this serious complication is required.

The Pattern of Superficial Body Temperatures in Leisure Horses Lunged with Commonly Used Lunging Aids.

BACKGROUND: The natural head and neck position (HNP) of horses differs from the position in horse riding when bit is used. The special lunging aids (LAs) are applied in order to modify HNP. Different types of LAs have the potential to affect the work of horse muscles and the superficial thermographic patterns (STPs). The effects of thre LAs on STPs of neck, chest, back, and hindquarters were investigated. METHODS: Sixteen leisure horses were lunged with freely moving head (FMH), rubber band (RB), chambon (CH), and triangle side reins (TRs). The thermographic images (n = 896) were analyzed before/after lunging for mean temperatures (Tmean) and minimum-maximum difference (Tdiff). RESULTS: Superficial Tmean increased (p < 0.001) in cranial part of neck, back, thoracic area, and limbs after lunging regardless of LAs application or its type. In comparison to other LAs: With RB, Tmean was higher in regions of interest (ROIs) 2,7 and lower in ROIs 3-4 (p < 0.05); with CH, Tmean was higher in ROIs 2-4 and 7 (p < 0.01); and with TRs, Tmean was higher in ROIs 2-4,7,9-11 (p < 0.01). In ROIs 2-4 and 7, Tdiff was lower with LAs than with FMH (p < 0.01) and in ROIs 9-10 with TRs. CONCLUSIONS: The choice of LAs should be dictated by the expected effect; however, all LAs increase the quality of the leisure horse lunging. LA use is more desirable than lunging with FMH.

The use of a rein tension device to compare different training methods for neck flexion in base-level trained Warmblood horses at the walk.

BACKGROUND: Debate surrounds the use of high rein tension for obtaining different head and neck positions in the training of sport horses on account of possible welfare issues. OBJECTIVES: To compare auxiliary rein tension in two methods (Draw Reins and Concord Leader) for obtaining a standardised head and neck position on a hard and a soft surface. STUDY DESIGN: Intervention study. METHODS: Left and right rein tensions were measured in 11 base-level trained client-owned sport horses (mean age ± s.d.; 10 ± 3.2 years) exercised in-hand with, in a random order, conventional draw reins or the newly developed Concord Leader in a standardised head and neck position. Rein tension was measured using a calibrated device operating at 10 Hz during six runs of 15 s in a straight line for each training method on both a hard and a soft surface. A linear mixed model and grouped logistic regression analysis were applied to compare the two methods (P<0.05). RESULTS: The odds of a tension of 0 N were lower with draw reins than with the Concord Leader. The rein tension (mean sum of the force applied, in N) of the draw reins was 13.8 times higher than that of the Concord Leader. MAIN LIMITATIONS: This study was performed on horses exercised in-hand; however, these auxiliary aids are normally used when lungeing. Possible redirection of rein tension towards the poll was not measured. CONCLUSIONS: We showed that when using the Concord Leader a similar head and neck position is achieved with a much lower rein tension than with the draw reins and, more importantly, with a much greater likelihood of 0 N. It is unnecessary to use high auxiliary rein tension to obtain a standard, flexed head and neck position.

[Immunotherapy: Activation of a system not a pathway]. / Immunothérapie : après le focus sur les voies de signalisation, l'activation d'un système.

Immunotherapy is on the roll. After revolutionary effects in melanoma, immunotherapy is invading other locations. If current treatments, chemotherapies or targeted therapies block one pathway, immunotherapy should be understood as the activation of a whole system. Indeed, oncogenesis process is defined as an escape of the immune system and the stimulation of this system can block the carcinogenic process. The aim of the present review is to describe the place of immunotherapy in the treatment of solid cancers.