Hypercholesterolemia-induced increase in plasma oxidized LDL abrogated pro angiogenic response in kidney grafts.

BACKGROUND: Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could affect vascular repair processes and promote post-transplant renal vascular remodeling through the over-expression of the anti-angiogenic thrombospondin-1 interacting with vascular endothelial growth factor-A levels. METHODS: We tested this hypothesis in vitro, in vivo and in a human cohort using (1) endothelial cells; (2) kidney auto-transplanted pig subjected (n = 5) or not (n = 6) to a diet enriched in cholesterol and (3) a renal transplanted patient cohort (16 patients). RESULTS: Cells exposed to oxidized LDL showed reduced proliferation and an increased expression of thrombospondin-1. In pigs, 3 months after transplantation of kidney grafts, we observed a deregulation of the hypoxia inducible factor 1a-vascular endothelial growth factor-A axis induced in cholesterol-enriched diet animals concomitant with an overexpression of thrombospondin-1 and a decrease in cortical microvessel density promoting vascular remodeling. In patients, hypercholesterolemia was associated with decreased vascular endothelial growth factor-A plasma levels during early follow up after renal transplantation and increased chronic graft dysfunction. CONCLUSIONS: These results support a potential mechanism through which a high fat-diet impedes vascular repair in kidney graft and suggest the value of controlling cholesterolemia in recipient even at the early stage of renal transplantation.

Renal auto-transplantation promotes cortical microvascular network remodeling in a preclinical porcine model.

The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin's preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 µm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.

Epidemiology, clinical features and treatment of lip cancers in Senegal

Introduction. Lip cancers are uncommon among black people but not unusual. The objectives of this study were to describe the epidemiological, clinical and therapeutic aspects of lip cancers at ENT Department of National University Hospital of Fann in Dakar, Senegal. Patients and methods. We performed a retrospective and descriptive study at ENT Department of Fann teaching Hospital in Dakar, Senegal, over a period of seven years, among patients with lip cancers confirmed by the pathology. The following data were studied: age, gender, past medical history, alcohol and tobacco intake, oral hygiene, the location of the lesions and their extensions, pathological findings, TNM classification, postoperative complications and mortality. Results. 19 cases were collected. The mean age of patients was 51 years, with a sex ratio of 1.4. Bad oral hygiene was the main risk factor followed by prolonged sunlight exposure. The lower lip was the main location of the lesion (73.7%). The budding ulcerative appearance was predominant (73.68%). Squamous cell carcinoma was found in all our patients. 68.42% of our patients were classified T3-T4. 63.15% of our patients underwent surgical resection of the tumor. The most common technique of reconstruction was Estlander flap (25%). Morbidity and mortality were respectively 50% and 31.6%. The global survival rate at one and three years was 85.7%. Conclusion. Lips cancers are relatively uncommon tumors in the black people. In our context, patients consult at advanced stages, making their treatment more difficult

L'amygdalectomie et l'adénoïdectomie à l'hôpital pour enfants de Diamniadio au Sénégal : une évaluation de 3 ans

INTRODUCTION. Les indications de l'amygdalectomie et l'adénoïdectomie sont un sujet de controverse. Notre objectif était de discuter nos indications opératoires en les confrontant à la littérature tout en précisant notre particularité dans la prise en charge des patients dans un hôpital pédiatrique sénégalais. METHODES. Etude rétrospective descriptive au service d'Oto-rhino-laryngologie de l'hôpital pour Enfants de Diamniadio du 1er janvier 2013 au 31 décembre 2015 incluant tous les patients de moins de 15 ans opérés d'une adénoïdectomie, d'une amygdalectomie ou d'une adéno-amygdalectomie. Les variables étudiées étaient l'âge, le sexe, l'indication opératoire, le type de chirurgie et la morbidité. RESULTATS. 522 patients ont été inclus. L'âge moyen était de 4 ans 9 mois avec des extrêmes de 4 mois et 15 ans. L'obstruction respiratoire chronique était la première indication opératoire (63%). Elle était dominée par le syndrome d'apnée obstructive du sommeil retrouvée chez 264 patients (50,6%). Avant l'âge de 10 ans, les indications opératoires étaient dominées par l'obstruction respiratoire chronique (68,2%). Après 10 ans, les infections prédominaient (81,5%). L'adéno-amygdalectomie était le geste chirurgical le plus réalisé (43,7%). La morbidité était de 0,6%, représentée exclusivement par un cas d'hémorragie postopératoire immédiate et deux cas d'hémorragie secondaire.CONCLUSION. L'obstruction respiratoire chronique est la principale indication opératoire particulièrement avant l'âge de 10 ans. Les complications postopératoires sont rares

Strategies to optimize kidney recovery and preservation in transplantation: specific aspects in pediatric transplantation.

In renal transplantation, live donor kidney grafts are associated with optimum success rates due to the shorter period of ischemia during the surgical procedure. The current shortage of donor organs for adult patients has caused a shift towards deceased donors, often with co-morbidity factors, whose organs are more sensitive to ischemia-reperfusion injury, which is unavoidable during transplantation. Donor management is pivotal to kidney graft survival through the control of the ischemia-reperfusion sequence, which is known to stimulate numerous deleterious or regenerative pathways. Although the key role of endothelial cells has been established, the complexity of the injury, associated with stimulation of different cell signaling pathways, such as unfolded protein response and cell death, prevents the definition of a unique therapeutic target. Preclinical transplant models in large animals are necessary to establish relationships and kinetics and have already contributed to the improvement of organ preservation. Therapeutic strategies using mesenchymal stem cells to induce allograft tolerance are promising advances in the treatment of the pediatric recipient in terms of reducing/withdrawing immunosuppressive therapy. In this review we focus on the different donor management strategies in kidney graft conditioning and on graft preservation consequences by highlighting the role of endothelial cells. We also propose strategies for preventing ischemia-reperfusion, such as cell therapy.