RANTES/CCL5-induced pro-angiogenic effects depend on CCR1, CCR5 and glycosaminoglycans.

Atherosclerosis involves angiogenesis and inflammation with the ability of endothelial cells and monocytes to respond to chemokines. We addressed here by in vitro and in vivo approaches, the role of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES)/CCL5 on angiogenesis through its receptors CCR1, CCR5, syndecan-1 (SDC-1), syndecan-4 (SDC-4) and CD-44. Our data demonstrate that RANTES/CCL5 is pro-angiogenic in a rat subcutaneous model. This RANTES/CCL5-activity may be related to the in vitro promotion of endothelial cell migration, spreading and neo-vessel formation. RANTES/CCL5-mediated angiogenesis depends at least partly on Vascular Endothelial Growth Factor (VEGF) secretion by endothelial cells, since this effect is decreased when endothelial cells are incubated with anti-VEGF receptor antibodies. RANTES/CCL5-induced chemotaxis is mediated by matrix metalloproteinase-9. We demonstrate that specific receptors of RANTES/CCL5 such as G protein-coupled receptors CCR1 and CCR5, and heparan sulfate proteoglycans, SDC-1, SDC-4 or CD-44, play a major role in RANTES/CCL5-induced angiogenic effects. By the use of two RANTES/CCL5 mutants, [E66A]-RANTES/CCL5 with impaired ability to oligomerize, and [44AANA47]-RANTES/CCL5 mutated in the main RANTES/CCL5-glycosaminoglycan (GAG) binding site, we demonstrate that chemokine oligomerization and binding to GAGs are essential in RANTES/CCL5-induced angiogenic effects. According to these results, new therapeutic strategies based on RANTES/CCL5 can be proposed for neo-angiogenesis after vascular injury. Mutants of RANTES/CCL5 may also represent an innovative approach to prevent the angiogenesis associated with the formation of atherosclerotic plaque.

Fucoidan/VEGF-based surface modification of decellularized pulmonary heart valve improves the antithrombotic and re-endothelialization potential of bioprostheses.

Decellularized porcine heart valves offer promising potential as biocompatible prostheses. However, this procedure alter matrix fibres and glycans, leading to lower biomechanical resistance and increased their thrombotic potential. Therefore, their durability is limited due to calcification and weak regeneration in vivo. Surface modifications are highly requested to improve the scaffolds re-endothelialization required to restore functional and haemocompatible heart valve. Fucoidan, a natural sulphated polysaccharide, carries antithrombotic and anti-inflammatory properties and is known to enhance endothelial adhesion and proliferation when associated with vascular endothelial growth factor (VEGF). Based on these features, we constructed fucoidan/VEGF polyelectrolyte multilayer film (PEM) coated valve scaffold in an attempt to develop functional heart valve bioprosthesis. We investigated the haemocompatibility of the PEM coated valve scaffolds, the adhesion and growth potential of endothelial cells (HUVECs) in flow, as well as long term culture with stem cells. Fucoidan/VEGF PEM coated scaffolds demonstrated antithrombotic and non-calcifying properties. The PEM application increased HUVECs adhesion in flow (6 h) and HUVECs viability over time (72 h). HUVECs were well spread and aligned in flow direction. Interestingly, stem cells infiltration was improved by the PEM coating at 21 days. Thus, the fucoidan/VEGF PEM is a promising surface modification to obtain valve bioprostheses for clinical applications with increased antithrombotic and re-endothelialization potential.

Pro-angiogenic effect of RANTES-loaded polysaccharide-based microparticles for a mouse ischemia therapy.

Peripheral arterial disease results from the chronic obstruction of arteries leading to critical hindlimb ischemia. The aim was to develop a new therapeutic strategy of revascularization by using biodegradable and biocompatible polysaccharides-based microparticles (MP) to treat the mouse hindlimb ischemia. For this purpose, we deliver the pro-angiogenic chemokine Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES)/CCL5 in the mouse ischemic hindlimb, in solution or incorporated into polysaccharide-based microparticles. We demonstrate that RANTES-loaded microparticles improve the clinical score, induce the revascularization and the muscle regeneration in injured mice limb. To decipher the mechanisms underlying RANTES effects in vivo, we demonstrate that RANTES increases the spreading, the migration of human endothelial progenitor cells (EPC) and the formation of vascular network. The main receptors of RANTES i.e. CCR5, syndecan-4 and CD44 expressed at endothelial progenitor cell surface are involved in RANTES-induced in vitro biological effects on EPC. By using two RANTES mutants, [E66A]-RANTES with impaired ability to oligomerize, and [44AANA47]-RANTES mutated in the main RANTES-glycosaminoglycan binding site, we demonstrate that both chemokine oligomerization and binding site to glycosaminoglycans are essential for RANTES-induced angiogenesis in vitro. Herein we improved the muscle regeneration and revascularization after RANTES-loaded MP local injection in mice hindlimb ischemia.

Diagnosis and management of adenocarcinoma of the ampulla of Vater during pregnancy.

BACKGROUND: Cancer of the biliary tract has a poor prognosis and its association with pregnancy is uncommon. Early diagnosis allowing curative surgical resection offers the only hope of long-term survival. CASE: This report describes the case of a young 26-week-pregnant woman admitted for cholestatis documented by clinical and laboratory examination. Ultrasonography (US) and magnetic resonance cholangiopancreatography (MRCP) were indicative of common bile tract obstruction. Caesarian section was performed at 32 weeks of pregnancy and the tumor was promptly biopsied. Histology demonstrated carcinoma of the ampulla of Vater. The patient underwent a Whipple procedure. Both mother and baby survived. CONCLUSION: Pregnant patients with digestive cancer require careful management. Acute non-invasive assessment and radical surgery improve outcome for both the mother and fetus.

Prevalence and risk factors for diabetic retinopathy among Omani diabetics.

AIMS: To study the prevalence of diabetic retinopathy in a population of patients attending a diabetic clinic and to evaluate the medical risk factors underlying its development. METHODS: 500 randomly selected diabetic patients attending the diabetes clinic in Al Buraimi hospital were referred to the ophthalmology department where they were fully evaluated for the absence or presence of retinopathy. Any retinopathy present was graded as mild non-proliferative retinopathy (NPR), moderate-severe NPR, and proliferative retinopathy. Several risk factors were then evaluated in order to delineate those related to occurrence of retinopathy in general as well as to the different grades of retinopathy in particular. RESULTS: Diabetic retinopathy was detected in 212 patients (42.4%), with mild NPR present in 128 patient (25.6% of the total population), moderate-severe NPR in 20 patients (4%), and proliferative diabetic retinopathy present in 64 patients (12.8%). Factors significantly related to occurrence of retinopathy were age of the patient, duration of diabetes, presence of ischaemic heart disease, presence of hypertension, a high fasting capillary glucose level as well as elevated serum levels of urea, creatinine, cholesterol, and triglycerides. After adjustment for covariates, it was found that duration of diabetes was the only risk factor associated with mild NPR, while high diastolic blood pressure and high levels of serum creatinine, cholesterol, and triglycerides were significantly associated with the occurrence of proliferative retinopathy. CONCLUSIONS: In addition to glycaemic control, lowering of blood lipids as well as diastolic blood pressure (in hypertensive patients) may be effective in lowering the incidence of retinopathy in compromised patients.

Serological response of chickens to infection with Salmonella gallinarum-S. pullorum detected by enzyme-linked immunosorbent assay.

The serological response to Salmonella pullorum and S. gallinarum infection in chickens was studied with an indirect enzyme-linked immunosorbent assay (ELISA). In broiler chickens, a more virulent strain of S. pullorum produced a significantly lower serum IgG titer than did a less virulent strain. In laying hens, the serum and egg-yolk IgG titers were very similar. In chickens infected with S. gallinarum, high IgG titers persisted for 30 weeks. In chickens reinfected with this strain, each reinfection was followed by transitory increases in IgG lasting no longer than 2 weeks. Serum samples from Brazil taken from a laying flock with evidence of fowl typhoid showed much higher antibody levels than did those from three uninfected flocks. Using lipopolysaccharide as the detecting antigen, infections caused by these salmonellae could be differentiated from those caused by other groups. Incorporation of the appropriate flagella antigen in the ELISA allowed differentiation between infections caused by S. pullorum and S. enteritidis.

CT scan findings of occult sinus pathology in asymptomatic individuals.

One hundred-fourteen computed tomographic(CT) scans of the skull region were revised for occult sinus pathology in asymptomatic individuals. The scans were conducted to investigate other skull regions. None of the patients had nasal or sinus symptoms. Twenty-nine percent of the ethmoid sinuses had occult pathology mostly in the form of thickened mucous membrane. Occult pathology occurred in 14% of maxillary sinuses, 4.8% of the frontal sinuses, and 4.6% of the sphenoid sinuses. As ethmoids carry a high incidence for possible occult pathology, isolated clouding of the ethmoids in CT scans should not be regarded as a cause for patients' symptoms in headache investigation.

[Arterio-ureteral fistula: diagnostic and therapeutic approach]. / Fistule artério-urétérale: approche diagnostique et thérapeutique.

The diagnosis of arterio-ureteric fistula must be considered in the case of sudden onset of abundant or intermittent haematuria occurring in a particular context (history of aorto-iliac vascular surgery, prolonged ureteric stenting, ilio-pelvic radiotherapy). Emergency treatment must control bleeding. Endovascular stenting may be a useful technique, followed by reconstructive surgery with vascular bypass graft and treatment of the ureteric lesion.

[Evaluation and treatment of endometrial cancer]. / Evaluation et traitement des cancers de l'endomètre.

Endometrial cancer is the most common gynaecologic cancer and its incidence increases with age. Prognosis is good because in over 80% of cases the cancer is discovered early. Preoperative work-up should include definition of the operability of such patients, who are often elderly with frequent co-morbidity. Preoperative evaluation and operative findings allow guiding the treatment and evaluating the prognosis. Main determinants are local extension, penetration into the myometrium, histologic stage of the tumour and involvement of lymph modes or peritoneum. Surgery is the first approach since it establishes the evaluation and comprises the first step of treatment. When necessary, subsequent treatment uses irradiation. Treatment with hormones or antimitotic drugs is less effective and is used for forms that are locally advanced, metastatic or recurrent after initial treatment.

Trapezius muscle activity in using ordinary and ergonomically designed dentistry chairs.

BACKGROUND: Most dentists complain of musculoskeletal disorders which can be caused by prolonged static posture, lack of suitable rest and other physical and psychological problems. OBJECTIVE: We evaluated a chair with a new ergonomic design which incorporated forward leaning chest and arm supports. METHODS: The chair was evaluated in the laboratory during task simulation and EMG analysis on 12 students and subjectively assessed by 30 professional dentists using an 18-item questionnaire. EMG activity of right and left trapezius muscles for 12 male students with no musculoskeletal disorders was measured while simulating common tasks like working on the teeth of the lower jaw. RESULTS: Normalized EMG data showed significant reduction (p<0.05) in all EMG recordings of the trapezius muscle. Dentists also unanimously preferred the ergonomically designed chair. CONCLUSION: Such ergonomically designed chairs should be introduced as early as possible in student training before bad postural habits are acquired.