Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical artery resistance in vitro

BACKGROUND: The non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs), and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP), and a PAR-1 antagonist on human umbilical artery tone in vitro. METHODS: Human umbilical artery samples were obtained from 17 women at term. Arterial rings were suspended under physiologic conditions for isometric recording. The in vitro effects of thrombin (0.5 units/mL to 3 units/mL), PAR1-AP TFLLR-NH2 [10(-9) to 10(-6) M], and PAR-1 antagonist (N-trans cinnamoyl- p-fluoroPhe-p-guanidinoPhe-Leu-Arg-Orn-NH2) [10(-9) M to 10(-5) M] on umbilical artery tone were measured. RESULTS: Both thrombin and TFLLR-NH2 exerted a potent cumulative vasodilatory effect on human umbilical artery resistance (P < 0.001). The mean net maximal inhibition (MMI) for thrombin was 53.05% (n = 6; SEM = 1.43) at tissue bath concentration of 3 units/mL. The MMI with TFLLR-NH2 was 61.50 % (n = 6; SEM = 1.43) at bath concentration of 10(-6) M. In comparison to vehicle control, the PAR-1 antagonist did not show a significant relaxant or contractile effect (P > 0.05). CONCLUSION: These findings highlight a potential role for thrombin and PAR-1 receptors in vascular regulation of feto-placental blood flow in normal pregnancy, and in association with the vascular lesions associated with IUGR and pre-eclampsia

Antimicrobial management of diabetic foot infection

Diabetic foot infections (DFIs) are a frequent and costly complication associated with diabetes mellitus. Osteomyelitis is present in 44–68% of patients admitted to hospital and DFIs account for 60% of lower extremity amputations in developed countries. Diagnosis of DFIs should be based upon the presence of local and systemic signs and symptoms, and the management and outcomes of DFIs are superior through the involvement of a multidisciplinary team. This article presents an overview of the current evidence for diagnosis and management of DFIs in practice

Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

Background : A venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines. Aim : The aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration. Methods : Through a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports

The profile of patients with venous leg ulcers: A systematic review and global perspective

A holistic profile that includes demographic, medical history and wound characteristics of individuals with venous leg ulceration is lacking. Lack of such a profile negatively impacts the ability to develop interventions to improve patient outcomes. To describe the profile of the patient population with venous leg ulceration from published observational (non-interventional) studies and to identify gaps in the knowledge base for future research in this area. A systematic review of observational studies that included more than 50 patients, from any world region, of any age and in any care setting. twenty studies, involving 3395 patients, from all world regions met our criteria. Demographic characteristics were well reported and showed a female to male ratio of 1.2:1, average age of 47-65 years, high levels of co-morbidities including hypertension (53-71%) and diabetes (16-20%), and only one study reporting ethnicity. When reported, approximately 4-30% had high levels of depression. The average wound size was 18.6-43.39 cm2; mean wound duration was 13.8-65.5 months, mean number of recurrences was four. No study reported on demographic factors plus medical history plus wound characteristics together. a comprehensive, holistic profile of the population with VLU is lacking. There is a critical need for more comprehensive profiling to enable the development of targeted interventions to improve outcomes.peer-reviewed2021-08-1