Activation of the ACE2/Angiotensin-(1-7)/Mas Receptor Axis Enhances the Reparative Function of Dysfunctional Diabetic Endothelial Progenitors

We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD34(+) cells from patients with diabetes were compared with those of nondiabetic controls. Ang-(1-7) restored impaired migration and nitric oxide bioavailability/cGMP in response to stromal cell-derived factor and resulted in a decrease in NADPH oxidase activity. The survival and proliferation of CD34(+) cells from diabetic individuals were enhanced by Ang-(1-7) in a Mas/phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. ACE2 expression was lower, and ACE2 activators xanthenone and diminazine aceturate were less effective in inducing the migration in cells from patients with diabetes compared with controls. Ang-(1-7) overexpression by lentiviral gene modification restored both the in vitro vasoreparative functions of diabetic cells and the in vivo homing efficiency to areas of ischemia. A cohort of patients who remained free of microvascular complications despite having a history of longstanding inadequate glycemic control had higher expression of ACE2/Mas mRNA than patients with diabetes with microvascular complications matched for age, sex, and glycemic control. Thus, ACE2/Ang-(1-7)\Mas pathway activation corrects existing diabetes-induced CD34(+) cell dysfunction and also confers protection from development of this dysfunction.

Reparative Complementarity: Ensuring an Effective Remedy for Victims in the Reparation Regime of the International Criminal Court

This article examines the reparation regime of the International Criminal Court in light of its first reparation decision. Based on the reparation jurisprudence established in international law and human rights law to provide victims of international crimes an effective remedy, this article suggests that in order for the International Criminal Court to achieve this objective it needs to go beyond individual criminal responsibility due to its limitations. This article considers the role of reparative complementarity in ensuring an effective remedy to victims of international crimes as part of the reparation regime of the International Criminal Court.

Minimal intervention dentistry and older patients part 2: minimally invasive operative interventions

As described in the first paper of this two part series, the expansion of our older population and the concomitant reduction in levels of edentulism will result in an increase in the number of patients presenting in general practice with complex restorative challenges. The application of the concepts of minimal intervention dentistry and minimally invasive operative techniques may offer a powerful armamentarium to the general dentist to provide ethical and conservative treatment to older patients.

Clinical Relevance: When it is unavoidable, operative intervention should be as minimally invasive as practicable in older patients to preserve the longevity of their natural dentition.

Subjective impact of minimally invasive dentistry in the oral health of older patients

OBJECTIVES: The aim of this study was to investigate if a minimally invasive oral health package with the use of atraumatic restorative treatment (ART) or a conventional restorative technique (CT) would result in any perceived benefit from the patients' perspective and if there would be any difference between the two treatment groups.

MATERIALS AND METHODS: In this randomised clinical trial, 99 independently living older adults (65-90 years) with carious lesions were randomly allocated to receive either ART or conventional restorations using minimally invasive/intervention dentistry (MID) principles. Patients completed an Oral Health Impact Profile (OHIP)-14 questionnaire before and 2 months after treatment. They were also asked to complete a global transition question about their oral health after treatment.

RESULTS: At baseline, the mean OHIP-14 scores recorded were 7.34 (ART) and 7.44 (CT). Two months after treatment intervention, 90 patients answered the OHIP-14 and the mean scores were 7.23 (not significant (n.s.)) and 10.38 (n.s.) for the ART and CT groups, respectively. Overall, 75.5 % of patients stated that their oral health was better compared to the beginning of treatment.

CONCLUSIONS: Although not shown by the OHIP-14, patients perceived an improvement in their overall oral status after treatment, as demonstrated by the global transition ratings in both groups.

CLINICAL RELEVANCE: Dental treatment using minimally invasive techniques might be a good alternative to treat older individuals, and it can improve their oral health both objectively and subjectively.

Minimal intervention dentistry and older patients Part 1: Risk assessment and caries prevention

Ten million people in the UK today are aged over 65. The latest projections estimate that there will be 5 1/2 million more people aged 65 and older in the next 20 years. This projected pattern of population ageing will have profound consequences for dentistry. Minimal intervention dentistry (MID) is a modern evidence-based approach to caries management in dentate patients that uses the 'medical model' whereby disease is controlled by the 'oral physician'. This approach offers considerable benefits over conventional dentistry for older patients. It encourages patients to be responsible for their oral health through the provision of both knowledge and motivation. MID encompasses risk assessment for dental disease, early detection and control of disease processes, and minimally invasive treatment. 

Clinical Relevance: Risk assessment tools can aid the general dental practitioner and the patient to develop a suitable caries prevention programme for that individual and reduce the need for future operative intervention.