Polio eradication in the African Region on course despite public health emergencies.

The World Health Organization, African Region is heading toward eradication of the three types of wild polio virus, from the Region. Cases of wild poliovirus (WPV) types 2 and 3 (WPV2 and WPV3) were last reported in 1998 and 2012, respectively, and WPV1 reported in Nigeria since July 2014 has been the last in the entire Region. This scenario in Nigeria, the only endemic country, marks a remarkable progress. This significant progress is as a result of commitment of key partners in providing the much needed resources, better implementation of strategies, accountability, and innovative approaches. This is taking place in the face of public emergencies and challenges, which overburden health systems of countries and threaten sustainability of health programmes. Outbreak of Ebola and other diseases, insecurity, civil strife and political instability led to displacement of populations and severely affected health service delivery. The goal of eradication is now within reach more than ever before and countries of the region should not relent in their efforts on polio eradication. WHO and partners will redouble their efforts and introduce better approaches to sustain the current momentum and to complete the job. The carefully planned withdrawal of oral polio vaccine type II (OPV2) with an earlier introduction of one dose of inactivated poliovirus vaccine (IPV), in routine immunization, will boost immunity of populations and stop cVDPVs. Environmental surveillance for polio viruses will supplement surveillance for AFP and improve sensitivity of detection of polio viruses.

[Molecular and cellular determinants of arterial stiffness: role of cell-matrix connections]. / Déterminants matriciels de la rigidité artérielle: importance des relations cellules-matrice.

Increased large artery stiffness is believed to be a cardiovascular risk factor independent from mean arterial pressure. The mechanical properties of large arteries depend not only on the amounts of their main constituents (elastin, collagen, and smooth muscle cells) but also on the spatial organization and mechanical interactions among these components. These interactions may be mediated by extracellular matrix adhesion proteins and their membrane receptors or integrins. From a mechanical viewpoint, a key element may be the dense plaque, which is composed of cytoskeletal proteins linked to matrix proteins via membrane integrin receptors. Integrin expression in normal and diseased blood vessels is currently the focus of active research. In humans, hypertension-related arterial hypertrophy is not associated with an increase in intrinsic arterial wall stiffness. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHRs). By increasing cell-matrix anchoring, fibronectin may contribute to protect arterial wall components from the increased mechanical loads associated with hypertension. In atherosclerosis, the increase in cell-matrix anchoring plays a key role in preventing atheroma plaque rupture. To determine the exact role of adhesion molecules in arterial stiffness, there is a need for studies involving use of specific anti-integrin agents and of transgenic animal models.

Arterial structural changes with verapamil in spontaneously hypertensive rats.

Reducing pulse pressure might be more powerful than reducing mean arterial pressure to obtain regression of vascular hypertrophy. However, this hypothesis has never been investigated in the conduit arteries of intact hypertensive animals. A group of 4-week-old spontaneously hypertensive rats (SHR) was treated with the calcium-entry blocker verapamil (50 mg/kg) for 16 weeks and compared with untreated SHR and control Wistar Kyoto (WKY) normotensive rats of the same age. At the end of the experiment, intraarterial thoracic aorta blood pressure was measured both in the conscious and anesthetized animals. Carotid artery diameter and stiffness (echo-tracking techniques) and aortic histomorphometry were determined in parallel. With verapamil, pulse pressure, but not mean arterial pressure, was significantly decreased but did not reach the normotensive values. Carotid internal diameter, medial thickness, and collagen content were significantly reduced by comparison with SHR and did not differ from the values of the WKY group. A significant positive and independent correlation was observed between pulse pressure and medial thickness in the overall population. The study shows that, in SHR chronically treated with verapamil, structural changes may be completely prevented without any change in mean arterial pressure. The parallel change in pulse pressure might suggest that mechanosensitive elements within the vascular wall may be selectively sensitive to the dynamic aspects of physical forces and are able to convert frequency and amplitude information into cellular responses that lead to vascular remodeling.

Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats.

We compared the chronic effects in spontaneously hypertensive rats (SHR) of low doses of an angiotensin converting enzyme inhibitor, trandolapril, a Ca2+ channel antagonist, verapamil, and their combination (trandolapril-verapamil), on arterial mechanical properties, arterial wall hypertrophy and extracellular matrix proteins. Four-week-old SHR were randomly allocated to oral treatment with verapamil (50 mg kg(-1) day(-1)), trandolapril (0.3 mg kg(-1) day(-1)), the combination of verapamil (50 mg kg(-1) day(-1)) plus trandolapril (0.3 mg kg(-1) day(-1)), or placebo for 4 months. A group of Wistar Kyoto (WKY) control rats received placebo for the same period of time. At the end of the treatment, mean blood pressure was lower in verapamil-trandolapril than in trandolapril SHR, but remained higher than in WKY. Verapamil had no effects on blood pressure. Equivalent reduction in aortic wall hypertrophy was obtained in all treated SHR. Trandolapril and verapamil-trandolapril combination produced a significant reduction of aortic collagen density compared with placebo SHR. Carotid total fibronectin, EIIIA fibronectin isoform and alpha5beta1 integrin, were higher in the media of placebo SHR than in WKY. EIIIA fibronectin isoform and alpha5beta1 integrin were reduced in verapamil-SHR compared with placebo-SHR and normalized in trandolapril and verapamil-trandolapril-SHR compared with WKY. SHR-placebo and SHR treated with either verapamil or trandolapril as single-drug treatment showed a 4-fold increase in total fibronectin compared to the WKY. Only SHR treated with verapamil-trandolapril combination had total fibronectin not significantly different from that of WKY. Carotid arterial distensibility increased only in verapamil-trandolapril treated rats. Multivariate analysis showed arterial distensibility to be negatively correlated to mean blood pressure (P < 0.0001) and total fibronectin (P < 0.01). In conclusion, chronic treatment with the verapamil-trandolapril combination significantly improved in vivo arterial distensibility in SHR. The most important effects of the combination on arterial mechanics compared to those of verapamil or trandolapril alone may have been the consequence of its stronger action on arterial pressure, arterial wall hypertrophy and total fibronectin density. However we suggest that, in addition to the structural effects, complete normalization of blood pressure is necessary to obtain normal arterial distensibility.