Specialized cleaning associated with antimicrobial coatings for reduction of hospital-acquired infection: opinion of the COST Action Network AMiCI (CA15114).

Recognized issues with poor hand hygiene compliance among healthcare workers and reports of recontamination of previously chemically disinfected surfaces through hand contact emphasize the need for novel hygiene methods in addition to those currently available. One such approach involves antimicrobial (nano) coatings (AMCs), whereby integrated active ingredients are responsible for elimination of micro-organisms that come into contact with treated surfaces. While widely studied under laboratory conditions with promising results, studies under real-life healthcare conditions are scarce. The views of 75 contributors from 30 European countries were collated regarding specialized cleaning associated with AMCs for reduction of healthcare-associated infection. There was unanimous agreement that generation of scientific guidelines for cleaning of AMCs, using traditional or new processes, is needed. Specific topics included: understanding mechanisms of action of cleaning materials and their physical interactions with conventional coatings and AMCs; that assessments mimic the life cycle of coatings to determine the impact of repetitive cleaning and other aspects of ageing (e.g. exposure to sunlight); determining concentrations of AMC-derived biocides in effluents; and development of effective de-activation and sterilization treatments for cleaning effluents. Further, the consensus opinion was that, prior to widespread implementation of AMCs, there is a need for clarification of the varying responsibilities of involved clinical, healthcare management, cleaning services and environmental safety stakeholders.

Surface modifications for antimicrobial effects in the healthcare setting: a critical overview.

The spread of infections in healthcare environments is a persistent and growing problem in most countries, aggravated by the development of microbial resistance to antibiotics and disinfectants. In addition to indwelling medical devices (e.g. implants, catheters), such infections may also result from adhesion of microbes either to external solid-water interfaces such as shower caps, taps, drains, etc., or to external solid-gas interfaces such as door handles, clothes, curtains, computer keyboards, etc. The latter are the main focus of the present work, where an overview of antimicrobial coatings for such applications is presented. This review addresses well-established and novel methodologies, including chemical and physical functional modification of surfaces to reduce microbial contamination, as well as the potential risks associated with the implementation of such anticontamination measures. Different chemistry-based approaches are discussed, for instance anti-adhesive surfaces (e.g. superhydrophobic, zwitterions), contact-killing surfaces (e.g. polymer brushes, phages), and biocide-releasing surfaces (e.g. triggered release, quorum sensing-based systems). The review also assesses the impact of topographical modifications at distinct dimensions (micrometre and nanometre orders of magnitude) and the importance of applying safe-by-design criteria (e.g. toxicity, contribution for unwanted acquisition of antimicrobial resistance, long-term stability) when developing and implementing antimicrobial surfaces.

Mechanical properties of mesenteric arteries in diabetic rats: consequences of outward remodeling.

Diabetes induces hemodynamic and biochemical changes that can influence mechanical properties of arteries. Structure and mechanics of mesenteric small arteries were investigated in rats with streptozotocin-induced diabetes (duration 7-9 wk). The external diameter of mesenteric artery branches was measured in control (n = 9) and diabetic (n = 7) Wistar Rp rats at baseline and during pressurization in situ (0-150 mmHg) under normal and passive smooth muscle conditions. Mean arterial pressure and mesenteric artery pressure were not significantly different. Baseline mesenteric artery diameter was larger in the diabetes-induced group (439 +/- 12 vs. 388 +/- 18 micrometers, P < 0.05). Media cross-sectional area of arteries from diabetic rats was not significantly increased (0.0149 +/- 0.0015 vs. 0.0122 +/- 0.0007 mm2). Cross-sectional compliance was significantly increased in diabetic rats at intraluminal pressures ranging from 25 to 75 mmHg (P < 0.005), whereas cross-sectional distensibility was not modified. Wall tension and circumferential wall stress were increased in diabetes. These results indicate that mesenteric small arteries of diabetic rats display eutrophic outward remodeling associated with increased wall tension and circumferential wall stress.

Breakers of advanced glycation end products restore large artery properties in experimental diabetes.

Glucose and other reducing sugars react with proteins by a nonenzymatic, posttranslational modification process called nonenzymatic glycation. The formation of advanced glycation end products (AGEs) on connective tissue and matrix components accounts largely for the increase in collagen crosslinking that accompanies normal aging and which occurs at an accelerated rate in diabetes, leading to an increase in arterial stiffness. A new class of AGE crosslink "breakers" reacts with and cleaves these covalent, AGE-derived protein crosslinks. Treatment of rats with streptozotocin-induced diabetes with the AGE-breaker ALT-711 for 1-3 weeks reversed the diabetes-induced increase of large artery stiffness as measured by systemic arterial compliance, aortic impedance, and carotid artery compliance and distensibility. These findings will have considerable implications for the treatment of patients with diabetes-related complications and aging.

Arteriolar reactivity in conscious diabetic rats: influence of aminoguanidine treatment.

The effect of 6 weeks' streptozotocin (STZ)-induced (70 mg/kg) diabetes and aminoguanidine (AG) treatment (50 mg/kg s.c. or 250-750 mg/l given in drinking water) on arteriolar reactivity to vasoactive substances was investigated in conscious rats. Studies were performed in untreated control rats (n = 13), STZ-induced diabetic rats (n = 11), AG-treated control rats (n = 12), and AG-treated diabetic rats (n = 12). Rats were provided with a dorsal microcirculatory chamber that allowed intravital microscopy of striated muscle arterioles of varying diameter (A1, large; A2, intermediate; and A3, small arterioles) in conscious animals. The mean arterial pressure (MAP) and arteriolar diameter responses to intravenous infusion of the following drugs were examined: the endothelium-dependent vasodilator acetylcholine (ACh; 3, 10, and 30 microg x kg(-1) x min(-1)), the potassium-channel opener levcromakalim (LC; 30 microg/kg), and the vasoconstrictor agents ANG II (0.1 and 0.3 microg x kg(-1) x min(-1)) and norepinephrine (NE; 0.2, 0.6, and 2.0 microg x kg(-1) x min(-1)). Baseline MAP was lower in both diabetic groups versus the nondiabetic groups (P < 0.05). AG treatment had no influence on baseline MAP. The absolute change in MAP after drug infusion tended to be lower in the diabetic rats than in their nondiabetic littermates. Arteriolar vasodilatory responses to ACh and LC were attenuated in the diabetic animals (1 +/- 7 vs. 19 +/- 7% [P < 0.05] and 7 +/- 3 vs. 34 +/- 8% [P < 0.01] in A2, respectively). AG treatment of diabetic animals did not prevent the development of this disturbance. Vasoconstrictor responses were not influenced by the diabetic state. In the intermediate arterioles of AG-treated control rats, a hyperresponse was observed after ANG II infusion (-10 +/- 2 vs. -2 +/- 2%; P < 0.05) and a hyporesponse was observed after ACh and LC infusion (2 +/- 3 and 15 +/- 6%, respectively; P < 0.05 vs. untreated control rats). These data indicate that 6 weeks of experimental diabetes is associated with a decreased endothelium-dependent and -independent vasodilatation. AG treatment had no beneficial effect on this disturbance.

Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats.

Advanced glycation end-product-formation is thought to play a role in the development of diabetic angiopathy. By altering the structure of different extracellular matrix components advanced glycation end-products might affect vascular and glomerular permeability. In this study we investigated the effect of treatment with an inhibitor of advanced glycation end-product-formation, aminoguanidine, on vascular permeability and the development of albuminuria in streptozotocin-induced diabetic rats. Male Wistar Rp rats were randomized into a control group, a diabetic group, and an aminoguanidine-treated diabetic group. After 8 weeks, 24-h urine collections were taken and rats were implanted with an arterial and a venous catheter. mean arterial blood pressure was determined by intra-arterial measurement. Regional albumin clearances were assessed in the eye, ileum, lung, skeletal muscle and skin using an isotope technique. Mean arterial pressure in the diabetic group was significantly lower in the control and aminoguanidine-treated groups (p < 0.02). Regional albumin clearances were significantly increased in all tissues of diabetic rats compared to control rats (p < 0.05). Aminoguanidine treatment of diabetic rats resulted in a significant decrease of regional albumin clearance in all tissues except the lung (p < 0.05, lung p = 0.07). The development of albuminuria in diabetic rats however, was not affected by aminoguanidine.

Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats.

The accumulation of advanced glycosylation end-products (AGEs) on collagen and the subsequent stiffening of this matrix protein in diabetes has been described many years ago. Structural modification of collagen in the arterial wall might have important effects on arterial elasticity. Aminoguanidine is known to decrease the formation of AGEs. In this study we evaluated the effects of aminoguanidine treatment on different parameters reflecting arterial wall elasticity in diabetic rats. We demonstrated that treatment of diabetic rats with aminoguanidine resulted in a significant increase in carotid static compliance (+39%, P < 0.01 under control conditions, and +27%, P < 0.01 after abolition of vascular tone by KCN), and a decrease in characteristic aortic input impedance (-40%, P < 0.01). The arterial pulse pressure in aminoguanidine-treated rats was decreased (-15%, P < 0.05) and the pulsatile component of left ventricular power output was relatively diminished (-35%, P < 0.05). In addition, we observed a lower fluid filtration across the carotid wall. These results indicate an increased vascular elasticity, an improved left ventricular-arterial coupling, and a decreased vascular permeability in diabetic rats after aminoguanidine treatment, suggesting that AGE-accumulation on collagen negatively affects arterial wall properties in experimental diabetes.

Inhibition of angiotensin-converting enzyme reduces urinary albumin excretion but not regional albumin clearance in experimental diabetes.

Albuminuria and increased regional albumin clearance are known to develop concomitantly in diabetes. The anti-proteinuric effect of angiotensin-converting enzyme inhibitor therapy is well established. We studied whether angiotensin-converting enzyme inhibitor therapy with perindoprilat in comparison with conventional antihypertensive treatment could influence the development of increased regional albumin clearance as well as albuminuria in experimental diabetes. Rats with streptozotocin-induced diabetes were randomized into a saline group (n = 7), a perindoprilat (1 mg/kg per day) group (n = 8), and a hydralazine (3 mg/kg per day) group (n = 6); six rats served as non-diabetic controls. After 6-8 weeks, blood pressure was equally reduced in the perindoprilat- and hydralazine-treated groups (P < 0.01). Twenty-four-hour urinary protein and albumin excretion were increased in diabetic rats compared to control rats (P < 0.001). Hydralazine did not reduce 24 h protein or albumin excretion, whereas perindoprilat treatment reduced both (P < 0.001) to levels comparable to those of control rats. Regional albumin clearance, assessed in the eye, ileum, lung, skeletal muscle and skin, was clearly elevated in diabetic rats compared to control rats; however, neither drug therapy had an effect on albumin clearance.