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Biomedical subjects

R Messina

Publications and source records attributed to R Messina.

11 recordsLinked to original sources

Strong electrostatic interactions in spherical colloidal systems.

We investigate spherical macroions in the strong Coulomb coupling regime within the primitive model in salt-free environment. We first show that the ground state of an isolated colloid is naturally overcharged by simple electrostatic arguments illustrated by the Gillespie rule. We furthermore demonstrate that in the strong Coulomb coupling this mechanism leads to ionized states and thus to long range attractions between like-charged spheres. We use molecular dynamics simulations to study in detail the counterion distribution for one and two highly charged colloids for the ground state as well as for finite temperatures. We compare our results in terms of a simple version of a Wigner crystal theory and find excellent qualitative and quantitative agreement.

Journal Article↗

L-arginine prevents bone loss and bone collagen breakdown in cyclosporin A-treated rats.

Cyclosporin A is implicated in the pathogenesis of post-transplantation bone disease. Because of recent evidence that cyclosporin A may cause renal and cardiovascular toxicity by inhibiting nitric oxide (NO) activity, and that NO slows bone remodeling and bone loss in animal and human studies, we investigated a possible link between NO production and beneficial effects on bone health in cyclosporin A-treated rats. Thirty-six 10-week-old male rats were assigned to six groups of six animals each, and treated for 4 weeks with: vehicle; cyclosporin A; L-arginine; N(G)-nitro-L-arginine methylester (L-NAME, a general inhibitor of NO synthase activity); a combination of cyclosporin A+L-arginine; and a combination of cyclosporin A+L-NAME. Whole body and regional (spine and pelvis) bone mineral content of rats were measured under basal conditions and at the end of the treatment period by dual-energy X-ray absorptiometry (DXA) scanning. Femur weights and serum concentrations of pyridinoline, a reliable marker of bone resorption, were measured at the end of the study period. Cyclosporin A-, L-NAME-, and cyclosporin A+L-NAME-treated rats had significantly lower bone mineral content and femur weights, and significantly higher pyridinoline levels than did control animals. The administration of L-arginine appeared to prevent bone loss caused by cyclosporin A, suggesting that this amino acid, which can be converted to produce NO, might prove useful in preventing disturbed bone modeling and inhibition of bone growth associated with cyclosporin A therapy.

Amino Acids↗

Strong attraction between charged spheres due to metastable ionized states

We report a mechanism which can lead to long-range attractions between like-charged spherical macroions, stemming from the existence of metastable ionized states. We show that the ground state of a single highly charged colloid plus a few excess counterions is overcharged. For the case of two highly charged macroions in their neutralizing divalent counterion solution we demonstrate that, in the regime of strong Coulomb coupling, the counterion clouds are very likely to be unevenly distributed, leading to one overcharged and one undercharged macroion. This long-living metastable configuration in turn leads to a long-range Coulomb attraction.

Journal Article↗

Impact of a 4-week treatment with prostaglandin E1 on health-related quality of life of patients with intermittent claudication.

Intermittent claudication impairs functional status and quality of life in many patients by limiting walking capacity. The aim of this study was to evaluate the effects of a 4-week treatment with prostaglandin E1 (PGE1), a drug inducing vasodilation and inhibiting platelet aggregation, on improving functional status and health-related quality of life in patients with disabling intermittent claudication. Forty-two untrained outpatients (37 men and five women, mean age 64 +/- 8 years) with intermittent claudication,and maximum walking distance (MWD) of at least 50 and no more than 200 m on treadmill test (5% slope, 3 km/hr) were randomized to 4 weeks of double-blind treatment either with 60 mcg PGE1 daily given IV in 250 mL saline over a period of 2 hours (21 patients) or placebo (250 mL saline, 21 patients). Treatment-free follow-up was completed 8 weeks after the final infusion. Pain free walking distance (PFWD), MWD, and questionnaire evaluation were determined at baseline, after the 4-week treatment period, and at the end of the 8 weeks of the treatment-free follow-up period. After 4 weeks of treatment with PGE1 PFWD and MWD increased from 72 +/- 16 m to 135 +/- 33 m (+87%, p<0.001)and from 140 +/- 30 m to 266 +/- 62 m (+90%, p<0.001), respectively. Analysis of the Walking Impairment Questionnaire responses in the PGE1 group at 4 weeks demonstrated significant improvements in the walking impairment score (+19 percentage points, p<0.001), in the distance score (+25 percentage points, p<0.001), in the speed score (+24 percentage points, p<0.001), in the stair climbing score (+20 percentage points, p<0.001). The RAND survey responses showed improvements in physical function and bodily pain scores (+14 percentage points, p<0.001, and +15 percentage points, p<0.01, respectively). After the treatment-free follow-up period of 8 weeks, increases in PFWD and MWD were maintained (113 +/- 26 m, +57%, p<0.001, and 229 +/- 55 m, +63%, p<0.001, respectively). Similarly, at the end of the treatment-free follow-up, the walking impairment score (+16 percentage points, p<0.001), the distance score (+23 percentage points, p<0.001), the speed score (+22 percentage points, p<0.001), the stair climbing score (+18 percentage points, p<0.001) as well as the RAND physical function and bodily pain scores (+10 percentage points, p<0.001, and +13 percentage points, p<0.01, respectively) were still increased compared with baseline. No change from baseline was found in all the target parameters in the placebo group after 4 weeks of treatment and at the end of the treatment-free follow-up period. These data show that a 4-week treatment with PGE1 improves functional status and quality of life as well as treadmill performance in patients with disabling intermittent claudication as compared with placebo-treated patients. The improvements are also maintained for a period of 8 weeks beyond the end of the treatment. Additional studies are needed to determine the duration of functional benefits after the end of treatment.

Aged↗

Treadmill exercise-induced release of endothelin-1 in patients with peripheral arterial occlusive disease at Fontaine stage IIb.

BACKGROUND: Endothelin-1 (ET-1) is an endothelial vasoconstrictor mitogenic peptide which is thought to be a marker of endothelial damage and a potential participant in the pathophysiological processes of the development of atherosclerotic lesions and disease states associated with vasoconstriction and vasospasm. METHODS: To investigate the endothelin-1 release in response to dynamic exercise in patients with peripheral arterial occlusive disease (PAOD), plasma concentrations were determined by radioimmunoassay in 16 patients (14 men, 2 women, mean age 56.2 +/- 8.1 years) with peripheral arterial occlusive disease at Fontaine stage IIb and in 10 control subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) in normal health during treadmill testing (slope 5%, speed 3 km/hr). Blood samples were collected at rest from an antecubital vein, at the onset of claudication pain, and 10 minutes after exercise. RESULTS: Mean plasma endothelin-concentrations during the stress test increased significantly in the patients with arterial disease, rising from basal values of 4.4 +/- 0.6 pmol/L to values of 8.9 +/- 0.7 pmol/L at the end of the test (p < 0.0001), whereas it did not change significantly in control subjects (rising from 2.6 +/- 0.4 pmol/L to 2.7 +/- 0.5 pmol/L). Further, plasma endothelin- in the patients with arterial disease was at all times higher than in the control subjects (p < 0.0001). CONCLUSIONS: In conclusion, this study shows that in patients with peripheral arterial occlusive disease, plasma endothelin-1 increases after treadmill exercise performed until claudication pain supervenes. Raised endothelin-1 could be a marker of ischaemic acute endothelial damage and/or could contribute to increase the vascular resistance in ischaemic limbs of these patients during dynamic exercise by promoting arterial/arteriolar vasoconstriction or vasospasm.

Arterial Occlusive Diseases↗

Plasma endothelin-1 levels in patients with peripheral arterial occlusive disease at different Fontaine's stages.

UNLABELLED: Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogenic peptide produced and secreted by endothelial cells, which can play a potential role in the development of atherosclerosis and in the pathophysiology of extreme vasoconstriction of various diseases. METHODS: To assess plasma endothelin-1 (ET-1) concentrations in patients with peripheral arterial occlusive disease (PAOD) at different Fontaine's stages, we measured plasma ET-1 by radioimmunoassay in 14 stage II PAOD patients (12 men, 2 women; mean age 59.5 +/- 3.4 years) and in 10 stage III-IV PAOD patients (8 men, 2 women, mean age 61.2 +/- 3.3 years). Ten normal subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) were considered as controls. RESULTS: Mean (+/- SD) plasma ET-1 levels, as measured by radioimmunoassay, were significantly greater in stage II and stage III-IV PAOD patients than in control subjects (4 +/- 0.4 and 5 +/- 0.4 pmol/L vs 2.5 +/- 0.6 pmol/L, respectively, p < 0.001). Furthermore, plasma levels of ET-1 in stage III-IV patients were significantly higher than in stage II patients (p < 0.01). A significant correlation was found between plasma ET-1 levels and number of the arterial obstructive lesions in PAOD patients (r = 0.698; p < 0.0001). No significant correlation was found between plasma ET-1 concentrations and pain-free walking distance (r = -0.279, p = 0.333, in stage II patients; r = 0.137, p = 0.705, in stage III-IV patients), and between plasma ET-1 levels and ankle/arm pressor index (r = 0.032, p = 0.913, in stage II patients; r = 0.149, p = 0.681, in stage III-IV patients) in the PAOD patients. CONCLUSIONS: Raised plasma ET-1 could be a sensible marker both of endothelial damage and disease extension. It could also promote the progression of atherosclerotic plaques and enhance the microvascular resistance in these patients.

Arterial Occlusive Diseases↗

Effects of a 4-week treatment with prostaglandin E1 on plasma endothelin-1 release in patients with intermittent claudication.

OBJECTIVE: Endothelin-1 (ET-1) is a vasoconstrictor mitogenic peptide whose plasma concentrations are increased in patients with peripheral arterial occlusive disease (PAOD). The aim of this study was to investigate whether changes in plasma ET-1 concentrations occur after a 4-week treatment with prostaglandin (PG) E1 in patients with intermittent claudication. PATIENTS, MATERIAL AND METHODS: Twenty-four non-trained outpatients with Fontaine stage II PAOD (20 men and 4 women, mean age 63+/-7 years, age range 48-72 years) were randomized to receive over a 4-week period either PGE1 (60 microg given daily i.v. over 2 hours in 250 ml saline, n = 12) or placebo (250 ml saline, n = 12). Plasma levels of ET-1 were measured by radioimmunoassay at baseline and after treatment period. Before and after treatment pain-free walking distance (PFWD) and maximum walking distance (MWD) were evaluated by treadmill walking test as the target parameters for assessing treatment efficacy. RESULTS: At week 4, PFWD and MWD significantly increased in comparison to baseline only in PGE1 treatment group (from 136+/-38 m to 246+/-95 m, p = 0.0004, and from 238+/-54 m to 411+/-137 m, p = 0.0001, respectively). At the end of the treatment period with PGE1, ET-1 plasma concentration decreased from 4.50+/-0.8 pmol/l to 3.6+/-1.1 pmol/l (p = 0.002), whereas it remained unchanged in placebo group. A significant correlation between the decrease in ET-1 plasma levels and the increase in the PFWD and MWD (r = -0.92, p < 0.0001; r = -0.78, p = 0.002, respectively) was detected in PGE1 treatment group. CONCLUSIONS: Reduced ET-1 plasma concentrations after PGE1 treatment could be an index of improved endothelial function and/or could contribute to a reduction in vascular resistance and vessel wall growth in PAOD patients. Moreover, plasma ET-1 could be a marker of clinical improvement in these patients.

Aged↗

[Quality of reawakening and dismissal after anesthesia with various techniques for minor surgical intervention. Clinical and medico-legal aspects].

Different drug combinations were compared in order to assess the quality of anesthesiological control, tolerability and the speed of reawakening and recovery of self-sufficiency in 60 patients undergoing minor surgery. Propofol, combined with fentanyl and N2O due to its inadequate analgesic cover, showed a quickness of action with scarse side-effects, prompt reawakening and rapid recovery of deambulatory self-sufficiency in comparison to the associations of thiopentonefentanyl and thiopentone-isoflurane, thus indicating its preferential use in short surgical operations which can be carried out under a day hospital regimen. In addition, some medico-legal aspects of dimissional of recent developments regarding professional responsibility.

Adult↗