Biomedical subjects
Publications and source records attributed to M Salerno.
We show that the linewidth of a Josephson flux-flow oscillator has the same functional dependence on temperature, static, and dynamic resistances as the ones of Josephson single-fluxon oscillators and small Josephson junctions. This suggests a universal formula for the linewidth of Josephson oscillators.
The present study examined how the multidrug resistance protein (MRP1), which is an ATP-dependent anionic conjugate transporter, also mediates the transport of reduced glutathione (GSH) and the co-transport of the cationic drug, daunorubicin, with GSH in living GLC4/Adr cells. To obtain information on the affinity of GSH for the multidrug resistance protein in GLC4/Adr cells, we investigated the GSH concentration dependence of the ATP-dependent GSH efflux. The intracellular GSH concentration was modulated by preincubation of the cells with 25 microM buthionine sulfoximine, an inhibitor of GSH synthetase, for 0-24 h. The transport of GSH was related to the intracellular GSH concentration up to approximately 5 mM and then plateaued. Fitting of the obtained data according to the Michaelis-Menten equation revealed a Km of 3.4+/-1.4 mM and a Vmax of 1.5+/-0.2x10(-18) mol/cell/s. The ATP-dependent transport of GSH was inhibited by 3-([[3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl]-[(3-dimethylamino-3-oxopropyl)-thio]-methyl]thio)propanoic acid (MK571), with 50% inhibition being obtained with 1.4 microM MK571. We investigated the GSH concentration dependence of the MRP1-mediated ATP-dependent transport of daunorubicin under conditions where the transport of daunorubicin became saturated. The daunorubicin transport was related to the intracellular GSH concentration up to approximately 5 mM and then plateaued. We were therefore in the situation where GSH acted as an activator: its presence was necessary for the binding and transport of daunorubicin by MRP1. However, GSH was also transported by the multidrug resistance protein. The concentration of GSH that gave half the maximal rate of daunorubicin efflux was 2.1+/-0.8 mM, very similar to the Km value obtained for GSH. In conclusion, the rate of daunorubicin efflux, under conditions where the transport of daunorubicin became saturated, and the rate of GSH efflux determined at any intracellular concentration of GSH were very similar, yielding a 1:1 stoichiometry with respect to GSH and daunorubicin transport. These results support a model in which daunorubicin is co-transported with GSH.
We study the influence of weak periodic signals on the transport properties of underdamped ratchets. We find that the constant current intervals related to the ratchet can be significantly enlarged by a weak subharmonic signal that is in phase with the internal driver. This stabilization phenomenon is found to exist both in absence and in presence of noise. The dependence of this effect on the phase of the applied signal is also investigated.
OBJECTIVES: A poor therapeutic compliance is a major cause of insufficient control of hypertension. As education of patients is fundamental in order to improve their compliance, we organised two pilot educational meetings aimed at (1) assessing the support of patients to this kind of meetings, and (2) verifying the impact on patient's education. METHODS: We invited 225 consecutive patients referred to our Hypertension Clinic (some of them regularly followed up and some referred for the first time) to participate to an educational meeting on hypertension. Patients were divided in two groups, for organising reasons each attending a single meeting. Each meeting included four sessions: (1) the first session included a multiple choice questionnaire (nine questions, with answers collected by an interactive electronic system) in order to evaluate the degree of patient's information about hypertension (definition, prevalence, aetiology, complications and treatment), (2) a traditional teaching session, (3) an interactive phase aimed to assess the improvement of knowledge in which the same questions as in the first session have been asked again, and (4) a general discussion session. RESULTS: A total of 144 patients (mean age 54 +/- 12 years; 76 M, 68 F) of the 225 invited attended the meeting. The answers to our questions in the initial session were correct in a percentage ranging from 60% to 80%. During the third phase immediately after the teaching session, the percentage of correct answers increased significantly (range: 75--98%, P < 0.05 at least in all questions). CONCLUSIONS: This study shows: (1) a satisfactory adherence of patients to this educational initiative; (2) a positive impact of a single educational meeting on patient's knowledge about issues related to hypertension. The potential role of improving patient's education on clinical outcomes such as blood pressure levels and the rate of blood pressure control requires future controlled studies. Journal of Human Hypertension (2001) 15, 57-61
The ability to sustain plasmon oscillations gives rise to unique properties of metal nanostructures, which can be exploited for the controlled manipulation of light fields on the nanoscale. In this context we investigate electromagnetic coupling effects within lithographically produced ensembles of gold nanoparticles with a photon scanning tunnelling microscope. To provide an interface between these nano-optical devices and classical far-field optics, we investigate surface plasmon propagation on microstructured metal thin films.
BACKGROUND: Decision about the management of hypertensive patients should not be based on the level of blood pressure alone, but also on the presence of other risk factors, target organ damage (TOD) and cardiovascular and renal disease. OBJECTIVE: To evaluate the impact of echocardiography and carotid ultrasonography in a more precise stratification of absolute cardiovascular risk. METHODS: Never-treated essential hypertensives (n = 141; 73 men, 68 women, mean age 46 +/- 11 years) referred for the first time to our out-patient clinic were included in the study. They underwent the following procedures: (1) family and personal medical history, (2) clinical blood pressure (BP) measurement, (3) routine blood chemistry and urine analysis, (4) electrocardiogram, (5) echocardiogram, (6) carotid ultrasonogram. Risk was stratified according to the criteria suggested by the 1999 WHO/ISH guidelines. TOD was initially evaluated by routine procedures only, and subsequently reassessed by using data on cardiac and vascular structure obtained by ultrasound examinations (left ventricular hypertrophy (LVH) as left ventricular mass index (LVMI) > 134 g/m2 in men and > 110 g/m2 in women; carotid plaque as focal thickening > 1.3 mm). RESULTS: According to the first classification 20% were low-risk patients, 50% medium-risk, 22% high-risk and 8% very-high-risk patients. A marked change in risk stratification was obtained when TOD was assessed by adding ultrasound examinations: low-risk patients 18%, medium-risk 28%, high-risk 45%, very-high-risk patients 9%. CONCLUSIONS: The detection of TOD by ultrasound techniques allowed a much more accurate identification of high-risk patients, who represented a very large fraction (45%) of the patient population seen at our hypertension clinic. In particular, a large proportion of patients classified as at moderate risk by routine investigations were instead found to be at high risk when ultrasound examinations were added. The results of this study suggest that cardiovascular risk stratification only based on simple routine work-up can often underestimate overall risk, thus leading to a potentially inadequate therapeutic management especially of low-medium risk patients.
Multidrug resistance (MDR) in model systems is known to be conferred by two different integral proteins--the 170-kDa P-glycoprotein (P-gp) and the 190-kDa multidrug resistance-associated protein (MRP1)--that pump drugs out of MDR cells. The intracellular level of a drug, which influences the drug's cytotoxic effect, is a function of the amount of drug transported inside the cell (influx) and the amount of drug expelled from the cell (efflux). One possible pharmacological approach to overcoming drug resistance is the use of specific inhibitors that enhance the cytotoxicity of known antineoplastic agents. Many compounds have been proven to be very efficient in inhibiting P-gp activity, but only some of them can inhibit MRP1. However, the clinical results obtained so far by this approach have been rather disappointing. The other likely approach is based on the design and synthesis of new non-cross-resistant drugs whose physicochemical properties favor the uptake of such drug by resistant cells. Our recent studies have shown that whereas the P-gp- and MRP1-mediated efflux of different anthracycline-based drugs may not differ considerably, their kinetics of uptake do. Thus, the high uptake of drug by cells may lead to concentrations at the cellular target site high enough to achieve the needed cytotoxicity against MDR cells. Therefore, increased drug lipophilicity might be one factor in improving drug cytotoxicity in MDR cells. In vitro studies have shown that idarubicin, an analogue of daunorub cin, is more effective than daunorubicin and doxorubicin against MDR tumor cell lines and that this increased effectiveness is related in part to the increased lipophilicity of idarubicin. Other studies have also confirmed the strong impact of lipophilicity on the uptake and retention of anthracyclines in MDR cells.
Multidrug resistance phenotype in mammalian cells is often correlated with overexpression of P-glycoprotein or Multidrug Resistance-Associated protein (MRP(1)). Both proteins are energy-dependent drug efflux pumps that efficiently reduce the intracellular accumulation and hence the cytotoxicity of many natural cytotoxins. Overexpression of these transporters by tumor cells is thought to be a significant factor in both intrinsic and acquired resistance to anticancer drugs. Consequently a great deal of interest is focused on identifying chemical agents that can either antagonise drug transport by these proteins or that can inhibit the proliferation of tumors cells despite the expression of these transporters. P-glycoprotein-mediated multidrug resistance is reversed by a variety of compounds, but surprisingly, few agents reverse the MRP(1)-mediated multidrug resistance. However, it has recently been shown that 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1, 3, 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P oxide (PAK-104P) was able to inhibit the P-glycoprotein and MRP(1)-mediated efflux of several compounds. Understanding of the interactions between transporters and multidrug resistance reversing agents is important in the design of more effective multidrug resistance modulators. We now examined the effect of PAK-104P on Pgp-and MRP1-mediated efflux of three anthracyclines, daunorubicin, pirarubicin, hydroxydoxorubicin and of calcein acetoxymethyl ester and calcein. Our data show that PAK-104P non-competitively inhibits the P-glycoprotein-mediated efflux of anthracycline derivatives and calcein acetoxymethyl ester with an inhibitory constant K(I)=0. 25+/-0.05 microM. PAK-104P also non-competitively inhibits the MRP(1)-mediated efflux of daunorubicin, pirarubicin, hydroxyrubicin, calcein acetoxymethyl ester and calcein. However, surprisingly, in this case the K(I) values obtained were very different ranging from 0.06 for hydroxyrubicin to 10 microM for calcein. These data strongly suggested the existence of two different mechanisms for the inhibition by PAK-104P of the MRP(1)-mediated efflux of molecules: a first mechanism, involving a low-affinity site for PAK-104P, and which would concern molecules such as calcein, cysteinyl leukotriene LCT(4) etc. whose efflux do not depend on glutathione. A second mechanism involving a high-affinity site for PAK-104P and which would concern molecules such as anthracyclines, calcein acetoxymethyl ester whose efflux depends on the presence of glutathione.
BACKGROUND: Pilot educational meetings were conducted to (1) verify the support of hypertensive patients in this initiative; (2) test the knowledge of patients regularly followed-up in our Hypertension Centre Outpatient Clinic concerning problems related to hypertension; (3) improve patients knowledge about hypertension through a formal teaching session, (4) compare the knowledge of these patients with that of a control group. METHODS: An invitation to participate in an educational program on hypertension was extended to 210 consecutive patients (group I ) followed-up in the outpatient clinic of our Hypertension Centre. Each meeting included four sessions: (1) an interactive phase with electronic devices aimed at evaluating the degree of information about hypertension by means of multiple-choice questionnaires, (2) a traditional teaching session, (3) an interactive phase to assess the compliance to treatment, and (4) a general discussion session. The control group (II) included 144 hypertensive patients referred for the first time to our Hypertension Centre. Before the initial visit the patients were asked to answer a questionnaire identical to that provided to group I during the meetings. RESULTS: The meetings were attended by 183 out of the 210 patients in group I (participation rate = 87%). The answers to the questions were corrected as a percentage ranging from 73.7 to 95.6 in group I and from 43.9 to 74.7 in group II (p < 0.01). The provision of more detailed information about problems in hypertension was associated with better compliance to treatment and blood pressure control. (BP under treatment 138 +/- 14/83 +/- 7 mmHg in group I, 152 +/- 15/91 +/- 11 mmHg in group II; (p < 0.01). CONCLUSIONS: Our data indicate that this type of educational approach is appreciated by patients (participation rate 87%) and that the level of knowledge about hypertension and compliance to treatment are greater in selected patients than in control patients.
OBJECTIVES: First, to evaluate the prevalence of left ventricular (LV) hypertrophy, LV concentric remodelling and microalbuminuria in a selected sample of treated hypertensive patients with effective and prolonged clinic blood pressure (BP) control (BP < 140/90 mmHg). Second, to compare the prevalence of these markers of organ damage in patients with and without ambulatory BP (ABP) control, defined as average daytime BP < 132/85 mmHg). DESIGN AND METHODS: Fifty-eight consecutive hypertensive patients who attended our hypertension outpatient clinic over a period of 3 months and were regularly followed up by the same medical team were included in the study. Obesity, diabetes mellitus, history or signs of cardiovascular or renal complications and major noncardiovascular diseases were the exclusion criteria from the study. Each patient underwent 24 h ABP monitoring, echocardiography and 24 h urine collection for albumin measurement. RESULTS: The prevalence of LV hypertrophy (LV mass index > 125 g/m2 in both sexes), LV concentric remodelling (relative wall thickness > 0.45) and microalbuminuria (urinary albumin excretion < 300 mg/ 24 h) in this selected group of patients (32 men, 26 women; mean age 53 +/- 9 years; mean clinic BP 122 +/- 9/ 78 +/- 6 mmHg) was markedly low (6.9, 8.6 and 5.1%, respectively). The 26 patients with effective ABP control (group I) were similar to the 32 patients without effective ABP control (group II) in age, gender, body surface area, clinic BP, smoking habit, glucose, cholesterol and creatinine plasma levels. Prevalence of LV hypertrophy, LV concentric remodelling and microalbuminuria was lower in group I than in group II (0 versus 12.9% P< 0.01, 7.7 versus 9.4% NS, 3.8 versus 6.2% NS, respectively). CONCLUSIONS: This study demonstrates that nonobese, nondiabetic hypertensive patients with an effective clinic BP control have a very low prevalence of target organ damage and that LVH is present only in individuals with insufficient ABP control.
BACKGROUND: Occasional and transient increase in liver enzymes is reported during growth hormone (GH) treatment in girls with Turner syndrome (TS). METHODS: Retrospectively, the specific role of GH treatment on liver and muscular enzymes was evaluated in 78 patients (48 boys; age range 4.0-20.8 years) affected by GH deficiency (GHD) who had been treated with GH for at least 1 year (range: 1-15 years). All patients had normal serum levels of liver and muscular enzymes before GH therapy was started. RESULTS: A clinically asymptomatic and mild increase in serum transaminase levels was observed in 6 of 78 patients with GHD during GH treatment; 3 (3.8%) of the patients showed an isolated, transitory and self-limiting increase in serum liver transaminase levels which was noticed 6 to 12 months after GH treatment was started, and normalized spontaneously within 3 to 6 months, without stopping the therapy. Three additional patients showed a transitory mild increase both in aspartate aminotransferase (AST) and creatine phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The increase in transaminase levels was not related to the brand of GH preparations nor to the dosage administered. CONCLUSIONS: A mild, transient, self-limiting increase in serum transaminase may occur during GH treatment. Concomitant determination of CK serum levels may quickly differentiate muscular from hepatic hypertransaminasemia. Except for persistent cases, this condition does not generally require further investigations.
In this paper we compare the analytical adiabatic exponential approximation and exact numerical description of fluctuation-induced transitions in a "quartic" potential with periodically driven barrier. We show that the adiabatic approximation gives an adequate description of the processes in a wide region of parameter space and the accuracy of the approximation improves with increasing noise intensity. For parameter values outside this region, a different kind of resonant activation, which we call parametric stochastic resonance, is observed.
We study the transport properties (currents) of deterministic underdamped ratchets in terms of phase locking dynamics. The occurrence of reverse currents is interpreted in terms of different stability properties of the periodic rotating orbits and is shown to exist also in the absence of bifurcations from chaos to periodic motion. We briefly discuss the effects of noise on this phase locked dynamics.
Propagation of a shock wave (SW), converting an energy-carrying domain into an empty one, is studied in a discrete version of the normal-dispersion nonlinear Schrodinger equation with viscosity, which may describe, e.g., an array of optical fibers in a weakly lossy medium. It is found that the SW in the discrete model is stable, as well as in its earlier studied continuum counterpart. In a strongly discrete case, the dependence of the SWs velocity upon the amplitude of the energy-carrying background is found to obey a simple linear law, which differs by a value of the proportionality coefficient from a similar law in the continuum model. For the underdamped case, the velocity of the shock wave is found to be vanishing along with the viscosity constant. We argue that the latter feature is universal for long but finite systems, both discrete and continuum. The dependence of the SW's width on the parameters of the system is also discussed.
AIM: The aim of the present study was to evaluate (1) the prevalence and patterns of left ventricular hypertrophy (LVH) and (2) the impact of blood pressure (BP) control, assessed by clinical and 24-hour ambulatory BP monitoring (ABPM) criteria on the persistence of LVH in a representative sample of treated patients attending our Hypertension Clinic. METHODS: One hundred consecutive essential hypertensives (61 m/39 f, age 56+/- 9 years) regularly followed up by the same medical team (average period 52 months, 12-156 months) were included in the study and underwent 24-hour ABPM and complete echocardiographic examination. RESULTS: Twenty-eight of the 100 patients were found to have LVH [left ventricular mass index (LVMI) >125 g/m(2) in men and >110 g/m(2) in women]; LVH was eccentric in 20 patients and concentric in the remaining 8. LVMI did not correlate with clinical BP values but only with ABPM values (mean 24 h systolic r = 0.34, p <0.01; diastolic r = 0.37, p <0.01). The prevalence of LVH in patients controlled according to clinical BP criteria (n = 43, BP <140/90 mm Hg) was 19%, in patients controlled according to ABPM criteria (n = 30, BP during daytime <132/85 mm Hg) 17%, and in those controlled with both criteria (n = 16) 6% (p <0. 01). CONCLUSIONS: The results of this study suggest that the eccentric type of LVH is the prevalent pattern in chronically treated patients. The persistence of LVH is significantly dependent on BP levels achieved during treatment; indeed the prevalence of LVH is very low in patients with an optimal BP control, whereas it is elevated (37%) in uncontrolled patients.
The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.
It has been reported that girls at onset of idiopathic central precocious puberty (ICPP) and during treatment have symbiotic character traits. The aim of this study was to investigate the development of character in a group of adolescents. Ten adolescent girls aged 14 years treated for ICPP were evaluated. All the adolescents in the study had a negative body image compared with age-matched controls and expressed a strong inhibition of their femininity. Their poor body image is reflected by their limited self-esteem. These adolescents have not been able to operate a reorganization of their affective life and therefore go through the necessarily slow and painful separation from their family. Symbiotic traits are "hard-wired" into their lives. These results suggest that at ICPP onset, in addition to setting up an educational program for the parents, it is equally important to supply psychological support for the patients in order to gain a better interaction between biological, psychological and cultural influences.
BACKGROUND: Peripheral arterial occlusive disease (PAOD) at II stage results in a moderate to severe impairment in walking ability. Aim of this study, controlled and randomized, was to evaluate the efficacy of an intensive 4 weeks exercise training in PAOD followed by a six-month period and to analyse the risk factors for atherosclerosis and the site of the lesion for possible predictors of result outcome. METHODS: Patients with PAOD were included in the study (ankle/arm ratio < or = 0.7 and < or = 0.5 after exercise) with initial claudication distance (ICD) < or = 200 m and absolute claudication distance (ACD) < or = 500 m evaluated on a constant-load treadmill test (3 km/hr, 0% slope). Forty patients were randomized (all with antiplatelet therapy): 20 to a supervised walking exercise (mean ICD 121.8 m, ACD 289.7 m) and 20 to a non exercising control group (ICD 111.6 m, ACD 230.1 m). Both groups were tested at 4 weeks (T1) and 6 months (T2). Training group was enrolled in a 4-week supervised training program. RESULTS: In the training group 10% of patients became asymptomatic (>1000 m). At T1 ICD increased 141% (p<0.001) and ACD was with low-pain-claudication >1000 m in 50%, at T2 ICD was 200% (p<0.05) with 70% of asymptomatic for ICD and ACD. Control group has a no significant increase of ICD and ACD at T1 and T2. Only arterial hypertension and intermittent claudication severity emerged as negative predictive factors for the results of training. CONCLUSIONS: Vascular training produces a significant and lasting improvement in walking distance in PAOD.