Search PubMed⌕ Search

Biomedical subjects

M Salerno

Publications and source records attributed to M Salerno.

At least 19 recordsLinked to original sources

Improved osteogenic differentiation of human marrow stromal cells cultured on ion-induced chemically structured poly-epsilon-caprolactone.

The ability to control cell proliferation/differentiation, using material surface, is a main goal in tissue engineering. The objective of this study was to evaluate the attachment, proliferation and differentiation to the osteoblastic phenotype of human marrow stromal cells (MSC) when seeded on poly-epsilon-caprolactone (PCL) thin films before and after irradiation with 10 keV He+. The polymeric surface was characterized as surface chemical structure and composition, roughness and morphology on the micro- and nano-scale, wettability and surface free energy parameters. MSC were obtained from patients undergoing routine hip replacement surgery, expanded in vitro and cultured on untreated PCL and He+ irradiated PCL films for up to 4-5 weeks in osteogenic medium. He+-irradiation led to slight smoothening of the surface and different nanoscale surface chemical structure, while surface free energy resulted unchanged in comparison to untreated PCL. The results from biological testing demonstrated that early attachment and further proliferation, as well as osteoblastic markers, were higher for MSC on He+-irradiated PCL. In conclusion, the change of PCL surface properties induced by ion beam irradiation is confirmed to enhance the adhesion of MSC and support their differentiation.

Biocompatible Materials↗

Adiabatic N-soliton interactions of Bose-Einstein condensates in external potentials.

A perturbed version of the complex Toda chain (CTC) has been employed to describe adiabatic interactions within an N-soliton train of the nonlinear Schrödinger equation. Perturbations induced by weak quadratic and periodic external potentials are studied by both analytical and numerical means. It is found that the perturbed CTC adequately models the N-soliton train dynamics for both types of potentials. As an application of the developed theory, we consider the dynamics of a train of matter-wave solitons confined to a parabolic trap and optical lattice, as well as tilted periodic potentials. In the last case, we demonstrate that there exist critical values of the strength of the linear potential for which one or more localized states can be extracted from a soliton train. An analytical expression for these critical strengths for expulsion is also derived.

Journal Article↗

Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor alpha through its interaction with Sp1.

In the present study, the molecular mechanism underlying the up-regulatory effect of estradiol (E2) on mouse insulin receptor substrate-1 (IRS-1) promoter was investigated in CHO cells on which the same promoter had first been functionally characterized. The mouse IRS-1 promoter bears four consensus half Estrogen Responsive Elements (ERE) sequences and thirteen AP-1- and ten Sp1-binding elements. We performed molecular dissection of this promoter gene providing 3' different deleted constructs, containing the same AP-1 rich region with a progressively increased number of ERE half sites located downstream. None of these constructs was responsive to E2, while a downstream region (nt -1420 to -160) rich in GC elements was induced by E2. However, the latter region lost its intrinsic E2 responsiveness when the whole IRS-1 promoter was mutated for deletion in all four ERE half sites. Deletion analysis of the ERE half sites demonstrated that only ERE located at the position -1500 to -1495, close to the GC-rich region, was able to maintain the induced activatory effect of E2 on the IRS-1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation assays identified the region containing the half ERE/Sp1 (nt -1500 to -1477) as the one conferring E2 responsiveness to the whole promoter. This effect occurs through the functional interaction between E2/ERalpha and Sp1.

Animals↗

Metabolic syndrome in patients with intermittent claudication referred to vascular rehabilitation.

AIM: The prevalence of the metabolic syndrome, a clustering of cardiovascular risk factors whose underlying pathophysiology is related to insulin resistance, was estimated in patients with intermittent claudication referred to a short-course intensive rehabilitation program focused on physical training. Improvements in walking distance at the end of the program were also compared among patients with and without the syndrome. METHODS: The metabolic syndrome was documented among 34 (39%) out of 87 enrolled patients, without significant differences between those with and without the syndrome concerning sex (males 91% vs 92% respectively, P=0.816), age (64+/-8 vs 65+/-7 years, P=0.54), coronary heart disease (44% vs 32%, P=0.365), localization of peripheral arterial disease, and impairment of walking capacity as evaluated by constant treadmill test (initial claudication distance (ICD) 156+/-93 vs 176+/-126 m, P=0.428; absolute claudication distance (ACD) 429+/-324 vs 409+/-269 m, P=0.756). RESULTS: At the end of the program, both ICD and ACD significantly improved without any of significant differences between the two groups (ICD +152% vs +174% respectively, P=0.518; ACD +112% vs +177%, P=0.053). CONCLUSIONS: Metabolic syndrome is frequent among patients with intermittent claudication and is not associated with poor response to physical training. Our data highlight the need for considering vascular rehabilitation in these patients in order to both improve walking capacity and minimize cardiovascular morbidity and mortality.

Aged↗

Relation between the ability of some compounds to modulate the MRP1-mediated efflux of glutathione and to inhibit the MRPl-mediated efflux of daunorubicin.

Much effort has been recently directed to identify the transport-modulating agents in order to overcome the P-gp- and MRP1-mediated drug resistance. Contrary to what is observed for P-gp, very few compounds have been shown to reverse multi-drug resistance (MDR) mediated by MRP1. On the other hand, despite of critical role of GSH in transporting the MRP1 substrates, not much is known about GSH interactions with MRP1. In this work, three compounds that were shown to inhibit the MRP1-mediated efflux of daunorubicin (DNR) have been studied. Depending on their nature the selected compounds have different effects, e.g. at 40 microM, verapamil inhibits 50% of DNR efflux whereas GSH efflux is increased about two-fold. PAK-104P has shown the same effect, i.e. the inhibition of the MRP1-mediated efflux of DNR is accompanied by a stimulation of GSH efflux. However, the PAK-104P concentration required to obtain the same effect is about 40 times smaller that in the case of verapamil. MK571 has been shown to inhibit the efflux of both DNR and GSH. Based on these observations and those reported earlier, a working model is proposed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Two-component Bose-Einstein condensates in periodic potential.

Coupled nonlinear Schrödinger (CNLS) equations with an external elliptic function potential model with high accuracy a quasi-one-dimensional interacting two-component Bose-Einstein condensate (BEC) trapped in a standing wave generated by a few laser beams. The construction of stationary solutions of the two-component CNLS equation with a periodic potential is detailed and their stability properties are studied by direct numerical simulations. Some of these solutions allow reduction to the Manakov system. From a physical point of view the trivial phase solutions can be interpreted as exact Bloch states at the edge of the Brillouin zone. Some of them are stable while others are found to be unstable against weak modulations of long wavelength. By numerical simulations it is shown that the modulationally unstable solutions lead to the formation of localized ground states of the coupled BEC system.

Journal Article↗

Base-sequence-dependent sliding of proteins on DNA.

The possibility that the sliding motion of proteins on DNA is influenced by the base sequence through a base pair reading interaction, is considered. Referring to the case of the T7 RNA-polymerase, we show that the protein should follow a noise-influenced sequence-dependent motion which deviate from the standard random walk usually assumed. The general validity and the implications of the results are discussed.

Base Pairing↗

Ratchetlike dynamics of fluxons in annular Josephson junctions driven by biharmonic microwave fields.

Experimental observation of the unidirectional motion of a topological soliton driven by a biharmonic ac force of zero mean is reported. The observation is made by measuring the current-voltage characteristics for a fluxon trapped in an annular Josephson junction that was placed into a microwave field. The dependence of the fluxon mean velocity at zero dc bias versus the phase shift between the first and second harmonic of the driving force is in qualitative agreement with theoretical expectations.

Journal Article↗

Quantum signatures of breather-breather interactions.

The spectrum of the quantum discrete nonlinear Schrödinger equation, or boson Hubbard Hamiltonian, on a periodic 1D lattice shows some interesting detailed band structure, which may be interpreted as the quantum signature of a two-breather interaction in the classical case. This fine structure is studied using degenerate perturbation theory. We also present a modification to this model, which increases the mobility of bound states.

Journal Article↗

Mild Wolf-Hirschhorn phenotype and partial GH deficiency in a patient with a 4p terminal deletion.

Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients.

Abnormalities, Multiple↗

Hydrodynamic limit of multichain driven diffusive models.

A class of models, generalizing asymmetric exclusion process for many parallel interacting channels, is proposed. We couple the models with boundary reservoirs, study boundary-driven phase transitions, and show that usually taken hydrodynamic description fails. The adequate hydrodynamic limit is then derived. We support our findings with Monte Carlo simulations of the original stochastic system.

Journal Article↗

Allogeneic bone marrow transplantation restores IGF-I production and linear growth in a gamma-SCID patient with abnormal growth hormone receptor signaling.

Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders characterized by a severe defect of both T- and B-cell immunity, which generally require allogeneic bone marrow transplantation (BMT) within the first years of life. We previously reported a patient affected with an X-linked SCID due to L183S hemizygous missense gamma chain mutation, whose severe short stature was due to a peripheral growth hormone (GH) hyporesponsiveness associated to abnormal GH receptor (GH-R) signal transduction. In this study, we report the effect of BMT on the GH-R/insulin-like growth factor I (IGF-I) axis. After BMT, the patient showed a significant improvement in linear growth and normalization of basal- and GH-stimulated IGF-I values, which paralleled a fully competent immunological reconstitution. This suggests that cells derived from the hematopoietic stem cell may exert an unexpectedly significant role in producing IGF-I. This may also suggest that stem cell-based therapies may be useful for the correction of non-hematopoietic inherited disorders, such as those of GH-R/IGF-I axis.

Bone Marrow Transplantation↗

Reproducibility of nocturnal blood pressure fall in early phases of untreated essential hypertension: a prospective observational study.

A number of studies have shown that a smaller than normal nocturnal blood pressure (BP) decrease is associated with cardiovascular disease. However, no large prospective studies have examined the reliability of nocturnal dipping within individuals. The aim of our study was to investigate the short-term variability of nocturnal BP fall in a large cohort of patients with recently diagnosed essential hypertension. In all, 414 uncomplicated never treated hypertensive patients referred to our outpatient hypertension hospital clinic (mean age 46+/-12 years; 257 M, 157 F) prospectively underwent: (1). repeated clinic BP measurements; (2). routine examinations recommended by WHO/ISH guidelines; and (3). ambulatory BP monitoring (ABPM) twice within a 4-week period. Dipping pattern was defined as a reduction in the average systolic and diastolic BP at night greater than 10% compared to average daytime values. Overall, 311 patients (75.1%) showed no change in their diurnal variations in BP. Of the 278 patients who had a dipping pattern on the first ABPM, 219 (78.7%) confirmed this type of profile on the second ABPM, while 59 (21.3%) showed a nondipping pattern. Among 37 dipper patients with >20% of nocturnal systolic BP decrease (extreme dippers), only 16 (43.2%) had this marked fall in BP on the second ABPM. Of the 136 patients who had a nondipping pattern on the first ABPM, 92 (67.6%) confirmed their initial profile on the second ABPM, while 44 (32.4%) did not. Patients with reproducible nondipping profile were older (48+/-12 years) than those with reproducible dipping profile (44+/-12 years, P<0.05). These findings indicate that: (1). short-term reproducibility of nocturnal fall in BP in untreated middle-aged hypertensives is rather limited: overall, one-fourth of patients changed their initial dipping patterns when they were studied again after a few weeks; (2). this was particularly true for extreme dipping and nondipping patterns; (3). abnormalities in nocturnal BP fall, assessed by a single ABPM, cannot be taken as independent predictors of increased cardiovascular risk.

Adult↗

Home blood pressure measurement and its relationship with blood pressure control in a large selected hypertensive population.

Despite the impressive increase of home blood pressure monitoring (BPM) among hypertensive patients over the last few years, a limited number of studies have analysed the rate of home BPM and its relationship with target blood pressure (BP) control, in representative samples of the hypertensive population. The objectives of the study were first to evaluate the prevalence of home BPM in a large selected group of treated hypertensive patients referred to our outpatient hypertension hospital clinic. Second, to assess the rate of satisfactory clinic BP control in patients with or without familiarity with home BPM. In all, 1350 consecutive hypertensive patients who attended our hypertension centre during a period of 12 months and were regularly followed up by the same medical team were included in the study. After informed consent all patients underwent the following procedures: (1) accurate medical history (implemented by a structured questionnaire on demographic and clinical characteristics, including questions concerning home BPM); (2) physical examination; (3) clinic BP measurement; (4) routine examinations; and (5) standard 12-lead electrocardiogram. A total of 897 patients (66%) out of 1350 (687 men, 663 women, age 58.6 +/- 12.3 years, mean clinic BP 141 +/- 16/87 +/- 9 mmHg ) were regularly practising home BPM. In this group of patients, home BPM was associated with a significantly greater rate of satisfactory BP control (49.2 vs 45.6%, P < 0.01). Patients performing home BPM were more frequently men (54 vs 46%, P < 0.02 ) younger (average age 57.8 +/- 12.0 vs 60.3 +/- 12.7 years, P < 0.001) and with a higher educational level (defined by more than 8 years of school, 71 vs 55%, P < 0.05) than their counterparts. There were no significant differences in duration of hypertension, hypercholesterolaemia, obesity, smoking, diabetes, associated cardiovascular diseases, left ventricular hypertrophy and compliance with drug treatment. This study demonstrates that: (1) home BPM is widely performed by hypertensive patients managed in a hypertension hospital clinic; (2) this practice is associated with a significantly higher rate of clinic BP control; and (3) age, male gender and educational level influence the adoption of home BPM.

Aged↗

Adopted girls with idiopathic central precocious puberty: observations about character.

The aim of this study was to investigate the psychological traits of adopted girls affected by idiopathic central precocious puberty (ICPP). Twelve adopted girls were evaluated before, during GnRH agonist (GnRHa) treatment, and after the treatment was stopped. Before, during and after treatment, adopted girls with ICPP showed a normal degree of anxiety, an adequate level of maturity, and a correct sexual identification. None of them had symbiotic character traits as previously reported in non-adopted girls with ICPP. The perception of their body was poor before treatment, but improved during GnRHa treatment and psychological support. The changes in the life of adopted girls are so numerous that precocious puberty may represent an additional risk for psychological discomfort. Therefore to treat precocious puberty it may not only be necessary to prevent premature changes in their body but also to give them enough time to face up to their emotional and psychological problems and to become competent adolescents.

Adolescent↗

Economic evaluation of a short-course intensive rehabilitation program in patients with intermittent claudication.

AIM: The aim of this study was to provide cost-description and cost-effectiveness of a short-course intensive in-hospital rehabilitation program in patients with intermittent claudication. METHODS: Costs per case treated were calculated according to a local standard protocol including diagnostic evaluation of peripheral arterial disease and other related cardiovascular conditions, physical training, and secondary prevention. Three additional less structured scenarios were also evaluated. RESULTS: All 107 enrolled patients (males 91%, mean age 65+/-8 years) completed the program (4-week duration; twice a day walking exercise) and showed significant increases in walking performance, as evaluated by constant treadmill-test. At admission, the mean values of initial claudication distance (ICD) and absolute claudication distance (ACD) were 150+/-111 and 432+/-327 m, respectively. At the end of the program, 12 (11%) patients completed the treadmill test without pain, while 31 (29%) completed the test without stopping due to maximal pain. Among the remaining 64 (60%) patients, the ICD and ACD increased by 137% and 112%, respectively. The cost per case treated ranged from Euro 1733.2 (standard protocol) to Euro 918.9 (physical training only). By adding the cost of hospitalization and indirect costs, the same costs ranged from Euro 4626.2 to Euro 3811.9. The average cost to walk one additional meter without pain as a result of the rehabilitation program was Euro 57.5, while the cost to walk one additional meter before stopping was Euro 27. As showed by sensitivity analysis, the maintenance of the expected level of treatment success was crucial for program's cost-effectiveness. CONCLUSION: From the societal viewpoint, short-course intensive rehabilitation may be cost-effective in patients with stable intermittent claudication and could be considered in decision models evaluating different therapeutic options.

Aged↗

Growth retardation, developmental delay, distinctive face, multiple endocrine abnormalities, and adenylyl cyclase dysfunction: a new syndrome?

We report on a 17-year-old male with severe pre- and postnatal growth retardation, craniosynostosis, distinctive facial features, acanthosis nigricans, deafness, mental retardation and progressive multi-organ involvement, particularly of the endocrine system, including hypothyroidism, hypogonadism, transitory hypoparathyroidism, and insulin resistance. In order to find a common mechanism explaining these multiple abnormalities, we searched for a possible defect in the signal transduction pathways from membrane to nucleus involving G-protein coupled receptors (GPCR). Adenylyl cyclase activity was evaluated by assaying c-AMP in the patient's cultured fibroblasts stimulated with several drugs and toxins acting on different effectors upstream of adenylyl cyclase. The preliminary results indicate a reduced cAMP accumulation in the patient, neither caused by constitutive activation of Gi nor inhibition of Gs signaling, and probably resulting from an alteration in the adenylyl cyclase system. The differential diagnosis with syndromes showing common clinical features with our patient is discussed.

Adenylyl Cyclases↗