Novel insights on acute myocarditis in pediatric patients.

Acute myocarditis (AM) is an inflammatory affliction of the heart muscle characterized by recent onset with a broad spectrum of clinical manifestations that globally affect millions of individuals, notably children and young adults. The absence of distinct patterns of onset or predictable progression poses a significant threat to survival, potentially leading to advanced heart failure and malignant arrhythmias. Myocardial fibrosis, a hallmark of myocardial remodeling, is increasingly recognized as a contributor to adverse outcomes in acute myocarditis cases. Advances in molecular and immunological techniques have highlighted the intricate interplay between viral infections, dysregulated immune responses, and genetic susceptibility. Currently, there is no clear consensus for diagnosis or ongoing follow-up in pediatric patients. The conventional diagnostic tool, endomyocardial biopsy (EMB), considered the gold standard, has been complemented by the effectiveness of cardiac magnetic resonance imaging (CMRI) techniques. Given the procedural complexities and associated complications, there is a pressing need to explore non-invasive alternatives. In this context, biomarkers emerge as promising contenders by evaluating both the inflammatory processes and cardiac remodeling, providing valuable observations into disease severity, progression, and treatment response. Therapeutic strategies in these cases, focusing on the specific pathways or immune components associated with the etiologies, have exhibited promise for better outcomes. Acute myocarditis in children remains a multifaceted clinical challenge, necessitating a comprehensive understanding of its pathophysiology, diagnosis, and management. This review aims to delve into novel insights surrounding the pathophysiology, diagnosis, and management of acute myocarditis in pediatric patients.

2D speckle tracking: a diagnostic and prognostic tool of paramount importance.

OBJECTIVE: We aimed to conduct a review of the literature relevant to cardiac imaging techniques and summarize the use of different non-invasive imaging modalities in the assessment of ventricular size, function, and mechanics. The current review emphasizes the benefits of speckle tracking imaging (STI), highlighting its use in demonstrating myocardial strain. This robust technique is a recent addition to the existing imaging techniques that are used to assess the myocardium. In terms of effectively determining the left ventricle ejection fraction, it is a comparable technique to cardiac magnetic resonance. The use of STI method for image acquisition relies on semiautomatic identification of the border and deformation of the region of interest, and is also independent of the angle of insonation, thus it increases the inter-and intra-observer reproducibility in contrast to the conventional tissue doppler imaging. MATERIALS AND METHODS: The databases of PubMed, Scopus, and Embase were thoroughly searched for the following keywords: 2- dimensional/ two-dimensional/ 2-D, speckle/strain tracking, systolic dysfunction, and heart failure. The studies selected described image acquisition techniques and the application of this imaging modality in various clinical settings. The selected journal articles were perused to provide the best possible analysis of STI. RESULTS: Our comparative analysis demonstrated that the STI, when compared with the conventional echocardiography, is a more sensitive image acquiring technique for detecting subclinical myocardial dysfunction. Based on the analysis it can be stated that the STI can provide valuable information on both regional and global myocardial function, and it can also quantify cardiac synchronicity and rotation. Additionally, it serves as a better prognostic indicator. CONCLUSIONS: The change in longitudinal strain can serve as an early marker of the left ventricular systolic dysfunction, and therefore, monitoring via STI has both diagnostic and prognostic value in heart failure, ischemic heart disease, valvulopathies, chemotherapy-induced cardiotoxicity, and cardiac resynchronization therapy. Despite the lack of standardization, the method is also effective in assessing the right ventricle and left atrial function and arterial rigidity.

New solutions for combatting implant bacterial infection based on silver nano-dispersed and gallium incorporated phosphate bioactive glass sputtered films: A preliminary study.

Ag/Ga were incorporated into resorbable orthopaedic phosphate bioactive glasses (PBG, containing P, Ca, Mg, Na, and Fe) thin films to demonstrate their potential to limit growth of Staphylococcus aureus and Escherichia coli in post-operative prosthetic implantation. Dual target consecutive co-sputtering was uniquely employed to produce a 46 nm Ag:PBG composite observed by high resolution TEM to consist of uniformly dispersed ~5 nm metallic Ag nano-particles in a glass matrix. Ga3+ was integrated into a phosphate glass preform target which was magnetron sputtered to film thicknesses of ~400 or 1400 nm. All coatings exhibited high surface energy of 75.4-77.3 mN/m, attributed to the presence of hydrolytic P-O-P structural surface bonds. Degradation profiles obtained in deionized water, nutrient broth and cell culture medium showed varying ion release profiles, whereby Ga release was measured in 1400 nm coating by ICP-MS to be ~6, 27, and 4 ppm respectively, fully dissolving by 24 h. Solubility of Ag nanoparticles was only observed in nutrient broth (~9 ppm by 24 h). Quantification of colony forming units after 24 h showed encouraging antibacterial efficacy towards both S. aureus (4-log reduction for Ag:PBG and 6-log reduction for Ga-PBG≈1400 nm) and E. coli (5-log reduction for all physical vapour deposited layers) strains. Human Hs27 fibroblast and mesenchymal stem cell line in vitro tests indicated good cytocompatibility for all sputtered layers, with a marginal cell proliferation inertia in the case of the Ag:PBG composite thin film. The study therefore highlights the (i) significant manufacturing development via the controlled inclusion of metallic nanoparticles into a PBG glass matrix by dual consecutive target co-sputtering and (ii) potential of PBG resorbable thin-film structures to incorporate and release cytocompatible/antibacterial oxides. Both architectures showed prospective bio-functional performance for a future generation of endo-osseous implant-type coatings.

Atypical attentional filtering of visual information in youth with chromosome 22q11.2 deletion syndrome as indexed by event-related potentials.

BACKGROUND: Youth with chromosome 22q11.2 deletion syndrome (22q) face one of the highest genetic risk factors for the development of schizophrenia. Previous research suggests impairments in attentional control and potential interactions with elevated anxiety and reduced adaptive functioning may increase the risk for developing psychosis in this population. Here, we examined how variations in attentional control relate to the presence or severity of psychosis-proneness symptoms in these individuals. METHODS: To achieve this, we measured attentional control in youth (12-18 years) with 22q (N = 35) compared to a typically developing group (N = 45), using a flanker task (the Distractor Target task) while measuring neural activity with event-related potentials. RESULTS: Similar to previous findings observed in people with schizophrenia, greater attentional capture by, and reduced suppression of, non-target flanker stimuli characterized participants with 22q and was indexed by the N2pc (N2-posterior-contralateral) and PD (distractor positivity) components. Although we observed no relationships between these components and measures of psychosis-proneness in youth with 22q, these individuals endorsed a relatively low incidence of positive symptoms overall. CONCLUSIONS: Our results provide neural evidence of an attentional control impairment in youth with 22q that suggests these individuals experience sustained attentional focus on irrelevant information and reduced suppression of distracting stimuli in their environment. Impairments in attentional control might be a valid biomarker of the potential to develop attenuated positive symptoms or frank psychosis in high-risk individuals long before the age at which such symptoms typically arise. The evaluation of such a hypothesis, and the preventive potential for the putative biomarker, should be the focus of future studies.

First Trimester Neurosonogram-Our Experience.

Central nervous system (CNS) malformations represent 1% of all births. For this reason, efforts are being made to increase detection of such anomalies prenatally. Consequently, a detailed assessment of the fetal nervous system in the first trimester of pregnancy is no longer a utopia as this kind of evaluation can detect severe malformation such as acrania, neural tube defects, holoprosencephaly or can draw attention regarding to anomalies currently detected in the second trimester due to certain markers of diagnosis. MATERIAL AND METHODS: The study included 1376 pregnant women with gestational ages between 11 and 14 weeks, who were referred to our unit for sonographic evaluation. We analyzed in all patients the fetal brain in axial and mid-sagittal views, assessing markers like intracranial translucency, brainstem/brainstem-occipital bone (BS/BSOB) ratio, choroid plexus (CP/HA) ratio, the octopus sign in order to detect as many anomalies in the first trimester of pregnancy. RESULTS: We detected 6 CNS anomalies during our search. All markers assessed were abnormal in all pathological cases. CONCLUSION: A detailed assessment of the fetal brain is recommended at 11-14 weeks because the earlier the diagnosis is confirmed, the lower the chances of obstetrical, psychological complications to supervene.

CARDIOVASCULAR RISK ASSESSMENT IN THE ADULT (AGED 40-79 YEARS) ROMANIAN POPULATION.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. AIM: To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. DESIGN: The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). SUBJECTS AND METHODS: Exclusion criteria: age <40/or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological sub-region where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. RESULTS: A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study.The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6-6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/obesity and smoking were associated with high CVR categories. CONCLUSION: Romania is one of the countries with high CVR, requiring CVD prevention measures.

LONG-TERM IMPROVEMENT OF GLUCOSE HOMEOSTASIS AND BODY COMPOSITION IN PATIENTS UNDERGOING LAPAROSCOPIC SLEEVE GASTRECTOMY.

CONTEXT: Laparoscopic sleeve gastrectomy (SG) has gained popularity as a metabolic procedure, but its long-term effectiveness for Romanian patients remains unclear. OBJECTIVES: To assess the long-term efficacy of SG for Romanian patients and to evaluate the differences between 5 years and 1 year follow-up. DESIGN: A longitudinal, prospective analysis of collected data from 68 patients undergoing SG between 2009 and 2014 was performed. Long-term outcomes at 5 years were analyzed in terms of total weight loss (%TWL), excess weight loss (%EWL), body composition and glucose homeostasis. SUBJECTS AND METHODS: All patients meeting the standard criteria for SG before inclusion were prospectively enrolled in the study. Of the 68 patients, eight were lost to follow-up, therefore, 60 patients (41.7±12.5 years, baseline body mass index [BMI] 44.6±9.9Kg/m2) were analyzed. RESULTS: The BMI decreased at 12 months with 30.7% from the preoperative BMI (p<0.001) and subsequently stabilized at 5 years.TWL and EWL were 30.6% and 83.1%, respectively at 1 year, with a slightly increase at 5 years.Therapeutic success rate (%EWL≥50) and diabetes remission rate (Buchwald criteria) were 93.3% and respectively 63.6% at 5 years. Insulin sensitivity index and metabolic clearance rate of glucose increased with 92.5% and 60.1% respectively, in the third month from baseline (p<0.001), while estimated second phase of insulin secretion decreased with 7.9% in the first month postoperatively (p=0.04), remaining stable afterwards. CONCLUSIONS: SG was effective in terms of %EWL, body composition and glucose homeostasis improvement for Romanian patients, the outcomes stabilizing after 1 year follow-up.

Bioglass implant-coating interactions in synthetic physiological fluids with varying degrees of biomimicry.

Synthetic physiological fluids are currently used as a first in vitro bioactivity assessment for bone grafts. Our understanding about the interactions taking place at the fluid-implant interface has evolved remarkably during the last decade, and does not comply with the traditional International Organization for Standardization/final draft International Standard 23317 protocol in purely inorganic simulated body fluid. The advances in our knowledge point to the need of a true paradigm shift toward testing physiological fluids with enhanced biomimicry and a better understanding of the materials' structure-dissolution behavior. This will contribute to "upgrade" our vision of entire cascades of events taking place at the implant surfaces upon immersion in the testing media or after implantation. Starting from an osteoinductive bioglass composition with the ability to alleviate the oxidative stress, thin bioglass films with different degrees of polymerization were deposited onto titanium substrates. Their biomineralization activity in simulated body fluid and in a series of new inorganic-organic media with increasing biomimicry that more closely simulated the human intercellular environment was compared. A comprehensive range of advanced characterization tools (scanning electron microscopy; grazing-incidence X-ray diffraction; Fourier-transform infrared, micro-Raman, energy-dispersive, X-ray photoelectron, and surface-enhanced laser desorption/ionization time-of-flight mass spectroscopies; and cytocompatibility assays using mesenchymal stem cells) were used. The information gathered is very useful to biologists, biophysicists, clinicians, and material scientists with special interest in teaching and research. By combining all the analyses, we propose herein a step forward toward establishing an improved unified protocol for testing the bioactivity of implant materials.

Development of the first polymorphic microsatellite markers for the Roman snail Helix pomatia L., 1758 (Helicidae) and cross-species amplification within the genus Helix.

The terrestrial snail Helix pomatia (Gastropoda: Stylommatophora: Helicidae) is one of the largest gastropod species in Europe. This species is strictly protected in some European Union countries; however, at the same time, it is also farmed and commercialized for human consumption. Here, we describe 11 microsatellite markers that are very useful in population genetic studies for assessing the status of both wild and farmed populations of this species of community interest. The microsatellites were isolated using 454 pyrosequencing technologies and 11 primer pairs were selected and used for genotyping an H. pomatia population and also checked for cross-species amplification on H. lucorum and H. lutescens specimens. The number of alleles per locus ranged from 3 to 13 and observed heterozygosity was between 0.458 and 0.917. Seven of these loci were polymorphic in H. lucorum, and four in H. lutescens. This set of nuclear markers provides a powerful tool for population genetic studies of this species of community interest, and also for closely related species. The described microsatellite markers should also facilitate the identification of populations of conservation concern.

Prevalence of overweight/obesity, abdominal obesity and metabolic syndrome and atypical cardiometabolic phenotypes in the adult Romanian population: PREDATORR study.

PURPOSE: The objectives were to assess the prevalence of overweight/obesity, abdominal obesity and metabolic syndrome (MetS), and to evaluate the characteristics of the metabolically unhealthy lean (MUHL) and metabolically healthy overweight/obese (MHO) phenotypes in a Romanian population-based sample from the PREDATORR study. METHODS: PREDATORR was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Participants were classified into four cardiometabolic phenotypes based on the BMI, the cut-off value being 25 kg/m(2), and the presence of MetS (defined according to the Harmonization definition 2009): MUHL, MHO, metabolically healthy lean (MHL) and metabolically unhealthy overweight/obese (MUHO). RESULTS: Overall, 2681 subjects aged 20-79 years were included in the analysis. The overall age and sex-adjusted prevalence of obesity was 31.90 %, overweight was 34.7 %, abdominal obesity was 73.90 % and MetS was 38.50 %. The age- and sex-adjusted prevalence of MHO phenotype was 31.60 %, while MUHL phenotype prevalence was 3.90 %. MUHL and MHO participants had a cardiometabolic profile, kidney function and CVD risk intermediary between MHL and MUHO. MUHL had higher odds of being associated with CVD risk (OR 5.8; p < 0.001), abdominal obesity, prediabetes, diabetes, hypertriglyceridemia and hypo-HDL cholesterolemia than MHL, while MHO phenotype was associated with hypo-HDL cholesterolemia (OR 3.1; p = 0.002), prediabetes (OR 2.9; p < 0.001) and abdominal obesity. CONCLUSIONS: PREDATORR study showed a high prevalence of obesity/overweight, abdominal obesity and MetS in the adult Romanian population, and their association with kidney function and several cardiometabolic factors.

Submicrometer Hollow Bioglass Cones Deposited by Radio Frequency Magnetron Sputtering: Formation Mechanism, Properties, and Prospective Biomedical Applications.

This work reports on the unprecedented magnetron sputtering deposition of submicrometric hollow cones of bioactive glass at low temperature in the absence of any template or catalyst. The influence of sputtering conditions on the formation and development of bioglass cones was studied. It was shown that larger populations of well-developed cones could be achieved by increasing the argon sputtering pressure. A mechanism describing the growth of bioglass hollow cones is presented, offering the links for process control and reproducibility of the cone features. The composition, structure, and morphology of the as-synthesized hollow cones were investigated by energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), grazing incidence geometry X-ray diffraction (GIXRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM)-selected area electron diffraction (SAED). The in vitro biological performance, assessed by degradation tests (ISO 10993-14) and cytocompatibility assays (ISO 10993-5) in endothelial cell cultures, was excellent. This allied with resorbability and the unique morphological features make the submicrometer hollow cones interesting candidate material devices for focal transitory permeabilization of the blood-brain barrier in the treatment of carcinoma and neurodegenerative disorders.

Study of the decomposition pathway of 12-molybdophosphoric acid in aqueous solutions by micro Raman spectroscopy.

Micro Raman spectroscopy was applied to investigate the speciation of heteropoly and isopoly molybdates in 0.05 and 0.005 M aqueous solutions of 12-molybdophosphoric acid at pH values between 1 and 6. For comparative purposes, (31)P NMR spectroscopy was applied too. It is shown that stability of Keggin anion is influenced both by pH and concentration of solution. The Keggin structure is stable in acidic solutions (pH<1.6) while defective Keggin structures are formed with further alkalization (up to pH5.6). Monolacunary anion PMo11O(39)(7-) is the main component in the pH region from 1.6 to 3.4. Further removal of molybdenyl species causes the appearance of other vacant Keggin structures such as PMo9O31(OH)(3)(6-) and PMo6O(25)(9-) at about pH4. At pH5.0, anion PMo6O(25)(9-) is the main species. In solutions with pH greater than 5.0, heteropolymolybdates disappear completely and isopolymolybdates Mo7O(24)(6-) and MoO(4)(2-) are formed in higher amounts. In more diluted solution of 0.005 M, the decomposition scheme of 12-molybdophosphoric acid solution with increasing of pH takes place without observation of significant amounts of Mo7O(24)(6-) species. If alkalinization is performed with 0.5 M instead of 5 M NaOH, there are no significant changes in the Raman spectra of solutions. It is shown that the spectra of evaporated samples may be used for the identification of molecular species in corresponding concentrated solutions. However, Raman spectra of dry residues of more diluted solutions differ from spectra of corresponding solutions due to the reactions performed during the process of drying and cannot be used for unambiguous identification of species in solution. Acidification of 0.05 M solution of Na2MoO4 shows that at pH>5.6, molybdate anion MoO(4)(2-) dominates, while in the pH range between 5.6 and 1, heptamolybdate anion Mo7O(24)(6-) is preferentially formed.

Fatal Evolution in the Pneumonia Caused by Diesel Fuel Aspiration - Case Report.

Aspiration pneumonia in infants emerges as a result of deglutition disorders, congenital malformations and severe gastroesophageal reflux. Hydrocarbon pneumonitis is caused by the accidental ingestion and aspiration of hydrocarbons into the body. In children, it can be seen as a result of both the lack of monitoring and the tendency for the exploration of the environment. The accidental ingestion of a large quantity is quite rare due to the bad taste of hydrocarbons. Initially, the central nervous system is the one affected, followed by the respiratory system, causing the chemical pneumonia (through direct injury of the lung). Furthermore, we shall present the case of an 18 month infant with severe trauma as a result of the accidental ingestion of diesel, followed by vomiting and who was brought late to the hospital. The pneumothorax that emerged as a complication was remitted after the treatment, but the initially chemical and then mixed pneumonia through bacterial overinfection led to the infant's death after 12 days of medical attention in the Anesthesia and Intensive Care Unit. The histopathological examination of the analyzed lung fragments did not point out any lipid or foam cells that are characteristic to this type of pathology, but which are not mentioned by the majority of toxicology textbooks and those of pathological anatomy, through the low rate of mortality and numerous factors that can lead to negative false results.

Superior biofunctionality of dental implant fixtures uniformly coated with durable bioglass films by magnetron sputtering.

Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to introduce a reliable technological recipe for coating fairly complex 3D-shaped implants (e.g. dental screws) with uniform and mechanical resistant bioactive glass films by the radio-frequency magnetron sputtering method. The mechanical reliability of the bioactive glass films applied to real Ti dental implant fixtures has been evaluated by a procedure comprised of "cold" implantation in pig mandibular bone from a dead animal, followed by immediate tension-free extraction tests. The effects of the complex mechanical strains occurring during implantation were analysed by scanning electron microscopy coupled with electron dispersive spectroscopy. Extensive biocompatibility assays (MTS, immunofluorescence, Western blot) revealed that the bioactive glass films stimulated strong cellular adhesion and proliferation of human dental pulp stem cells, without promoting their differentiation. The ability of the implant coatings to conserve a healthy stem cell pool is promising to further endorse the fabrication of new osseointegration implant designs with extended lifetime.

Structural and biological evaluation of lignin addition to simple and silver-doped hydroxyapatite thin films synthesized by matrix-assisted pulsed laser evaporation.

We report on thin film deposition by matrix-assisted pulsed laser evaporation of simple hydroxyapatite (HA) or silver (Ag) doped HA combined with the natural biopolymer organosolv lignin (Lig) (Ag:HA-Lig). Solid cryogenic target of aqueous dispersions of Ag:HA-Lig composite and its counterpart without silver (HA-Lig) were prepared for evaporation using a KrF* excimer laser source. The expulsed material was assembled onto TiO2/Ti substrata or silicon wafers and subjected to physical-chemical investigations. Smooth, uniform films adherent to substratum were observed. The chemical analyses confirmed the presence of the HA components, but also evidenced traces of Ag and Lig. Deposited HA was Ca deficient, which is indicative of a film with increased solubility. Recorded X-ray Diffraction patterns were characteristic for amorphous films. Lig presence in thin films was undoubtedly proved by both X-ray Photoelectron and Fourier Transform Infra-Red Spectroscopy analyses. The microbiological evaluation showed that the newly assembled surfaces exhibited an inhibitory activity both on the initial steps of biofilm forming, and on mature bacterial and fungal biofilm development. The intensity of the anti-biofilm activity was positively influenced by the presence of the Lig and/or Ag, in the case of Staphylococcus aureus, Pseudomonas aeruginosa and Candida famata biofilms. The obtained surfaces exhibited a low cytotoxicity toward human mesenchymal stem cells, being therefore promising candidates for fabricating implantable biomaterials with increased biocompatibility and resistance to microbial colonization and further biofilm development.

Covalent immobilisation of VEGF on plasma-coated electrospun scaffolds for tissue engineering applications.

Recent findings in the field of biomaterials and tissue engineering provide evidence that surface immobilised growth factors display enhanced stability and induce prolonged function. Cell response can be regulated by material properties and at the site of interest. To this end, we developed scaffolds with covalently bound vascular endothelial growth factor (VEGF) and evaluated their mitogenic effect on endothelial cells in vitro. Nano- (254±133 nm) or micro-fibrous (4.0±0.4 µm) poly(ɛ-caprolactone) (PCL) non-wovens were produced by electrospinning and coated in a radio frequency (RF) plasma process to induce an oxygen functional hydrocarbon layer. Implemented carboxylic acid groups were converted into amine-reactive esters and covalently coupled to VEGF by forming stable amide bonds (standard EDC/NHS chemistry). Substrates were analysed by X-ray photoelectron spectroscopy (XPS), enzyme-linked immuno-assays (ELISA) and immunohistochemistry (anti-VEGF antibody and VEGF-R2 binding). Depending on the reaction conditions, immobilised VEGF was present at 127±47 ng to 941±199 ng per substrate (6mm diameter; concentrations of 4.5 ng mm(-2) or 33.3 ng mm(-2), respectively). Immunohistochemistry provided evidence for biological integrity of immobilised VEGF. Endothelial cell number of primary endothelial cells or immortalised endothelial cells were significantly enhanced on VEGF-functionalised scaffolds compared to native PCL scaffolds. This indicates a sustained activity of immobilised VEGF over a culture period of nine days. We present a versatile method for the fabrication of growth factor-loaded scaffolds at specific concentrations.

A pharmacokinetic drug interaction study between nebivolol and paroxetine in healthy volunteers.

WHAT IS KNOWN AND OBJECTIVE: Nebivolol is a highly selective beta-blocker with additional vasodilator properties, widely used in the clinical practice for the treatment of hypertension and heart failure. Paroxetine is a second-generation antidepressant and a potent inhibitor of CYP2D6, the same isoenzyme involved in the metabolism of nebivolol. The objective of this study was to investigate the effect of multiple-dose paroxetine intake on the pharmacokinetics of nebivolol in healthy volunteers and its potential consequences upon nebivolol pharmacodynamics. METHODS: The study included 23 healthy subjects and was designed as an open-label, single-centre, non-randomized, two-period clinical trial. During period 1 (reference), each volunteer received a single dose of 5 mg nebivolol, whereas during period 2 (test), each volunteer received a single dose of 5 mg nebivolol and 20 mg paroxetine, after a pretreatment regimen with paroxetine (20-40 mg/day for 6 days). The pharmacokinetic parameters of nebivolol and its active metabolite were analysed by non-compartmental modelling. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest, after each nebivolol intake. RESULTS AND DISCUSSION: Pretreatment with paroxetine increased the mean peak plasma concentrations (Cmax ) for unchanged nebivolol (1·78 ± 1·17 vs. 4·24 ± 1·67 ng/mL) and for its active metabolite (0·58 ± 0·21 vs. 0·79 ± 0·24 ng/mL) compared to nebivolol alone. The time (tmax ) to reach Cmax was 1·37 ± 0·88 (h) and 3·11 ± 1·76 (h) for the parent compound and its active metabolite after nebivolol administered alone and 3·96 ± 1·76 (h), respectively, 7·33 ± 7·84 (h) after pretreatment with paroxetine. Also, the total areas under the curve (AUC0-∞ ) were significantly increased from 17·26 ± 43·06 to 106·20 ± 65·56 h ng/mL for nebivolol unchanged and 13·03 ± 11·29 to 74·56 ± 88·77 h ng/mL for its hydroxylated metabolite, before and after paroxetine intake. All the pharmacokinetic parameters presented statistically significant differences when paroxetine was administered with nebivolol. Nonetheless, statistical analysis did not show a significant difference between the vital signs measured during the two periods. WHAT IS NEW AND CONCLUSION: After pretreatment with paroxetine, the exposure to nebivolol was increased by 6·1-fold for the parent drug and 5·7-fold for the hydroxylated active metabolite. Paroxetine influenced nebivolol pharmacokinetics in healthy volunteers, but it did not have a significant effect on nebivolol pharmacodynamic parameters measured at rest, although the clinical relevance of this drug interaction needs further investigation.

Multi-layer haemocompatible diamond-like carbon coatings obtained by combined radio frequency plasma enhanced chemical vapor deposition and magnetron sputtering.

Radio-frequency Plasma Enhanced Chemical Vapour Deposition (in different methane dilutions) was used to synthesize adherent and haemocompatible diamond-like carbon (DLC) films on medical grade titanium substrates. The improvement of the adherence has been achieved by interposing a functional buffer layer with graded composition TixTiC1-x (x = 0-1) synthesized by magnetron co-sputtering. Bonding strength values of up to ~67 MPa have been measured by pull-out tests. Films with different sp(3)/sp(2) ratio have been obtained by changing the methane concentration in the deposition chamber. Raman spectroscopy, X-ray photoelectron spectroscopy and X-ray diffraction were employed for the physical-chemical characterization of the samples. The highest concentration of sp(3)-C (~87 %), corresponding to a lower DLC surface energy (28.7 mJ/m(2) ), was deposited in a pure methane atmosphere. The biological response of the DLC films was assayed by a state-of-the-art biological analysis method (surface enhanced laser desorption/ionization-time of flight mass spectroscopy), in conjunction with other dedicated testing techniques: Western blot and partial thromboplastin time. The data support a cause-effect relationship between sp(3)-C content, surface energy and coagulation time, as well as between platelet-surface adherence properties and protein adsorption profiles.

[Septic metastases of suppuration of odontogenic origin]. / Metastazele septice ale supuratiilor de origine odontogena.

The infections of odontogenic origin, set in the soft tissues region of the viscerocranium are among the most frequent conditions specific to this anatomical level. A distinct category among these, represented by the conditions with diffuse character, may have serious forms, developing systemic septic metastases. The current paper displays a study approaching seven cases of odontogenic diffuse infections with metastases at distance. The ways in which the septic metastases appeared, as well as the topic and general prescribed treatment have been analyzed. The expanding at distance of the suppuration occurred at those patients who were suffering from cervical necroziting fasciitis associated to some immunodepressing conditions. Out of the 7 patients involved in the study, 4 were suffering from uncompensated diabetes and obesity. All those 7 patients had septic conditions localized in mediastinal region, and in 3 cases hepatic septic affections were observed. The best treatment possible for these conditions proved to be the surgical one associated with that concerned with the sustenance of the general state of health, the rebalancing of the homeostatic constants and the antibacterial one. The post-surgical evolution in case of 5 patients was a good one, in case of 2 patients being unfavourable because of the appearance of the multiorganic insufficiency and of death.