Peak or sustained antibiotic serum levels for optimal tissue penetration

A comparative study of the levels of netilmicin in bronchial secretions after intermittent and during continuous intravenous injections was performed. During the first 2 h, the areas under the drug concentration curves in the bolus injection experiment were greater in serum and in bronchial secretions (206 and 150% respectively) than those associated with the continuous infusion (P<0.001); however, during the 8 h experimental period, the areas under the curves were similar in serum and bronchial secretions with the two modes of administration. The percentages of penetration of netilmicin from the blood to the bronchial lumen were also similar with the two modes of administration (19%). After intramuscular administration of amikacin (7.5 and 12.5 mg/kg twice daily), the peak bronchial secretion levels of the drug were 4.4 and 10.1 mg/l respectively and the trough levels about 1 mg/l. During continuous iv injection of amikacin (7-12 mg/kg/8 h), the drug level in the bronchial secretions was only 2.0 mg/l and the percentage of penetration was 14.9% adequate anti-Pseudomonas activity in bronchial secretions was rarely achieved. It is therefore suggested that intermittent injections of aminoglycosides can result in at least transitory higher bronchial secretion levels than continuous injection: the intermittent schedule of antibiotic administration could therefore be recommended in the treatment of bronchopulmonary infections since it has been suggested that the concentration of antibiotic in bronchial secretions could be important in the outcome of these infection

Chemical Range of Stability for Self-Dusting Ladle Furnace Slags and Destabilizing Effect of Sulfur

Ladle furnace slags are characterized by volumetric expansions associated with the transition of dicalcium silicate (C2S) from β to γ phase, which generates fine dust during cooling, causing handling and storage issues that further reduce their recycling opportunities. The present work focuses on the effect of slag basicity on dusting and the role of sulfur on slag stability. Seven synthetic ladle slag precursors were made by mixing lime, magnesia, quartz and alumina in different proportions to match effective industrial compositions, increasing the binary basicity and keeping the ternary and quaternary indexes unchanged. Samples were heated to 1500&nbsp;°C for 15&nbsp;min and monitored during air cooling (&lt; 5&nbsp;°C/s) through thermocouples and camera to characterize the behavior, temperature, and time interval of dusting. The cooled samples were characterized chemically, mineralogically and morphologically. Starting from the chemistry of a self-stabilized slag, five additional slag precursors, characterized by increasing amounts of S, were created and analyzed using the same procedures. Experimental evidence showed the presence of three different dusting behaviors (stable, partial and complete) and stabilization of the slag once an optical basicity of 0.748 or higher was reached. In addition, mayenite was identified as the main phase capable of suppressing the β to γ transition by exerting hydrostatic pressure on C2S. Finally, although S can stabilize the β phase when dissolved in it, after saturation it precipitates as CaS, which can react with mayenite, locally decreasing the optical basicity and allowing dusting. Graphical Abstract: [Figure not available: see fulltext.]

Individual dosage of digoxin in patients with heart failure

Backgroud: After the publication of DIG trial, the therapeutic target of serum digoxin concentration (SDC) for the treatment of heart failure (HF) has been lowered (0.40-1.00 ng/ml). However, the majority of equations to calculate digoxin dosages were developed for higher SDCs. Recently, a new equation was validated in Asian population for low SDCs by Konishi et al., but results in Caucasians are unknown. Aim: This study was aimed to test the Konishi equation in Caucasians specifically targeting low SDCs. Furthermore, the Konishi equation was compared with other frequently used equations. Design: This was a prospective, multicenter study. Methods: Clinically indicated digoxin was given in 40 HF patients. The dosage was calculated with the Konishi equation. The SDC was measured at 1 and 6 months after starting digoxin. Adherence to digoxin was monitored with a specific questionnaire. Results: After exclusion of patients admitting poor adherence, we found a reasonable correlation between predicted and measured SDC (r = 0.48; P < 0.01) by the Konishi equation. Excluding patients with poor adherence and relevant worsening of renal function, the measured SDC (n = 54 measurements) was within the pre-defined therapeutic range in 95% of the cases. The mean, maximal and minimal measured SDC were 0.69 ± 0.19, 1.00 and 0.32 ng/ml, respectively. The correlation was weaker for the Jelliffe, the Koup and Jusko, and the Bauman equations. Conclusions: This study supports the clinical validity of the Konishi equation for calculating individual digoxin dosage in Caucasians, targeting SDCs according to current HF guideline

Phytochemical profile and biological activities of crude and purified Leonurus cardiaca extracts

Leonurus cardiaca L. (Lamiaceae) is a perennial herb distributed in Asia and Southeastern Europe and has been used in traditional medicine since antiquity for its role against cardiac and gynecological disorders. The polar extracts obtained from L. cardiaca aerial parts contain several compounds among which alkaloids, iridoids, labdane diterpenes, and phenylethanoid glycosides play a major role in conferring protection against the aforementioned diseases. On the other hand, the antioxidant activities and the enzyme inhibitory properties of these extracts have not yet been deeply studied. On the above, in the present study, crude and purified extracts were prepared from the aerial parts of L. cardiaca and have been chemically characterized by spectrophotometric assays and HPLC-DAD-MS analyses. Notably, the content of twelve secondary metabolites, namely phenolic acids (chlorogenic, caffeic, caffeoylmalic and trans-ferulic acids), flavonoids (rutin and quercetin), phenylethanoid glycosides (verbascoside and lavandulifolioside), guanidine pseudoalkaloids (leonurine), iridoids (harpagide), diterpenes (forskolin), and triterpenes (ursolic acid), has been determined. Furthermore, the extracts were tested for their antioxidant capabilities (phosphomolybdenum, DPPH, ABTS, FRAP, CUPRAC, and ferrous chelating assays) and enzyme inhibitory properties against cholinesterase, tyrosinase, amylase, and glucosidase. The purified extracts contained higher phytochemical content than the crude ones, with caffeoylmalic acid and verbascoside as the most abundant compounds. A linear correlation between total phenolics, radical scavenging activity, and reducing power of extracts has been found. Notably, quercetin, caffeic acid, lavandulifolioside, verbascoside, chlorogenic acid, rutin, and ursolic acid influenced the main variations in the bioactivities found in L. cardiaca extracts. Our findings provide further insights into the chemico-biological traits of L. cardiaca and a scientific basis for the development of nutraceuticals and food supplements

Thermodynamics of a mixed quantum-classical Heisenberg model in two dimensions

We study the planar antiferromagnetic Heisenberg model on a decorated hexagonal lattice, involving both classical spins (occupying the vertices) and quantum spins (occupying the middle of the links). This study is motivated by the description of a recently synthesized molecular magnetic compound. First, we trace out the spin 1/2 degrees of freedom to obtain a fully classical model with an effective ferromagnetic interaction. Then, using high temperature expansions and Monte Carlo simulations, we analyse its thermal and magnetic properties. We show that it provides a good quantitative description of the magnetic susceptibility of the molecular magnet in its paramagnetic phase.Comment: Revtex, 6 pages, 4 included postscript figures, fig.1 upon request to [email protected] . To appear in J. of Physic C (condensed matter

Assessing Sleep Habits in Italian Community-Dwelling Adolescents: Psychometric Properties of the School Sleep Habits Survey Scales

Background. In the field of adolescent sleep research, different sleep surveys have been implemented; however, psychometric properties of these instruments have been investigated only minimally. Methods. In order to assess the psychometric properties of the Sleep-Wake Problems Behaviour Scale (SWP), the Sleepiness Scale (SLS), and the Morningness/Eveningness Questionnaire (ME), a moderately large sample of community-dwelling Italian adolescents (N = 778; 59.8% female; mean age = 15.77 years) was administered the Italian translation of the School Sleep Habits Survey. Results. Internal consistency estimates values were satisfactory for all measures; dimensionality analyses suggested a unidimensional structure for SWP, SLS and ME, respectively. Goodness-of-fit statistics for the one-factor model of the SLS, SWP, and ME scale items were adequate for all measures. Non -redundant taxometric analysis results consistently suggested a dimensional latent structure for the SLS, SWP, and ME, respectively. Conclusion. Our findings supported the use of the SLS, SWP, and ME total scores as measures of sleepiness, sleep-wake problem, and morningness/eveningness, at least among Italian community -dwelling adolescents, and encourage practitioners to rely on the conventional percentiles in order to interpret the SLS, SWP, and ME total scores

Antioxidant and enzyme inhibitory properties of the polyphenolic-rich extract from an ancient apple variety of central Italy (Mela Rosa dei Monti Sibillini)

This study was undertaken to evaluate the nutraceutical potential of the Mela Rosa dei Monti Sibillini (MR), an ancient apple variety of the Sibillini Mountains, central Italy. The chemical profile of the apple''s polyphenolic-rich extract (MRE) obtained from first-and second-choice samples using the Amberlite® XAD7HP resin was analyzed by High Performance Liquid Chromatography with Diode-Array and Mass spectrometry (HPLC-DAD-MS) and 21 phytochemicals were quali–quantitatively determined. For comparative purposes, the polyphenol-rich extract of Annurca (ANE), a southern Italian variety, was analyzed. The antioxidant capacity of MREs was evaluated by Folin–Ciocalteu, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. The inhibitory capacity of MREs for the enzymes a-glucosidase, lipase, monoamine oxidase A, tyrosinase, and acetylcholinesterase was also determined. The MREs showed higher polyphenolic and triterpene profiles than the ANE. Their radical scavenging activity was higher than that of ANE and comparable to the reference trolox. The MRE from the second-choice apples displayed higher contents of the 21 phytochemicals investigated. Either MRE from second-choice or first-choice samples showed enzymatic inhibition with IC50 values higher than those of reference inhibitors but worthy of nutraceutical consideration. Taken together, these results show the potential of MRE as a source of bioactive compounds to be used for pharmaceutical, nutraceutical, and cosmeceutical applications has been confirmed

Artificial neural networks improve the prediction of Kt/V, follow-up dietary protein intake and hypotension risk in haemodialysis patients

BACKGROUND: Artificial neural networks (ANN) represent a promising alternative to classical statistical and mathematical methods to solve multidimensional non-linear problems. The aim of the study was to compare the performance of ANN in predicting the dialysis quality (Kt/V), the follow-up dietary protein intake and the risk of intradialytic hypotension in haemodialysis patients with that predicted by experienced nephrologists. METHODS: A combined retrospective and prospective observational study was performed in two Swiss dialysis units (80 chronic haemodialysis patients, 480 monthly clinical observations and biochemical test results). Using mathematical models based on linear and logistic regressions as background, ANN were built and then prospectively compared with the ability of six experienced nephrologists to predict the Kt/V and the follow-up protein catabolic rate (PCR) and to detect a Kt/V &lt; 1.30, a follow-up PCR &lt; 1.00 g/kg/day and the occurrence of hypotension. RESULTS: ANN compared with nephrologists gave a more accurate correlation between estimated and calculated Kt/V and follow-up PCR (P&lt;0.001). The same superiority of ANN was also seen in the ability to detect a Kt/V &lt; 1.30, a follow-up PCR &lt; 1.00 g/kg/day and the occurrence of hypotension expressed as a percentage of correct answers, sensitivity, specificity and predictivity. CONCLUSIONS: The use of ANN significantly improves the ability of experienced nephrologists to estimate the Kt/V and the follow-up PCR and to detect a Kt/V &lt; 1.30, a follow-up PCR &lt; 1.00 g/kg/day and the occurrence of intradialytic hypotension

Neuropsychological changes in isolated REM sleep behavior disorder: A systematic review and meta-analysis of cross-sectional and longitudinal studies

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = –0.69), memory (RE model = –0.64), and executive function (RE model = –0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD