Search

Background: In recent decades, grain amaranths have attracted attention due to their valuable combination of nutritional traits, with higher protein and oil content than conventional cereals. Before they can be proposed as an unconventional ingredient in animal feed, many aspects still need to be investigated from field production to nutritive value. The present research aimed to study the agronomic traits, proximate composition, and digestibility/degradability, fatty acid profile, antioxidant activity, and total phenolic content of two grain amaranth species, Amaranthus cruentus and Amaranthus hypochondriacus (for a total of six accessions), grown in a Mediterranean environment. Results: Both species showed seed yields comparable to or higher than the traditional cereal crops in the same environment. On the whole, A. cruentus resulted in a higher seed production than A. hypochondriacus. Mexico and Montana accessions, both belonging to A. cruentus, showed the highest yield (3.73 t ha-1 , on average). Few differences emerged in nutritive value between species and accessions: the Illinois accession of A. cruentus showed the best performance in terms of in vitro degradability and gas production, but not for volatile fatty acid production; the fermentation kinetics was slowest in the Illinois accession and fastest in the Montana accession of A. cruentus and the India accession of A. hypochondriacus. Conclusion: From a health perspective, the Nebraska accession of A. hypochondriacus represents the best accession, with the lowest saturated fatty acid content and the highest polyunsaturated fatty acid content. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

In a previous article, Rigano et al. established a new linear retention index system for the identification of triacylglycerols by liquid chromatography methods only on the basis of the retention behavior and independently from many experimental parameters. In that work, a database of 209 compounds was built, but only 54 of them, typical of vegetable oils, were confirmed by mass spectrometry. The aim of the present research is to extend the applicability of the novel approach to more complex samples, such as fish lipid extracts, and assess the complementarity between mass spectromtery and retention information to achieve univocal identification. With this purpose, a new software was implemented to make the identification process easy and automatic as in gas chromatography-mass spectrometry where the retention index filter is added in the spectral search to discriminate between compounds with similar mass spectrometry spectra. A total of 69 species were identified and, thanks to their baseline separation obtained by an ultra high performance liquid chromatography method, a semiquantification was also performed. The species under investigation were Dicentrarchus labrax, coming from aquaculture and the wild. Some differences in their native lipid composition were observed, probably related to a different diet. A major number of samples would be necessary to confirm such a preliminary finding.

textabstractIntroduction: Antipsychotic drugs (APDs) are used to treat several mental illnesses. Some APDs have long been known to be associated with QT prolongation, potentially leading to torsades de pointes (TdP) and sudden cardiac death (SCD). In 2005, thioridazine was withdrawn because of the risk of SCD, bringing further attention to the arrhythmogenic potential of APDs. Aim: The aim of the current study was to evaluate the use of APDs in five European countries during the years 1996–2010. Methods: A cohort study was conducted using prescription/dispensing data from seven healthcare databases [the AARHUS University Hospital Database (Denmark), the German Pharmacoepidemiological Research Database (GePaRD) (Germany), Health Search Database/Thales (HSD) and Emilia Romagna Regional Database (ERD) (Italy), PHARMO Database Network and Integrated Primary Care Information (IPCI) (the Netherlands) and The Health Improvement Network (THIN) (the UK), covering a population of 27 million individuals. The annual prescription rate of APDs was measured overall and for individual medications. APDs were classified as torsadogenic according to the Arizona-CERT list. All analyses were stratified by age, gender and calendar year. Results: A total of 559 276 person-years (PYs) of exposure to APDs was captured. The crude annual prescription rate of APD use ranged from 3.0/1000 PYs in ERD to 7.7/1000 PYs in AARHUS. Among APDs with established torsadogenic potential, thioridazine was the most frequently used medication in the UK. Haloperidol was commonly prescribed in Italy and the Netherlands. The use of APDs with torsadogenic potential was much higher in elderly patients. Conclusions: Substantial use of APDs with torsadogenic potential has been reported in Europe in recent years, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of SCD.

The structural/dynamical properties of three truncated octahedral DNA nano-cages composed by identical double helices but single strand linkers with different composition, namely 7 thymidines, 7 adenines, and 7 alternated thymidines and adenines, have been investigated through classical molecular dynamics simulations. Trajectories have been analyzed to investigate the role of the linkers in defining nano-cages stability and flexibility, including possible influence on the internal cages motions. The data indicate that the cages behavior is almost identical and that the structural/dynamical parameters measured along the trajectories are not particularly affected by the presence of different bases. These results demonstrate that the constraints imposed by the nano-structure geometry are the main factor in modulating these properties

Aim In the last decade, new glucose lowering drugs (GLDs) have been launched, and also several warnings regarding their safety. The cardiovascular safety of thiazolidinediones (TZD) has been questioned. We analyzed the prescription pattern of GLDs from 2000 to November 2009 in the United Kingdom (UK) using the THIN database with special focus on the effects of the safety warnings about rosiglitazone issued in May 2007 and January 2008. Methods Annual prevalence and incidence of GLD prescriptions were measured. For TZD, the monthly prevalence and incidence of prescription were calculated from May 2006 to January 2009. The switching pattern around the FDA alert and the characteristics of subjects starting treatment with TZD before and after the alerts were observed. Results The prevalence of prescriptions of GLDs increased during the 10 year period, metformin increasing more than three times. Rosiglitazone prevalence showed an increased trend until May 2007, (2.3/1000 person-years) and decreased thereafter (January 2009: 1.1/1000 person-years). The use of pioglitazone increased surpassing rosiglitazone from April 2008 onwards. The incidence of rosiglitazone use decreased sharply after May 2007 (0.8/1000 person-years). The prevalence of use of other therapies remained rather stable from 2000 to 2007 but increased afterwards. After May 2007, rosiglitazone users were increasingly switched to pioglitazone. There was an increased proportion of new users of pioglitazone with cardiovascular risk after the alerts. Conclusions The prescription of GLDs in the UK has increased in the last decade. For TZDs, it changed after May 2007 as well as the characteristics of the subjects treated with them.

Here, we explored the effects of the novel class II-specific histone deacetylase inhibitors (HDACis) MC1568 and MC1575 on interleukin-8 (IL-8) expression and cell proliferation in cutaneous melanoma cell line GR-M and uveal melanoma cell line OCM-3 upon stimulation with phorbol 12-myristate 13-acetate (PMA). We found that PMA upregulated IL-8 transcription via the AP-1 binding site and identified c-Jun as the transcription factor involved in this eventS. MC1568 and MC1575 inhibited IL-8 levels and cell proliferation in either unstimulated or PMA-stimulated melanoma cells. They acted by suppressing (i) c-Jun binding to the IL-8 promoter, (ii) recruitment of histones 3 and 4, RNA polymerase II and TFIIB to the c-Jun promoter, and (iii) c-Jun expression. Our findings provide new insights into mechanisms underlying anti-tumoral activities of class II-specific HDACis in human melanoma and suggest that they may constitute a novel therapeutic strategy for improving the treatment of this cancer.

AIM Adenosine receptors modulate inflammation in periodontal tissues. No data are available regarding the effects of adenosine A(2A) receptor stimulation in experimental periodontitis (EPD). The aim of this study was to investigate the effects of polynucleotides (also known as polydeoxyribonucleotide, PDRN), a ligand of A(2A) receptor, in EPD in rats. MATERIALS AND METHODS EPD was induced ligating the cervix of the lower left first molar. Sham-EPD had no ligature. After 7 days, EPD animals were randomized to a daily treatment with vehicle gel or 0.75% PDRN gel or PDRN gel with a specific A(2A) antagonist (DMPX). Treatments lasted 7 days. Animals were then euthanized and the periodontium and surrounding gingival tissue were excised for histological evaluation and bio-molecular analysis of inflammatory (p-JNK, p-ERK, TNF-α, IL-6, HMGB-1) and apoptotic proteins (BAX and Bcl-2). RESULTS Vehicle-treated EPD rats showed severe inflammatory infiltrate in both gingival and periodontal ligament, as well as an enhanced expression of p-JNK, p-ERK, TNF-α, IL-6, HMGB-1 and BAX and a reduction in Bcl-2. PDRN gel restored the histological features, blunted inflammatory and apoptotic proteins expression and preserved Bcl-2 expression. DMPX abrogated PDRN positive effects. CONCLUSION Our data suggest that adenosine receptor stimulation by PDRN might represent a new therapeutic strategy for periodontitis.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In the last years there has been a growing trend in anti-epileptic drug (AED) use, particularly in elderly patients, but few data concerning indication of use are available in general practice. • Various AEDs, including newer agents, have been approved for indications other than epilepsy and are increasingly also used for unlicensed indications. • No data about the impact of re-imbursement restrictions on the choice of anti-epileptic drugs in general practice are available. WHAT THIS STUDY ADDS • In general practice, a rapid increase of AED prescriptions in the elderly was observed, principally due to the use of newer AEDs for indications other than epilepsy. • Re-imbursement restrictions influenced newer AED use, particularly pregabalin and gabapentin prescriptions. • Phenobarbital, accounting for more than 50% of total AED volume, was the most prescribed medication during the entire study period. This finding should be considered in light of the potential risks associated with phenobarbital use in the geriatric population. AIMS The aims of the study were to assess the trend of older and newer anti-epileptic drugs (AEDs) in the elderly population and to analyze the effects of a health-policy intervention with regard to AED use in general practice in a setting in Southern Italy. METHODS Data were extracted from the ‘Caserta-1’ Local-Health-Unit Arianna database in the years 2004–07. Patients aged over 65 years, receiving at least one AED prescription and registered in the lists of 88 general practitioners, were selected. The use of older and newer AEDs was calculated as 1 year prevalence and incidence of use and defined daily dose (DDD) per 1000 inhabitants day−1. Sub-analyses by gender, age and indication of use were performed. RESULTS Most of AED users were treated because of neuropathic pain (64.8%). However, the main indication of use for older AEDs (57.8%) was epilepsy, whereas newer AEDs (79.5%) were used for neuropathic pain. Prevalence and incidence of newer AED use increased until 2006, followed by a reduction in 2007. Newer AEDs, particularly gabapentin and pregabalin, were used in the treatment of more patients than older AEDs. However phenobarbital, accounting for more than 50% of total AED volume, was the most prescribed medication during the entire study period. CONCLUSIONS An increasing use of AEDs has been observed during 2004–07, mostly due to the prescription of newer compounds for neuropathic pain. The fall in the use of newer AEDs during 2007 coincides with revised re-imbursement criteria for gabapentin and pregabalin. The large use of phenobarbital in the elderly should be considered in the light of a risk of adverse drug reactions.

SUMMARY Purpose: Brain atrophy (BA) is observed in 20–50% of patients with epilepsy. Hyper-totalhomocysteinemia (hyper-tHcy), which occurs in 10–40% of patients, is considered to be a risk factor for cardiovascular diseases and BA. The present study was aimed at investigating the possible association of hyper-tHcy with BA in a population of patients with epilepsy. Methods: Fifty-eight patients (33 M/25 F, 43.5 ± 13.1 years of age) chronically treated with antiepileptic drugs (AEDs) and 60 controls matched for age and sex were enrolled. All participants underwent determination of plasma tHcy, folate, vitamin B12, and C677T methylene-tetrahydrofolate-reductase (MTHFR) polymorphism genotyping, and brain magnetic resonance imaging (MRI). Results: Patients exhibited significantly higher tHcy and lower folate levels than controls; hypertHcy was significantly associated with the variables group (patients vs. controls), MTHFR genotype, and their interaction terms. BA was observed in 30.1% of patients and was significantly associated with hyper-tHcy (b = 0.45, p = 0.003) and polytherapy (b = 0.31, p < 0.001). Discussion: Our investigation suggests that hypertHcy plays a role in the development of BA in patients with epilepsy. Although the real origin of this phenomenon is not yet fully elucidated, experimental data support the hypothesis of a link of the neuronal Hcy-mediated damage with oxidative stress and excitotoxicity.

Background and purpose: Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-α in an experimental model of periodontitis. Experimental approach: Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg−1, s.c., after placement of the ligature. Key results: Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg−1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-α)) and (4) apoptosis (Bax and Bcl-2 expression). Conclusions and Implications: Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis. British Journal of Pharmacology (2007) 150, 286–297. doi:10.1038/sj.bjp.0706979

Purpose: To investigate the risk of accidents in a cohort of patients with epilepsy and in matched nonepilepsy controls. by type, circumstances, and complications. Methods: A total of 95 1 children and adults with idiopathic, cryptogenic, or remote symptomatic epilepsy and 904 matched controls seen in secondary and tertiary centers in eight European Countries (England. Estonia, Germany, Italy, the Netherlands, Portugal. Russia. and Slovenia) were followed Lip prospectively for 17,484 and 17.206 person-months and asked to report any accident requiring medical attention. its site, and complications. Risk assessment was done by using actuarial methods, relative risks (RRs). and 95% confidence intervals (CIs). Results: During the study period, 199 (21%) patients and 123 (14%) controls reported all accident (p < 0.0001); 24% were seizure related. The Cumulative probability of accidents at 12 and 24 months was 17 and 27% in the cases and 12 and 17% in the controls. The risk was highest for concussions (RR, 2.6; 95% Cl, 1.2-5.8), abrasions (RR, 2.1; 95% Cl, 1.1-4.0), and Wounds (RR, 1.9; Cl, 1.2-3.1). Domestic accidents prevailed in both groups, followed by street and work accidents, and were more common among cases. Compared with controls, patients with epilepsy reported more hospitalization, complications, and medical action. Disease characteristics associated with an increased risk of accidents included generalized epilepsy (conclusions), active epilepsy, and at least monthly seizures (abrasions). Most risks decreased, becoming nonsignificant after excluding, seizure-related events. Conclusions: Patients with epilepsy are at higher risk of accidents and their complications. However, the risk was substantially lower after exclusion of seizure-related events

Summary: Purpose: To assess the risk of illnesses and accidents in patients with epilepsy and to evaluate the proportion of those risks attributable to epilepsy. Methods: Nine hundred fifty-one referral patients with idiopathic, cryptogenic, or remote symptomatic epilepsy and 909 matched controls (relatives or friends) were followed up prospectively for 1–2 years in eight European countries (Italy, Germany, Holland, England, Portugal, Russia, Estonia, and Slovenia). Each patient and control received a diary to keep notes regarding any illness or accident. Patients with epilepsy specifically recorded relations with seizures. Results: Six hundred forty-four patients recorded 2,491 illnesses compared with 1,665 illnesses in 508 controls. The cumulative probability of illness in patients was 49% by 12 months and 86% by 24 months (controls, 39 and 75%; p < 0.0001). One hundred ninety-nine patients and 124 controls had 270 and 140 accidents, respectively. The cumulative probability of accident in the cases was 17 and 27% by 12 and 24 months (controls, 12 and 17%; p < 0.0001). The chance of two or more illnesses or accidents was modestly but significantly greater in the patients. Illnesses and accidents were mostly trivial. Thirty percent of illnesses and 24% of accidents were seizure related. When illnesses and accidents related to seizures were excluded, the chance of illnesses and accidents was fairly similar in the two groups. Conclusions: Patients with idiopathic, cryptogenic, or remote symptomatic epilepsy have a moderately higher risk of illnesses and accidents than do the general population. With few exceptions, the events are trivial. When seizure-related events are excluded, patients with epilepsy are not at any significantly higher risk of illnesses and accidents.

Summary: Purpose: To assess the comparative therapeutic value of valproate (VPA), lamotrigine (LTG), and their combination in patients with complex partial seizures resistant to other established antiepileptic drugs (AEDs). Methods: After a 3-month prospective baseline, 20 adults with refractory complex partial seizures not exposed previously to VPA and LTG were scheduled to receive three consecutive add-on treatments with VPA, LTG, or their combination, according to an open, response-conditional, crossover design. Each period consisted of a 6- to 12-week dose optimization followed by 3-month evaluation at stabilized serum drug levels. Only patients not responding to one phase proceeded to the next. Results: A >50% reduction in seizure frequency was observed in three of 20 patients given VPA and in four of 17 patients given LTG. Of the remaining 13 patients, four became seizure free, and an additional four experienced seizure reductions of 62–78% when VPA and LTG were given in combination. Mild tremor was observed in three patients receiving VPA and in all patients taking the VPA—LTG combination. In patients responding to combination therapy, optimized dosages and peak serum levels of both VPA and LTG were lower than those during separate administration. Conclusions: A considerable proportion of patients who failed to respond to VPA and LTG separately improved when the two drugs were combined, although serum levels of both agents were lower during combination therapy. Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy. The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects.

Summary: The mechanism responsible for the valproate (VPA)-induced elevation of serum carbamazepine-10,11-epoxide (CBZ-E) levels was investigated in 6 normal subjects who received single oral doses of CBZ-E (100 mg) in a control session and during concurrent treatment with sodium VPA [500 mg twice daily (b.i.d.)]. VPA caused a significant prolongation of CBZ-E terminal half-life (t± from 6.3 ± 1.2 to 9.0 ± 2.0 h, mean values ± SD) and decreased CBZ-E clearance (from 90.6 ± 18.8 to 63.2 ± 16.1 ml h -1 kg-1, mean values ± SD) without affecting CBZ-E apparent volume of distribution (from 0.82 ± 0.19 to 0.81 ± 0.241 kg-1, mean values ± SD). These findings indicate that VPA impairs the elimination of CBZ-E, presumably by inhibiting its metabolism. RESUMEN En seis enfermos normales que recibian dosis orales unicas de 100 mg de carbamacepina-10,11-epoxido (CBZ-E), se ha inves-tigado el mechanismo responsable de la elevacion de los niveles sericos de la CBZ-E inducida por el valproate (VPA). Esto se realizo en una sesion control y durante el tratamiento concomi-tante con 500 mg, dos veces diarias de VPA. El VPA causo una prolongation significativa de la vida media terminal del CBZ-E (de 6.3 ± 1.2 a 9.0 ± 2.0, valores medios ± SID), redujo el aclaramiento del CBZ-E (de 90.6 ± 18.8 a 63.2 ± 16.1 ml h“1 kg-1 valores medios ± SD) sin alterar el volumen aparente de distribucion (de 0.82 ± 0.19 a 0.81 ± 0.24lkg1, valores medios ± SD). Estos hallazgos indican que el VPA altera la eliminacion del CBZ-E, probablemente debido a una inhibition de su meta-bolismo. ZUSAMMENFASSUNG Es wurden die Mechanismen untersucht, die fur den Anstieg von Carbamazepin-Epoxid bei Valproatgabe verantwortlich sind. Sechs gesunde Personen erhielten eine Einzeldosis CBZ-E (lOOmg) in der Kontrollphase und eine Kombinationstherapie mit VPA (500mg) in der Untersuchungsphase. VPA verursachte eine signifikante Verlangerung der terminalen CBZ-E Halbwertzeit (von 6.3 ± 1.2 auf 9.0 ± 2.0 Studen), verminderte CBZ-E Clearance (von 90.6 ± 18.9 auf 63.2 ± 16.1 ml/Std./kg), ohne das Verteilungsvolumen zu beeintrachtigen (0.82 ± 0.19 bzw. 0.81 ± 0.24 1/kg). Diese Befunde zeigen, das VPA die Elimination von CBZ-E verschlechtert, moglicherweise durch Inhibition des Ab-baus.

The effect of the valpromide isomer valnoctamide (VCD, 200 mg three times daily for 8 days), an over-the-counter tranquillizer, on the elimination kinetics of a single oral dose of carbamazepine-10, 11-epoxide (CBZ-E, 100 mg) was investigated in healthy subjects. During VCD treatment, the half-life of CBZ-E was prolonged significantly compared with control (19.7 +/- 6.7 h vs 6.9 +/- 2.0 h, means +/- s.d., P less than 0.01), and its oral clearance decreased four-fold (from 109.6 +/- 30.7 to 28.8 +/- 11.1 ml h-1 kg-1, P less than 0.01). These findings indicate that VCM, like valpromide, strongly inhibits epoxide hydrolase in vivo.