Cannabidiol - therapeutic and legal aspects.

Cannabidiol (CBD) is an alkaloid present in Cannabis sativa, along with tetrahydrocannabinol (THC) and more than 100 other substances belonging to a group of compounds called cannabinoids. Whereas the legal status and medical use of Cannabis is a controversial issue in many countries, inconsistent legislation makes CBD status even more complicated. Some CBD products are legal in some countries, while banned in other countries, further compounding the confusion. In 2018, the Food and Drug Administration (FDA) approved the first CBD containing medical product, Epidiolex®, for the treatment of paediatric seizures. Currently, several clinical trials are in progress for the potential treatment of neurologic and behavioural disorders. CBD's current legal and regulatory status is a continuously evolving issue; the current review is presenting historical and present information regarding the use of CBD products worldwide.

Assessment of platelet respiration as emerging biomarker of disease.

Mitochondrial dysfunction is currently acknowledged as a central pathomechanism of most common diseases of the 21(st) century. Recently, the assessment of the bioenergetic profile of human peripheral blood cells has emerged as a novel research field with potential applications in the development of disease biomarkers. In particular, platelets have been successfully used for the ex vivo analysis of mitochondrial respiratory function in several acute and chronic pathologies. An increasing number of studies support the idea that evaluation of the bioenergetic function in circulating platelets may represent the peripheral signature of mitochondrial dysfunction in metabolically active tissues (brain, heart, liver, skeletal muscle). Accordingly, impairment of mitochondrial respiration in peripheral platelets might have potential clinical applicability as a diagnostic and prognostic tool as well as a biomarker in treatment monitoring. The aim of this minireview is to summarize current information in the field of platelet mitochondrial dysfunction in both acute and chronic diseases.

Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts.

Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD) and diabetes mellitus (DM). Recently, mitochondrial monoamine oxidases (MAOs) have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs-related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1) Control (CTRL), valvular patients without CHD; (2) CHD, patients with confirmed CHD; and (3) CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2) emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM.

Genotype-phenotype correlation in multiresistant Escherichia coli and Klebsiella pneumoniae strains isolated in Western Romania.

OBJECTIVE: Bacterial multidrug-resistance (MDR) to antimicrobials has become an important public health issue all over the world and it involves both hospital and community-acquired strains. MATERIALS AND METHODS: A number of 75 Escherichia coli and 77 Klebsiella pneumoniae (K.) strains identified in biological samples collected from community (CA) and hospital-acquired (HA) infections were found to be resistant to the third generation cephalosporins. Of these, 93 MDR strains were subjected to microarray analysis to detect the expression of 31 antimicrobial resistance genes. RESULTS: We found that all HA extended-spectrum ß-lactamase (ESBL) producing E. coli strains had at least one resistance gene to third generation cephalosporins, while in 54% of all CA strains genetic substrates justifying their antibiotic resistance were identified. Almost 81% of HA-ESBL (Extended-Spectrum ß Lactamase) K. pneumoniae strains had at least one resistance gene to third generation cephalosporins, while in only 6% of the CA strains a similar genotype was identified. In the HA group, the blaCTX-M-15 genotype proved to be most frequent in multidrug-resistant E. coli strains and second most frequent (after ampC) in K. pneumoniae, while in the CA group, this genotype was the fourth most frequent in ESBL E. coli (after ampC, sul1, tet(R)). CONCLUSIONS: Overall, in 67% of all ESBL producing Enterobacteriaceae strains a genetic substrate justifying the resistance to beta-lactam antibiotics was identified; most of the remaining 33.33% strains were CA with a predominance of K. pneumoniae, in which a different antibiotic resistance genetic substrate (outside the detection limit of the kit used in this study) might have been involved.

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.

Pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers.

WHAT IS KNOWN AND OBJECTIVE: Ivabradine is a novel heart rate-lowering agent that selectively and specifically inhibits the depolarizing cardiac pacemaker If current in the sinus node. Our objective was to evaluate a possible pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers. METHODS: The study consisted of two periods: Period 1 (Reference), when each volunteer received a single dose of 10 mg ivabradine and Period 2 (Test), when each volunteer received a single dose of 10 mg ivabradine and 400 mg carbamazepine. Between the two periods, the subjects were treated for 15 days with a single daily dose of 400 mg carbamazepine. Plasma concentrations of ivabradine were determined during a 12-h period following drug administration, using a high-throughput liquid chromatography with mass spectrometry analytical method. Pharmacokinetic parameters of ivabradine administered in each treatment period were calculated using non-compartmental and compartmental analysis to determine if there were statistically significant differences. RESULTS AND DISCUSSION: In the two periods of treatments, the mean peak plasma concentrations (C(max)) were 16·25 ng/mL (ivabradine alone) and 3·69 ng/mL (ivabradine after pretreatment with carbamazepine). The time taken to reach C(max), t(max), were 0·97 and 1·14 h, respectively, and the total areas under the curve (AUC(0-∞)) were 52·49 and 10·33 ng h/mL, respectively. These differences were statistically significant for C(max) and AUC(0-∞) when ivabradine was administered with carbamazepine, whereas they were not for t(max), half-life and mean residence time. WHAT IS NEW AND CONCLUSION: T Carbamazepine interacts with ivabradine in healthy volunteers, and lowers its bioavailability by about 80%. This magnitude of effect is likely to be clinically significant.

Identification and quantification of phenolic compounds from Balanites aegyptiaca (L) Del (Balanitaceae) galls and leaves by HPLC-MS.

Balanites aegyptiaca is a tropical plant which is widely used for medicinal purposes in several African countries, including Burkina Faso. Despite its widespread use, little is known about its phenolic content. This study sought to carry out a screening of the polyphenols from the leaves and galls of B. aegyptiaca. A high-performance liquid chromatography-mass spectrometry method was used to investigate the phenolic content in the parts of the plant studied here. The phenolic acid profile showed the presence of gentisic, p-coumaric, caffeic, ferulic and sinapic acids in the crude and hydrolysed extracts. The flavonoids pattern showed hyperoside, isoquercitrin, rutoside and quercitrin in the crude extract of leaves. Myricetol, quercetol and kaempferol were found after acid hydrolysis of the leaves extract. Ferulic acid, isoquercitrin, rutoside and quercitrin were identified as major phenolic compounds in this study.

[Test for determination of attention in patients with sleep apnea syndrome]. / Test pentru determinarea atentiei la pacientii cu sindrom de apnee în somn.

To investigate the daytime sleepiness in patients with sleep apnea syndrome, we used a test for measurement of sustained attention. The present study was performed on 65 participants: 10 healthy non-snoring volunteers, 25 snoring volunteers and 30 patients with symptoms of sleep apnea. The error rate (percentage of incorrect responses) appears to be most suitable for the evaluation of the test. The difference between the habitual snorers and the healthy non-snoring volunteers was statistically significant. At the apneic patients, there are significant differences in age, sex, and body mass index; attention decreases significantly in the last 10 minutes of the test. The attention test can be helpful for the measurement of daytime sleepiness in apneic patients.