Decarbonylation: A metabolic pathway of cannabidiol in humans

Cannabidiol (CBD) is a non‐psychoactive cannabinoid, which is of growing medical interest. Previous studies on the metabolism of CBD showed mainly the formation of hydroxylated or oxidized derivatives, the formation of carboxylic acids or modifications of the aliphatic side chain. Using incubation of CBD with hepatic microsomes of mice, the formation of carbon monoxide was reported. We investigated the phase I metabolism of CBD and cannabidivarin (CBDV) using in vitro experiments with human liver microsomes in order to discover so far not considered metabolites. Identification of metabolites was done by liquid chromatography coupled with quadrupole time of flight mass spectrometry (LC?QToF?MS). Within these experiments, we came across decarbonylation of CBD and CBDV. Further investigations were focused on observed decarbonylated CBD (DCBD). To confirm this metabolite in humans in vivo, plasma samples containing large amounts of cannabinoids as well as serum and urine samples, collected after a voluntary intake of a CBD‐containing food supplement, were analyzed by LC coupled to triple quadrupole mass spectrometry (LC?QQQ?MS). DCBD was detected in in vitro incubation mixtures, serum samples, and urine samples (after alkaline or enzymatic hydrolysis) collected after the voluntary intake, as well as in plasma samples of cannabis users. DCBD appears to be an important supplementary human metabolite that might be helpful for the analytical confirmation of a CBD uptake and might improve the interpretation of the consumption of CBD‐containing products. Results of this study indicate a prolonged detectability of DCBD (in serum) in comparison to CBD after oral CBD ingestion.     

Can ultrasound guidance reduce the risk of pneumothorax following thoracentesis?,

OBJECTIVE:

Thoracentesis is one of the bedside procedures most commonly associated with iatrogenic complications, particularly pneumothorax. Various risk factors for complications associated with thoracentesis have recently been identified, including an inexperienced operator; an inadequate or inexperienced support team; the lack of a standardized protocol; and the lack of ultrasound guidance. We sought to determine whether ultrasound-guided thoracentesis can reduce the risk of pneumothorax and improve outcomes (fewer procedures without fluid removal and greater volumes of fluid removed during the procedures). In our comparison of thoracentesis with and without ultrasound guidance, all procedures were performed by a team of expert pulmonologists, using the same standardized protocol in both conditions.

METHODS:

A total of 160 participants were randomly allocated to undergo thoracentesis with or without ultrasound guidance (n = 80 per group). The primary outcome was pneumothorax following thoracentesis. Secondary outcomes included the number of procedures without fluid removal and the volume of fluid drained during the procedure.

RESULTS:

Pneumothorax occurred in 1 of the 80 patients who underwent ultrasound-guided thoracentesis and in 10 of the 80 patients who underwent thoracentesis without ultrasound guidance, the difference being statistically significant (p = 0.009). Fluid was removed in 79 of the 80 procedures performed with ultrasound guidance and in 72 of the 80 procedures performed without it. The mean volume of fluid drained was larger during the former than during the latter (960 ± 500 mL vs. 770 ± 480 mL), the difference being statistically significant (p = 0.03).

CONCLUSIONS:

Ultrasound guidance increases the yield of thoracentesis and reduces the risk of post-procedure pneumothorax. (Chinese Clinical Trial Registry identifier: ChiCTR-TRC-12002174 [http://www.chictr.org/en/])     

The effect of current used bone substitution materials and platelet-rich plasma on periosteal cells by ectopic site implantation: An in-vivo pilot study

The aim of this study was to investigate de novo bone formation following ectopic site implantation of bone substitutes covered by periosteum, with and without the application of autologous platelet-rich plasma (PRP). Twenty-four weeks after subcutaneous implantation of various bone substitutes (bovine hydroxyapatite (bHAP), phycogenic hydroxyapatite (pHAP), and bioglass (BG)) in 35 mini-pigs, bone regeneration rates were compared microradiographically and histologically. Without PRP, bHAP showed a mean de novo bone formation of 32.41% ± 29.99, in contrast to the other substitute materials where no mineralization could be detected. In combination with PRP, in the bHAP (63.61% ± 12.98; p ± 0.03) and pHAP (34.37 ± 29.38; p = 0.015) group, significantly higher de novo bone formation was ascertained than without PRP. No ossification could be detected in the BG group. In conclusion, bHAP and pHAP bone substitutes in combination with PRP showed a significant positive effect on periosteal cells by de novo bone formation after ectopic, subcutaneous, low-vascular site implantation.     

Self-rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study

Abstract. Grool AM, van der Graaf Y, Visseren FLJ, de Borst GJ, Algra A, Geerlings MI, on behalf of the SMART Study Group (University Medical Center Utrecht, Utrecht, The Netherlands). Self‐rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study. J Intern Med 2012; 272: 277–286. Objectives. Lower self‐rated health status has been associated with worse prognosis in patients with coronary artery disease (CAD). We investigated the influence of self‐rated physical and mental health status on the risk of future vascular events and mortality for various locations of symptomatic atherosclerotic disease and asymptomatic disease. Design. Patients with CAD (n = 2547), cerebrovascular disease (n = 1061), peripheral arterial disease (PAD; n = 648), abdominal aortic aneurysm (AAA; n = 272) and asymptomatic atherosclerotic disease (n = 1933) were followed for a median of 4 years for the occurrence of a new vascular event or death. Self‐rated health status was assessed with the Short Form‐36 physical and mental component summary scales. Cox regression models were used to estimate associations between health status and vascular events and death, adjusted for age, sex, vascular risk factors and intima–media thickness. Results. In the total population, lower self‐rated physical health status (per 10‐point decrease) increased the risk of vascular events [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.24–1.52], and all‐cause (HR = 1.45, 95% CI 1.29–1.63) and vascular mortality (HR = 1.40, 95% CI 1.20–1.64). A 10‐point decrease in mental health status was associated with a modest increase in the risk of vascular events (HR = 1.19, 95% CI 1.08–1.32), and all‐cause (HR = 1.19, 95% CI 1.05–1.34) and vascular mortality (HR = 1.28, 95% CI 1.09–1.49). Risk estimates of physical and mental health status were highest in patients with asymptomatic atherosclerotic disease and lowest in those with PAD. Conclusions. Poorer self‐rated physical and mental health status increases the risk of vascular events and mortality in a broad population of patients with symptomatic and asymptomatic atherosclerotic disease.     

The role of facemasks and hand hygiene in the prevention of influenza transmission in households: results from a cluster randomised trial; Berlin, Germany, 2009-2011

Background

Previous controlled studies on the effect of non-pharmaceutical interventions (NPI) - namely the use of facemasks and intensified hand hygiene - in preventing household transmission of influenza have not produced definitive results. We aimed to investigate efficacy, acceptability, and tolerability of NPI in households with influenza index patients.

Methods

We conducted a cluster randomized controlled trial during the pandemic season 2009/10 and the ensuing influenza season 2010/11. We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days. Study arms were wearing a facemask and practicing intensified hand hygiene (MH group), wearing facemasks only (M group) and none of the two (control group). Main outcome measure was laboratory confirmed influenza infection in a household contact. We used daily questionnaires to examine adherence and tolerability of the interventions.

Results

We recruited 84 households (30 control, 26 M and 28 MH households) with 82, 69 and 67 household contacts, respectively. In 2009/10 all 41 index cases had a influenza A (H1N1) pdm09 infection, in 2010/11 24 had an A (H1N1) pdm09 and 20 had a B infection. The total secondary attack rate was 16% (35/218). In intention-to-treat analysis there was no statistically significant effect of the M and MH interventions on secondary infections. When analysing only households where intervention was implemented within 36 h after symptom onset of the index case, secondary infection in the pooled M and MH groups was significantly lower compared to the control group (adjusted odds ratio 0.16, 95% CI, 0.03-0.92). In a per-protocol analysis odds ratios were significantly reduced among participants of the M group (adjusted odds ratio, 0.30, 95% CI, 0.10-0.94). With the exception of MH index cases in 2010/11 adherence was good for adults and children, contacts and index cases.

Conclusions

Results suggest that household transmission of influenza can be reduced by the use of NPI, such as facemasks and intensified hand hygiene, when implemented early and used diligently. Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation.

Trial registration

The study was registered with ClinicalTrials.gov (Identifier NCT00833885).