Detection of metabolites of the new synthetic cannabinoid CUMYL‐4CN‐BINACA in authentic urine samples and human liver microsomes using high‐resolution mass spectrometry

CUMYL‐4CN‐BINACA(1‐(4‐cyanobutyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H–indazole‐3‐carboxamide) is a recently introduced indazole‐3‐carboxamide‐type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine, Istanbul Narcotics Department, in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL‐4CN‐BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n = 80). In this study, 5 μM CUMYL‐4CN‐BINACA was incubated with human liver microsomes (HLMs) for up to 3 hours, and metabolites were identified using liquid chromatography–high‐resolution mass spectrometry (LC–HRMS). Less than 21% of the CUMYL‐4CN‐BINACA parent compound remained after 3 hours of incubation. We identified 18 metabolites that were formed via monohydroxylation, dealkylation, oxidative decyanation to aldehyde, alcohol, and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL‐4CN‐BINACA was not detected; CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was major metabolite after β‐glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL‐4CN‐BINACA N‐butanoic acid), M8 and M11 (hydroxylcumyl CUMYL‐4CN‐BINACA) as urinary marker metabolites to confirm CUMYL‐4CN‐BINACA intake.     

Evaluation of parafoveal vascular density using optical coherence tomography angiography in patients with central serous chorioretinopathy

Lasers in Medical Science - Using optical coherence tomography angiography (OCTA), we sought to evaluate parafoveal vascular density (VD) in patients with central serous chorioretinopathy (CSCR)....     

Predicting intraoperative feasibility of combined TES-mMEP and cSSEP monitoring during scoliosis surgery based on preoperative neurophysiological assessment

Background contextCombined monitoring of muscle motor evoked potentials elicited by transcranial electric stimulation (TES-mMEP) and cortical somatosensory evoked potentials (cSSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, TES-mMEP/cSSEP is not always feasible. Predictors of feasibility would help to plan the monitoring strategy.PurposeTo identify predictors of the feasibility of TES-mMEP/cSSEP during scoliosis surgery.Study design/settingProspective cohort study in a clinical neurophysiology unit and pediatric orthopedic department of a French university hospital.Patient sampleA total of 103 children aged 2 to 19 years scheduled for scoliosis surgery.Outcome measuresFeasibility rate of intraoperative TES-mMEP/cSSEP monitoring.MethodsAll patients underwent a preoperative neurological evaluation and preoperative mMEP and cSSEP recordings at both legs. For each factor associated with feasibility, we computed sensitivity, specificity, positive predictive value (PPV), and negative predictive value. A decision tree was designed.ResultsPresence of any of the following factors was associated with 100% feasibility, 100% specificity, and 100% PPV: idiopathic scoliosis, normal preoperative neurological findings, and normal preoperative mMEP and cSSEP recordings. Feasibility was 0% in the eight patients with no recordable mMEPs or cSSEPs during preoperative testing. A decision tree involving three screening steps can be used to identify patients in whom intraoperative TES-mMEP/cSSEP is feasible.ConclusionsPreoperative neurological and neurophysiological assessments are helpful for identifying patients who can be successfully monitored by TES-mMEP/cSSEP during scoliosis surgery.     

Efficient in situ N-heterocyclic carbene palladium(ii) generated from Pd(OAc)2 catalysts for carbonylative Suzuki coupling reactions of arylboronic acids with 2-bromopyridine under inert conditions leading to unsymmetrical arylpyridine ketones: synthesis,characterization and cytotoxic activities

N,N-Substituted benzimidazole salts were successfully synthesized and characterized by ¹H-NMR, ¹³C {¹H} NMR and IR techniques, which support the proposed structures. Catalysts generated in situ were efficiently used for the carbonylative cross-coupling reaction of 2 bromopyridine with various boronic acids. The reaction was carried out in THF at 110 °C in the presence of K₂CO₃ under inert conditions and yields unsymmetrical arylpyridine ketones. All N,N-substituted benzimidazole salts 2a–i and 4a–i studied in this work were screened for their cytotoxic activities against human cancer cell lines such us MDA-MB-231, MCF-7 and T47D. The N,N-substituted benzimidazoles 2e and 2f exhibited the most cytotoxic effect with promising cytotoxic activity with IC₅₀ values of 4.45 μg mL⁻¹ against MDA-MB-231 and 4.85 μg mL⁻¹ against MCF7 respectively.

The in situ prepared four component system Pd(OAc)₂, 1,3-dialkylbenzimidazolium halides 2a–i and 4a–i, K₂CO₃ under CO atmosphere catalyses carbonylative cross-coupling reaction of 2-bromopyridine with various boronic acids to yield unsymmetrical arylpyridine ketones.     

Single coronary artery with anomalous origin of the right coronary artery from the left anterior descending artery with a unique proximal course

A 62-year-old man with hypertension and hypercholesterolemia was referred to our unit for evaluation of chest pain. A very rare variant of single coronary artery, in which the anomalous right coronary artery originated as a separate branch from the left anterior descending artery, was incidentally found on his coronary angiography. The anomalous right coronary artery in our case appears to be unique in that it courses intraseptally rather than rightwards proximally and has obstructive atherosclerotic lesions resulting in inferior ischemia. Moreover, the acute angle made by the anomalous right coronary artery to turn toward the atrioventricular groove may have reduced the flow velocity and contributed to the development of inferior ischemia.     

Serum positive cagA in patients with non-ulcer dyspepsia and peptic ulcer disease from two centers in different regions of Turkey

AIM: To investigate and compare frequencies of serum positive cagA in patients from two separate regions of Turkey who were grouped according to the presence of peptic ulcer disease or non-ulcer dyspepsia. METHODS: One hundred and eighty Helicobacter pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia were included in the study. One hundred and fourteen patients had non-ulcer dyspepsia and 66 had peptic ulcer disease (32 with gastric ulcers and/or erosions and 34 with duodenal ulcers). Each patient was tested for serum antibody to H. pylori cagA protein by enzyme immunoassay. RESULTS: The total frequency of serum positive cagA in the study group was 97.2 %. The rates in the patients with peptic ulcers and in those with non-ulcer dyspepsia were 100 % and 95.6 %, respectively. These results were similar to those reported in Asian studies, but higher than those that have been noted in other studies from Turkey and Western countries. CONCLUSION: The high rates of serum positive cagA in these patients with peptic ulcer disease and non-ulcer dyspepsia were similar to results reported in Asia. The fact that there was high seroum prevalence regardless of ulcer status suggests that factors other than cagA might be responsible for ulceration or other types of severe pathology in H. pylori-positive individuals.     

Taurine attenuates lung ischemia–reperfusion injury after lung transplantation in rats

Purpose

Taurine, the major intracellular free amino acid found in high concentrations in mammalian cells, is known to be an endogenous antioxidant and a membrane-stabilizing agent. It was hypothesized that taurine may be effective in reducing ischemia–reperfusion injury after lung transplantation and an experimental study was conducted in a rat model.

Methods

The number of Sprague–Dawley rats used in the study was 35. Animals were randomized into five groups of 7 rats each, including control, donor I, donor II, ischemia–reperfusion injury, and treatment groups. All animals were exposed to the same experimental conditions in the preoperative period. Rats were fixed in a supine position after the induction. After the rats were shaved, a left pneumonectomy was performed following sternotomy in control, donor I, and donor II groups. The harvested grafts in donor I and donor II groups were transplanted to the rats of the ischemia–reperfusion group and treatment group, respectively. However, taurine was administered intraperitoneally for 3 days before the harvesting procedure in donor II. All harvested lungs were kept in a Euro-Collins solution at +4 °C for 24 h in a half-inflated manner. After harvesting and transplantation, lungs were sampled for histopathological and biochemical analysis.

Results

Malondialdehyde and superoxide dismutase, glutathione peroxidase, and catalase levels were lower in the treatment group than the other groups (p < 0.05). Histopathological findings were better in treatment group than the ischemia–reperfusion group (p < 0.05).

Conclusion

It was demonstrated that donor treatment with taurine resulted in preservation of transplanted lung tissue in respect to histopathological and biochemical findings.