Different localizations of drugs simultaneously administered in a strand of hair by micro‐segmental analysis

Segmental hair analysis is used to estimate the time of drug intake at monthly precision in drug‐related crimes. Previously, we advanced this analytical method to specify the day of drug intake by cutting a strand of hair into 0.4‐mm segments, which correspond to daily hair growth. Herein, we investigated the distributions of 7 compounds in a strand of hair using micro‐segmental analysis. Several strands of hair were collected 33.1?229.4 days after subjects were administered 4 pharmaceutical products that contained 10 drugs in single doses within 32 hours. The administered drugs and resulting metabolites were extracted from 0.4‐mm hair segments and quantified using liquid chromatography–tandem mass spectrometry. Acidic and neutral compounds were detected at low amounts in any of the hair segments analyzed. Epinastine, fexofenadine, dihydrocodeine, chlorpheniramine, and the chlorpheniramine metabolite, desmethylchlorpheniramine each was localized to 2 regions within a strand of hair. By contrast, methylephedrine and its metabolite, ephedrine, each was localized to only a region. Among 20 individual strands of hair associated with different subjects and head regions, few differences in the shapes of drug concentration–hair segment curves for each compound were detected. Our data indicated that 2 mechanisms for drug uptake into hair can operate depending on drug properties and that co‐administered drugs can be localized to different regions in a strand of hair. Micro‐segmental analysis may aid in the identification of the day of drug intake and help to elucidate the mechanisms of drug uptake into hair.     

Influence of tempering method on residual stress in dental porcelain.

The porcelain component of a porcelain-fused-to-metal restoration is strengthened by residual (tempering) stresses which are induced by cooling procedures followed in dental laboratories. The thermophysical properties of materials and cooling rate are the main factors which determine the residual stress. In this paper, the temperatures in the midplane of body-porcelain disks were measured from a heat-soak temperature (1000 degrees C) to room temperature during two different cooling procedures: slow cooling in air and forced-air cooling. Experimental results approximated exponential cooling wherein the cooling rates could be represented by a linear equation of temperature. Residual stresses, as affected by the tempering method and thickness of a porcelain disk, were calculated by computer simulation for regions away from the edges. The following temperature-dependent factors were incorporated into the simulation: elastic modulus, viscosity, and coefficient of thermal expansion. The cooling rate dependencies of the glass transition temperature and the temperature distribution during cooling were also included. The cooling rates used in this simulation were derived from the tempering data. The agreement between development of transient and residual stresses--calculated by computer simulation for various cooling methods, and the tendency toward failures of porcelain disks subjected to the tempering processes--was examined. Simulated residual stresses were also in good agreement with those measured by the indentation fracture method of Marshall and Lawn (1977) and Anusavice et al. (1989).     

Simultaneous determination of tryptamine analogues in designer drugs using gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry

In recent years, a large number of tryptamine-based designer drugs have been encountered in forensic samples. We have developed simultaneous analytical methods for 14 tryptamine analogues using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–tandem mass spectrometry (LC–MS–MS). Trimethylsilyl (TMS) derivatives of the analytes were separated on a DB-1ms column within 15 min. The structural isomers could be differentiated by electron ionization GC–MS. LC–MS–MS with a C₁₈ column could separate structural isomers of tryptamines except for a combination of 5-methoxy-N,N-diethyltryptamine and 5-methoxy-N-methyl-N-isopropyltryptamine. Higher collision energy gave different product ion spectra between the structural isomers. The results indicate that GC–MS is the first choice for identification of tryptamines, preferably after TMS derivatization, and LC–MS–MS can be used as a complementary approach for the unequivocal differentiation of tryptamine isomers.     

Chlamydia pneumoniae infection is not involved in carotid artery stenosis

Recent studies have suggested the existence of a close relationship between Chlamydia pneumoniae infection and atherosclerosis. However, it has been speculated that C. pneumoniae infection is not associated with early atherosclerosis but with advanced atherosclerosis. In the present study, we test this hypothesis. In 524 consecutive patients who underwent cerebral angiography were recruited for the study. From the films obtained during angiography, percent stenosis of neck internal carotid artery was calculated according to the method of the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Serum C. pneumoniae IgG and IgA antibodies were measured by a commercial ELISA enzyme immunoassay kit. Cerebrovascular risk factors such as age, gender, hypertension, diabetes mellitus, hyperlipidemis and smoking were assessed by interview. Old age above 60 years and diabetes mellitus were found to be independent risk factors for carotid artery stenosis in this study after adjustment for cerebrovascular risk factors. When we defined carotid artery stenosis as the presence of greater than 30% stenosis of one artery, there was no association after adjustment for other risk factors between C. pneumoniae IgG and IgA seropositivity and the presence of carotid artery stenosis for any cut-off value of seropositivity. When we defined carotid artery stenosis as the presence of greater than 70%, there was also no association between C. pneumoniae IgG and IgA seropositivity and the presence of carotid artery stenosis for any cut-off value of seropositivity. These results suggest that C. pneumoniae infection is not associated with carotid artery atherosclerosis.     

Multicenter,Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension

Introduction

This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM).

Methods

This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire.

Results

In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n?=?60) or LAT/TIM (n?=?55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4–6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group.

Conclusion

TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores.

Trial Registration

UMIN Clinical Trials Registry Identifier, UMIN000023862.

Funding

Santen Pharmaceutical Co., Ltd., Osaka, Japan.

     

Micro-segmental hair analysis: detailed procedures and applications in forensic toxicology

Forensic Toxicology - Since the 1980s, the detection sensitivity of mass spectrometers has increased by improving the analysis of drugs in hair. Accordingly, the number of hair strands required for...