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.     

Case of multiple intrapulmonary lymph nodes]

A 45-year-old man who had hypertension, hyperthyroidism, and bronchial asthma was admitted to our hospital because of a low-grade fever and chest pain. The physical findings and laboratory data were almost all within normal limits except for evidence of mild inflammation and liver dysfunction. The chest X-ray findings seemed normal, but a computed tomography (CT) scan showed multiple nodules in both lower lung fields. We suspected the cryptococcosis or lung cancer. Biopsy by video-assisted thoracoscopic surgery (VATS) yielded a diagnosis of multiple intrapulmonary lymph nodes. In cases with the above radiologic findings, careful attention should be paid to making the differential diagnosis between intrapulmonary lymph nodes and primary lung cancer. The promotion of diagnostic imaging and advances in techniques have made it easier to identify small peripheral nodules in the lungs, and we now know of their existence. Solitary intrapulmonary lymph nodes are encountered frequently, but multiple or increasing numbers of nodes, as in our case, are very rare. Moreover, because cases with elevated CEA levels have been reported, differentiation from lung cancer appears to be important.     

Westernized food habits and concentrations of serum lipids in the Japanese

To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese-Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese-Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia.     

Short‐ and long‐term effect of sitagliptin after near normalization of glycemic control with insulin in poorly controlled Japanese type 2 diabetic patients

Aims/Introduction

The aim of the present study was to examine the short‐ and long‐term effect of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin in poorly controlled type 2 diabetic patients.

Materials and Methods

We consecutively enrolled a total of 30 type 2 diabetic patients whose glycated hemoglobin levels (National Glycohemoglobin Standardization Program) were ≥7.4%, stopped all oral antidiabetic drugs and started insulin therapy. When fasting plasma glucose levels became <140 mg/dL, we carried out the first oral glucose tolerance test (OGTT). After 1‐week sitagliptin treatment (50 mg/day), the second OGTT was carried out. Furthermore, we evaluated the long‐term efficacy of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin.

Results

After 1‐week sitagliptin treatment, the area under the curve of insulin was markedly increased, and the area under the curve of glucagon and glucose was markedly decreased. Duration of diabetes and insulin secretory capacity were correlated with the effect of sitagliptin. Furthermore, interestingly, near normalization of glycemic control with insulin therapy for 1–2 weeks brought out the long‐term effectiveness of sitagliptin on glucose tolerance for 24 weeks, which was not observed with other antidiabetic drugs.

Conclusions

These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.     

Effects of oral ingestion on physical functions before tube feeding in adults with severe motor and intellectual disabilities

Odontology - This study aimed to determine the significance of oral ingestion in tube-fed adults. Six males and three females (mean age 48.1 ± 12.4&nbsp;years) with severe...     

Stratification of atopic dermatitis patients by patterns of response to proactive therapy with topical tacrolimus: low serum IgE levels and inadequately controlled disease activity at the start of treatment predict its failure

PurposeTopical calcineurin inhibitors (TCIs) are an important anti-inflammatory drug for treating atopic dermatitis (AD). However, those treatment responses are variable. In this study, we stratified AD patients by patterns of response to remission maintenance therapy (proactive therapy) with topical tacrolimus, a typical TCI. Thereafter, we explored patient features that predict the success or failure of proactive therapy using TCI (TCI proactive therapy).MethodsA single-arm open-label clinical study aimed to evaluate the efficacy of TCI proactive therapy was conducted in 31 patients with AD. Patients were treated with TCS to induce remission (remission-induction period) followed by daily TCI ointment (0.1% tacrolimus) application for 4 weeks (maintenance therapy period), and twice-weekly application for 12 weeks (proactive therapy period). Based on its results, treatment outcomes were correlated with the patients’ clinical and laboratory findings.ResultsOf the 31 patients enrolled in the study, 21 successfully completed maintenance therapy (TCI responders). Among them, 13 completed (proactive-completed group) and 8 failed proactive therapy (proactive-dropout group). At the beginning of maintenance therapy, the serum IgE level was significantly higher in the TCI responders than in those who failed maintenance therapy (p = 0.049). At the beginning of proactive therapy, the mean-SCORing Atopic Dermatitis (SCORAD) score was significantly different between the proactive-completed (11.7 ± 4.6) and proactive-dropout (16.6 ± 4.2) groups (p = 0.025). In proactive-dropout group patients, worsened disease activity correlated well with the elevation of serum lactate dehydrogenase (LDH) and Thymus and activation-regulated chemokine (TARC) levels and peripheral eosinophil count.ConclusionAD patients were stratified into three different response patterns to TCI proactive therapy. Patients with less involvement of IgE in the pathogenesis and inadequate remission induction by TCS may not be expected to respond well to TCI proactive therapy.

Key messages

• AD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy.
• The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels.
• TCI proactive therapy should be done after the achievement of adequate remission induction by TCS.

     

HPLC with electrochemical detection for determining the distribution of free fatty acids in skin surface lipids from the human face and scalp

Free fatty acids (FFAs) in human skin surface lipids were determined by high-performance liquid chromatography with electrochemical detection. The amperometric detection of FFAs was based on electrochemical reduction of quinone, 2-methyl-1,4-naphthoquinone (vitamin K(3), VK(3)) in unbuffered solution. The peak heights for lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, and arachidonic acids at a detection potential of -415 mV vs a saturated calomel electrode showed a linear relationship with the amounts of acid in the range of 50-1600 pmol. Standard acids at 200 pmol were determined ten times with a relative standard deviations (RSD) of less than 1.5%. FFAs from about 1 mg of skin surface lipids absorbed on 5 x 5 mm pieces of oil-absorbing paper were extracted with 200 microl ethanol-acetonitrile (20:80) to prepare the test solution, of which 20 microl was injected into the octadecylsilica column. The results of the analysis of skin surface lipids from the forehead of a male subject were measured within 15 min of obtaining the sample. The RSD ( n=5) in all cases was less than 4.5%, and the recovery of FFAs was more than 94%. Since the size of the lipid samples was very small for the analytical method, FFAs were determined in skin surface lipids from 50 points on the head of a male volunteer and the FFA distribution on the face and scalp were mapped. The present method is noninvasive, sensitive, selective for FFAs and suitable for the determination of FFAs in skin surface lipids of humans, and has the potential to help in the diagnosis and treatment of various skin disorders.     

Comparison of gadobenate dimeglumine and gadopentetate dimeglumine: a study of MR imaging and inductively coupled plasma atomic emission spectroscopy in rat brain tumors

BACKGROUND AND PURPOSE: After the advent of extracellular contrast media, hepatobiliary-specific gadolinium chelates were developed to improve the diagnostic value of MR imaging of the liver. Gadobenate dimeglumine (Gd-BOPTA) is a new paramagnetic contrast agent with partial biliary excretion that produces prolonged enhancement of liver parenchyma on T1-weighted images. However, whether Gd-BOPTA is useful as a contrast agent in central nervous system disease, particularly in brain tumors, is unclear. METHODS: The behavior of Gd-BOPTA as a brain tumor-selective contrast agent was compared with that of gadopentetate dimeglumine (Gd-DTPA), an MR contrast agent used in central nervous system disease, in a common dose of 0.1 mmol/kg. An MR imaging study of these two contrast agents was performed, and tissue concentrations were measured with inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: Gd-BOPTA showed better MR imaging enhancement in brain tumors than did Gd-DTPA at every time course until 2 hours after administration and no enhancement in peritumoral tissue and normal brain. Corresponding results with ICP-AES showed significantly greater uptake of Gd-BOPTA in tumor samples than that in peritumoral tissue and normal brain 5 minutes after administration. Gadolinium was retained for a longer time in brain tumors when Gd-BOPTA rather than Gd-DTPA was administered. CONCLUSION: Gd-BOPTA is a useful contrast agent for MR imaging in brain tumors and possibly an effective absorption agent for neutron capture therapy.