Differentiation of the Isomers of N-Alkylated Cathinones by GC-EI-MS-MS and LC-PDA.

Synthetic compounds structurally derived from the mild stimulant 2-amino-1-phenyl-1-propanone, known as cathinone derivatives, are one of the largest growing class of synthetic designer drugs. The characterization of these drugs is complicated by the structural diversity and similarity of compounds in the ever-growing cathinone family. This paper demonstrates the successful application of gas chromatography-electron ionization-tandem mass spectrometry (GC-EI-MS-MS) and liquid chromatography-photodiode array (LC-PDA) analysis to differentiate structurally similar derivatives including regioisomers of cathinones. Product ion spectrometry of iminium ions allows for an univocal differentiation of the studied cathinones with the same aminoalkyl moiety. Furthermore, the product ion spectrometry of acylium ions and ultraviolet spectra obtained by LC-PDA enabled differentiation of regioisomers resulting from different substitution patterns on the aromatic ring. The validity of the method was demonstrated by the analysis of N-alkylated ortho-, meta-, and para-alkylcathinones along with the scaffolds of buphedrones and pentiophenones.

Analysis and characterization of anthocyanins and carotenoids in Japanese blue tomato.

Tomato (Solanum lycopersicum) is rich in anthocyanins, which are polyphenolic pigments. This study aimed to analyze and characterize the anthocyanin composition in cultivated blue tomato in Japan. The extracts of peel, seed, and pulp of tomatoes were purified following which anthocyanins and lycopene contents were analyzed using high-performance liquid chromatography and electrospray ionization mass spectrometry. Eleven types of anthocyanins were identified, including delphinidin, petunidin, and malvidin. Further, the antioxidant activity of anthocyanins was evaluated using 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt radical quenching assays and electron spin resonance. "Blue tomato" extracts exert antioxidant activity. Thus, we showed that petunidin was present in the "blue tomato" peel while lycopene was present in the peel and pulp. Additionally, the blue tomato peel extract was found to significantly inhibit H2O2-induced cell death in vitro. This is the first study on cell protective effects of Japanese blue tomato extract and petunidin in murine photoreceptor cells.

Large-area surface-enhanced Raman spectroscopy imaging of brain ischemia by gold nanoparticles grown on random nanoarrays of transparent boehmite.

Although SERS spectroscopy, which is sensitive to molecular vibration states, offers label-free visualization of molecules, identification of molecules and their reliable large-area imaging remains to be developed. Limitation comes from difficulties in fabricating a SERS-active substrate with homogeneity over a large area. Here, we overcome this hurdle by utilizing a self-assembled nanostructure of boehmite that is easily achieved by a hydrothermal preparation of aluminum as a template for subsequent gold (Au) deposition. This approach brought about random arrays of Au-nanostructures with a diameter of ∼125 nm and a spacing of <10 nm, ideal for the hot-spots formation. The substrate, which we named "gold nanocoral" (GNC) after its coral reef-like shape, exhibited a small variability of signal intensities (coefficient value <11.2%) in detecting rhodamine 6G molecule when 121 spots were measured over an area of 10 × 10 mm(2), confirming high uniformity. The transparent nature of boehmite enabled us to conduct the measurement from the back-side of the substrate as efficiently as that from the front-side. We then conducted tissue imaging using the mouse ischemic brain adhered on the GNC substrate. Through nontargeted construction of two-dimensional-Raman-intensity map using differential bands from two metabolically distinct regions, that is, ischemic core and contralateral-control areas, we found that mapping using the adenine ring vibration band at 736 cm(-1) clearly demarcated ischemic core where high-energy adenine phosphonucleotides were degraded as judged by imaging mass spectrometry. Such a detection capability makes the GNC-based SERS technology especially promising for revealing acute energy derangement of tissues.

TOF-SIMS imaging of halide/thiocyanate anions and hydrogen sulfide in mouse kidney sections using silver-deposited plates.

In vivo imaging of reactive small molecule metabolites with high spatial resolution and specificity could give clues to understanding pathophysiology of various diseases. We herein applied time of flight-secondary ion mass spectrometry (TOF-SIMS) to newly developed silver-deposited plates that were stamped on mouse tissues, and succeeded in visualization of halide (Cl(-), Br(-), and I(-)) and pseudohalide thiocyanate (SCN(-)) anions, a class of substrates for neutrophils/eosinophil peroxidases to produce hypohalous acids (HOX/OX(-) mixture; X: (pseudo)halides), as well as hydrogen sulfide (H(2)S). Forty-micrometer frozen mouse kidney sections on cover glasses were attached to 37 °C preheated silver-deposited plates and incubated at -10 °C for 1 h. After sputter cleaning to remove surface contaminants, the plates were analyzed by TOF-SIMS to identify distribution of Br(-), AgBr(2)(-), I(-), AgI(2)(-), SCN(-), as well as S(2-) and AgS(-) as products of tissue-derived H(2)S. Br(-), AgBr(2)(-), I(-), and SCN(-) anions were mainly distributed in core regions including the inner medulla and inner stripe of the outer medulla (except for I(-)), rather than outer regions such as the cortex and outer stripe of the outer medulla. AgI(2)(-) anion was spread over the whole kidney, although its levels were relatively low. In contrast, S(2-) and AgS(-) anions were mainly present in the outer regions. To our knowledge, this is the first imaging study to reveal the distribution of (pseudo)halides and H(2)S in animal tissue sections.

[Annual lifelong learning program for pharmaceutical care practice by the Gifu Pharmaceutical University].

Knowledge and techniques involved in medical affairs have been steadily advancing. The lifelong learning programs supported by Gifu Pharmaceutical University are introduced. The 3 unique programs consist of (1) a lifelong learning program concerning recent medical topics provided by our university, (2) a reeducation program containing some lectures and practices concerning the most advanced knowledge and techniques on pharmacy and medicine, provided by co-organization of 3 public universities (Nagoya City University, University of Shizuoka, and Gifu Pharmaceutical University), and (3) an annual lifelong learning program promoted by Gifu Pharmaceutical University Pharmacy. Gifu Pharmaceutical University Pharmacy accommodates 100 prescriptions daily from hospitals. The annual lifelong learning programs held by our pharmacy have comprehensively provided practical knowledge and techniques on newly developed medicines, pharmaceutical care practice, pharmacotherapy, community pharmaceutics, and so on, for the last 10 years. Pharmacists should have full responsibility for pharmacotherapy as health care workers. The pharmacists should make a concerted effort to understand pharmacotherapy through pharmaceutical care practice by cooperation with community pharmacists, hospital pharmacists, and pharmaceutical associations. Our lifelong learning program has contributed to the improvement of pharmaceutical skills and communication among pharmacists, medical doctors, and other health care workers.

[Contribution of the pharmacists to self-care and primary care with nonprescription medications].

Peoples have been much concerned on their healthy life. Recently, many kinds of dietary supplements and food for specified health uses are distributed and consumed in large quantities. Concurrently, medical case insurance in Japan has been accommodating a lot of patients increasingly year by year, when the importance and enlightenment of self-care and primary care of people with nonprescription medications is proposed. The Pharmacists Law defines the responsibility of the pharmacists for the public health and welfare with medication and hygienic affairs. The recent pharmacy education for 6 years in Japan is likely to orient pharmaceutical care practice for contribution to the treatment of patients by appropriate management of medication. The multidisciplinary knowledge on medicines and diseases, and the patient consultation technique are required in the pharmacy practice. The contribution and accountability of the community pharmacists to self-care and primary care with nonprescription medications, as social needs, is expected. In this review, social responsibility on the treatment with nonprescription medications and their information provided by the community pharmacists in future is discussed.

Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.

BACKGROUND: Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia. OBJECTIVES: The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization. DESIGN AND SETTING: An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan. PATIENTS: Thirty-one adult CAP patients who required hospitalization were enrolled. MEASUREMENTS AND RESULTS: Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses. CONCLUSIONS: In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.

[A case of steroid-resistant acute hypersensitivity pneumonitis successfully treated with an immunosuppressive drug].

A 28-year-old man complaining of cough and fever was hospitalized because of bilateral diffuse granular lung shadows. Hypersensitivity pneumonitis was diagnosed based on bronchoalveolar lavage fluid (BALF) and transbronchial lung biopsy (TBLB). Since antigen avoidance alone was not effective, steroid pulse therapy was started, and his symptoms and chest X-ray findings improved. After discharge, he moved to another residence. A few weeks later, fever and dyspnea recurred, then he was hospitalized on the suspicion of acute exacerbation of hypersensitivity pneumonitis. Steroid therapy resulted in no improvement on this occasion. Lung biopsy under video-assisted thoracoscopy was performed, and acute hypersensitivity pneumonitis was diagnosed pathologically. Although steroid therapy was continued, hypoxia still remained and a KL-6 level markedly increased. Combined therapy with steroid and cyclosporin A was started, and his symptoms, physical findings, laboratory data, and chest X-ray findings gradually improved. There has been no report in which cyclosporin A was used for acute hypersensitivity pneumonitis but this case indicates that cyclosporin A is efficacious for its treatment.

Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Asthma is recognized as an inflammatory disease in which various cytokines are involved. Among these, granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to play a critical role in the survival of eosinophils and in the activation of antigen-presenting cells (APC). We studied the effects of neutralization of GM-CSF in a murine model of asthma, to elucidate its role in enhanced airway responsiveness and in airway inflammation. A/J mice, which are genetically predisposed to acetylcholine hyperresponsiveness, were immunized with ovalbumin (OA) and alum. Thereafter, the mice were subjected to a two-week regimen of OA inhalation, during which either goat anti-mouse polyclonal GM-CSF antibody or isotype control goat IgG was administered intranasally. Pulmonary function was then analyzed using whole body plethysmography before and after acetylcholine (Ach) inhalation. Here we show that OA inhalation following OA immunization increased airway responsiveness to acetylcholine and induced GM-CSF as well as IL-4 and IL-5 mRNA expression in the lung. The administration of GM-CSF-neutralizing antibody during OA inhalation significantly reduced this increased airway hyperresponsiveness and also inhibited airway inflammation. Thus, endogenous GM-CSF plays an important role in the process of airway inflammation and airway hyperresponsiveness after antigen-specific immunity has been established.