ABSTRACT
Pellagra is a type of dietary deficiency disease caused by an insufficiency of niacin or tryptophan. Symptoms of pellagra include diarrhea, dermatitis, and dementia. It is usually diagnosed based on a patient's dietary history and clinical symptoms. The diagnostic triad of pellagra includes symptoms of dermatitis, dementia, and diarrhea. Dermatitis is important for the diagnosis of this condition, because dementia and diarrhea show low specificity. In the modern era, pellagra rarely occurs in developed countries. However, pellagra should be considered in the differential diagnoses of dermatitis occurring on the sun-exposed areas of skin. Additionally, a hypoalimentation state with concomitant vitamin and/or zinc deficiency is observed in patients with pellagra. After checking the patient's overall nutritional status specifically with respect to pellagra, it is important to provide adequate food, supplemented with vitamins, zinc, and nicotinic acid to treat the patient's nutritional deficiencies.
Subject(s)
Pellagra/pathology , Skin Diseases/etiology , Dermatitis/etiology , Humans , Niacin/deficiency , Pellagra/complicationsABSTRACT
The magnetic orientation of single-walled carbon nanotubes (SWNTs) or the SWNT composites wrapped with polymer using poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene] (MEHPPV) as the conducting polymer were examined. The formation of SWNT/MEHPPV composites was confirmed by examining absorption and fluorescence spectra. The N,N-dimethylformamide solution of SWNT/MEHPPV composites or the aqueous solution of the shortened SWNTs was introduced dropwise onto a mica or glass plate. The magnetic processing of the composites or the SWNTs was carried out using a superconducting magnet with a horizontal direction (8 T). The AFM images indicated that the SWNT/MEHPPV composites or the SWNTs were oriented randomly without magnetic processing, while with magnetic processing (8 T), they were oriented with the tube axis of the composites or the SWNTs parallel to the magnetic field. In polarized absorption spectra of SWNT/MEHPPV composites on glass plates without magnetic processing, the absorbance due to semiconducting SWNT in the near-IR region in horizontal polarized light was almost the same as that in vertical polarized light. In contrast, with magnetic processing (8 T), the absorbance due to semiconducting SWNT in the horizontal polarization direction against the direction of magnetic field was stronger than that in the vertical polarization direction. Similar results were obtained from the polarized absorption spectra for the shortened SWNTs. These results of polarized absorption spectra also support the magnetic orientation of the SWNT/MEHPPV composites or the SWNTs. On the basis of a comparison of the composites and the SWNTs alone, the magnetic orientation of SWNT/MEHPPV composites is most likely ascribable to the anisotropy in susceptibilities of SWNTs.
ABSTRACT
High-throughput screening for inhibitors of the human metalloprotease, methionine aminopeptidase-2 (MetAP2), identified a potent class of 3-anilino-5-benzylthio-1,2,4-triazole compounds. Efficient array and interative synthesis of triazoles led to rapid SAR development around the aniline, benzylthio, and triazole moeities. Evaluation of these analogs in a human MetAP2 enzyme assay led to the identification of several inhibitors with potencies in the 50-100 picomolar range. The deleterious effects on inhibitor potency by methylation of the anilino-triazole nitrogens, as well as the X-ray crystal structure of triazole 102 bound in the active site of MetAP2, confirm the key interactions between the triazole nitrogens, the active site cobalt atoms, and the His-231 side-chain. The structure has also provided a rationale for interpreting SAR within the triazole series. Key aniline (2-isopropylphenyl) and sulfur substituents (furanylmethyl) identified in the SAR studies led to the identification of potent inhibitors (103 and 104) of endothelial cell proliferation. Triazoles 103 and 104 also exhibited dose-dependent activity in an aortic ring tissue model of angiogenesis highlighting the potential utility of MetAP2 inhibitors as anticancer agents.
Subject(s)
Aminopeptidases/antagonists & inhibitors , Angiogenesis Inhibitors/chemical synthesis , Furans/chemical synthesis , Metalloendopeptidases/antagonists & inhibitors , Thiazoles/chemical synthesis , Thiophenes/chemical synthesis , Triazoles/chemical synthesis , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/pharmacology , Animals , Aorta, Thoracic/drug effects , Capillaries/drug effects , Cell Proliferation/drug effects , Crystallography, X-Ray , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelium, Vascular/cytology , Furans/chemistry , Furans/pharmacology , In Vitro Techniques , Male , Models, Molecular , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacology , Thiophenes/chemistry , Thiophenes/pharmacology , Triazoles/chemistry , Triazoles/pharmacologyABSTRACT
A 81-year-old man was diagnosed as multiple myeloma and had received melphalan for 6 years. After that, he developed acute myeloid leukemia (AML) with monosomy 7 and minor bcr/abl transcripts. Fluorescence in situ hybridization identified no detectable level of bcr/abl rearrangement. During chemotherapy for AML, minor bcr/abl transcripts disappeared and instead major bcr/abl transcripts emerged. He died of pneumonia 3 months later. At that time, neither minor nor major bcr/abl transcripts were seen. These observations suggest that certain therapy related leukemia may be susceptible to generate very small clones with bcr/abl rearrangements.
