Brown adipose tissue (BAT) is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose-positron emission tomography, in combination with computed tomography, demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT differs among individuals, being lower in older and obese individuals. Thus, BAT is recognized as a regulator of whole-body energy expenditure and body fat in humans as in small rodents, and a hopeful target combating obesity and related disorders. In fact, there are some food ingredients such as capsaicin and capsinoids, which have potential to activate and recruit BAT via activity on the specific receptor, transient receptor potential channels, thereby increasing energy expenditure and decreasing body fat modestly and consistently.
Adipose Tissue ; Adipose Tissue, Brown ; Adult ; Capsaicin ; Cold Temperature ; Energy Metabolism ; Humans ; Hyperphagia ; Obesity ; Rodentia ; Thermogenesis ; Transient Receptor Potential Channels

Brown adipose tissue (BAT) is a site of sympathetically activated non-shivering thermognenesis during cold exposure and after spontaneous hyperphagia, thereby involving in the autonomic regulation of energy balance and body fatness. Recent radionuclide studies have demonstrated the existence of metabolically active BAT in adult humans. Human BAT is activated by acute cold exposure, particularly in winter, and contributes to cold-induced increase in whole-body energy expenditure. The metabolic activity of BAT is lower in older and obese individuals. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruited BAT in association with increased energy expenditure and decreased body fatness. Thus, BAT is a promising target for combating obesity and related metabolic disorders in humans.
Adipose Tissue ; Adipose Tissue, Brown ; Adult ; Animals ; Eating ; Energy Metabolism ; Humans ; Hyperphagia ; Mice ; Obesity ; Transient Receptor Potential Channels

　　It usually takes several days to detect slow-growing bacteria by a blood culture system. Moreover, even if the microbial growths are detected in blood samples, they will escape our notice at a microscopic examination using Gram’s stain. Consequently, the results are often regarded as false positive.　　This paper reports case of malignant lymphoma in which bloodstream infection caused by slow-growing spirillum was observed. The patient in chemotherapy for malignant lymphoma, complained of repeated fever. Repeated blood cultures were taken and occasionally positive signals, which mean increased CO2 concentrations in the culture bottle, were detected by BACTEC 9240 (Becton Dickinson). However, routine microscopic examination with Gram’s stain did not detect any bacteria. Thus, the results of BACTEC were thought to be false positive. Thereafter, the bacterial culture period was extended. Finally, a spirillum, suspected of one of Helicobacter species, was observed microscopically. The detected spirillum was regarded as Helicobacter canadensis with 98.08% homology, using polymerase chain reaction with the 16S rRNA method and basic local alignment search tool (BLAST).　　H. canadensis is one of new species isolated from humans with diarrhea. This bacterium is considered to cause a zoonotic infection. There have been some case reports that this bacterium infected immunosuppressive patients, so we should exercise caution against such conditions. Moreover, we should keep vigilant against the spread of slow-growing bacteria when there are discrepancies in findings between blood culture system and microscopic examination. It is useful to extend the culture period to detect such slow-growing bacteria.

Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.

In mammals including humans, there are two types of adipose tissue, white and brown adipose tissues (BATs). White adipose tissue is the primary site of energy storage, while BAT is a specialized tissue for non-shivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. It is now established that BAT, through its thermogenic and energy dissipating activities, plays a role in the regulation of body temperature, wholebody energy expenditure, and body fatness. Moreover, increasing evidence has demonstrated that BAT secretes various paracrine and endocrine factors, which influence other peripheral tissues and control systemic metabolic homeostasis, suggesting BAT as a metabolic regulator, other than for thermogenesis. In fact, clinical studies have revealed an association of BAT not only with metabolic disorders such as insulin resistance, diabetes, dyslipidemia, and fatty liver, but also with cardiovascular diseases including hypertension and atherosclerosis. Thus, BAT is an intriguing tissue combating obesity and related metabolic diseases. In this review, we summarize current knowledge on human BAT, focusing its patho-physiological roles in energy homeostasis, obesity and related metabolic disorders. The effects of aging and sex on BAT are also discussed.

A19-year-old man was admitted to the hospital because of severe congestive heart failure on 7 April 2000. In the previous year his case had been diagnosed as Churg-Strauss syndrome (allergic granulomatous angiitis, AGA) with bronchial asthma and mononeuritis multiplex. Echocardiography revealed the dilatation of the left ventricle (LVDd 74 mm) and impaired left ventricular systolic function (LVEF 20%). On the 21st hospital day, the irregularity of peripheral branches of left and right coronary arteries was detected by coronary arteriography. Right ventricular endomyocardial biopsy yielded little fibrosis and no infiltration of eosinophil. Although all the laboratory tests showed lower activity of AGA, steroid pulse therapy was tried and the use of steroids was tapered at intervals of two weeks. Left ventricular function was slowly improved (LVDd 60 mm, LVEF 36%). He was discharged on foot on the 71st hospital day.

The development of clinically applicable scaffolds is important for the application of cell transplantation in various human diseases. The aims of this study are to evaluate fibrin glue in a novel protein replacement therapy using proliferative adipocytes and to develop a mouse model system to monitor the delivery of the transgene product into the blood and the fate of the transduced cells after transplantation. Proliferative adipocytes from mouse adipose tissue were transduced by a retroviral vector harboring the human lecithin-cholesterol acyltransferase (lcat) gene, and were subcutaneously transplanted into mice combined with fibrin glue. The lcat gene transduction efficiency and the subsequent secretion of the product in mouse adipocytes were enhanced using a protamine concentration of 500 microg/ml. Adipogenesis induction did not significantly affect the lcat gene-transduced cell survival after transplantation. Immunohistochemistry showed the ectopic enzyme production to persist for 28 days in the subcutaneously transplanted gene-transduced adipocytes. The increased viability of transplanted cells with fibrin glue was accompanied with the decrease in apoptotic cell death. The immunodetectable serum LCAT levels in mice implanted with the fibrin glue were comparable with those observed in mice implanted with Matrigel, indicating that the transplanted lcat gene-transduced adipocytes survived and functioned in the transplanted spaces with fibrin glue as well as with Matrigel for 28 days. Thus, this in vivo system using fibrin is expected to serve as a good model to further improve the transplanted cell/scaffold conditions for the stable and durable cell-based replacement of defective proteins in patients with LCAT deficiency.
Adipocytes/*cytology/transplantation ; Animals ; Blotting, Western ; Cell Differentiation ; Cell Survival/drug effects ; Cells, Cultured ; Collagen/metabolism ; Drug Combinations ; Drug Delivery Systems ; Fibrin Tissue Adhesive/*administration & dosage ; Genetic Vectors/administration & dosage ; Humans ; Laminin/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Phosphatidylcholine-Sterol O-Acyltransferase/*genetics/*metabolism ; Proteoglycans/metabolism ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; *Tissue Engineering

BACKGROUND/AIMS: Amino acids have many physiological activities. We report the correlation between gastric emptying and gastric adaptive relaxation using tryptophan and amino acids with a straight alkyl chain, hydroxylated chain, and branched chain. Here we sought to further clarify the correlation between gastric emptying and gastric adaptive relaxation by using other amino acids. METHODS: In Sprague-Dawley rats, gastric emptying was evaluated by a breath test using [1-¹³C] acetic acid. The expired ¹³CO₂ pattern, T(max), C(max), and AUC(120min) values were used as evaluation items. Gastric adaptive relaxation was evaluated in a barostat experiment. Individual amino acids (1 g/kg) were administered orally 30 minutes before each breath test or barostat test. RESULTS: L-phenylalanine and L-tyrosine did not influence gastric emptying. All other amino acids, ie, L-proline, L-histidine, L-cysteine, L-methionine, L-aspartic acid, L-glutamic acid, L-asparagine, L-arginine, L-glutamine, and L-lysine significantly delayed and inhibited gastric emptying. L-Cysteine and L-aspartic acid significantly enhanced and L-methionine and L-glutamine significantly inhibited gastric adaptive relaxation. L-Phenylalanine moved the balloon toward the antrum, suggesting strong contraction of the fundus. T(max) showed a significant positive correlation (r = 0.709), and C(max) and AUC(120min) each showed negative correlations (r = 0.613 and 0.667, respectively) with gastric adaptive relaxation. CONCLUSION: From the above findings, it was found that a close correlation exists between gastric emptying and adaptive relaxation, suggesting that enhanced gastric adaptive relaxation inhibits gastric emptying.
Acetic Acid ; Amino Acids* ; Animals ; Arginine ; Asparagine ; Aspartic Acid ; Breath Tests ; Cysteine ; Gastric Emptying* ; Glutamic Acid ; Glutamine ; Histidine ; Lysine ; Methionine ; Phenylalanine ; Proline ; Rats ; Rats, Sprague-Dawley ; Relaxation* ; Tryptophan ; Tyrosine

Auto-transplantation of adipose tissue is commonly used for the treatment of tissue defects in plastic surgery. The survival of the transplanted adipose tissue is not always constant, and one of reasons is the accelerated apoptosis of the implanted preadipocytes. We have recently established highly homogeneous preadipocytes, named ccdPAs. The aim of the current study was to evaluate the regulation of the potency of platelet-rich plasma (PRP) on the apoptosis of ccdPAs in vitro. PRP stimulated the proliferation of the preadipocytes in a dose-dependent manner, and the stimulatory activity of 2% PRP was significantly higher than that of 2% FBS or 2% platelet-poor plasma (PPP). The presence of 2% PRP significantly inhibited serum starvation- or TNF-alpha/cycloheximide-induced apoptosis in comparison to 2% FBS or 2% PPP. DAPK1 and Bcl-2-interacting mediator of cell death (BIM) mRNAs were reduced in the preadipocytes cultured with 2% PRP in comparison to those cultured in 2% FBS. The gene expression levels were significantly higher in cells cultured without serum in comparison to cells cultured with 2% FBS, and the levels in the cells with 2% PRP were reduced to 5-10% of those in the cells without serum. These results indicated that ccdPAs exhibit anti-apoptotic activities, in addition to increased proliferation, when cultured in 2% PRP in comparison to the same concentration of FBS, and that this was accompanied with reduced levels of DAPK1 and BIM mRNA expression in in vitro culture. PRP may improve the outcome of transplantation of adipose tissue by enhancing the anti-apoptotic activities of the implanted preadipocytes.
Adipocytes/*cytology ; Adipose Tissue/cytology/metabolism ; Apoptosis/*physiology ; Apoptosis Regulatory Proteins/antagonists & inhibitors/metabolism ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Cell Culture Techniques/*methods ; *Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Gene Expression Regulation ; Humans ; Membrane Proteins/antagonists & inhibitors/metabolism ; *Platelet-Rich Plasma/metabolism/physiology ; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism ; Tissue Transplantation

  In 2008, Japanese Society of Drug Informatics (JASDI) organized the Future Vision Committee (the Committee) to propose the essential focus of drug informatics.  To explore a future vision about the drug information sciences, it was necessary to collect a variety of opinions widely from researchers.  Therefore, at the 11^th annual meeting of JASDI in July 5-6, 2008, the Committee convened a workshop to extract problems in the researches of drug informatics by using KJ method and evaluated the contents.  The major problems raised were “the field of drug informatics is too broad” and “there is no definition and/or no system of the drug informatics”.  Related problems raised are the shortness of the history and lack of originality in the study.  From different viewpoints, it was also pointed out that the methodology of the research is not well established and no systematic education is provided.  Taken together, major problems in drug informatics are concluded to be the lack of definition and the lack of systematizations, and will be solved to a certain extent by defining the outcome of the researches in drug informatics.