Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect

WSTĘP. Tiazolidinediony (TZD) to grupa leków zwiększających wrażliwość na insulinę, które stosuje się w leczeniu cukrzycy typu 2. Działają one także przeciwmiażdżycowo. Celem badania było wyjaśnienie zależności między przeciwmiażdżycowym a przeciwcukrzycowym działaniem pioglitazonu, leku z grupy TZD, u chorych na cukrzycę typu 2. MATERIAŁ I METODY. W badaniu wzięło udział 136 chorych na cukrzycę typu 2 narodowości japońskiej. Uczestników podzielono na 2 grupy: chorych leczonych pioglitazonem w dawce 30 mg na dobę przez 3 miesiące (n = 70) oraz pacjentów niepoddanych leczeniu (grupę kontrolną, n = 66). Podczas badania kontrolowano zmiany metabolizmu glikolipidów, stężenia w osoczu białka C-reaktywnego (CRP, C-reactive protein), leptyny i adiponektyny oraz prędkość fali tętna (PWV, pulse-wave velocity), aby przeanalizować zależność między przeciwmiażdżycowym a przeciwcukrzycowym działaniem pioglitazonu. WYNIKI. U osób leczonych pioglitazonem stwierdzono istotne obniżenie hiperglikemii, hiperinsulinemii i stężenia HbA1c oraz wzrost stężenia adiponektyny w osoczu w porównaniu z grupą kontrolną (p < 0,01). Ponadto, odnotowano istotne obniżenie stężenia CRP i PWV (p < 0,01). Przeciwmiażdżycowe działanie pioglitazonu zaobserwowano zarówno u pacjentów, u których nie uzyskano poprawy wyrównania cukrzycy, a redukcja stężenia HbA1c wynosiła poniżej 1% (n = 30) (nonresponders, osoby niepodatne na leczenie), jak i u chorych z dobrą odpowiedzią na terapię (responders, osoby podatne na leczenie), u których redukcja stężenia HbA1c przekraczała 1% (n = 40). Stosując model ANCOVA wykazano, że leczenie pioglitazonem wiązało się z niskimi wartościami CRP i PWV, niezależnie od zmian parametrów związanych z metabolizmem glukozy. WNIOSKI. W omawianym badaniu po raz pierwszy przedstawiono przeciwmiażdżycowe działanie pioglitazonu zarówno u chorych podatnych, jak i niepodatnych na przeciwcukrzycowe działanie leku. Wyniki badania sugerują, że pioglitazon może wywierać efekt przeciwmiażdżycowy niezależnie od wpływu na glikemię.INTRODUCTION. Thiazolidinediones (TZD), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type diabetic patients. MATERIAL AND METHODS. A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. RESULTS. The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA1c levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing < 1% of reduction in HbA1c (n = 30) and responders showing > 1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. CONCLUSIONS. This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect

The Far-Infrared Surveyor (FIS) for AKARI

The Far-Infrared Surveyor (FIS) is one of two focal plane instruments on the AKARI satellite. FIS has four photometric bands at 65, 90, 140, and 160 um, and uses two kinds of array detectors. The FIS arrays and optics are designed to sweep the sky with high spatial resolution and redundancy. The actual scan width is more than eight arcmin, and the pixel pitch is matches the diffraction limit of the telescope. Derived point spread functions (PSFs) from observations of asteroids are similar to the optical model. Significant excesses, however, are clearly seen around tails of the PSFs, whose contributions are about 30% of the total power. All FIS functions are operating well in orbit, and its performance meets the laboratory characterizations, except for the two longer wavelength bands, which are not performing as well as characterized. Furthermore, the FIS has a spectroscopic capability using a Fourier transform spectrometer (FTS). Because the FTS takes advantage of the optics and detectors of the photometer, it can simultaneously make a spectral map. This paper summarizes the in-flight technical and operational performance of the FIS.Comment: 23 pages, 10 figures, and 2 tables. Accepted for publication in the AKARI special issue of the Publications of the Astronomical Society of Japa

White matter microstructural alterations across four major psychiatric disorders : mega-analysis study in 2937 individuals

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd

Use of a Designed Peptide Library to Screen for Binders to a Particular DNA G-Quadruplex Sequence

We demonstrated a method to screen for binders to a particular G-quadruplex sequence using easily designed short peptides consisting of naturally occurring amino acids and mining of binding data using statistical methods such as hierarchical clustering analysis (HCA). Despite the small size of the library used in this study, candidates of specific binders were identified. In addition, a selected peptide stabilized the G-quadruplex structure of a DNA oligonucleotide derived from the promoter region of the protooncogene c-MYC. This study illustrates how a peptide library can be designed and presents a screening guideline for construction of G-quadruplex binders. Such G-quadruplex peptide binders could be functionally modified to enable switching, cellular penetration, and organelle-targeting for cell and tissue engineering