However, Kim et al [32] used a different system that utilized an inducible

lentiviral vector expressing shRNA rather than oligonucleotide transfection of siRNA. Taken together our results suggest that in addition to the correlation of UCH-L1 expression with histological type, the functional effects of UCH-L1 on NSCLC cells may also be subtype-dependent. Analysis of UCH-L1 in the large cell carcinoma cell line H1299 presents yet another different role for this protein in NSCLC since UCH-L1 was found to be antiproliferative in this case and the authors concluded that it is expressed as a response to tumour growth [41]. Our cell line studies suggest that UCH-L1 expression may be important Selleck INCB024360 in the pathogenesis of lung cancer. Acalabrutinib in vivo In vivo studies of UCH-L1 expression in the lung have also demonstrated a role for UCH-L1 in lung carcinogenesis in two separate reports.

When BALB/C nude mice were injected with UCH-L1-expressing metastatic melanoma cells, black melanoma colonies were generated in the lungs but when melanoma cells treated with UCH-L1 siRNA were introduced there was a significant decrease in the number of metastatic lung colonies [32]. Additionally, Hussain et al [3] demonstrated the spontaneous development of lung tumours in an UCH-L1-overexpressing transgenic Carnitine palmitoyltransferase II mouse model. To assess the relevance of UCH-L1 in patient samples we looked at whether high or low UCH-L1 expression resulted in any difference in survival status of NSCLC patients. Despite the evidence supporting a role for UCH-L1 in lung carcinogenesis in the cell line study, UCH-L1 status was not significantly associated with patient outcome. This was particularly surprising considering high UCH-L1 expression in NSCLC was previously correlated with an advanced tumour stage. However, Sasaki et al [34] also failed to find a link with survival. Therefore, although cell line models seem to indicate an oncogenic role of UCH-L1 this does not appear

to translate into patient samples. Conclusions In conclusion, this study shows the expression of UCH-L1 in NSCLC is variable and dependent on histological type. In cell line models UCH-L1 appears to have an oncogenic role in NSCLC leading to increased apoptotic resistance in H838 adenocarcinoma cells and a greater capacity for migration in the squamous cell carcinoma cell line (H157). Despite the promising observations in the NSCLC cell lines following UCH-L1 knockdown, translation to the clinical setting did not indicate any correlation with patient survival. Thus caution is required when using UCH-L1 as a prognostic marker in isolation for advanced stage and metastasis in lung carcinoma as other factors may be involved.

Floram Scanicam, Uppsala Fries EM (1838) Epicrisis systematis mycologici seu synopsis Hymenomycetum. Uppsala Fries EM (1849) EPZ-6438 molecular weight Summa vegetabilium Scandinaviae. II. Typographica Academica, Uppsala, pp 259–572 Fries EM (1861) Hymenomycetes novi vel minus cogniti, in Suecia 1852–1860

observati. Öfvers K Vetensk Akad Förh 18:19–34 Fries EM (1874) Hymenomycetes europaei sive Epicriseos systematis mycologici 1–755 Gams W (1995) Report of the committee for fungi: 5. Taxon 44:411–414 Gärdenfors U (ed) (2010) The 2010 redlist of Swedish species. ArtDatabanken, SLU, Swedish Species Information Centre, Uppsala, Sweden (www.​artdata.​slu.​se/​rodlista) Gardes M, Bruns TD (1993) ITS primers with enhanced specificity for basidiomycetes —application to the identification of mycorrhizae and rusts. Mol Ecol 2:113–118PubMed Gargas A, DePriest PT, Grube M, Tehler A (1995) Multiple origins of Lichen Symbioses in fungi suggested by SSU rDNA phylogeny. Science 268:1492–1496PubMed

Geml J, Kauff F, Brochmann C, Lutzoni F, Laursen GA, Redhead SA, Taylor DL (2012) Frequent circumpolar and rare transequatorial dispersals in the lichenised agaric genus Lichenomphalia (Hygrophoraceae, Basidiomycota). Fungal Biol 116:388–400PubMed Gill M, Steglich W (1987) Pigments of fungi (Macromycetes). Prog Chem Org Nat Prod 51:1–317 Gillardoni G, Claricuzio M, Tosi S, Zanoni G, Vidari G (2006) Antifungal acylcyclopentenediones from fruiting bodies of www.selleckchem.com/products/ganetespib-sta-9090.html Hygrophorus chrysodon. J Nat Prod 70:137–139 Goodwin TW (1952) Fungal carotenoids. Bot Rev 18:291–316 Gouy M, Guindon S, Gascuel O (2010) SeaView ver. 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol Biol Evol 27:221–224PubMed Greuter W, McNeill J, Barrie FR, Burdet HM, Demoulin nearly V, Filgueiras TS, Nicolson DH, Silva PC, Skog JE, Trehane

P, Turland NJ, Hawksworth DL (eds) (2000) International code of botanical nomenclature (Saint Louis code). Adopted by the Sixteenth International Botanical Congress St. Louis, Missouri, July–August 1999. (Regnum Veg. 238). Koeltz Scientific Books, Königstein Griffith GW (2004) The use of stable isotopes in fungal ecology. Mycologist 18:177–183 Griffith GW, Easton GL, Jones AW (2002) Ecology and diversity of waxcap (Hygrocybe spp.) fungi. Bot J Scot 54:7–22 Griffith GW, Bratton JL, Easton GL (2004) Charismatic megafungi: the conservation of waxcap grasslands. Brit Wildlife 15:31–43 Gröger F (1980) Was ist Hygrophorus leucophaeus Scop. Ex Fr. (H. carpini, H. unicolor sp. nov.). Zeit Mykol 46:157–164 Grotewold E (2006) The genetics and biochemistry of floral pigments. Ann Rev Plant Biol 57:761–780 Haas H (1958) Clitocybe venustissima Fr. in Stuttgart wiederentdeckt. Zeitschr Pilzk 4:9–12 Haas H (1962) Die systematische Stellung von Clitocybe venustissima Fries. Zeitschr Pilzk 28:12–13 Halling RE, Mueller GM (2005) Common mushrooms of the Talamanca mountains, Costa Rica.

Membranes were Navitoclax cell line incubated with rabbit anti-human anti-DNMT1 antibody (1:1000; Abcam, Cambridge, MA),

DNMT3a (1:1000; Epitomics, Burlingame, CA) and DNMT3b (1:1000; Imagenex, Port Coquitlam, BC) at room temperature overnight. After three washes with TTBS, blots were incubated with horseradish peroxidase (HRP)-conjugated goat anti-rabbit IgG antibody (1:5000) for 2 h at room temperature. The membranes were visualized with an enhanced chemiluminescence (ECL) detection system (Pierce) and images acquired using a Fluores-max instrument (Alpha Innotech, Santa Clara, CA). The gray scale value of the respective bands was quantified using Quantity One imaging software (Bio-Rad Laboratories, Hercules, CA). Animal model of pancreatic cancer and animal group The animals used in this study received humane care in compliance with the Guide to the Care and Use of Experimental Animals formulated by the Medical Ethical Committee on animal experiments of the Second Military Medical University. Twenty four BMN 673 mouse 4 week old nude mice weighing 18 to 20 g were anesthetized by intraperitoneal injection

of sodium pentobarbital (50 mg/kg). In a mini-laparotomy, the recipient rat pancreas was exposed and a small stab wound made in the pancreas parenchyma with a knife blade. The SW1990 cell suspension (1 × 105 cells/ml, 0.2 ml) was inoculated under the parenchyma of the pancreatic tail. Any leakage of the cell suspension into abdominal cavity was carefully removed with 75% ethanol to avoid peritoneal metastasis. Ten days later, the ultrasonic

images demonstrated the formation of in situ pancreatic cancer with a tumor diameter of 1.52 ± 0.31 cm. After the diagnosis of pancreatic cancer was established by ultrasound images during laparotomy, the 18-gauge needles were implanted into the visible mass at the tail of pancreas, and spaced in a parallel array at intervals of approximately 0.5 cm. After the needles were implanted, 125I seeds were implanted using a Mick-applicator with the spacing maintained at approximately 0.5 cm. The mice with pancreatic cancer were randomly divided into three groups. Groups I, II, and III underwent the implantation of 0 Gy, 2 Gy, and 4 Gy 125I seeds, http://www.selleck.co.jp/products/DAPT-GSI-IX.html respectively. The 2 Gy or 4Gy irradiation were achieved through implantation of 1 or 2 seeds, respectively, into the pancreatic tumor. The 125I seed have a average activity of 0.5 – 0.8 mCi. No seed implantation was performed in the 0 Gy irradiation group. After 125I seed implantation, two mice in the 0 Gy group died; however, no death was observed in the 2 Gy and 4 Gy groups. Measurement of tumor volume by ultrasonic images Ultrasonic inspection was performed through using a GF-UCT240-AL5 (Olympus Co Ltd, Tokyo, Japan) endoscopic ultrasound (EUS) 0 and 28 d post-implantation with a probe frequency of 12 MHz. After anesthetizing the animals by intraperitoneal injection of sodium pentobarbital (50 mg/kg), the mouse abdomen was soaked with sterile deionized water.

e Protein annotations are based on the genome annotation of C. thermocellum ATCC 27405. f Approximate mass observed on BN-PAGE. Complexes in energy production and conversion In prokaryotes, three evolutionarily related sub

types of ATPases/synthases were found, categorized Selleck Ensartinib as F- (F1-F0-), V- (V1-V0) and A- (A1-A0) type ATPases on the basis of their function and taxonomic origins. Although eukaryotes contain both F- and V-ATPases, each highly specialized in its physiological functions; archaea and eubacteria typically contain only one subtype of

ATPase [15]. Most eubacteria contain F-ATPases, but some eubacteria contain both F- and V-ATPases, whereas PXD101 chemical structure all known archaea contain complexes that are evolutionarily closer to V-ATPases and are referred to as A-ATPases due to their archael origin. Generally, the F1-F0-ATP synthase contains eight subunits arranged in two subcomplexes: F1 (α3, β3, γ, δ, ε) and F0 (a, b2, c10-14) [16]. The V1-V0-ATP synthase contains nine subunits arranged in two subcomplexes: V1 (A3, B3, D, F) and V0 (G, E, C, I, L) [17]. Interestingly, in the genome of C. thermocellum, there are two ATPase gene clusters: a F1-F0-ATP synthase (Cthe_2602–Cthe_2609) and V1-V0-ATP synthase (Cthe_2261-Cthe_2269), both with a complete set of subunits. We detected two subunits of F1-F0-ATPase, F1 subunit

second α (Cthe_2606, 55.8 kDa) and F1 subunit β (Cthe_2608, 51 kDa), with an estimated molecular mass of 300 kDa and two subunits of V1-V0-ATPase, V1 subunit A (Cthe_2267, 65 kDa) and V1 subunit B (Cthe_2268, 50 kDa), with an estimated molecular mass of 300 kDa. These may represent a subcomplex of α3β3 and A3B3 in F1 and V1, respectively. We conducted a large scale search of ATPase in published genomes of eubacteria from NCBI, 700 genomes were found to contain genes encoding F-type ATPases, 93 genomes contain genes encoding V-type ATPases, and only 44 genomes contain both F-type and V-type ATPases (see Additional file 1). The co-presence of both ATPases in a bacterium is limited to a few genera, which include several Streptococcus, Clostridium, Anaeromyxobacter strains, two Cyanothece species, an Enterococcus faecalis and a Nitrosococcus oceani.

The MD models in this study can also be used to gain physical insight into the origin of the size effect. It is well known that crystalline [27–29] and amorphous materials [30–33] have molecular structures at the surface (or bi-material interface) that differ substantially than in the bulk. In fact, the CG potential used for the research described herein was developed specifically to accurately predict the bulk and surface structure of PE [15]. For amorphous

polymers, the above-cited references show that the mass density of the polymer is higher on the surface than in the bulk. This high-density layer has a thickness on the order of 1 nm. The cause of the densification of polymer molecules on a surface is classically explained by the concept ICG-001 cost of surface tension. Segments of polymer molecules in the bulk have a relatively low energy PD0325901 datasheet state because of the balance of attractive short-range (e.g., covalent bonds) and long-range (e.g., van der Waals bonds) interactions in every direction. Segments of polymer molecules on a free surface (or a non-bonded bi-material interface of two dissimilar materials) do not have these strong attractive interactions

in the direction normal to the surface and are thus pulled by the attractive forces in the opposite direction towards the bulk. As a result, there is a densification of the top layer of polymer molecules on a surface. This densified surface layer of material has a constant thickness regardless of the size and geometry of the overall material structure. For polymer particles, this means that the surface layer will have the same finite thickness for any particle

size. For decreasing particle sizes, the relative volume fraction of the densified material increases. Therefore, it follows that the smaller polymer particles studied herein are expected to have stiffer mechanical responses than the larger particles, as observed experimentally Chloroambucil [5–7] and discussed in ‘Simulated compression loading’ and ‘Simulated compression unloading’ sections. In order to quantify the influence of the surface layer on the mechanical response of the polymer particles, the surface energy has been determined for each diameter. The total internal energy associated with the presence of the surface (i.e., surface energy) in a molecular system can be determined by (8) where U particle is the total energy (kinetic plus potential) of a polymer particle, and U b is the total energy in a bulk sample of material with the same number of CG beads. These potential energies were calculated using the potential shown in Table  1 using the procedures outlined in ‘Spherical particle molecular models’ section. Figure  9 shows a plot of the ratio U sur/U b over the ratio of the surface area to volume for each of the five particles.

: Construction of the baeR deletion mutant. (A) A single crossover between pEX18Tc containing baeR upstream and downstream sequences joined by a kan r cassette and the ATCC 17978 chromosome. (B) Two mechanisms by which the plasmid can integrate into the chromosome are diagrammed. (C) The suicide plasmid was excised by 10% sucrose counter-selection and selection of the in-frame baeR deletion strain with kanamycin. (TIFF 719 KB) Additional file 4: Figure S4.: Shuttle vector pWH1266 and verification of pWH1266 introduction into different strains of Acinetobacter baumannii. (A) pWH1266. (B) pWH1266 with kanamycin cassette insertion. (C) baeR insertion into the XbaI/XhoI restriction sites in pWH1266.

(D) Successful baeR

gene fragment insertion into the kanamycin cassette was deduced based on a change in the PCR band size from 1375 bp to 983 bp. AB1027, AB1028, and AB1029 represent the baeR reconstituted Ibrutinib in vivo strain, the baeR-overexpressing strain, and the A. baumannii ATCC 17978 strain with pWH1266, respectively. (TIFF 2 MB) Additional file 5: Figure S5.: baeR gene expression in different A. baumannii strains as determined by reverse transcription polymerase chain reaction. No baeR expression could be observed in AB1026. AB1027 was the baeR-reconstituted strain derived from AB1026, which had a baeR expression level similar to that of the wild-type strain. AB1028 and AB1029 represent the baeR-overexpressing strain and A. baumannii ATCC 17978 with pWH1266, respectively. (TIFF 840 KB) References 1. Fournier PE, Vemurafenib ic50 Richet H: The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 2006,42(5):692–699.PubMedCrossRef 2. Perez F, Hujer AM, Hujer KM, Decker

BK, Rather PN, Bonomo RA: Global challenge of multidrug-resistant Acinetobacter baumannii . Antimicrob Agents Chemother 2007,51(10):3471–3484.PubMedCentralPubMedCrossRef 3. Mendes RE, Farrell DJ, Sader HS, Jones RN: Comprehensive assessment of tigecycline activity tested against a worldwide collection of Acinetobacter spp. (2005–2009). Diagn Microbiol Infect Dis 2010,68(3):307–311.PubMedCrossRef 4. Lauderdale TL, Clifford McDonald L, Shiau YR, Chen PC, Wang HY, Lai JF, FER Ho M: The status of antimicrobial resistance in Taiwan among gram-negative pathogens: the Taiwan surveillance of antimicrobial resistance (TSAR) program, 2000. Diagn Microbiol Infect Dis 2004,48(3):211–219.PubMedCrossRef 5. Gordon NC, Wareham DW: Multidrug-resistant Acinetobacter baumannii : mechanisms of virulence and resistance. Int J Antimicrob Agents 2010,35(3):219–226.PubMedCrossRef 6. Rose WE, Rybak MJ: Tigecycline: first of a new class of antimicrobial agents. Pharmacotherapy 2006,26(8):1099–1110.PubMedCrossRef 7. Peleg AY, Adams J, Paterson DL: Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii . Antimicrob Agents Chemother 2007,51(6):2065–2069.PubMedCentralPubMedCrossRef 8.

To cross-correlate buy VX-765 between the secretome and proteome data sets, we first searched for Leishmania orthologs in T. brucei using BLAST (Basic Local Alignment Search Tool) analysis. 281 out of the 358 Leishmania secretome entries were found to have an ortholog in Trypanosoma (additional file 3, Table S3), including 115 actively secreted proteins and 166 cell-associated proteins. Interestingly, a high proportion (61%) of the former was present in our Trypanosoma secretome, suggesting a close relationship between the actively secreted proteins in Leishmania

and the Trypanosoma secreted proteins. In contrast, only 8% of the Trypanosoma secretome was shared with the glycosome proteome (additional file 4, Table S4). We also compared the trypanosome total proteome (additional file 5, Table S5) and the secretomes from Trypanosoma and Leishmania. Figure 5 shows that 41% and 39%, respectively, of the trypanosome and Leishmania secretomes were not shared with any of the other proteomes. Simultaneously, secretome proteins shared with

Selleck LY2157299 the Trypanosoma total proteome amounted to 47% and 43% for Trypanosoma and Leishmania, respectively, indicating that a major part of these secretomes resulted from an active secretion process. Figure 5 Overlap between Trypanosoma total proteome and the T. brucei gambiense and L. donovanii secretome. Proteins identified in 3 different compartments (T. brucei total proteome, T. brucei gambiense secretome, and L. donovanii secretome) were compared as to determine part of the proteins that were either specific to each compartment or common to different compartments. So, the black circle in the middle shows that 84 proteins selleck kinase inhibitor are common to T. brucei total proteome, T. brucei gambiense secretome, and L. donovanii secretome. Among the other proteins of the T. brucei gambiense secretome, for example, 182 (41%) were specific to this compartment, whereas 52 were common with L. donovanii secretome, and 126 with the total

proteome; out of the proteins identified in the total T. brucei proteome, 824 were specific to this compartment. Finally, these different proteomes were compared at the functional level (Figure 6; additional files 1, 2, 3, 4 and 5, Tables S1-S5). Interestingly, the two secretomes showed large similarities with almost the same proportion of proteins involved in folding and degradation and protein synthesis or with unassigned function. In contrast, the comparison between secretomes and glycosome functional categories showed major differences, the glycosome proteome displaying an expected bias toward sugar (15%) and lipid metabolism (7%) and, more surprisingly, toward nucleotide metabolism (7%). Also, the total proteome differed from all sub-proteomes by a deeper investment in cell organization and RNA/DNA metabolism.

7). The smaller paryphoplasm-equivalent compartment surrounds the pirellulosome and lies between the ICM and the CM. Figure 7 Transmission electron micrograph of high-pressure frozen and cryosubstituted cell of Chthoniobacter flavus , showing paryphoplasm (P) and an intracytoplasmic Venetoclax membrane (ICM) enclosing a pirellulosome region containing a condensed fibrillar nucleoid (N) which surrounds an electron-dense granule. Inset – enlarged

view of region of cell outlined in the white box showing cytoplasmic membrane (CM), paryphoplasm (P) and intracytoplasmic membrane (ICM). Bar – 200 nm. Cell compartmentalization in strain Ellin514 In high-pressure frozen and cryosubstituted strain Ellin514, known to be a representative of subdivision 3 of the phylum Verrucomicrobia, cells were also found to possess a major pirellulosome compartment separated by an ICM from an outer paryphoplasm, MK-1775 molecular weight again analogous to the planctomycete cell plan (Fig. 8). The

pirellulosome compartment possessed a condensed fibrillar nucleoid associated with electron-transparent oval granules, and was filled with polyhedral bodies of varying electron density. Ribosomes were not clearly visible and the polyhedral bodies seem to occupy most of the pirellulosome. Figure 8 Transmission electron micrograph of high-pressure frozen and cryosubstituted cell of verrucomicrobia strain Ellin514, showing paryphoplasm (P),

and intracytoplasmic membrane (ICM) enclosing a pirellulosome possessing polyhedral bodies (PB) surrounding a condensed fibrillar nucleoid (N) containing granules. Inset: enlarged view of region of cell outlined in the white box showing cytoplasmic membrane (CM), paryphoplasm (P) and intracytoplasmic membrane (ICM). Bar – 200 nm. Discussion We have demonstrated that all four members of the phylum Verrucomicrobia examined, Verrucomicrobium spinosum, Prosthecobacter dejongeii, Chthoniobacter flavus, and verrucomicrobia strain Ellin514, share a basic cell plan analogous to that found in members of the phylum Planctomycetes. This cell plan is characterized Ribose-5-phosphate isomerase by compartmentalization of the cell cytoplasm by a major cell organelle bounded by a single membrane containing all the cell DNA in a fibrillar condensed nucleoid, as well as ribosome-like particles. This major membrane-bounded organelle is equivalent to the pirellulosome of planctomycetes, and its bounding membrane is equivalent to the intracytoplasmic membrane (ICM) defined in planctomycetes as surrounding the pirellulosome [18]. Consistent with the structural analogies between verrucomicrobia and planctomycetes, the ribosome-free region between the ICM of the pirellulosome and the cytoplasmic membrane in verrucomicrobia can be considered equivalent to the paryphoplasm of planctomycetes.

One primer contained homology to the first 7 codons of the 3 × FLAG sequence, 40 bp of homology to the 5′ end of the target gene, excluding the stop codon, and an EcoRI restriction site (primer D61350 for rsd and

D61352 for yacL). The second primer contained homology to the P-REV sequence, 40 bp of homology to the chromosome, immediately downstream of the target gene primer and a KpnI restriction site (D61351 for rsd and D61353 for yacL). DNA fragments generated by PCR using pDOC-F as a template were cloned into pDOC-C, which was subsequently co-transformed with pACBSCE LY2835219 into K-12 MG1655, EHEC O157:H7 Sakai and UPEC CFT073 cells. The Gene Doctoring protocol was followed and the results are reported in table 2. For both genes, in all three strains, a large number of colonies were identified with a kanamycin resistant, sucrose insensitive phenotype. After PCR analysis of the relevant chromosomal region (using primer pairs D57786 (CC1) and D61354, and D57785 Poziotinib order (CC2) and D61355 for rsd and D57786 and D61356, and D57785 and D61357 for yacL) the vast majority of candidates were found to be true recombinants and in each case, more than 90% were sensitive

to both ampicillin and chloramphenicol, indicating loss of both pDOC donor and pACBSCE plasmids. Where a candidate was found to have the wild-type form of the gene after PCR verification, we assumed that the kanamycin cassette had inserted into a different part of the chromosome, since we were unable to isolate any donor plasmid DNA from cells using standard plasmid isolation techniques. Hence, for each gene, in each strain, more than 150 recombinants were identified that had the correct chromosomal modification and were free of the recombineering plasmid pACBSCE. Table 2 Comparison

of recombination efficiency of E. coli strains   KanR SucI (A) recombinants Plasmid free recombinants (B) % plasmid free recombinants (B/A) rsd         MG1655 249 248 232 93 O157:H7 Sakai 193 193 184 95 CFT073 174 170 156 90 yacL         MG1655 287 286 258 90 O157:H7 Farnesyltransferase Sakai 218 218 209 96 CFT073 209 205 192 92 To test the effectiveness of recombination using our recombineering plasmid pACBSCE, compared with the recombineering plasmid pACBSR, used by Herring and co-workers [4] we repeated the gene coupling analysis of the rsd gene. The results in table 3 show that more kanamycin resistant, sucrose insensitive recombinants were identified in each strain when pACBSR was used as the recombineering plasmid, with a comparable percentage being free of pDOC donor plasmid, when compared to using pACBSCE as the recombineering plasmid. However, very few candidates had lost the recombineering plasmid, and in strain CFT073, all of the recombinant candidates still carried pACBSR, thus exposing cells to the potential effects of excess of λ-Red expression and requiring additional steps to cure cells of the plasmid [4, 13–15].

Switching to miglitol did not affect VAS values for digestive symptoms such as abdominal distention, flatulence, and abnormalities of bowel function. The α-GI switch had no effects on levels of HbA1c, Opaganib solubility dmso fasting glucose, T-cho, and CRP. The results indicate that the switch from acarbose or voglibose to miglitol did not affect basic clinical parameters. Table 2 Clinical characteristics at baseline and 3 months after switching to miglitol   n Baseline 3 months p-Value HbA1c (%) 35 7.26 ± 0.51 7.27 ± 0.61 0.817 Fasting glucose (mg/100 mL) 35 130.6 ± 29.6 129.0 ± 30.2 0.771 Triglycerides (mg/100 mL) 35 73.9 ± 35.9 77.8 ± 34.4 0.501 Total cholesterol

(mg/100 mL) 33 179.9 ± 28.4 183.8 ± 27.4 0.340 CRP (mg/100 mL) 35 0.09 ± 0.16 0.08 ± 0.18 0.815 Abdominal distention (score 1–10) 35 2.6 ± 2.1 2.8 ± 2.1 0.546 Flatulence (score 1–10) 35 4.2 ± 2.7 3.1 ± 2.0 0.161 Abnormalities of RAD001 order bowel function (score 1–10) 29 1.7 ± 1.2

2.1 ± 1.5 0.206 Data are expressed as mean ± SD, or frequency Statistical analyses were performed using two-sided, paired Student’s t test CRP C-reactive protein Figure 1 shows blood glucose concentrations pre- and post-meals compared with periods just before and after the α-GI switch. Blood glucose concentrations were significantly higher just before lunch (p = 0.018), significantly lower 1 h after lunch (p = 0.012), significantly higher just before dinner (p < 0.001), and significantly lower 1 h after dinner (p = 0.045) after the ADP ribosylation factor switch compared with before the switch. M-values were significantly reduced by the switch to miglitol (p = 0.010). Glucose fluctuations were improved by the switch without changing the total rise of glucose (HbA1c). Fig. 1 Effects on glucose fluctuations of switching from the highest approved doses of the α-glucosidase inhibitors acarbose or voglibose to a medium dose of miglitol

in patients with type 2 diabetes mellitus. a Glucose concentrations determined by SMBG. b M-value. Values are means ± SD. Statistical analyses were performed using two-sided paired Student’s t test. Asterisks denote significant differences compared with the value before switching to miglitol (*p < 0.05 and **p < 0.01). SMBG self-monitoring of blood glucose, SD standard deviation Serum protein concentrations of CVD risk factors are shown in Fig. 2. Serum MCP-1 and sE-selectin concentrations decreased at levels of 82 % (p < 0.001) and 78 % (p = 0.014), respectively, and serum sVCAM-1 concentrations increased at levels of 107 % (p = 0.014) 3 months after the switch compared with baseline. Serum protein concentrations of sICAM-1, tPAI-1, and FABP4 were unchanged by the switch. These results indicate the switch from acarbose or voglibose to miglitol reduced circulating protein concentrations of CVD risk factors such as MCP-1 and sE-selectin. Fig.