bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone
Authors: Charbonnel Bernard , Karasik Avraham , Liu Ji , Wu Mei , Meininger Gary ,   for the Sitagliptin Study 020 Group
Published: November 2006

OBJECTIVE—The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, added to ongoing metformin therapy, were assessed in patients with type 2 diabetes who had inadequate glycemic control (HbA1c [A1C] ≥7 and ≤10%) with metformin alone.
RESEARCH DESIGN AND METHODS—After a screening diet/exercise run-in period, a metformin dose titration/stabilization period, and a 2-week, single-blind, placebo run-in period, 701 patients, aged 19–78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (≥1,500 mg/day) were randomly assigned to receive the addition of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 weeks. Patients exceeding specific glycemic limits were provided rescue therapy (pioglitazone) until the end of the study. The efficacy analyses were based on an all-patients-treated population using an ANCOVA and excluded data obtained after glycemic rescue.
RESULTS—At week 24, sitagliptin treatment led to significant reductions compared with placebo in A1C (−0.65%), fasting plasma glucose, and 2-h postmeal glucose. Fasting insulin, fasting C-peptide, fasting proinsulin-to-insulin ratio, postmeal insulin and C-peptide areas under the curve (AUCs), postmeal insulin AUC–to–glucose AUC ratio, homeostasis model assessment of β-cell function, and quantitative insulin sensitivity check index were significantly improved with sitagliptin relative to placebo. A significantly greater proportion of patients achieved an A1C &lt;7% with sitagliptin (47.0%) than with placebo (18.3%). There was no increased risk of hypoglycemia or gastrointestinal adverse experiences with sitagliptin compared with placebo. Body weight decreased similarly with sitagliptin and placebo.
CONCLUSIONS—Sitagliptin 100 mg once-daily added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone.
Transforming Growth Factor-β in Human Diabetic Nephropathy
Authors: Langham Robyn G. , Kelly Darren J. , Gow Renae M. , Zhang Yuan , Cordonnier Daniel J. , Pinel Nicole , Zaoui Phillipe , Gilbert Richard E. 
Published: November 2006

OBJECTIVE—Studies in rodent models have suggested that reduction in renal transforming growth factor (TGF)-β1 may underlie the renoprotective effects of the renin-angiotensin system (RAS) blockade. However, the role of the RAS blockade in abrogating TGF-β in human disease is unknown. Accordingly, we sought to examine TGF-β gene expression and biological activity in human renal biopsies, before and after ACE inhibition.
RESEARCH DESIGN AND METHODS—RNA was extracted from renal biopsies taken from participants in the Diabiopsies study, a randomized controlled 2-year trial of 4 mg/day perindopril versus placebo that reported a reduction in proteinuria and cortical matrix expansion in type 2 diabetic nephropathy. Biopsies taken at study entry and at 2 years were obtained in 12 patients (6 placebo and 6 taking perindopril). TGF-β1 and its receptor mRNA were quantified by real-time PCR, and its biological activity was assessed by examining the activation of its intracellular signaling pathway (phosphorylated Smad2) and the expression TGF-β–inducible gene H3 (βig-H3).
RESULTS—At baseline, TGF-β1 expression was similar in both placebo- and perindopril-treated groups and was unchanged over a 2-year period in biopsies of placebo-treated subjects. In contrast, perindopril treatment led to a substantial diminution in TGF-β1 mRNA (mean 83% reduction, P &lt; 0.05). Phosphorylated Smad2 immunolabeling and βig-H3 mRNA were similarly reduced with ACE inhibition (P &lt; 0.05) but unchanged in the placebo group. No differences were noted in the gene expression of TGF-β receptor II in biopsies of either placebo- or perindopril-treated subjects.
CONCLUSIONS—This study demonstrates that over a 2-year period, treatment with perindopril in patients with type 2 diabetes and nephropathy leads to a reduction in both renal TGF-β1 gene expression and its downstream activation.
Plasma Metallothionein Antibody, Urinary Cadmium, and Renal Dysfunction in a Chinese Type 2 Diabetic Population
Authors: Chen Liang , Lei Lijian , Jin Taiyi , Nordberg Monica , Nordberg Gunnar F. 
Published: November 2006

OBJECTIVE—It has been reported that diabetes may increase the risk of cadmium-induced kidney damage. The presence of metallothionein antibody (MT-Ab) increased the susceptibility for tubular damage among cadmium workers. This study focused on the relationships between levels of MT-Ab, urinary cadmium, and kidney function in a Chinese type 2 diabetic population.
RESEARCH DESIGN AND METHODS—A cross-sectional study was performed on 229 type 2 diabetic patients (92 men and 137 women) who were recruited from two community centers in one district of Shanghai City in China. Information was obtained from interviews, health records, and blood and urine samples.
RESULTS—Levels of the tubular biomarker β2-microglobulin increased significantly when the levels of MT-Ab and urinary cadmium were elevated in male and female subjects; in contrast, the levels of urinary albumin, a glomerular biomarker, did not display such a pattern. After adjusting for potential confounding covariates, logistic regression showed that the odds ratios (ORs) of tubular dysfunction increased upon 1) increasing the MT-Ab concentration from a low to high level (OR 5.56 [95% CI 2.25–13.73]) and 2) increasing the level of urinary cadmium from &lt;1 to ≥1 μg/g creatinine (3.34 [1.17–9.53]); the OR of patients currently smoking was 3.51 (1.14–10.80) relative to that of those who had never smoked.
CONCLUSIONS—This study proves that the presence of MT-Ab can potentiate tubular dysfunction among diabetic subjects and that patients with high MT-Ab levels are more prone to development of tubular damage.
Prediction of Postprandial Glycemic Exposure
Authors: Cohen Ohad , Basu Rita , Bock Gerlies , Dalla Man Chiara , Campioni Marco , Basu Ananda , Toffolo Gianna , Cobelli Claudio , Rizza Robert A. 
Published: November 2006

OBJECTIVE—To determine the best predictors of total postprandial glycemic exposure and peak glucose concentrations in nondiabetic humans.
RESEARCH DESIGN AND METHODS—Data from 203 nondiabetic volunteers who ingested a carbohydrate-containing mixed meal were analyzed.
RESULTS—Fasting glucose and insulin concentrations were poor predictors of postprandial glucose area above basal (R2 = ∼0.07, P &lt; 0.001). The correlation was stronger for 2-h glucose concentration (R2 = 0.55, P &lt; 0.001) and improved slightly but significantly (P &lt; 0.001) with the addition of fasting glucose, insulin, age, sex, and body weight to the model (r2 = 0.58). The 2-h glucose concentration also predicted the peak glucose concentration (R2 = 0.37, P &lt; 0.001) with strength of the prediction increasing (P &lt; 0.001) modestly with the addition of fasting glucose, insulin, age, sex, and body weight to the model (R2 = 0.48, P &lt; 0.001). On the other hand, addition of measures of body function and composition did not improve prediction of total glycemic exposure or peak glucose concentration.
CONCLUSIONS—Isolated measures of fasting or 2-h glucose concentrations alone or in combination with more complex measures of body composition and function are poor predictors of postprandial glycemic exposure or peak glucose concentration. This may explain, at least in part, the weak and at times inconsistent relationship between these parameters and cardiovascular risk.
Relationship of Fasting and Hourly Blood Glucose Levels to HbA1c Values
Authors: Garg Satish , Jovanovic Lois 
Published: November 2006

OBJECTIVE—In this study, we evaluated the safety and efficacy of 7-day transcutaneous, real-time, continuous glucose monitoring (CGM) in subjects with insulin-requiring diabetes.
RESEARCH DESIGN AND METHODS—Eighty-six subjects were enrolled at five U.S. centers. Subjects wore a sensor inserted under the skin of the abdomen for 7 days during each of three consecutive periods. Data were blinded during period 1 and unblinded during periods 2 and 3.
RESULTS—Of the 6,811 matched self-monitoring of blood glucose to sensor values prospectively analyzed, 97.2% fell in the Clarke error grid zones A and B, and median absolute relative difference was 11.4%. After unblinding, subjects reduced time spent at &lt;55 mg/dl by 0.3 h/day, reduced time spent at &gt;240 mg/dl by 1.5 h/day, and increased time in the target zone (81–140 mg/dl) by 1.4 h/day (P &lt; 0.05 for all three comparisons). Improvements were seen in both types 1 and 2 diabetes and with use of both multiple daily injections and continuous subcutaneous insulin infusion. Modal day graphs were generated in six groups of subjects based on HbA1c (A1C) (≤6, 6–7, 7–8, 8–9, 9–10, and &gt;10%). Mean glucose levels from midnight to 7:00 a.m. (fasting and dawn phenomenon periods) were only normal for subjects with A1C ≤6%. All other groups were hyperglycemic during this and all periods. Reductions in overall mean glucose were achieved for the four highest A1C groupings with unblinded device use.
CONCLUSIONS—This is the first report of a real-time, transcutaneous glucose sensor that functioned for 7 days. The use of CGM in the unblinded phase resulted in improvements in target-range glycemia across all A1C values.
Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes
Authors: Shpakov Alexander , Kuznetsova Ludmila , Plesneva Svetlana , Kolychev Alexander , Bondareva Vera , Chistyakova Oksana , Pertseva Marianna 
Published: November 2006

Abstract
Functional disturbance in the novel adenylyl cyclase signaling mechanism (ACSM) of insulin and relaxin action in rat streptozotocin (STZ) type I diabetes was studied on the basis of the authors’ conception of molecular defects in hormonal signaling systems as the main causes of endocrine diseases. Studying the functional state of molecular components of the ACSM and the mechanism as a whole, the following changes were found in the skeletal muscles of diabetic rats compared with control animals: 1) increase of insulin receptor binding due to an increase in the number of insulin binding sites with high and low affinity; 2) increase of the basal adenylyl cyclase (AC) activity and the reduction of AC-activating effect of non-hormonal agents (guanine nucleotides, sodium fluoride, forskolin); 3) reduction of ACSM response to stimulatory action of insulin and relaxin; 4) decrease of the insulin-activating effect on the key enzymes of carbohydrate metabolism, glycogen synthase and glucose-6-phosphate dehydrogenase. Hence, the functional activity of GTP-binding protein of stimulatory type, AC and their functional coupling are decreased during experimental type 1 diabetes that leads to the impairment of the transduction of insulin and relaxin signals via ACSM.
Synthesis of Indolizines and Benzoindolizines by Annulation of Donor‐Acceptor Cyclopropanes with Electron‐Deficient Pyridines and Quinolines
Authors: Morra Nicholas A. , Morales Christian L. , Bajtos Barbora , Wang Xin , Jang Hyosook , Wang Jian , Yu Ming , Pagenkopf Brian L. 
Published: November 2006

AbstractThe formal [3+2] dipolar cycloaddition (or annulation) of donor‐acceptor cyclopropanoate esters with pyridines and 5‐nitroquinoline is reported. Electron‐deficient pyridine dipolarophiles (R=CN, CO2Et, COMe) participate in the annulation whereas electron rich species do not. The product 2,3‐dihydroindolizines undergo rapid autooxidation, and the X‐ray structures for two of the aromatic products are reported.
Iridium‐Catalyzed Enantioselective [2+2+2] Cycloaddition of Diynes and Monoalkynes for the Generation of Axial Chiralities
Authors: Shibata Takanori , Arai Yoshikazu , Takami Kyoko , Tsuchikama Kyoji , Fujimoto Takayoshi , Takebayashi Satoshi , Takagi Kentaro 
Published: November 2006

AbstractA highly enantioselective intermolecular [2+2+2] cycloaddition of alkynes was catalyzed by a chiral iridium complex. Symmetrical and unsymmetrical diynes, and monoalkynes possessing functional group(s) were subjected to the reaction and various types of axially chiral compounds possessing biaryl skeletons were obtained in good to excellent enantiomeric excesses.
Stereoselective Synthesis of Multifunctionalized 1,2,4‐Triazolidines by a Ruthenium Porphyrin‐Catalyzed Three‐Component Coupling Reaction
Authors: Wang Ming‐Zhong , Xu Hai‐Wei , Liu Yungen , Wong Man‐Kin , Che Chi‐Ming 
Published: November 2006

AbstractMultifunctionalized 1,2,4‐triazolidines have been synthesized by a ruthenium porphyrin‐catalyzed three‐component coupling reaction. In a one‐pot reaction, ruthenium porphyrins catalyzed the in situ generation of azomethine ylides from α‐diazo esters and imines. Stereoselective 1,3‐dipolar cycloaddition reactions of the azomethine ylides with dialkyl azodicarboxylates gave the corresponding 1,2,4‐triazolidines in good yields (up to 85 %). Using chiral 8‐phenylmenthanol α‐diazo ester as the carbenoid source, chiral 1,2,4‐triazolidines have been obtained with good diastereoselectivity (up to 84 % de). Some of the 1,2,4‐triazolidines exhibited good cytotoxicity against human nasopharyngeal carcinoma (SUNE1) (IC50=10.4 μM) and human cervical carcinoma (Hela) (IC50=10.7 μM) cell lines.
Recent Advances in the Catalytic Pauson–Khand‐Type Reaction
Authors: Shibata Takanori 
Published: November 2006

AbstractThe Pauson–Khand‐type reaction is formally a [2+2+1] cycloaddition involving an alkyne, an alkene and carbon monoxide catalyzed or mediated by transition metal complexes. This review focuses on the catalytic reaction and describes the recent research on the Pauson–Khand‐type reaction.
Enantioselective Cyclopropanation with TADDOL‐Derived Phosphate Ligands
Authors: Voituriez Arnaud , Charette André B. 
Published: November 2006

AbstractThe synthesis of new chiral TADDOL‐derived phosphate ligands is described. The ligands were efficiently synthesized on a multi‐gram scale in three steps starting from the readily available corresponding TADDOL and were fully characterized. An X‐ray structure was obtained and compared to known BINOL‐phosphates. Their use in the asymmetric Simmons–Smith cyclopropanation of both functionalized and unfunctionalized olefins gave the desired cyclopropanes in good yields and good to moderate enantioselectivities.
Copper Salt‐Catalyzed Azide‐[3 + 2] Cycloadditions of Ynamides and Bis‐Ynamides
Authors: Zhang Xuejun , Li Hongyan , You Lingfeng , Tang Yu , Hsung Richard P. 
Published: November 2006

AbstractA one‐pot synthesis of amide‐substituted triazoles from alkyl bromides and ynamides is described here along with syntheses of novel bis‐ynamides and their applications in [3+2] cycloadditions with azides to construct unique bis‐triazoles.
A correlation for the diameter of electrospun polymer nanofibers
Authors: Helgeson Matthew E. , Wagner Norman J. 
Published: November 2006

AbstractA rational method to control morphology of polymer nanofibers produced by electrospinning is developed using dimensional analysis of the electrospinning process. The analysis is validated against data sets from the literature, which provides an empirical correlation between fiber size, controllable operating conditions, and measurable spinning solution properties. A stable jet operating regime is identified for which scaling of dimensionless groups is presented. Deviations from this scaling are qualitatively consistent with capillary instability of the electrospinning jet, for which a beaded fiber morphology is obtained. The results provide criteria for designing and controlling electrospinning of polymer solutions and resulting nanofiber morphology. © 2006 American Institute of Chemical Engineers AIChE J, 2007
Fitness and extra‐group reproduction in male Verreaux's sifaka: An analysis of reproductive success from 1989–1999
Authors: Lawler Richard R. 
Published: November 2006

AbstractAdult males in social groups often compete with other male group members for access to adult females. In some primate species, males also seek mating opportunities in neighboring social groups. Such extra‐group fertilizations (EGFs) provide an additional source of variation in male fitness. This additional component of fitness provided by EGFs must be incorporated into analyses that investigate sources of variation in male lifetime reproductive success. In this study, a model is analyzed in which male fitness over a 10‐year sample period is decomposed into additive and multiplicative variance and covariance components. The data come from an ongoing study of a wild population of Verreaux's sifaka (Propithecus verreauxi verreauxi) located at Beza Mahafaly Special Reserve, Southwest Madagascar. Paternity and demographic data for 134 males are used to decompose male fitness into the following three multiplicative components: reproductive lifespan during sample period, fertility, and offspring survival. These multiplicative components are estimated for males reproducing within their resident groups plus (i.e., the additive portion) for males reproducing in neighboring social groups. The analysis shows that variation in fertility makes the largest contribution to variation in total fitness, followed by variation in amount of time spent in sample period (which is a proxy of total reproductive lifespan) and variation in offspring survival. EGFs contribute an important source of variation to male fitness, and numerous factors enhance the opportunities for EGFs in male sifaka. These include female choice, a high degree of home range overlap, and a limited mating season. Am J Phys Anthropol, 2007. © 2006 Wiley‐Liss, Inc.
Gold‐Katalyse
Authors: Hashmi A. Stephen K. , Hutchings Graham J. 
Published: November 2006

AbstractDie Katalyse durch Gold ist schnell ein “heißes Thema” der Chemie geworden – fast wöchentlich werden neue Entdeckungen gemacht. Gold ist gleichermaßen als heterogener wie auch als homogener Katalysator aktiv, und im folgenden Aufsatz wollen wir diese beiden Facetten gemeinsam präsentieren, um so die vielfältigen Möglichkeiten der Gold‐Katalyse darzulegen. Die neuesten Entdeckungen werden im historischen Kontext diskutiert, Hauptziel ist aber, die neuen Optionen aufzuzeigen, die Gold‐Katalysatoren dem Synthesechemiker bieten – besonders auf den Gebieten der Redoxreaktionen und nucleophilen Additionen an π‐Systeme. Oft erweist sich Gold sogar als guter Katalysator für zuvor unbekannte Reaktionen, und in diesem Bereich gibt es mit Sicherheit noch viel zu entdecken.
Natural fiber suspensions in thermoplastic polymers. I. Analysis of fiber damage during processing
Authors: Terenzi Andrea , Kenny José M. , Barbosa Silvia E. 
Published: November 2006

AbstractThe final properties of the composites materials are strongly dependent on the residual aspect ratio, orientation, and distribution of the fibers, which are determined by the processing conditions. Present work is a systematic study of the influence of natural fiber concentration on its damage during all the steps involved in the composite compounding. The system under study is cellulose fiber‐reinforced polypropylene. The fiber geometrical parameters—length, diameter, and aspect ratio—are measured, and their statistical distributions are assessed for different concentrations. It is found that the higher the fiber concentration, the lower the fiber damage. These results evidence a difference in behavior between the damage of flexible natural fiber and rigid ones. The results are analyzed in terms of fiber concentration regimes, fiber–fiber interaction, flexibility, and entanglements. Two competitive mechanisms of the fiber interaction are proposed for explaining the fiber damage behavior during the flow of the flexible natural fiber suspensions. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2501–2506, 2007
Effect of organosilica isomers on the interfacial interaction in polyimide/aromatic organosilica hybrids
Authors: Choi Seokwon , Kim Youngkyoo , Kim Il , Ha Chang‐Sik 
Published: November 2006

AbstractWe report the effect of organosilica precursor isomers on the interfacial interaction between polyimide and organosilica in polyimide/organosilica hybrid composite films. Poly(4,4′‐oxydianiline biphenyltetracarboxamic acid) (BPDA‐ODA PAA) was used as the polyimide precursor, while the organosilica was made using o‐substituted, m‐substituted, and p‐substituted phenyl organosilica precursor isomers. For the preparation of precursor hybrid films, BPDA‐ODA PAA and organosilica precursors were mixed and then the organosilica precursors were converted to corresponding organosilica via sol–gel process. Finally, these precursor films were converted to corresponding polyimide/organosilica hybrid films by the thermal imidization of BPDA‐ODA PAA, which results in poly(4,4′‐oxydianiline biphenyltetracarboximide) (BPDA‐ODA PI). The polyimide/organosilica hybrid films were characterized using three distinctive nuclear magnetic resonance spectroscopies (1H NMR, 13C‐CPMAS‐NMR, and 29Si‐MAS‐NMR), wide‐angle X‐ray diffraction (WAXD), small‐angle X‐ray scattering (SAXS), and peel strength measurement. We found that the m‐substituted phenyl organosilica shows poorer interfacial interaction with BPDA‐ODA PI than do the o‐ or p‐substituted phenyl organosilicas. It was observed, however, that the peel strength of the hybrid films against an aluminum substrate increased with increasing contents of organosilicas, regardless of the nature of the organosilica isomers. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2507–2513, 2007
Influence of alkyl chain length on the gelation mechanism of thermoreversible gels of regioregular poly(3‐alkyl thiophenes) in xylene
Authors: Malik Sudip , Nandi Arun K. 
Published: November 2006

AbstractThe gelation rates of poly(3‐alkyl thiophenes) (P3AT) are strongly dependent on the pendent alkyl chain length. Poly(3‐hexyl thiophene (P3HT) gels at higher isothermal temperatures than that of poly(3‐dodecyl thiophene), (P3DDT). Gelation rate has been expressed as a combination of a temperature dependent function f(T) and a concentration dependent function (φn); φ being the reduced overlapping concentration of P3AT. From the slope of double logarithmic plot of gelation rate and φ, n values are calculated to be 0.52 and 0.60 for P3HT and P3DDT, respectively. These values are close to the value of percolation exponent β (0.45) for three‐dimensional lattice; so both the gels may approximately obey three dimensional percolation model. The f(T) of gelation rate consists of two steps (i) coil‐to‐rod transformation followed by (ii) fibrillar crystallization. The coil‐to‐rod transition is accompanied by a red shift in the π–π* transition band in UV–vis spectra. Flory and Weaver theory is used to understand the coil‐to‐rod transformation process. The theory of fibrillar crystallization extended to dilute solution has been employed to understand the crystallization process. The results clearly indicate that the activation energy of conformational change (ΔF) is higher for P3DDT than that of P3HT. But the free energy change for the formation of critical size nucleus (Δ G) is lower for P3DDT than that of P3HT. A comparison of ΔF and Δ G values indicate conformational ordering is the rate‐determining step for P3AT with dodecyl substituent whereas crystallization is the rate‐determining step for P3AT with hexyl substituent. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2528–2537, 2007