bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases
Authors: Oleson Lauren , Court Michael H 
Published: August 2008

AbstractGlucuronidation studies using microsomes and recombinant uridine diphosphoglucuronosyltransferases (UGTs) can be complicated by the presence of endogenous β-glucuronidases, leading to underestimation of glucuronide formation rates. Saccharolactone is the most frequently used β-glucuronidase inhibitor, although it is not clear whether this reagent should be added routinely to glucuronidation incubations. Here we have determined the effect of saccharolactone on eight different UGT probe activities using pooled human liver microsomes (pHLMs) and recombinant UGTs (rUGTs). Despite the use of buffered incubation solutions, it was necessary to adjust the pH of saccharolactone solutions to avoid effects (enhancement or inhibition) of lowered pH on UGT activity. Saccharolactone at concentrations ranging from 1 to 20 mM did not enhance any of the glucuronidation activities evaluated that could be considered consistent with inhibition of β-glucuronidase. However, for most activities, higher saccharolactone concentrations resulted in a modest degree of inhibition. The greatest inhibitory effect was observed for glucuronidation of 5-hydroxytryptamine and estradiol by pHLMs, with a 35% decrease at 20 mM saccharolactone concentration. Endogenous β-glucuronidase activities were also measured using various human tissue microsomes and rUGTs with estradiol-3-glucuronide and estradiol-17-glucuronide as substrates. Glucuronide hydrolysis was observed for pHLMs, lung microsomes and insect-cell expressed rUGTs, but not for kidney, intestinal or human embryonic kidney HEK293 microsomes. However, the extent of hydrolysis was relatively small, representing only 9–19% of the glucuronide formation rate measured in the same preparations. Consequently, these data do not support the routine inclusion of saccharolactone in glucuronidation incubations. If saccharolactone is used, concentrations should be titrated to achieve activity enhancement without inhibition.
Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment
Authors: Hamabe Wakako , Yamane Hiroyuki , Harada Shinichi , Tokuyama Shogo 
Published: August 2008

AbstractAnalgesic tolerance to morphine can develop from long-term use of this drug for the treatment of pain. Many reports have shown that stimulation of the kappa opioid receptor (KOR) suppresses development of analgesic tolerance to morphine. Here, we studied the KOR-mediated inhibition of morphine tolerance during repeated morphine treatment, with a focus on desensitization of the receptor. The development of analgesic tolerance to morphine during repeated morphine administration (10 mgkg−1 s.c.) was completely suppressed by U-50488H (2 mgkg−1 i.p.), a KOR agonist. The decrease in [35S] GTPγS binding activity stimulated by the mu opioid receptor (MOR) agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) was also significantly inhibited by U-50488H. These results indicate that stimulation of KOR caused by repeated morphine treatment either inhibits MOR desensitization or accelerates recycling of MOR on the cell surface, thereby suppressing morphine tolerance. Furthermore, we found that activity of protein kinase C (PKC) was significantly decreased in mice treated with both U-50488H and morphine. These results suggest that the mechanisms underlying KOR-mediated inhibition of analgesic tolerance to morphine may be partly due to suppression of PKC activation and prevention of receptor desensitization.
Presence or absence of a gallate moiety on catechins affects their cellular transport
Authors: Kadowaki Masaaki , Sugihara Narumi , Tagashira Tomohiko , Terao Kazumi , Furuno Koji 
Published: August 2008

AbstractThe accumulation of (—)-epicatechin (EC), a non-gallate catechin, was significantly lower than that of (—)-epicatechin gallate (ECG), a gallate catechin, in Caco-2 cells. Using Caco-2 cell monolayers cultured in transwells, the transport of catechins in the basolateral-to-apical direction was much higher than that in the apical-to-basolateral direction, suggesting the involvement of an efflux transporter. Moreover, the results suggest that involvement of a transporter in EC efflux is greater than that for ECG. Treatment with transporter inhibitors MK571, quinidine or mitoxantrone, which inhibit MRP2, P-glycoprotein (P-gp) and BCRP, respectively, led to an increase in the accumulation of EC into Caco-2 cells and a decrease in the Papp ratio (Papp B→A/Papp A→B) for EC. These transporters seemed to be involved in EC efflux. BCRP was not an efflux transporter for ECG, and the influences of MRP2 and P-gp on ECG efflux were lower than for EC. Thus, efflux transporters appear to be responsible for the difference in cellular accumulation of EC versus ECG, suggesting that the presence or absence of a gallate moiety in the catechin structure influences the transporters.
Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats
Authors: Ji Wei , Guo Lei , Lian Jihong , Gong Bangqiang 
Published: August 2008

Abstract
In the present study, the molecular mechanisms by which CM108, a flavone derivative, improves lipid profiles were investigated further. Hyperlipidaemia was induced by oral administration of high cholesterol and fat. After 4 weeks of treatment, the lipid levels in the serum, liver and faeces were measured and the liver genes involved in lipid metabolism were analysed to explore the molecular mechanisms of lowering lipids. CM108 modulated lipid profiles, including elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and reducing serum levels of triglyceride (10%), total cholesterol (10%) and low-density lipoprotein cholesterol (26%). Levels of triglyceride and total cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL-C level was attributed to the synergic effects of CM108 in increasing levels of ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein AII in the liver. Intriguingly, CM108 induced genes, including fatty acid transport protein, acyl-CoA synthetase and lipoprotein lipase that are important for more efficient fatty acid β-oxidation, thereby reducing serum and liver triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol 7α-hydroxylase contributed to cholesterol metabolism, leading to decreases in serum and liver cholesterol levels. Thus, the genes involved in lipid metabolism were systemically modulated by CM108, which contributed to the improvement of lipid profiles in hyperlipidaemic rats.
Inhibitory activities of prenylated flavonoids from Sophora flavescens against aldose reductase and generation of advanced glycation endproducts
Authors: Jung Hyun Ah , Yoon Na Young , Kang Sam Sik , Kim Yeong Shik , Choi Jae Sue 
Published: August 2008

Abstract
Important targets for the prevention and treatment of diabetic complications include aldose reductase (AR) inhibitors (ARIs) and inhibitors of advanced glycation endproduct (AGE) formation. Here we evaluate the inhibitory activities of prenylated flavonoids isolated from Sophora flavescens, a traditional herbal medicine, on rat lens AR (RLAR), human recombinant AR (HRAR) and AGE formation. Among the tested compounds, two prenylated chalcones — desmethylanhydroicaritin (1) and 8-lavandulylkaempferol (2) — along with five prenylated flavanones — kurarinol (8), kurarinone (9), (2S)-2′-methoxykurarinone (10), (2S)-3β,7,4′-trihydroxy-5-methoxy-8-(γ,γ-dimethylally)-flavanone (11), and kushenol E (13) were potent inhibitors of RLAR, with IC50 values of 0.95, 3.80, 2.13, 2.99, 3.77, 3.63 and 7.74 μM, respectively, compared with quercetin (IC50 7.73 μM). In the HRAR assay, most of the prenylated flavonoids tested showed marked inhibitory activity compared with quercetin (IC50 2.54 μM). In particular, all tested prenylated flavonols, such as desmethylanhydroicaritin (1, IC50 0.45 μM), 8-lavandulylkaempferol (2, IC50 0.79 μM) and kushenol C (3, IC50 0.85 μM), as well as a prenylated chalcone, kuraridin (5, IC50 0.27 μM), and a prenylated flavanone, (2S)-7,4′-dihydroxy-5-methoxy-8-(γ,γ-dimethylally)-flavanone (12, IC50 0.37 μM), showed significant inhibitory activities compared with the potent AR inhibitor epalrestat (IC50 0.28 μM). Interestingly, prenylated flavonoids 1 (IC50 104.3 μgmL−1), 2 (IC50 132.1 μgmL−1), 3 (IC50 84.6 μgmL−1) and 11 (IC50 261.0 μgmL−1), which harbour a 3-hydroxyl group, also possessed good inhibitory activity toward AGE formation compared with the positive control aminoguanidine (IC50 115.7 μgmL−1). Thus, S. flavescens and its prenylated flavonoids inhibit the processes that underlie diabetic complications and related diseases and may therefore have therapeutic benefit.
Zinc-mediated Allylation of Aryl 2-Propynyl Acetates: A Facile Synthesis of 1,5-Enynes
Authors: Yadav J S , Reddy B V Subba , Chandrakanth D , Prashant B 
Published: August 2008

Abstract
Aryl 2-propynyl acetates undergo smooth allylation with allylzinc bromide (generated in situ from allyl bromide and zinc metal) in THF at room temperature under mild conditions to furnish the corresponding 1,5-enynes in good to excellent yields and with high selectivity. Indium metal is also found to accomplish the nucleophilic substitution of aryl 2-propynylic acetates with allyl bromide.
Facile Preparation of Nickel Ferrite Nanocrystals via a Novel Reduction–Oxidation Route
Authors: Gu Zhijun , Fan Guoli , Yang Lan , Xiang Xu , Liu Shubin , Li Feng 
Published: August 2008

Abstract
Nickel ferrite nanocrystals with narrow distribution of crystallite sizes have been obtained through a novel and facile reduction–oxidation approach. The as-prepared samples with the stoichiometric and nanocrystalline nature exhibit a promising superparamagnetic behavior.
Postanalytical External Quality Assessment of Urine Albumin in Primary Health Care: An International Survey
Authors: Aakre Kristin M , Thue Geir , Subramaniam-Haavik Sumathi , Bukve Tone , Morris Howard , Müller Mathias , Lovrencic Marijana V , Plum Inger , Kallion Kaja , Aab Alar , Kutt Marge , Gillery Philippe , Schneider Nathalie , Horvath Andrea R , Onody Rita , Oosterhuis Wytze , Ricos Carmen , Perich Carmen , Nordin Gunnar , Sandberg Sverre 
Published: August 2008

Abstractbackground: Microalbuminuria (MA) is recognized as an important risk factor for cardiovascular and renal complications in diabetes. We sought to evaluate how screening for MA is conducted and how urine albumin (UA) results are interpreted in primary care internationally.methods: General practitioners (GPs) received a case history–based questionnaire depicting a male type 2 diabetes patient in whom UA testing had not been performed. Questions were related to type of urine sample used for UA testing, need for a repeat test, whether UA testing was performed in the office laboratory, and what changes in UA results were considered clinically important [critical difference (CD)]. Participants received national benchmarking feedback reports.results: We included 2078 GPs from 9 European countries. Spot urine samples were used most commonly for first time office-based testing, whereas timed collections were used to a larger extent for hospital-based repeat tests. Repeat tests were requested by 45%–77% of GPs if the first test was positive. Four different measurement units were used by 70% of participants in estimating clinically important changes in albumin values. Stated CDs varied considerably among GPs, with similar variations in each country. A median CD of 33% was considered clinically important for both improvement and deterioration in MA, corresponding to an achievable analytical imprecision of 14%, when UA is reported as an albumin/creatinine ratio.conclusions: Guidelines on diagnosing MA are followed only partially, and should be made more practicable, addressing issues such as type of samples, measurement units, and repeat tests.
Plasma Insulinlike Growth Factor 1 and Binding-Protein 3 and Risk of Myocardial Infarction in Women: A Prospective Study
Authors: Page John H , Ma Jing , Pollak Michael , Manson JoAnn E , Hankinson Susan E 
Published: August 2008

AbstractBackground: The aim of this study was to prospectively evaluate relationships between plasma concentrations of insulinlike growth factor 1 (IGF1) and insulinlike growth factor binding protein 3 (IGFBP3) and subsequent myocardial infarction (MI) in women.Methods: We used case-control sampling to select study participants from women who had already been selected for inclusion in the prospective Nurses’ Health Study cohort. Blood samples were collected from 32 826 women in 1989–1990. During the follow-up period from sample collection through June 1998, MI (fatal and nonfatal) was diagnosed in 245 women. Cases were matched to controls 1:2 by age, cigarette-smoking status, and month and fasting status at the time of blood collection. Conditional logistic regression was used to adjust for potential confounders (menopausal status, parental history of MI, postmenopausal hormone use, diabetes mellitus, hypertension, hypercholesterolemia, aspirin use, alcohol use, body mass index, and physical activity).Results: Multivariable adjusted analyses did not reveal a statistically significant linear relationship between IGF1 or IGFBP3 concentrations or their molar ratio and risk of MI. Women in the highest IGF1 quartile had a multivariable-adjusted rate ratio of 1.46 (95% CI 0.79, 2.72; P for trend = 0.46) for MI, compared with those in the lowest. The corresponding rate ratios (95% CI) for IGFBP3 and the IGF1:IGFBP3 mol/L ratio were 1.24 (0.71, 2.17) and 1.29 (0.70, 2.37), respectively.Conclusions: We did not observe a monotonic relationship between IGF1 or IGFBP3 and MI among predominantly postmenopausal women. Future studies are warranted to evaluate these relationships in other demographic groups including younger women.
Anchor-Based Fluorescent Amplicon Generation Assays (FLAG) for Real-Time Measurement of Human Cytomegalovirus, Epstein–Barr Virus, and Varicella-Zoster Virus Viral Loads
Authors: Di Nicola Alessandro , Ghezzi Elisa , Gillio Federico , Zerilli Francesco , Shehi Erlet , Maritano Diego , Panizzo Massimo , Bonelli Fabrizio , Adlerstein Daniel 
Published: August 2008

Abstract
Background: Monitoring the human cytomegalovirus (HCMV), Epstein–Barr virus (EBV), or varicella-zoster virus (VZV) viral load is an important factor in the management of immunosuppressed patients, such as recipients of solid-organ or bone marrow transplants. The advent of real-time PCR technologies has prompted the widespread development of quantitative PCR assays for the detection of viral loads and other diagnostic purposes.
Methods: The fluorescent amplicon generation (FLAG) technology uses the PspGI restriction enzyme to monitor PCR product generation. We modified the FLAG technology by introducing an accessory oligonucleotide “anchor” that stabilizes the binding of the forward primer to the target sequence (a-FLAG). We developed assays for HCMV, EBV, and VZV that incorporated an internal amplification-control reaction to validate negative results and extensively analyzed the performance of the HCMV a-FLAG assay.
Results: The 3 assays performed similarly with respect to reaction efficiency and linear range. Compared with a commercially available kit, the HCMV a-FLAG assay results showed good correlation with calculated concentrations (r = 0.9617), excellent diagnostic sensitivity and specificity (99% and 95%, respectively), and similar values for the linear range (1–107 copies/μL), analytical sensitivity (0.420 copies/μL), and intra- and interassay imprecision.
Conclusions: The a-FLAG assay is an alternative real-time PCR technology suitable for detecting and quantifying target-DNA sequences. For clinical applications such as the measurement of viral load, a-FLAG assays provide multiplex capability, internal amplification control, and high diagnostic sensitivity and specificity.
Newborn Screening for Pompe Disease by Measuring Acid α-Glucosidase Activity Using Tandem Mass Spectrometry
Authors: Dajnoki Angéla , Mühl Adolf , Fekete György , Keutzer Joan , Orsini Joe , DeJesus Victor , Zhang X Kate , Bodamer Olaf A 
Published: August 2008

Abstract
background: Pompe disease, caused by the deficiency of acid α-glucosidase (GAA), is a lysosomal storage disorder that manifests itself in its most severe form within the first months of life. Early detection by newborn screening is warranted, since prompt initiation of enzyme replacement therapy may improve morbidity and mortality. We evaluated a tandem mass spectrometry (MS/MS) method to measure GAA activity for newborn screening for Pompe disease.
methods: We incubated 3.2-mm punches from dried blood spots (DBS) for 22 h with the substrate [7-benzoylamino-heptyl)-{2-[4-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-phenylcarbamoyl]- ethyl}-carbamic acid tert-butyl ester] and internal standard [7-d5-benzoylamino-heptyl)-[2-(4-hydroxy-phenylcarbamoyl)-ethyl]-carbamic acid tertbutyl ester]. We quantified the resulting product and internal standard using MS/MS. We assessed inter- and intrarun imprecision, carryover, stability, and correlation between enzyme activities and hematocrit and punch location and generated a Pompe disease–specific cutoff value using routine newborn screening samples.
results: GAA activities in DBS from 29 known Pompe patients were &lt;2 μmol/h/L. GAA activities in routine newborn screening samples were [mean (SD)] 14.7 (7.2) μmol/h/L (n = 10 279, median 13.3, 95% CI 14.46–14.74 μmol/h/L) and in normal adult samples 9.3 (3.3) μmol/h/L (n = 229, median 9, 95% CI 8.88–9.72 μmol/h/L). GAA activity was stable for 28 days between 37 °C and −80 °C. Carryover could not be observed, whereas intrarun and interrun imprecision were &lt;10%. The limit of detection was 0.26 μmol/h/L and limit of quantification 0.35 μmol/h/L.
conclusions: The measurement of GAA activities in dry blood spots using MS/MS is suitable for high-throughput analysis and newborn screening for Pompe disease.
Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide
Authors: Puig-Domingo Manel , Díaz Gonzalo , Nicolau Joanna , Fernández Cristián , Rueda Sergio , Halperin Irene 
Published: August 2008

ObjectiveHypoparathyroidism is usually controlled with calcium and vitamin-D supplements; in very few cases this treatment fails and teriparatide may be an alternative. We report the first case of hypoparathyroidism refractory to vitamin-D therapy requiring multipulse teriparatide treatment.Case reportA 53 year-old woman presented severe hypocalcemia and hypomagnesemia after thyroidectomy. Preoperatively, mild hypercalciuria was detected with parathyroid hormone (PTH) 69 pg/ml (normal 10–45) and 25-OH-vitamin D 9 ng/ml (normal 20–40) and normal levels of magnesium. No response was seen with oral and i.v. calcium and magnesium, or even with 5 μg calcitriol/day, suggesting a vitamin-D resistance status. Calcium sensor and vitamin-D receptor gene mutation studies were negative.Interventions and resultsThe following treatments were tried: i) s.c. recombinant human PTH (rhPTH) 1–34 plus oral calcitriol, calcium, and magnesium, was partially effective, but symptoms resumed 4 h after the injection of 20 μg rhPTH; stable calcemia was not achieved even with 4–6 injections/day of teriparatide; ii) two trials of heterologous parathyroid transplant were performed but rejection was detected 3 months after; iii) i.v. magnesium decreased rhPTH requirements but i.m. administration was not tolerated and iv) multipulse s.c. infusion of teriparatide achieved complete normalization of serum calcium, phosphate, magnesium, calciuria and magnesuria with relatively low rhPTH doses (25–35 μg/day) for more than a year.ConclusionsVitamin-D unresponsiveness leads to uncontrolled hypocalcemia when postsurgical hypoparathyroidism occurs; in situations of no response to usual or higher doses of vitamin-D and s.c. injections of rhPTH, treatment with teriparatide multipulse s.c. infusor is an effective and safe alternative.
Elevated ghrelin levels in preterm born children during prepubertal ages and relationship with catch-up growth
Authors: Darendeliler Feyza , Bas Firdevs , Bundak Ruveyde , Coban Asuman , Disci Rian , Sancakli Ozlem , Gokcay Gulbin , Ince Zeynep , Can Gulay 
Published: August 2008

BackgroundGhrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effect. Ghrelin levels are negatively associated with insulin secretion, increased in anorexia, and reduced in obesity. Increased ghrelin levels may be associated with early postnatal growth in preterm born children.ObjectiveAim of this study was to evaluate ghrelin and insulin levels at prepubertal ages in preterm born children born appropriate for gestational age (AGA) or small for gestational age (SGA) and relationships with catch-up growth (CUG) in a prospective cross-sectional study.MethodsEighty-four preterm born children grouped as preterm SGA (n=28) and preterm AGA (n=56) were evaluated at age 4.7±0.2 and 4.7±0.1 years with respect to their ghrelin and insulin levels. Their data were compared with that of body mass index matched term SGA (n=35) and term AGA (n=44) children of age 4.6±0.2 and 3.8±0.1 years. All children had height appropriate for their target height. CUG was defined as the difference between birth size and recent size and expressed as Δ height and Δ weight SDS.ResultsPreterm SGA and preterm AGA children had similar ghrelin levels (1717.0±166.9 and 1656.5±103.8 pg/ml), although Δ height and Δ weight SDS in preterm SGA were significantly higher than in preterm AGA children (P<0.001). Ghrelin levels in both preterm groups were higher than term SGA (469.2±132.5 pg/ml) and term AGA children (659.6±143.3 pg/ml; P<0.001 for all). Δ Height and Δ weight SDS of the term SGA children were similar to that of preterm SGA children. Ghrelin did not have correlation with CUG but had inverse correlation with recent anthropometric indices. Insulin was significantly higher in term SGA children than other groups (P<0.001).ConclusionsPreterm children have higher ghrelin levels at prepubertal ages regardless of the magnitude of their CUG. Term SGA children, on the other hand, behave differently and have lower ghrelin levels than preterm children at prepubertal ages, which may be related to elevated insulin levels in this group.