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71.
α-Alkylation of amino acid derivatives: Synthesis and chiral resolution of [C]β-aminoisobutyric acid
A synthesis of 11C-labeled β-aminoisobutyric acid ([11C]β-AIB) and its enantiomeric resolution by high performance liquid chromatography (HPLC) are reported. β-Alanine ethyl ester 2 was converted to benzaldimine-β-alanine ethyl ester 3 in 87% yield. Treatment of the imine derivative 3 with lithium diisopropylamide (1.1 eq) in tetrahydrofuran at −78 °C, followed by addition of cold iodomethane (1.1 eq) produced the -methylated benzaldimine-β-alanine ethyl ester 4 in 73% chemical yield. Deprotection of the amino group by acidic hydrolysis followed by basic hydrolysis of the ester group produced the desired product 1 in 37% chemical yield. Labeling was accomplished using [11C]methyl iodide. The radiola-beled product was purified by HPLC using a semipreparative reversed-phase C-18 column and 2 mM phosphate buffer (pH 5.9) as the mobile phase. The synthesis time was 35–40 min including HPLC purification, with 20–60% radiochemical yield (decay corrected). Radiochemical purity was >99%, with average specific activity being 450 mCi/μmol. Enantiomers of β-AIB were well separated by analytical HPLC using a chiral column and aqueous perchloric acid as the mobile phase. (S)-β-AIB was eluted at 17.4 min and the (R)-enantiomer was eluted at 20.0 min when the jacketed column was maintained at low temperature by circulation of ice-cold water, and the pH of the mobile phase was 1.05. 相似文献
72.
Edmond Zahedi Kalaivani Chellappan Mohd Alauddin Mohd Ali Harwant Singh 《Cardiovascular Engineering》2007,7(4):172-181
Ageing is one of the main contributing factors towards increasing arterial stiffness, leading to changes in peripheral pulses
propagation. Therefore the characteristics of the photoplethysmogram (PPG) pulse, especially the rising edge and peak position,
are greatly affected. In this study, the PPG pulse rising edge and corresponding peak position have been investigated non-invasively
in human subjects as a function of age. Fifteen healthy subjects were selected and grouped in five age intervals, from 20
to 59 years, based on their comparable systolic-diastolic blood pressure and PPG amplitude. As expected, the peripheral pulse
shows a steep rise and early peak in younger subjects. With age, the slope becomes blunted and in older subjects, the rise
is very gradual and the pulse peak appears much later. Qualitative results were further verified by a modified 10-element
Windkessel model to quantify the lumped parameter changes with ageing. This verification highlighted some specific changes
in vascular parameters with aging. The rising edge could be considered as one parameter in determining the age-dependent vascular
state. 相似文献
73.
Mustafa Uysal Metin Ozalay Alihan Derincek Alauddin Kochai Mehmet Turker 《Acta orthopaedica et traumatologica turcica》2018,52(4):272-276
Objective
The aim of this study was to evaluate the effects of PLIF and TLIF on sagittal spinopelvic balance and to compare radiological results of two surgical procedures with regard to spinopelvic parameters.Methods
Thirty-five patients (34 female and 1 male; mean age: 52.29 ± 13.08 (range: 35–75)) with degenerative spondylolisthesis cases were included in the study. Patients were divided into two groups according to surgical technique: PLIF and TLIF. The level and the severity of listhesis according to Meyerding classification were assessed and spinopelvic parameters including sacral slope, pelvic tilt, pelvic incidence (PI), lumbar lordosis, and segmental lumbar lordosis were measured on digital X-rays. All preoperative and postoperative parameters and the results were compared between two groups.Results
The age distribution was similar in both groups (p = 0.825) and there was no difference between the mean PI of the groups (p = 0.616). In 15 patients, spondylolisthesis level were at the L5-S1 level (PLIF: 8, TLIF: 7), in 16 patients at the L4-L5 level (PLIF: 6, TLIF: 10) and in 4 patients at the L3-L4 level (PLIF: 2, TLIF: 2). According to Meyerding classification, before the operation, the sliding grades were 0 in 4 patients, 1 in 21 patients, 2 in 7 patients, and 3 in 3 patients. The grades changed into 0 in 28 patients, 1 in 5 patients, and 2 in 2 patients after surgery. There were no differences in the grade of listhesis between PLIF and TLIF groups preoperatively (p = 0.190) and postoperatively (p = 0.208). In both groups, the spondylolisthesis-related deformities of patients were significantly corrected after surgery (p < 0.001).Conclusion
PLIF and TLIF techniques have similar radiological results in restoring the sagittal spinopelvic balance in patients with degenerative spondylolisthesis. Both techniques are good options to achieve reduction and fusion in patients with degenerative spondylolisthesis, but have no advantage over each other for restoring spinopelvic balance.Level of evidence
Level III, Therapeutic study. 相似文献74.
Fatih Yildiz Abdulkadir Sari Anil Pulatkan Vahdet Ucan Alauddin Kochai Kerem Bilsel 《Acta orthopaedica et traumatologica turcica》2018,52(4):245-248
Objective
The aim of this study was to investigate whether coexistent intraarticular lesions are negative prognostic factors for the results of arthroscopic capsular release in frozen shoulder patients.Methods
Seventy-two patients who met inclusion criteria and underwent arthroscopic capsular release between March 2011 and August 2015 for the frozen shoulder were retrospectively evaluated. The patients were divided into two groups according to existence of concomitant intraarticular pathologies detected during arthroscopy. Preoperative and postoperative functional results were assessed with Constant score and shoulder ranges of motion; and the amount of pain was evaluated using visual analog scale (VAS).Results
Group I consisted of 46 patients (mean age 47.2 years and mean follow-up 26 months) without concomitant shoulder pathologies and group II consisted of 26 patients (mean age 48.6 years and mean follow-up 15 months) with coexistent lesions (SLAP lesions, n = 8; SLAP and partial rupture of the RC, n = 4; SLAP, partial rupture of RC and impingement, n = 10; SLAP and impingement, n = 2; and AC arthritis and impingement, n = 2). Preoperatively, the mean ranges of forward flexion (p = 0.221), abduction (p = 0.065), internal rotation (p = 0.564), Constant (p = 0.148) and VAS (p = 0.365) scores were similar between the groups. After a minimum 12 months of follow-up, all patients significantly improved but no statistically significant difference was detected in the mean ranges of forward flexion (152 vs 150; p = 0.902), abduction (137 vs 129; p = 0.095), external rotation (45 vs 40; p = 0.866), internal rotation (5 vs 5 point; p = 0.474), Constant (82 vs 82.3; p = 0.685) and VAS (1.2 vs 1.2; p = 0.634) scores between the groups.Conclusion
The presence of concomitant shoulder pathologies does not appear to affect the clinical outcomes in patients undergoing arthroscopic capsular release for frozen shoulder.Level of evidence
Level III, Therapeutic study. 相似文献75.
Fen Wu Farzana Jasmine Muhammad G. Kibriya Mengling Liu Xin Cheng Faruque Parvez Tariqul Islam Alauddin Ahmed Muhammad Rakibuz-Zaman Jieying Jiang Shantanu Roy Rachelle Paul-Brutus Vesna Slavkovich Tariqul Islam Diane Levy Tyler J. VanderWeele Brandon L. Pierce Joseph H. Graziano Habibul Ahsan Yu Chen 《Environmental health perspectives》2015,123(5):451-457
Background: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited.Objective: We investigated whether the association between well-water arsenic and cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction.Method: We conducted a prospective case-cohort study nested in the Health Effects of Arsenic Longitudinal Study, with a random subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD. Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke cases, and 44 deaths due to other CVD identified during follow-up from 2000 to 2012.Results: Of the 170 SNPs tested, multiplicative interactions between well-water arsenic and two SNPs, rs281432 in ICAM1 (padj = 0.0002) and rs3176867 in VCAM1 (padj = 0.035), were significant for CVD after adjustment for multiple testing. Compared with those with GC or CC genotype in rs281432 and lower well-water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31, 2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype, which was greater than expected given aHRs of 1.08 and 0.96 for separate effects of arsenic and the genotype alone, respectively. Similarly, the joint aHR for arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than expected given aHRs for their separate effects of 1.02 and 0.84, respectively.Conclusions: Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.Citation: Wu F, Jasmine F, Kibriya MG, Liu M, Cheng X, Parvez F, Islam T, Ahmed A, Rakibuz-Zaman M, Jiang J, Roy S, Paul-Brutus R, Slavkovich V, Islam T, Levy D, VanderWeele TJ, Pierce BL, Graziano JH, Ahsan H, Chen Y. 2015. Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort study. Environ Health Perspect 123:451–457; http://dx.doi.org/10.1289/ehp.1307883 相似文献
76.
Jieying Jiang Mengling Liu Faruque Parvez Binhuan Wang Fen Wu Mahbub Eunus Sripal Bangalore Jonathan D. Newman Alauddin Ahmed Tariqul Islam Muhammad Rakibuz-Zaman Rabiul Hasan Golam Sarwar Diane Levy Vesna Slavkovich Maria Argos Molly Scannell Bryan Shohreh F. Farzan Richard B. Hayes Joseph H. Graziano Habibul Ahsan Yu Chen 《Environmental health perspectives》2015,123(8):806-812
Background
Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking.Method
We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure during follow-up (median, 6.7 years).Result
In the HEALS population, the median water arsenic concentration at baseline was 62 μg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in systolic blood pressure compared with those in the reference group (β = 0.48 mmHg/year; 95% CI: 0.35, 0.61, and β = 0.43 mmHg/year; 95% CI: 0.29, 0.56 for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in diastolic blood pressure for water arsenic and urinary creatinine-adjusted arsenic, (β = 0.39 mmHg/year; 95% CI: 0.30, 0.49, and β = 0.45 mmHg/year; 95% CI: 0.36, 0.55, respectively) compared with those in the lowest quartile.Conclusion
Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease.Citation
Jiang J, Liu M, Parvez F, Wang B, Wu F, Eunus M, Bangalore S, Newman JD, Ahmed A, Islam T, Rakibuz-Zaman M, Hasan R, Sarwar G, Levy D, Slavkovich V, Argos M, Scannell Bryan M, Farzan SF, Hayes RB, Graziano JH, Ahsan H, Chen Y. 2015. Association between arsenic exposure from drinking water and longitudinal change in blood pressure among HEALS cohort participants. Environ Health Perspect 123:806–812; http://dx.doi.org/10.1289/ehp.1409004 相似文献77.
Hafiza Alauddin Noor-Adilah Jaapar Raja Z. Azma Azlin Ithnin Noor-Farisah A. Razak C-Khai Loh 《Hemoglobin》2014,38(4):277-281
Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a rare hemoglobin (Hb) variant due to a mutation at codon 59 of the α2- or α1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, α142, Term→Gln, TAA>CAA; HBA2: c.427?T>C) (αcodon 59α/αCSα), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7?kb deletion (αcodon 59α/?α3.7). Although they all had α-thalassemia intermedia (α-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison. 相似文献
78.
Fen Wu Farzana Jasmine Muhammad G. Kibriya Mengling Liu Xin Cheng Faruque Parvez Rachelle Paul-Brutus Tariqul Islam Rina Rani Paul Golam Sarwar Alauddin Ahmed Jieying Jiang Tariqul Islam Vesna Slavkovich Tatjana Rundek Ryan T. Demmer Moise Desvarieux Habibul Ahsan Yu Chen 《Toxicology and applied pharmacology》2014
Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. 相似文献
79.
Mian M Alauddin Antranic Shahinian Ryan Park Michel Tohme John D Fissekis Peter S Conti 《Journal of nuclear medicine》2004,45(12):2063-2069
2'-deoxy-2'-(18)F-fluoro-5-fluoro-1-beta-D-arabinofuranosyluracil ((18)F-FFAU) has been synthesized and evaluated in HT-29 cells as a potential PET agent for herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression. METHODS: 2-Deoxy-2-(18)F-fluoro-1,3,5-tri-O-benzoyl-alpha-D-arabinofuranose was prepared by the reaction of the respective 2-triflate with tetrabutylammonium (18)F-fluoride. The fluorosugar was converted to its 1-bromo derivative and coupled with protected 5-fluorouracil. The crude product was hydrolyzed in base and purified by high-performance liquid chromatography to obtain the (18)F-FFAU. In vitro studies were performed in HT-29 cells by incubation at various time points. In vivo studies including biodistribution and microPET were performed in tumor-bearing nude mice. RESULTS: The radiochemical yield was 20%-30% decay corrected with an average of 25% in 4 runs. Radiochemical purity was >99% and average specific activity was 85 GBq/micromol (2,300 mCi/micromol) (end of synthesis). In vitro accumulation of (3)H-FFAU in HSV1-tk-expressing cells was approximately 180-fold (P < 0.001) higher than that in the wild-type cells between 30 and 120 min. In vivo uptake of (3)H-FFAU in HSV1-tk-positive tumors at 2 h was approximately 8-fold (P < 0.001) higher than that in the control tumors. Tumor uptake (percentage injected dose per gram of tissue) and the uptake ratio (tk-positive to wild type) of (3)H-FFAU in tk-positive cells was higher compared with those of our earlier studies using 2'-(14)C-deoxy-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ((14)C-FMAU) and 9-(4-(18)F-fluoro-3-hydroxymethylbutyl)guanine ((18)F-FHBG) in the same cell lines. microPET on tumor-bearing nude mice also demonstrated a very high uptake of (18)F-FFAU in tk-positive tumors compared with that of the control tumor without significant accumulation in other organs. CONCLUSION: These results demonstrate that (18)F-FFAU has superior biodistribution characteristics and significantly higher in vivo uptake in HSV1-tk-expressing tumor compared with previously studied agents. 相似文献
80.
Peter S. Conti John Hilton Dean F. Wong Mian M. Alauddin Robert F. Dannals Hayden T. Ravert Alan A. Wilson James H. Anderson 《Nuclear medicine and biology》1994,21(8):1045-1051
The identity and pharmacology of the rapidly formed radiolabeled metabolites formed following i.v. injection of C-11 thymidine (TdR) labeled in the 5-methyl-position are being studied in animal models and patients with cancer. A high performance liquid chromatographic (HPLC) procedure has been developed for the separation of these metabolites including thymine, dihydrothymine, β-ureidoisobutyric acid, and β-aminoisobutyric acid from plasma and tissue extracts. Information obtained regarding the pharmacokinetics of the metabolites are being used to generate mathematical models for C-11 TdR incorporation rates into DNA. 相似文献