ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInternal H-C-C angle dependence of vicinal 1H-1H coupling constantsMichael Barfield and William B. SmithCite this: J. Am. Chem. Soc. 1992, 114, 5, 1574–1581Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/ja00031a006https://doi.org/10.1021/ja00031a006research-articleACS PublicationsRequest reuse permissionsArticle Views210Altmetric-Citations81LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and the HolocaustWilliam B. Smith Cite this: J. Chem. Educ. 1982, 59, 10, 836Publication Date (Print):October 1, 1982Publication History Received3 August 2009Published online1 October 1982Published inissue 1 October 1982https://doi.org/10.1021/ed059p836RIGHTS & PERMISSIONSArticle Views365Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-Alerts Get e-Alerts
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Nature of the Reaction of 2-Methylpyridine with Aniline and N-MethylanilineWilliam B. SmithCite this: J. Org. Chem. 1962, 27, 12, 4641–4643Publication Date (Print):December 1, 1962Publication History Published online1 May 2002Published inissue 1 December 1962https://pubs.acs.org/doi/10.1021/jo01059a506https://doi.org/10.1021/jo01059a506research-articleACS PublicationsRequest reuse permissionsArticle Views83Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Study Objectives. To compare the effects of gatifloxacin and ciprofloxacin on glucose homeostasis, including glucose tolerance test (GTT), pancreatic β‐cell function, and insulin production and secretion in patients with noninsulin‐dependent (type 2) diabetes mellitus (NIDDM) maintained with diet and exercise; and to evaluate the pharmacokinetics, safety, and tolerability of gatifloxacin. Design. Randomized, double‐blind, placebo‐controlled, multiple‐dose study. Setting. GFI Pharmaceutical Services, Inc., Evansville, Indiana; Chicago Center for Clinical Research, Chicago, Illinois; and New Orleans Center for Clinical Research, New Orleans, Louisiana, USA. Patients. Forty‐eight men and women with NIDDM. Interventions. Patients were assigned sequentially at enrollment to receive gatifloxacin 400 mg/day orally, ciprofloxacin 500 mg twice/day orally, or placebo for 10 days. Oral GTTs were performed on specific days throughout the study, as well as measurements of serum glucose, serum insulin, and C‐peptide levels. Physical examinations, electrocardiograms, spirometry, and clinical laboratory tests were performed before dosing and on selected dosing days. Measurements and Main Results. Gatifloxacin had no significant effect on glucose tolerance and pancreatic β‐cell function, as shown by oral GTT results and insulin and C‐peptide levels. Fasting glucose levels 0–6 hours after gatifloxacin administration on days 1 and 10 showed a downward trend, but it was not significant compared with placebo; results were similar with ciprofloxacin. Gatifloxacin also lacked a long‐term effect on fasting insulin levels, but this was not shown for a short‐term effect, suggesting a modest, transient effect on insulin release. On the other hand, ciprofloxacin had no short‐term effect but produced a more sustained effect on insulin release and production. The pharmacokinetics of gatifloxacin in patients with NIDDM were similar to those in healthy subjects. Overall, subjects tolerated treatment well. All reported drug‐related adverse events were mild to moderate in intensity. The frequency of adverse events was similar in gatifloxacin‐ and ciprofloxacin‐treated patients, and only slightly higher than in placebo‐treated patients. Conclusion. Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, β‐cell function, or long‐term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.
BACKGROUND/AIMS This study was conducted to evaluate the influence of renal insufficiency (RI) on the pharmacokinetics (PK) of sitagliptin (SIT), a selective DPP-IV inhibitor in Phase III development for the treatment of type 2 diabetes. METHODS 6 patients/subjects in each of the following groups: mild RI (creatinine clearance (CrCl) = 50 to 80 mL/min), moderate RI (CrCl = 30 to 50 mL/min), severe RI (CrCl < 30 mL/min) and healthy subjects (CrCl > 80 mL/min). Each group received a single oral 50-mg dose of SIT. End-stage renal disease (ESRD) patients received 2 single oral 50-mg doses (hemodialysis 4-hr or 48-hr postdose). SIT PK in RI patients was compared to concurrent and historical control subjects. Less than 2-fold increases in AUC0-∞were not considered clinically meaningful changes. RESULTS SIT AUC0-∞ was approximately inversely related to CrCl. Renal clearance (ClR) was approximately proportional to CrCl. AUC0-∞ increased less than 2-fold for CrCl > 50 mL/min. AUC0-∞ was 1.6, 2.3, 3.8 and 4.5-fold higher in mild RI, moderate RI, severe RI and ESRD patients, respectively, compared to healthy subjects. Cmax was 1.4, 1.4, 1.8 and 1.4 higher in mild moderate and severe RI and ESRD, respectively. Dialysis removed ∼13.5% of the dose. SIT was well tolerated in all groups. CONCLUSIONS Mild RI patients do not require dose-adjustment. To obtain an exposure of SIT similar to patients without renal insufficiency, moderate RI, and severe RI and ESRD patients should receive ½ and ¼ of the usual SIT dose, respectively. Clinical Pharmacology & Therapeutics (2005) 79, P75–P75; doi: 10.1016/j.clpt.2005.12.268
Abstract Background The ExPEC4V vaccine contains 4 Escherichia coli O-antigens (O1A, O2, O6A, O25B) conjugated to exotoxin protein A and is being studied for prevention of Invasive Extraintestinal pathogenic E. coli (ExPEC) Disease (IED). This phase-2 double-blind study assessed safety and immunogenicity of ExPEC4V Clinical Trial Material (CTM), manufactured via a redesigned process (optimized O1A strain). Methods Participants (≥18 years) in stable health were randomized (3:1) to receive ExPEC4V dose 4:4:4:8 μg PS/serotype or placebo on Day 1 and second vaccination on Day 181 (6 months after first vaccination). Participants will be followed for safety until end of study at Day 360. Reactogenicity and immunogenicity (by ELISA, opsonophagocytic killing [OPA] assays) were evaluated pre-vaccination, and 15 days after first and second vaccinations (Day 195). Results Of 100 participants randomized (mean age 56, 48% males) and vaccinated (ExPEC4V, n = 75; placebo, n = 25), 97 completed Day 30. Solicited local AEs were higher for ExPEC4V (38.7%) than placebo (20%); most frequent was pain/tenderness (38.7% vs 20%). Solicited systemic AEs were higher in ExPEC4V (49.3%) than placebo (20%); most frequent was fatigue (32% vs. 12%). No serious or grade 3 solicited local AEs were reported. One participant in ExPEC4V experienced a grade 3 solicited systemic fatigue considered vaccine-related by investigator. ExPEC4V demonstrated immune responses against all serotypes at Day 15. Geometric mean titer effective concentration rank by serotypes was O2 > O1A > O6 > O25B (Figures 1 and 2). At Day 15, ≥ 82% of participants in ExPEC4V and none in placebo had ≥2-fold increase from baseline of ELISA titer for all serotypes. In ExPEC4V, ≥47% had ≥2-fold increase from baseline of OPA titer for all serotypes, while 8% in placebo had ≥2-fold increase only for O6A. Good correlation was observed between ELISA and OPA across serotypes (r ≥ 0.76). Conclusion ExPEC4V elicited robust and functional immune responses across all serotypes and was well tolerated with no vaccine safety findings. This study supports the development of future multivalent ExPEC vaccine to prevent IED. Disclosures All authors: No reported disclosures.
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