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1.
Hum Reprod ; 38(7): 1325-1331, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37208860

ABSTRACT

STUDY QUESTION: How often do patients undergoing frozen embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) choose to select for sex and do sex selection rates differ before and after successful delivery of a first baby? SUMMARY ANSWER: When a choice was available between male and female embryos, patients selected the sex more frequently when trying to conceive the second child (62%) as compared to the first child (32.4%) and most commonly selected for the opposite sex of the first child. WHAT IS KNOWN ALREADY: Sex selection is widely available in US fertility clinics. However, the rate of sex selection for patients undergoing FET after PGT-A is unknown. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of 585 patients that took place between January 2013 and February 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study took place at a single, urban academic fertility center in the USA. Patients were included if they had a live birth after single euploid FET and returned for at least one subsequent euploid FET. The primary outcomes were the rates of sex selection for first versus second baby. Secondary outcomes were rate of selection for same versus opposite sex as first live birth and overall rate of selection for males versus females. MAIN RESULTS AND THE ROLE OF CHANCE: Five hundred and eighty-five patients underwent a total of 1560 single euploid FETs resulting in either one or two live births. A choice between male and female euploid embryos was available for 919 FETs (first child: 67.5% (519/769) versus second child: 50.6% (400/791), P < 0.01). When a choice was available, patients selected the sex more frequently when trying to conceive the second child (first child: 32.4% (168/519) versus second child: 62.0% (248/400), P < 0.01). When sex was selected after first live birth, the opposite sex of the first child was selected 81.8% (203/248 FETs) of the time. Of transfers that involved sex selection, rates of male and female selection were similar for the first child, but selection for females was greater for the second child (first child: 51.2% (86/168) male versus 48.9% (82/168) female, second child: 41.1% (102/248) male versus 58.9% (146/248) female, P < 0.04). LIMITATIONS, REASONS FOR CAUTION: The study was performed at one urban academic medical center in the Northeastern US, which may limit generalizability to other settings where PGT-A may be performed less frequently, or sex selection may be limited or not permitted. In addition, we could not reliably account for whether patients or their partners had prior children and if so, of what sex. WIDER IMPLICATIONS OF THE FINDINGS: Patients undergoing PGT-A with both male and female euploid embryos were more likely to select for sex when attempting a second child and usually selected for the opposite sex of their first child. These findings highlight the potential for family balancing for patients who undergo PGT-A in settings where sex selection is permitted. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Preimplantation Diagnosis , Sex Preselection , Pregnancy , Child , Humans , Female , Male , Retrospective Studies , Embryo Implantation , Genetic Testing , Aneuploidy , Preimplantation Diagnosis/methods , Blastocyst
2.
Nat Mater ; 20(1): 49-54, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32690911

ABSTRACT

Engineering of defects located in grains or at grain boundaries is central to the development of functional materials. Although there is a surge of interest in the formation, migration and annihilation of defects during ion and plasma irradiation of bulk materials, these processes are rarely assessed in low-dimensional materials and remain mostly unexplored spectroscopically at the micrometre scale due to experimental limitations. Here, we use a hyperspectral Raman imaging scheme providing high selectivity and diffraction-limited spatial resolution to examine plasma-induced damage in a polycrystalline graphene film. Measurements conducted before and after very low-energy (11-13 eV) ion bombardment show defect generation in graphene grains following a zero-dimensional defect curve, whereas domain boundaries tend to develop as one-dimensional defects. Damage generation is slower at grain boundaries than within the grains, a behaviour ascribed to preferential self-healing. This evidence of local defect migration and structural recovery in graphene sheds light on the complexity of chemical and physical processes at the grain boundaries of two-dimensional materials.

3.
Int Nurs Rev ; 67(2): 275-281, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31898328

ABSTRACT

AIM: This paper describes an initiative facilitating comprehensive assessment and delivery of brief interventions for Maori youth in Northland, New Zealand. BACKGROUND: The population in Northland is predominantly Maori and is one of New Zealand's most deprived populations. Maori youth have the highest youth suicide rate in the developed world and elevated numbers of youth displaying mental health issues and/or risk behaviours are of grave national concern. Like Indigenous peoples worldwide, inequities persist for Maori youth accessing and engaging with healthcare services. DESCRIPTION: Taking services out to Maori youth in remote and isolated areas, Northland's youth specialist nurses are reducing some barriers to accessing health care. The youth version of the Case-finding and Help Assessment Tool is a New Zealand-developed, e-screening tool for youth psychosocial issues, facilitating comprehensive assessment and brief intervention delivery. DISCUSSION: Early detection of, and timely intervention for, mental health and risk behaviours can significantly improve health outcomes in youth. However, for this to happen barriers preventing youth from accessing appropriate care need to be overcome. CONCLUSION: Youth specialist nurses could improve access to care for youth from ethnic minorities, rural and isolated regions, and areas of high deprivation without overwhelming the medical profession. IMPLICATIONS FOR NURSING POLICY: Specialist nurses are trained and empowered to practice at the top of their scope. With general practitioner oversight and standing order sign off specialist nurses can work autonomously to improve access to health services, without increasing the workload of doctors. IMPLICATIONS FOR NURSING PRACTICE: Encouraging continuous self-reflection of the nurse's effectiveness in meeting patient needs, holistically and culturally, facilitates the provision of accessible care that is patient-centred and culturally safe.


Subject(s)
Ethnicity/statistics & numerical data , Health Services Accessibility/organization & administration , Healthcare Disparities/organization & administration , Indigenous Peoples/statistics & numerical data , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Nursing Care/organization & administration , Rural Population/statistics & numerical data , Adolescent , Female , Humans , Male , New Zealand , Qualitative Research , Young Adult
4.
J Nanosci Nanotechnol ; 18(7): 4565-4579, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-29442633

ABSTRACT

Heteroatom doping into carbon structures is an effective approach to enhance the electrochemical performance of carbon materials. In the work presented here, the electrocatalysts including: nitrogen and co-doped nitrogen and sulfur on porous graphene (PG) were synthesized by different precursors. The physico-chemical properties of the prepared samples were determined using X-ray Diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), N2 sorption-desorption, Transmission electron microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS). The prepared samples were further applied for oxygen reduction reaction (ORR) and the effects of pyrolysis temperature, precursor type and dose, on the prepared samples structure and their electrochemical performances were investigated. The results revealed that synergistic effect of nitrogen and sulfur co-doped on the graphene structure leads to improvement in catalytic activity and current. Furthermore, S and N co-doped graphene prepared using sulfur trioxide pyridine complex exhibited excellent methanol tolerance and long-term stability.

5.
Nano Lett ; 17(8): 4970-4975, 2017 08 09.
Article in English | MEDLINE | ID: mdl-28678509

ABSTRACT

The lack of large-area synthesis processes on substrates compatible with industry requirements has been one of the major hurdles facing the integration of 2D materials in mainstream technologies. This is particularly the case for the recently discovered monoelemental group V 2D materials which can only be produced by exfoliation or growth on exotic substrates. Herein, to overcome this limitation, we demonstrate a scalable method to synthesize antimonene on germanium substrates using solid-source molecular beam epitaxy. This emerging 2D material has been attracting a great deal of attention due to its high environmental stability and its outstanding optical and electronic properties. In situ low energy electron microscopy allowed the real time investigation and optimization of the 2D growth. Theoretical calculations combined with atomic-scale microscopic and spectroscopic measurements demonstrated that the grown antimonene sheets are of high crystalline quality, interact weakly with germanium, exhibit semimetallic characteristics, and remain stable under ambient conditions. This achievement paves the way for the integration of antimonene in innovative nanoscale and quantum technologies compatible with the current semiconductor manufacturing.

6.
Phys Rev Lett ; 110(17): 176801, 2013 Apr 26.
Article in English | MEDLINE | ID: mdl-23679754

ABSTRACT

The quantum Hall effect is observed in a two-dimensional electron gas formed in millimeter-scale hydrogenated graphene, with a mobility less than 10 cm2/V·s and corresponding Ioffe-Regel disorder parameter (k(F)λ)(-1) ≫ 1. In a zero magnetic field and low temperatures, the hydrogenated graphene is insulating with a two-point resistance of the order of 250h/e2. The application of a strong magnetic field generates a negative colossal magnetoresistance, with the two-point resistance saturating within 0.5% of h/2e2 at 45 T. Our observations are consistent with the opening of an impurity-induced gap in the density of states of graphene. The interplay between electron localization by defect scattering and magnetic confinement in two-dimensional atomic crystals is discussed.

7.
Mater Horiz ; 10(3): 983-992, 2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36644986

ABSTRACT

Polarized fluorescence emission of nanoscale emitters has been extensively studied for applications such as bioimaging, displays, and optical communication. Extending the polarization properties in large assemblies of compact emitters is, however, challenging because of self-aggregation processes, which can induce depolarization effects, quenching, and cancellations of molecular dipoles. Here we use α-sexithiophene (6T) molecules confined inside boron nitride nanotubes (6T@BNNTs) to induce fluorescence anisotropy in a transparent host. The experiments first indicate that individual 6T@BNNTs exhibit a high polarization extinction ratio, up to 700, at room temperature. Using aberration-corrected HRTEM, we show that the fluorescence anisotropy is consistent with a general alignment of encapsulated 6T molecules along the nanotube axis. The molecular alignment is weakly influenced by the nanotube diameter, a phenomenon ascribed to stronger molecule-to-sidewall interactions compared to intermolecular interactions. By stretching a flexible thin film made of transparent polymers mixed with 6T@BNNTs, we induce a macroscopic fluorescence anisotropy within the film. This work demonstrates that the dyes@BNNT system can be used as an easy-to-handle platform to induce fluorescence anisotropy in photonic materials.

8.
Nanoscale ; 13(5): 2891-2901, 2021 Feb 07.
Article in English | MEDLINE | ID: mdl-33533789

ABSTRACT

Monolayer graphene films are exposed to the flowing afterglow of a low-pressure microwave nitrogen plasma, characterized by the absence of ion irradiation and significant populations of N atoms and N2(A) metastables. Hyperspectral Raman imaging of graphene domains reveals damage generation with a progressive rise of the D/G and D/2D band ratios following subsequent plasma treatments. Plasma-induced damage is mostly zero-dimensional and the graphene state remains in the pre-amorphous regime. Over the range of experimental conditions investigated, damage formation increases with the fluence of energy provided by heterogenous surface recombination of N atoms and deexcitation of N2(A) metastable species. In such conditions, X-ray photoelectron spectroscopy reveals that the nitrogen incorporation (either as pyridine, pyrrole, or quaternary moieties) does not simply increase with the fluence of plasma-generated N atoms but is also linked to the damage generation. Based on these findings, a surface reaction model for monolayer graphene nitrogenation is proposed. It is shown that the nitrogen incorporation is first limited by the plasma-induced formation of defect sites at low damage and then by the adsorption of nitrogen atoms at high damage.

9.
Nano Lett ; 9(4): 1457-61, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19290611

ABSTRACT

We have investigated the charge injection efficiency of carbon nanotube electrodes for organic semiconducting layers and compared their performance to that of traditional noble metal electrodes. Our results reveal that charge injection from a single carbon nanotube electrode is more than an order of magnitude more efficient than charge injection from metal electrodes. Moreover, organic thin film transistors that use arrays of carbon nanotube electrodes display considerable effective mobilities (0.14 cm(2)/(V.s)) and nearly ideal linear output characteristics. These results indicate that carbon nanotubes should be considered a viable alternative to metal electrodes for next-generation organic field-effect transistors.

10.
Actas Dermosifiliogr ; 101(5): 415-20, 2010 Jun.
Article in Spanish | MEDLINE | ID: mdl-20525484

ABSTRACT

BACKGROUND: In a small number of cases of childhood atopic dermatitis, topical therapy is ineffective, necessitating prolonged use of systemic immunosuppressants. Over the last few years, a better understanding of the metabolic pathways involved in azathioprine breakdown has enabled us to use this drug more safely. In this study, we evaluated the toxicity of azathioprine treatment adjusted to thiopurine methyltransferase activity in children with severe atopic dermatitis. MATERIAL AND METHODS: We performed a retrospective study of the side effects of azathioprine therapy adjusted to thiopurine methyltransferase activity in children aged under 14 years with atopic dermatitis who were treated in the dermatology department of Hospital Universitario Insular de Gran Canaria in Gran Canaria, Spain. Side effects were evaluated by analysis of leukocyte count and transaminase levels at baseline, after 1 month of treatment, and every 3 months thereafter. RESULTS: During the last 4 years, 7 children (mean age, 10 years) with severe atopic dermatitis received azathioprine in our department. Mean duration of treatment was 12 months (range, 1 to 38 months). Only 2 patients presented mild transient leukopenia that did not require treatment to be suspended. DISCUSSION: Our experience shows that, when adjusted to thiopurine methyltransferase activity, azathioprine is a safe drug for the treatment of children with severe atopic dermatitis. However, clinical trials should be performed to compare the risk-benefit ratios of the different immunosuppressants used to treat these patients.


Subject(s)
Azathioprine/adverse effects , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/enzymology , Immunosuppressive Agents/adverse effects , Methyltransferases/metabolism , Adolescent , Azathioprine/therapeutic use , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Retrospective Studies , Severity of Illness Index
11.
Rev Sci Instrum ; 91(6): 063903, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32611065

ABSTRACT

Raman spectroscopy provides rich optical signals that can be used, after data analysis, to assess if a graphene layer is pristine, doped, damaged, functionalized, or stressed. The area being probed by a conventional Raman spectrometer is, however, limited to the size of the laser beam (∼1 µm); hence, detailed mapping of inhomogeneities in a graphene sample requires slow and sequential acquisition of a Raman spectrum at each pixel. Studies of physical and chemical processes on polycrystalline and heterogeneous graphene films require more advanced hyperspectral Raman capable of fast imaging at a high spatial resolution over hundreds of microns. Here, we compare the capacity of two different Raman imaging schemes (scanning and global) to probe graphene films modified by a low-pressure plasma treatment and present an analysis method providing assessments of the surface properties at local defects, grain boundaries, and other heterogeneities. By comparing statistically initial and plasma-treated regions of graphene, we highlight the presence of inhomogeneities after plasma treatment linked to the initial state of the graphene surface. These results provided statistical results on the correlation between the graphene initial state and the corresponding graphene-plasma interaction. This work further demonstrates the potential use of global hyperspectral Raman imaging with advanced Raman spectra analysis to study graphene physics and chemistry on a scale of hundreds of microns.

12.
J Phys Chem B ; 110(9): 3949-54, 2006 Mar 09.
Article in English | MEDLINE | ID: mdl-16509681

ABSTRACT

Polyelectrolyte solutions of Na-doped single-wall carbon nanotube (SWNT) salts are studied by Raman spectroscopy. Their Raman signature is first compared to undoped SWNT suspensions and dry alkali-doped SWNT powders, and the results indicate that the nanotube solutions consist of heavily doped (charged) SWNT. Raman signature of doping is then used to monitor in situ the oxidation reaction of the nanotube salt solutions upon exposure to air and to an acceptor molecule (benzoquinone). The results indicate a direct charge-transfer reaction from the acceptor molecule to the SWNT, leading to their gradual charge neutralization and eventual precipitation in solution. The results are consistent with a simple redox titration process occurring at the thermodynamical equilibrium.

13.
Nat Commun ; 6: 7702, 2015 Jul 07.
Article in English | MEDLINE | ID: mdl-26151889

ABSTRACT

Black phosphorus (bP) is the second known elemental allotrope with a layered crystal structure that can be mechanically exfoliated to atomic layer thickness. Unlike metallic graphite and semi-metallic graphene, bP is a semiconductor in both bulk and few-layer form. Here we fabricate bP-naked quantum wells in a back-gated field effect transistor geometry with bP thicknesses ranging from 6±1 nm to 47±1 nm. Using a polymer encapsulant, we suppress bP oxidation and observe field effect mobilities up to 900 cm(2) V(-1) s(-1) and on/off current ratios exceeding 10(5). Shubnikov-de Haas oscillations observed in magnetic fields up to 35 T reveal a 2D hole gas with Schrödinger fermion character in a surface accumulation layer. Our work demonstrates that 2D electronic structure and 2D atomic structure are independent. 2D carrier confinement can be achieved without approaching atomic layer thickness, advantageous for materials that become increasingly reactive in the few-layer limit such as bP.

14.
Gene ; 94(2): 181-7, 1990 Oct 15.
Article in English | MEDLINE | ID: mdl-1979547

ABSTRACT

Molecular chaperones of the chaperonin family occur in prokaryotes and in plastids and mitochondria. Prokaryotic and mitochondrial chaperonin-60 oligomers (Cpn-60) are composed of a single subunit type (p60cpn-60). In contrast, preparations of purified plastid Cpn-60 contain approximately equal quantities of two polypeptides, p60cpn-60 alpha and p60cpn-60 beta, with slightly different electrophoretic mobilities. We have isolated cDNA clones encoding plastid p60cpn-60 alpha and p60cpn-60 beta polypeptides from Brassica napus and Arabidopsis thaliana. The unexpected degree of sequence divergence observed between p60cpn-60 alpha and p60cpn-60 beta raises questions concerning the structure of the oligomer and the functions of these polypeptides. We have also found an amino acid sequence motif within all p60cpn-60 sequences which resembles the p10cpn-10 sequences.


Subject(s)
Bacterial Proteins/genetics , Fungal Proteins/genetics , Proteins/genetics , Amino Acid Sequence , Base Sequence , Brassica/genetics , Chaperonins , DNA/isolation & purification , Molecular Sequence Data , Prokaryotic Cells/drug effects , Sequence Homology, Nucleic Acid
15.
Int J Radiat Oncol Biol Phys ; 50(1): 213-20, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11316566

ABSTRACT

PURPOSE: Late thrombosis of irradiated vascular segments may be the consequence of endothelial cell (EC) dysfunction after radiation therapy. We investigated the effects of beta ionizing radiation on human EC viability, thymidine uptake, and differentiation. METHODS AND MATERIALS: Endothelial cells were exposed to (32)P-labeled DNA oligonucleotides in incremental doses of 2, 6, and 10 Gy. The modulation of the VEGFR2 receptor expression after irradiation and the overall potential radioprotective effect of VEGF(165) on these functions were assayed. RESULTS: A dose-dependent inhibitory effect of beta irradiation on ECs' thymidine uptake and differentiation was observed. EC viability, however, was not affected at levels of radiation up to 10 Gy. VEGF(165) proved to have a radioprotective effect as ECs' thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was increased by 1.5-, 2-, and 4-fold, respectively, in the presence of 10 ng/ml of VEGF(165) (p < 0.05 vs. LacZ). This concentration of VEGF(165) also proved beneficial in maintaining cell differentiation at 16 h postirradiation when compared to controls. These biologic effects were in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs. CONCLUSIONS: beta irradiation interacts directly with EC functions by significantly reducing their ability to differentiate and proliferate, associated with upregulation of VEGFR2. These effects can be prevented in part by pretreating cells with VEGF(165), an effect potentially favored by the upregulation of VEGFR2 receptor expression after irradiation.


Subject(s)
Endothelial Growth Factors/physiology , Endothelium, Vascular/radiation effects , Lymphokines/physiology , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptors, Growth Factor/biosynthesis , Thymidine/pharmacokinetics , Adenoviruses, Human/genetics , Beta Particles , Cell Differentiation/radiation effects , Cell Division/radiation effects , Cell Survival/radiation effects , Cells, Cultured , Endothelial Growth Factors/biosynthesis , Endothelial Growth Factors/genetics , Endothelial Growth Factors/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Humans , Lymphokines/biosynthesis , Lymphokines/genetics , Lymphokines/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/physiology , Muscle, Smooth, Vascular/virology , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Growth Factor/genetics , Receptors, Vascular Endothelial Growth Factor , Up-Regulation/radiation effects , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
16.
J Med Chem ; 23(12): 1372-6, 1980 Dec.
Article in English | MEDLINE | ID: mdl-7452691

ABSTRACT

A series of novel 2-carboxylic acids of the title ring systems has been synthesized from the corresponding 3-acetyl-4H-[1]benzopyran-4-one and benzothiopyran-4-one. These acids were examined for their ability to inhibit the rat passive cutaneous anaphylaxis; the pyridinone carboxylic acids 6 displayed a higher degree of iv and ip anaphylactic activities than their pyranone analogues 5. The potassium salt 5a (R6 = K) was the only compound that exhibited a moderate oral activity.


Subject(s)
Benzopyrans/chemical synthesis , Hypersensitivity/drug therapy , Animals , Benzopyrans/pharmacology , Chemical Phenomena , Chemistry , Male , Passive Cutaneous Anaphylaxis/drug effects , Rats
17.
J Med Chem ; 22(10): 1186-93, 1979 Oct.
Article in English | MEDLINE | ID: mdl-229222

ABSTRACT

A number of oxamic acid derivatives of tropones and tropolones were synthesized and their antianaphylactic activity was determined in passive paw anaphylaxis (PPA). Several of these esters possessed oral activity. A comparison of the effect on the biological activity of the esters and the corresponding acid and its salt is reported. The experiments suggesting a relationship between the activity and the bioavailability of the ester 19 are also described. A study of the fate of ester 19 in serum on oral or intravenous administration to rats and dogs is reported. In vitro results of the effect of the compounds 19, 45, and 45a on the activity of the guinea pig lung and beef heart phosphodiesterase are presented. The various factors that may contribute to the antiallergy activity of compounds of this series are discussed.


Subject(s)
Amino Acids/analogs & derivatives , Cycloheptanes/chemical synthesis , Oxamic Acid/analogs & derivatives , Passive Cutaneous Anaphylaxis/drug effects , Tropolone/chemical synthesis , 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Adenylyl Cyclases/metabolism , Animals , Cattle , Dogs , Guinea Pigs , In Vitro Techniques , Lung/enzymology , Mice , Oxamic Acid/chemical synthesis , Structure-Activity Relationship , Time Factors , Tropolone/analogs & derivatives
18.
J Med Chem ; 18(2): 189-91, 1975 Feb.
Article in English | MEDLINE | ID: mdl-1120985

ABSTRACT

The synthesis and antiinflammatory activities of a series of 23 novel 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-alkanoic acids are described and some relationships between structure and activity are discussed. One of these compounds, 1,3,4,9-tetrahydro-1-propylpyrano[3,4-b]indole-1-acetic acid (prodolic acid, USAN), has been selected for further studies.


Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Indoles/chemical synthesis , Animals , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Carboxylic Acids/chemical synthesis , Carboxylic Acids/therapeutic use , Freund's Adjuvant , Indoleacetic Acids , Indoles/therapeutic use , Magnetic Resonance Spectroscopy , Molecular Conformation , Pyrans/chemical synthesis , Pyrans/therapeutic use , Rats , Stereoisomerism , Structure-Activity Relationship
19.
J Med Chem ; 19(3): 391-5, 1976 Mar.
Article in English | MEDLINE | ID: mdl-1255663

ABSTRACT

A series of 37 1-ethyl- and 1-n-propyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids bearing one, or two, substituents on the benzene ring has been synthesized via the acid-catalyzed condensation of a substituted tryptophol with ethyl propionylacetate or ethyl butyrylacetate. Antiinflammatory and ulcerogenic effects were examined and the results show that 1, 8-diethyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acid (etodolic acid, USAN) is a potent agent, particularly active against a chronic rat model of inflammation (ED50 0.7 + 1-0.1 mg/kg po in the adjuvant arthritis model) and which has a relatively low acute ulcerogenic potential in the same species.


Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Indoleacetic Acids/chemical synthesis , Animals , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Carrageenan , Freund's Adjuvant , Indoleacetic Acids/adverse effects , Indoleacetic Acids/therapeutic use , Male , Pyrans/adverse effects , Pyrans/chemical synthesis , Pyrans/therapeutic use , Rats , Stomach Ulcer/chemically induced
20.
J Med Chem ; 26(12): 1778-80, 1983 Dec.
Article in English | MEDLINE | ID: mdl-6227748

ABSTRACT

Etodolac, 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, a clinically effective analgesic and antiinflammatory agent, has been resolved via a chromatographic separation of its diastereoisomeric esters with (-)-borneol. The effects of the enantiomers were studied in vitro on prostaglandin synthetase and on adjuvant-induced arthritis in rats. The biochemical and pharmacological results show that virtually all of the effects of etodolac are due to the (+) enantiomer.


Subject(s)
Acetates/isolation & purification , Anti-Inflammatory Agents/therapeutic use , Cyclooxygenase Inhibitors , Acetates/therapeutic use , Animals , Arthritis, Experimental/drug therapy , Chromatography, High Pressure Liquid , Etodolac , Male , Rats , Rats, Inbred Strains , Stereoisomerism
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