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1.
Biol Lett ; 16(2): 20190865, 2020 02.
Article in English | MEDLINE | ID: mdl-32019462

ABSTRACT

The Gulf of Mexico (GoM) is home to the world's largest remaining wild oyster fisheries, but baseline surveys needed to assess habitat condition are recent and may represent an already-shifted reference state. Here, we use prehistoric oysters from archaeological middens to show that oyster size, an indicator of habitat function and population resilience, declined prior to the earliest assessments of reef condition in an area of the GoM previously considered pristine. Stable isotope sclerochronlogy reveals extirpation of colossal oysters occurred through truncated life history and slowed growth. More broadly, our study suggests that management strategies affected by shifting baselines may overestimate resilience and perpetuate practices that risk irreversible decline.


Subject(s)
Crassostrea , Animals , Ecosystem , Fisheries , Gulf of Mexico , Mexico
2.
Obstet Gynecol ; 135(1): 133-140, 2020 01.
Article in English | MEDLINE | ID: mdl-31809437

ABSTRACT

OBJECTIVE: To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects. METHODS: We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns. We estimated risks of stillbirth specific to birth defects among pregnancies overall and among those with isolated birth defects; potential bias owing to elective termination was quantified. RESULTS: Of 19,170 eligible neonates and fetuses with birth defects, 17,224 were liveborn, 852 stillborn, and 672 electively terminated. Overall, stillbirth risks ranged from 11 per 1,000 fetuses with bladder exstrophy (95% CI 0-57) to 490 per 1,000 fetuses with limb-body-wall complex (95% CI 368-623). Among those with isolated birth defects not affecting major vital organs, elevated risks (per 1,000 fetuses) were observed for cleft lip with cleft palate (10; 95% CI 7-15), transverse limb deficiencies (26; 95% CI 16-39), longitudinal limb deficiencies (11; 95% CI 3-28), and limb defects due to amniotic bands (110; 95% CI 68-171). Quantified bias analysis suggests that failure to account for terminations may lead to up to fourfold underestimation of the observed risks of stillbirth for sacral agenesis (13/1,000; 95% CI 2-47), isolated spina bifida (24/1,000; 95% CI 17-34), and holoprosencephaly (30/1,000; 95% CI 10-68). CONCLUSION: Birth defect-specific stillbirth risk was high compared with the U.S. stillbirth risk (6/1,000 fetuses), even for isolated cases of oral clefts and limb defects; elective termination may appreciably bias some estimates. These data can inform clinical care and counseling after prenatal diagnosis.


Subject(s)
Fetal Diseases/epidemiology , Spinal Dysraphism/epidemiology , Stillbirth/epidemiology , Adult , Female , Fetal Diseases/diagnosis , Fetus , Humans , Infant, Newborn , Live Birth/epidemiology , Population Surveillance , Pregnancy , Prenatal Diagnosis , Retrospective Studies , Risk Assessment , Spinal Dysraphism/diagnosis , United States/epidemiology
3.
Bioorg Med Chem Lett ; 28(17): 2914-2919, 2018 09 15.
Article in English | MEDLINE | ID: mdl-30017319

ABSTRACT

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78 µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.


Subject(s)
Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Benzoates/pharmacology , Hydrazones/pharmacology , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Benzoates/chemical synthesis , Benzoates/chemistry , Dose-Response Relationship, Drug , Hydrazones/chemical synthesis , Hydrazones/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
4.
Matern Child Health J ; 21(5): 966-973, 2017 05.
Article in English | MEDLINE | ID: mdl-28083732

ABSTRACT

Introduction To determine the association of fruit and vegetable consumption with overall sleep duration among pregnant women. Methods Data from the 2011 and 2012 Behavioral Risk Factors Surveillance System (BRFSS) were used. All women (n = 2951) of childbearing age (18-44 years) who were pregnant and responded to all fruit and vegetable consumption and sleep duration questions were included. Covariates included age, race, education level, exercise, and marital status. Data were analyzed using linear and ordinal logistic regression. Results Total daily fruit and vegetable consumption was not associated with sleep duration among pregnant women, controlling for confounders [ß = -0.03, (-0.07, 0.00)]. Orange and green vegetable consumption were both inversely associated with sleep duration [ß = -0.19, (-0.38, -0.01) and ß = -0.20, (-0.33, -0.08) respectively]. Ordinal logistic regression found that the odds of meeting or exceeding sleep time recommendations increased slightly with each unit increase in total fruit and vegetable consumption [OR = 1.05 (1.003, 1.092)] and for every unit increase in fruit consumption [OR = 1.12 (1.038, 1.208)]. Women who exercised within the past 30 days reported approximately 20 min of additional sleep compared to those who did not [ß = 0.32 (0.16, 0.49)]. Age, employment status, and marital status were also independently associated with sleep duration. Discussion Sleep duration in pregnant women was associated with exercise and other demographic factors, but only mildly associated with fruit and vegetable consumption. Future research should investigate the effects of additional factors including sleep quality, gestational age, family status and other medications as potential confounders.


Subject(s)
Diet, Healthy/standards , Fruit , Sleep/physiology , Time Factors , Vegetables , Adolescent , Adult , Female , Humans , Pregnancy
5.
J Registry Manag ; 39(1): 13-8, quiz 36, 2012.
Article in English | MEDLINE | ID: mdl-23270086

ABSTRACT

BACKGROUND: In 2005, a pilot project was started at the Centers for Disease Control and Prevention (CDC) to expand an existing birth defects surveillance program, the Metropolitan Atlanta Congenital Defects Program (MACDP), to conduct active surveillance of stillbirth. This pilot project was evaluated using CDC's current guidelines for evaluating surveillance systems. METHODS: We conducted stakeholder interviews with the staff of MACDP's stillbirth surveillance system. We reviewed the published literature on stillbirth ascertainment including 4 previous publications about the MACDP stillbirth surveillance system. Using fetal death certificates (FDC) as a second, independent data source, we estimated the total number and prevalence of stillbirths in metropolitan Atlanta using capture-recapture methods, and calculated the sensitivity of the MACDP stillbirth surveillance system. RESULTS: The MACDP stillbirth surveillance system is useful, flexible, acceptable, and stable. The system's data quality is improved because it uses multiple sources for case ascertainment. Based on 2006 data, estimated sensitivities of FDCs, MACDP, and both sources combined for identifying a stillbirth were 78.5%, 76.8%, and 95.0%, respectively. The prevalence of stillbirths per 1,000 live births and stillbirths was 8.2 (95% confidence interval [CI]: 7.5-9.0) based on FDC data alone and 9.9 (95% CI: 9.1-10.8) when combined with MACDP data. CONCLUSION: Use of MACDP as an additional data source for stillbirth surveillance resulted in higher levels of case ascertainment, better data quality, and a higher estimate of stillbirth prevalence than using FDC data alone. MACDP could be considered as a model to enhance stillbirth surveillance by other active birth defects surveillance programs.


Subject(s)
Population Surveillance , Stillbirth/epidemiology , Georgia/epidemiology , Humans , Pilot Projects , Sensitivity and Specificity , Urban Population
6.
Science ; 334(6052): 69-72, 2011 Oct 07.
Article in English | MEDLINE | ID: mdl-21980105

ABSTRACT

We report the detection of pulsed gamma rays from the Crab pulsar at energies above 100 giga-electron volts (GeV) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) array of atmospheric Cherenkov telescopes. The detection cannot be explained on the basis of current pulsar models. The photon spectrum of pulsed emission between 100 mega-electron volts and 400 GeV is described by a broken power law that is statistically preferred over a power law with an exponential cutoff. It is unlikely that the observation can be explained by invoking curvature radiation as the origin of the observed gamma rays above 100 GeV. Our findings require that these gamma rays be produced more than 10 stellar radii from the neutron star.

7.
Public Health Rep ; 124(5): 652-9, 2009.
Article in English | MEDLINE | ID: mdl-19753943

ABSTRACT

Stillbirths, those with and without birth defects, are an important public health topic. The National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention conducted two workshops during April and July 2005. Both workshops explored the challenges of conducting surveillance of stillbirths. Workshop participants considered an approach that added the surveillance of stillbirths, those with and without birth defects, as part of existing population-based birth defects surveillance programs in Iowa and Atlanta. The workshops addressed three key aspects for expanding birth defects programs to conduct active, population-based surveillance on stillbirths: (1) case identification and ascertainment, (2) data collection, and (3) data use and project evaluation. Participants included experts in pediatrics, obstetrics, epidemiology, maternal-fetal medicine, perinatology and pediatric pathology, midwifery, as well as practicing clinicians and pathologists. Expanding existing birth defects surveillance programs to include information of stillbirths could potentially enhance the data available on fetal death reports and also could benefit such programs by improving the ascertainment of birth defects.


Subject(s)
Stillbirth/epidemiology , Centers for Disease Control and Prevention, U.S. , Congenital Abnormalities/epidemiology , Female , Humans , Population Surveillance/methods , Pregnancy , United States/epidemiology
8.
Public Health Rep ; 122(5): 664-9, 2007.
Article in English | MEDLINE | ID: mdl-17877314

ABSTRACT

OBJECTIVE: We assessed fetal death certificates (FDCs) as a source of surveillance for stillbirths with birth defects by linkage with data from the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based birth defects surveillance system. METHODS: Stillbirths with defects in MACDP were identified from 1994 through 2002 and linked to FDCs. Sensitivity of FDCs for capturing stillbirths with defects was estimated, and predictors for a case being reported were assessed. Concordance for selected variables from each data source was evaluated. RESILTS: Two hundred twenty-four of 257 stillbirths with birth defects in MACDP were linked to an FDC (linkage rate = 87.2%; 95% confidence interval [CI] 82.4, 91.0). Stillbirths of non-Hispanic black and Hispanic/other mothers were more likely to be issued an FDC (odds ratio [OR] = 5.6 [95% CI 1.9, 17.0] and 14.0 [95% CI 1.7, 114.0], respectively). Cases undergoing autopsy were more likely to be issued an FDC (OR = 3.2; 95% CI 1.1, 8.7). Performance of an amniocentesis was poorly recorded on FDCs. The sensitivity and positive predictive value of FDCs for selected classes of defects ranged from 10% to 70% and 25% to 93%, respectively. CONCLUSIONS: Compared to FDCs, MACDP's active case identification improves the ascertainment of stillbirths with birth defects and the quality of certain recorded data.


Subject(s)
Congenital Abnormalities/epidemiology , Death Certificates , Fetal Death/epidemiology , Population Surveillance/methods , Stillbirth/epidemiology , Female , Georgia/epidemiology , Humans , Infant, Newborn , Pregnancy , United States/epidemiology
9.
J Appl Microbiol ; 102(5): 1337-49, 2007 May.
Article in English | MEDLINE | ID: mdl-17448169

ABSTRACT

AIMS: Bacteriophage vectors have potential as gene transfer and vaccine delivery vectors because of their low cost, safety and physical stability. However, little is known concerning phage-mediated gene transfer in mammalian hosts. We therefore performed experiments to examine phage-mediated gene transfer in vivo. METHODS AND RESULTS: Mice were inoculated with recombinant lambda phage containing a mammalian expression cassette encoding firefly luciferase (luc). Efficient, dose-dependent in vivo luc expression was detected, which peaked within 24 h of delivery and declined to undetectable levels within a week. Display of an integrin-binding peptide increased cellular internalization of phage in vitro and enhanced phage-mediated gene transfer in vivo. Finally, in vivo depletion of phagocytic cells using clodronate liposomes had only a minor effect on the efficiency of phage-mediated gene transfer. CONCLUSIONS: Unmodified lambda phage particles are capable of transducing mammalian cells in vivo, and may be taken up -- at least in part -- by nonphagocytic mechanisms. Surface modifications that enhance phage uptake result in more efficient in vivo gene transfer. SIGNIFICANCE AND IMPACT OF THE STUDY: These experiments shed light on the mechanisms involved in phage-mediated gene transfer in vivo, and suggest new approaches that may enhance the efficiency of this process.


Subject(s)
Bacteriophage lambda/genetics , Gene Transfer Techniques , Genetic Vectors , Animals , Gene Expression , Mice , Mice, Inbred BALB C/microbiology , Vaccines
11.
Curr Med Chem ; 11(11): 1513-25, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15180581

ABSTRACT

The increasing use of herbal medicinal products (HMPs) in the community where people are also receiving prescription medicines suggests that adverse herb-drug interactions may be of significant public health consequence. The evidence available to guide practitioners in decision making is complex and consists of a range of sources including adverse event database entries, spontaneous or case reports, in vivo and in vitro drug metabolism studies, and in vivo drug interaction studies in healthy subjects and patients. In the absence of further rigorous studies to assess the clinical significance of herb-drug interactions, an evidence-based appraisal of the current literature is essential to guide practitioners involved in patient care.


Subject(s)
Evidence-Based Medicine/methods , Herb-Drug Interactions , Plant Preparations/pharmacology , Animals , Herbal Medicine/classification , Humans , Plant Preparations/administration & dosage , Randomized Controlled Trials as Topic
13.
Heart ; 89(8): 905-12, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12860870

ABSTRACT

OBJECTIVES: To assess the extent of neointimal proliferation and the safety and efficacy of stent redilatation in patients with stents implanted for aortic coarctation or branch pulmonary artery stenosis. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTIONS: Of 60 patients with Palmaz stents, 12 with coarctation and 12 with branch pulmonary artery stenosis (with 21 stented sites) underwent recatheterisation and stent redilatation. RESULTS: Neointimal thickening > 1 mm was detected in six of the 12 coarctation stents and at nine of the 21 stented sites in branch pulmonary arteries (five of which had been overdilated at implantation). Eight of the coarctation stents were electively underdilated at implantation. Coarctation stent redilatation increased median (range) lumen diameter from 9.2 (6.3-11.1) mm to 11.7 (9.8-14.1) mm (p = 0.002), decreased gradient from 10.5 (0-20) mm Hg to 0.5 (0-15) mm Hg (p = 0.008), and increased the ratio of stent diameter to descending aorta diameter from 0.66 (0.38-1.02) to 0.85 (0.52-1.2) (p = 0.008). Pulmonary artery stent redilatation increased lumen diameter from 6.9 (3.8-13.5) mm to 8.8 (4.8-14.1) mm (p < 0.001), decreased gradient from 24 (2-62) mm Hg to 12 (0-29) mm Hg (p < 0.001), and increased the ratio of stent diameter to diameter of distal pulmonary artery from 0.66 (0.44-1.5) to 0.86 (0.48-1.88) (p = 0.001). Dilatation of one peripheral pulmonary artery stent resulted in rupture of the vessel distal to the stent. CONCLUSIONS: Neointimal proliferation is precipitated by overdilating stents at implantation. Redilatation using balloons matched to distal vessel diameter increases stent lumen size, but may not optimise vessel diameter. Redilatation is effective whether the indication for redilatation is a resistant stenosis at implantation, underexpansion at implantation, neointimal proliferation, or relative stenosis caused by growth.


Subject(s)
Aortic Coarctation/therapy , Arterial Occlusive Diseases/therapy , Catheterization/methods , Pulmonary Artery/pathology , Stents , Adolescent , Adult , Aged , Aortic Coarctation/pathology , Arterial Occlusive Diseases/congenital , Arterial Occlusive Diseases/pathology , Cardiac Catheterization/methods , Cell Division , Child , Child, Preschool , Humans , Middle Aged , Recurrence , Retrospective Studies , Treatment Outcome
14.
Proc Natl Acad Sci U S A ; 100(7): 3858-64, 2003 Apr 01.
Article in English | MEDLINE | ID: mdl-12651946

ABSTRACT

This article is an account of the birth and evolution of surface science as an interdisciplinary research area. Surface science emanated from the confluence of concepts and tools in physics and chemistry with technological innovations that made it possible to determine the structure and properties of surfaces and interfaces and the dynamics of chemical reactions at surfaces. The combination in the 1960s and 1970s of ultra-high-vacuum (i.e., P < 10(-7) Pascal or 10(-9) Torr) technology with the recognition that electrons in the energy range from 50 to 500 eV exhibited inelastic collision mean free paths of the order of a few angstroms fostered an explosion of activity. The results were a reformulation of the theory of electron solid scattering, the nearly universal use of electron spectroscopies for surface characterization, the rise of surface science as an independent interdisciplinary research area, and the emergence of the American Vacuum Society (AVS) as a major international scientific society. The rise of microelectronics in the 1970s and 1980s resulted in huge increases in computational power. These increases enabled more complex experiments and the utilization of density functional theory for the quantitative prediction of surface structure and dynamics. Development of scanning-probe microscopies in the 1990s led to atomic-resolution images of macroscopic surfaces and interfaces as well as videos of atoms moving about on surfaces during growth and diffusion. Scanning probes have since brought solid-liquid interfaces into the realm of atomic-level surface science, expanding its scope to more complex systems, including fragile biological materials and processes.

15.
J Pharm Sci ; 90(10): 1658-64, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11745724

ABSTRACT

Gingerols, pungent principles of ginger (the rhizome of Zingiber officinale), are biologically active components that may make a significant contribution towards medicinal applications of ginger and some products derived from ginger. Gingerols, however, are thermally labile due to the presence of a beta-hydroxy keto group in the structure, and undergo dehydration readily to form the corresponding shogaols. This study investigated the stability of [6]-gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one] at temperatures ranging from 37 to 100 degrees C in aqueous solutions, at pH 1, 4, and 7. Quantitative measurements of [6]-gingerol and its major degradation product [6]-shogaol [1-(4-hydroxy-3-methoxyphenyl)decan-4-ene-3-one] were performed by HPLC. Kinetics of [6]-gingerol degradation was characterized by least square fitting of a rate equation. It was found that gingerol exhibited novel reversible kinetics, in which it undergoes dehydration-hydration transformations with shogaol, the major degradation product. Degradation rates were found to be pH dependent with greatest stability observed at pH 4. The reversible degradation of [6]-gingerol at 100 degrees C and pH 1 was relatively fast and reached equilibrium within 2 h. Activation energies for the forward and reverse reactions for [6]-gingerol were calculated from the Arrhenius equation using reaction rates obtained at temperatures ranging from 37 to 100 degrees C.


Subject(s)
Catechols/metabolism , Fatty Alcohols/metabolism , Catechols/chemical synthesis , Catechols/isolation & purification , Drug Stability , Fatty Alcohols/chemical synthesis , Fatty Alcohols/isolation & purification , Zingiber officinale/chemistry , Hot Temperature , Hydrogen-Ion Concentration , Kinetics , Plant Extracts/chemistry , Solutions , Water/chemistry
16.
Am J Cardiol ; 88(12): 1379-84, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11741556

ABSTRACT

There are few data on the outcome of truncus arteriosus when this diagnosis is made during fetal life. Such prognostic information is important to assist parental counseling during pregnancy. This study aimed to analyze, retrospectively, the echocardiographic features and outcome of fetuses with truncus arteriosus. A database of those presenting to a tertiary center for fetal cardiology between 1990 and 1999 was reviewed. Cases in which truncus arteriosus was identified as a firm or differential diagnosis were selected. Outcome data were derived from clinical records, and fetal echocardiograms were reviewed retrospectively. At presentation, truncus arteriosus was firmly diagnosed in 16 patients and was a differential diagnosis in 12. Fourteen of 16 (87%) of the firm diagnoses were correct. There were 17 confirmed cases of truncus arteriosus. Pregnancy was terminated in 4 patients (24%) and there were 13 live births. One child was not actively treated, 4 (31%) died preoperatively, and 8 (61%) underwent surgery. Thirty-day surgical mortality was 2 of 8 (25%). There was 1 late death after cardiac catheterization, and overall survival on an intention-to-treat basis was 5 of 12 (42%). Five of 6 patients with a prenatal truncal valve Doppler velocity above the normal aortic range were found to have postnatal truncal valve stenosis. Two fetuses with stenotic valves died preoperatively with sudden cardiovascular collapse. Counseling of parents for fetuses with truncus arteriosus should include the relatively high nonsurgical mortality as well as surgical results. Elevated prenatal truncal valve Doppler velocity predicts postnatal truncal valve stenosis. Fetuses with truncal valve stenosis may be at risk of early sudden death.


Subject(s)
Truncus Arteriosus, Persistent/diagnostic imaging , Ultrasonography, Prenatal , Female , Humans , Male , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Retrospective Studies
17.
Thromb Res ; 103(5): 387-97, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11553371

ABSTRACT

Gingerols, the active components of ginger (the rhizome of Zingiber officinale, Roscoe), represent a potential new class of platelet activation inhibitors. In this study, we examined the ability of a series of synthetic gingerols and related phenylalkanol analogues (G1-G7) to inhibit human platelet activation, compared to aspirin, by measuring their effects on arachidonic acid (AA)-induced platelet serotonin release and aggregation in vitro. The IC(50) for inhibition of AA-induced (at EC(50)=0.75 mM) serotonin release by aspirin was 23.4+/-3.6 microM. Gingerols and related analogues (G1-G7) inhibited the AA-induced platelet release reaction in a similar dose range as aspirin, with IC(50) values between 45.3 and 82.6 microM. G1-G7 were also effective inhibitors of AA-induced human platelet aggregation. Maximum inhibitory (IC(max)) values of 10.5+/-3.9 and 10.4+/-3.2 microM for G3 and G4, respectively, were approximately 2-fold greater than aspirin (IC(max)=6.0+/-1.0 microM). The remaining gingerols and related analogues maximally inhibited AA-induced platelet aggregation at approximately 20-25 microM. The mechanism underlying inhibition of the AA-induced platelet release reaction and aggregation by G1-G7 may be via an effect on cyclooxygenase (COX) activity in platelets because representative gingerols and related analogues (G3-G6) potently inhibited COX activity in rat basophilic leukemia (RBL-2H3) cells. These results provide a basis for the design of more potent synthetic gingerol analogues, with similar potencies to aspirin, as platelet activation inhibitors with potential value in cardiovascular disease.


Subject(s)
Arachidonic Acid/pharmacology , Blood Platelets/drug effects , Fatty Alcohols/pharmacology , Platelet Aggregation/drug effects , Serotonin/metabolism , Adult , Animals , Aspirin/pharmacology , Blood Platelets/metabolism , Catechols , Fatty Alcohols/chemical synthesis , Humans , Inhibitory Concentration 50 , Middle Aged , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , Prostaglandin-Endoperoxide Synthases/drug effects , Rats , Solubility , Structure-Activity Relationship , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/enzymology
18.
Bioorg Chem ; 29(3): 156-63, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11437391

ABSTRACT

Seventeen pungent oleoresin principles of ginger (Zingiber officinale, Roscoe) and synthetic analogues were evaluated for inhibition of cyclooxygenase-2 (COX-2) enzyme activity in the intact cell. These compounds exhibited a concentration and structure dependent inhibition of the enzyme, with IC(50) values in the range of 1-25 microM. Ginger constituents, [8]-paradol and [8]-shogaol, as well as two synthetic analogues, 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decane and 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)dodecane, showed strong inhibitory effects on COX-2 enzyme activity. The SAR analysis of these phenolic compounds revealed three important structural features that affect COX-2 inhibition: (i) lipophilicity of the alkyl side chain, (ii) substitution pattern of hydroxy and carbonyl groups on the side chain, and (iii) substitution pattern of hydroxy and methoxy groups on the aromatic moiety.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , Isoenzymes/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Zingiber officinale/chemistry , Catechols , Cells, Cultured , Chemical Phenomena , Chemistry, Physical , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/isolation & purification , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Epithelial Cells/enzymology , Fatty Alcohols/chemistry , Fatty Alcohols/pharmacology , Humans , Hydroxylation , Membrane Proteins , Models, Chemical , Structure-Activity Relationship
19.
Pediatr Cardiol ; 22(1): 80-2, 2001.
Article in English | MEDLINE | ID: mdl-11123139

ABSTRACT

A patient with an isolated left innominate artery (with a right-sided cervical aortic arch) is described. This is the first report of such an anomaly associated with chromosome 22q11 microdeletion. The abnormality represents an interruption in the primitive aortic arch that is atypical for this chromosome deletion.


Subject(s)
Brachiocephalic Trunk/abnormalities , Chromosome Deletion , Chromosomes, Human, Pair 22 , DiGeorge Syndrome/etiology , DiGeorge Syndrome/genetics , Fatal Outcome , Heart Septal Defects, Ventricular/genetics , Humans , Infant, Newborn , Male , Tetralogy of Fallot/complications , Tetralogy of Fallot/genetics
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