U 73343

Long-Acting Reversible Contraceptive Placement Among Active-Duty U.S. Army Servicewomen.[Pubmed:28383371]

Obstet Gynecol. 2017 May;129(5):800-809.

OBJECTIVE: To quantify uptake of long-acting reversible contraceptives (LARC)-intrauterine devices (IUDs) and hormonal implants-among U.S. Army active-duty female soldiers and identify characteristics associated with uptake. METHODS: This retrospective cohort study used the Stanford Military Data Repository, which includes all digitally recorded health encounters for active-duty U.S. Army soldiers from 2011 to 2014. We analyzed data from women aged 18-44 years to assess rates of LARC initiation using medical billing codes. We then evaluated predictors of LARC initiation using multivariable regression. RESULTS: Among 114,661 servicewomen, 14.5% received a LARC method; among those, 60% received an IUD. Intrauterine device insertions decreased over the study period (38.7-35.9 insertions per 1,000 women per year, beta=0.14, 95% confidence interval [CI] -0.23 to -0.05, P<.05), whereas LARC uptake increased, driven by an increase in implant insertions (20.3-35.4/1,000 women per year, beta=0.41, CI 0.33-0.48, P<.001). Younger age was a positive predictor of LARC uptake: 32.4% of IUD users and 62.6% of implant users were in the youngest age category (18-22 years) compared with 9.6% and 2.0% in the oldest (36-44 years). The likelihood of uptake among the youngest women (compared with oldest) was most marked for implants (adjusted relative risk 7.12, CI 5.92-8.55; P<.001). A total of 26.2% of IUD users had one child compared with 13.2% among non-LARC users (adjusted relative risk 1.94, CI 1.85-2.04, P<.001). The majority (52.2%) of those initiating IUDs were married, which was predictive of uptake over never-married women (adjusted relative risk 1.52, CI 1.44-1.59, P<.001). CONCLUSION: Among servicewomen, we observed low but rising rates of LARC insertion, driven by increasing implant use. Unmarried and childless soldiers were less likely to initiate LARC. These findings are consistent with potential underutilization and a need for education about LARC safety and reversibility in a population facing unique consequences for unintended pregnancies.

Airborne measurements of isoprene and monoterpene emissions from southeastern U.S. forests.[Pubmed:28384571]

Sci Total Environ. 2017 Oct 1;595:149-158.

Isoprene and monoterpene emission rates are essential inputs for atmospheric chemistry models that simulate atmospheric oxidant and particle distributions. Process studies of the biochemical and physiological mechanisms controlling these emissions are advancing our understanding and the accuracy of model predictions but efforts to quantify regional emissions have been limited by a lack of constraints on regional distributions of ecosystem emission capacities. We used an airborne wavelet-based eddy covariance measurement technique to characterize isoprene and monoterpene fluxes with high spatial resolution during the 2013 SAS (Southeast Atmosphere Study) in the southeastern United States. The fluxes measured by direct eddy covariance were comparable to emissions independently estimated using an indirect inverse modeling approach. Isoprene emission factors based on the aircraft wavelet flux estimates for high isoprene chemotypes (e.g., oaks) were similar to the MEGAN2.1 biogenic emission model estimates for landscapes dominated by oaks. Aircraft flux measurement estimates for landscapes with fewer isoprene emitting trees (e.g., pine plantations), were about a factor of two lower than MEGAN2.1 model estimates. The tendency for high isoprene emitters in these landscapes to occur in the shaded understory, where light dependent isoprene emissions are diminished, may explain the lower than expected emissions. This result demonstrates the importance of accurately representing the vertical profile of isoprene emitting biomass in biogenic emission models. Airborne measurement-based emission factors for high monoterpene chemotypes agreed with MEGAN2.1 in landscapes dominated by pine (high monoterpene chemotype) trees but were more than a factor of three higher than model estimates for landscapes dominated by oak (relatively low monoterpene emitting) trees. This results suggests that unaccounted processes, such as floral emissions or light dependent monoterpene emissions, or vegetation other than high monoterpene emitting trees may be an important source of monoterpene emissions in those landscapes and should be identified and included in biogenic emission models.

U-shaped PN junctions for efficient silicon Mach-Zehnder and microring modulators in the O-band.[Pubmed:28380954]

Opt Express. 2017 Apr 3;25(7):8425-8439.

We demonstrate U-shaped silicon PN junctions for energy efficient Mach-Zehnder modulators and ring modulators in the O-band. This type of junction has an improved modulation efficiency compared to existing PN junction geometries, has low losses, and supports high-speed operation. The U-shaped junctions were fabricated in an 8" silicon photonics platform, and they were incorporated in travelling-wave Mach-Zehnder modulators and microring modulators. For the high-bandwidth Mach-Zehnder modulator, the DC V_piL at -0.5 V bias was 4.6 V.mm. It exhibited a 3dB bandwidth of 13 GHz, and eye patterns at up to 24 Gb/s were observed. A V_piL as low as ~2.6 V.mm at a -0.5 V bias was measured in another device. The ring modulator tuning efficiency was 40 pm.V^-1 between 0 V and -0.5 V bias. It had a 3-dB bandwidth of 13.5 GHz and open eye patterns at up to 13 Gb/s were measured. This type of PN junctions can be easily fabricated without extra masks and can be incorporated into generic silicon photonics platforms.

Vital Signs: Update on Zika Virus-Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure - U.S. Zika Pregnancy Registry, 2016.[Pubmed:28384133]

MMWR Morb Mortal Wkly Rep. 2017 Apr 7;66(13):366-373.

BACKGROUND: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. METHODS: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. RESULTS: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

Activation of P2X7 receptors induces CCL3 production in microglial cells through transcription factor NFAT.[Pubmed:19014371]

J Neurochem. 2009 Jan;108(1):115-25.

Microglia are implicated as a source of diverse proinflammatory factors in the CNS. Extracellular nucleotides are well known to be potent activators of glial cells and trigger the release of cytokines from microglia through purinergic receptors. However, little is known about the role of purinoceptors in microglial chemokine release. In this study, we found that high concentrations of ATP evoked release of CC-chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1alpha from MG-5 cells, a mouse microglial cell line, and rapid up-regulation of CCL3 mRNA was elicited within 30 min of ATP stimulation. The release of CCL3 was also stimulated by 2'- and 3'-O-(4-benzoylbenzoyl) ATP, an agonist of P2X(7) receptors. Brilliant Blue G, an antagonist of P2X(7) receptors, strongly inhibited this ATP-induced CCL3 release. Similar pharmacological profile was observed in primary microglia. In MG-5 cells, ATP caused de-phosphorylation and nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT). ATP-induced NFAT de-phosphorylation was also dependent on P2X(7) receptor activation. Furthermore, ATP-induced CCL3 release and production were prevented by a selective inhibitor of NFAT. Taken together, the results of this study demonstrate an involvement of NFAT in the mechanism underlying P2X(7) receptor-mediated CCL3 release.

Pharmacological characterization of pannexin-1 currents expressed in mammalian cells.[Pubmed:19023039]

J Pharmacol Exp Ther. 2009 Feb;328(2):409-18.

Pannexin (Panx) 1 is a widely expressed protein that shares structural, but not amino acid, homology with gap junction proteins, the connexins. Panx1 does not form gap junctions in mammalian cells, but it may function as a plasma membrane hemichannel. Little is known of the pharmacological properties of panx1 expression in mammalian cells. Here, we identify three variants in the human PANX1 gene. We expressed these variants and mouse Panx1 in mammalian cells and compared Panx1-induced currents. All human Panx1 variants and the mouse Panx1 showed identical protein expression levels, localization patterns, and functional properties, although the frequency of functional expression was species-dependent. Panx1 currents were independent of changes in extracellular or intracellular calcium or phospholipase C transduction. We found compounds that inhibited Panx1 currents with a rank order of potency: carbenoxolone > disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) approximately disodium 4-acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate approximately 5-nitro-2-(3-phenylpropylamino)benzoic acid > indanyloxyacetic acid 94 >> probenecid >> flufenamic acid = niflumic acid. Triphosphate nucleotides (ATP, GTP, and UTP) rapidly and reversibly inhibited Panx1 currents via mechanism(s) independent of purine receptors. When Panx1 was coexpressed with purinergic P2X(7) receptor (P2X(7)R), DIDS was found to act as a P2X(7)R antagonist to inhibit ATP-evoked currents, but none of the other compounds inhibited P2X(7)R currents. This is the first detailed pharmacological characterization of Panx1-mediated currents in mammalian cells and sheds new, although contradictory, light on the hypothesis that Panx1 acts as a hemichannel to allow passage of large molecules in response to P2X(7)R activation.

The putative phospholipase C inhibitor U73122 and its negative control, U73343, elicit unexpected effects on the rabbit parietal cell.[Pubmed:9316850]

J Pharmacol Exp Ther. 1997 Sep;282(3):1379-88.

In order to elucidate the role of phospholipase C (PLC) in gastric acid secretion, we used U73122, a commonly employed specific inhibitor of receptor-mediated PLC, and its negative control, U73343. Although 10 microM U73122 inhibited the increase in [Ca++]i induced by U46619 in rabbit platelets, Ca++ transients in the rabbit parietal cells elicited by histamine and carbachol were both resistant to the inhibitor. U73122 augmented the acid secretion of isolated gastric glands stimulated by histamine, carbachol and dbcAMP, possibly through its indirect Ca++-releasing effect on the intracellular calcium store. U73122 potently inhibited K+-p-nitrophenylphosphatase without affecting overall H+,K+-ATPase activity. On the other hand, the negative control, U73343, strongly inhibited the acid secretion stimulated by all agonists tested. The inhibitory effect was also evident on digitonin-permeabilized glands and on the proton gradient of gastric vesicles. U73343 itself is not a proton pump inhibitor, so it was considered a protonophore. In conclusion, the widely used PLC-inhibitor, U73122, and its negative control, U73343, are both useless as tools for analyzing the role of PLC in rabbit parietal cells. The former is ineffective on gastric PLC and works as an intracellular calcium releaser, and the latter works as a protonophore.

Evidence obtained using single hepatocytes for inhibition by the phospholipase C inhibitor U73122 of store-operated Ca2+ inflow.[Pubmed:7763279]

Biochem Pharmacol. 1995 May 17;49(10):1373-9.

The ability of 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122), an inhibitor of phospholipase C (Smith et al., J Pharmacol Exp Ther 253:688-697, 1992), to inhibit agonist-stimulated and store-operated Ca2+ inflow in single hepatocytes was investigated with the aim of testing whether the activation of phospholipase C is a necessary step in the process of agonist-stimulated Ca2+ inflow in this cell type. U73122 inhibited the release of Ca2+ from intracellular stores and plasma membrane Ca2+ inflow induced by vasopressin. An inactive analogue of U73122, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]- 2,5-pyrrolidone-dione (U73433), did not inhibit vasopressin-induced release of Ca2+ from intracellular stores, but did partially inhibit Ca2+ inflow. Neither U73122 nor 'inactive' analogue U73433 inhibited the release of Ca2+ from intracellular stores when this was initiated by the photolysis of 'caged' guanosine (5'-[gamma-thio]triphosphate (GTP gamma S) introduced to the cytoplasmic space by microinjection. However, both compounds inhibited GTP gamma S-stimulated Ca2+ inflow. U73122 also inhibited the actions of glycerophosphoryl-myo-inositol-4,5-diphosphate (GPIP2), a slowly-hydrolysed analogue of inositol 1,4,5-triphosphate (InsP3) which is released by photolysis of 'caged' 1-(alpha-glycerophosphoryl)-myo-inositol-4,5-diphosphate, P4(5)-1-(2-nitrophenyl)ethyl ester, and thapsigargin in stimulating Ca2+ inflow. U73122 did not inhibit GPIP2-stimulated release of Ca2+ from intracellular stores, but did partially inhibit the ability of thapsigargin to induce Ca2+ release. It is concluded that, while U73122 does inhibit phospholipase C beta in hepatocytes, complete inhibition of this enzyme in situ requires an intracellular concentration of U73122 higher than that achieved in the present experiments. Moreover, both U73122 and 'inactive' analogue U73433 have one or possibly two additional sites of action. These are likely to be the hepatocyte plasma membrane Ca2+ inflow channel protein (or a protein involved in the activation of this channel by the InsP3-sensitive intracellular Ca2+ store), and a protein involved in thapsigargin action.

U-73343, an inhibitor of PLC (putative phospholipase C)-dependent processes, is an analog of U-73122 and can be used as a negative control.

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