Isothermal Fourier transform infrared microspectrosopic studies on the stability kinetics of solid-state intramolecular cyclization of aspartame sweetener.

PubMed

Cheng, Y D; Lin, S Y

2000-03-01

A novel Fourier transform infrared (FT-IR) microspectrophotometer equipped with differential scanning calorimetry (DSC) was used to investigate the kinetics of intramolecular cyclization of aspartame (APM) sweetener in the solid state under isothermal conditions. The thermal-dependent changes in the peak intensity of IR spectra at 1543, 1283, and 1259 cm(-1) were examined to explore the reaction. The results support that the intramolecular cyclization process in APM proceeded in three steps: the methoxyl group of ester was first thermolyzed to release methanol, then an acyl cation was attacked by the lone pair of electrons available on nitrogen by an S(N)1 pathway, and finally ring-closure occurred. The intramolecular cyclization of APM determined by this microscopic FT-IR/DSC system was found to follow zero-order kinetics after a brief induction period. The bond cleavage energy (259.38 kJ/mol) of thermolysis for the leaving group of -OCH(3), the bond conversion energy (328.88 kJ/mol) for the amide II NH band to DKP NH band, and the CN bond formation energy (326.93 kJ/mol) of cyclization for the DKP in the APM molecule were also calculated from the Arrhenius equation. The total activation energy of the DKP formation via intramolecular cyclization was 261.33 kJ/mol, calculated by the above summation of the bond energy of cleavage, conversion, and formation, which was near to the value determined by the DSC or TGA method. This indicates that the microscopic FT-IR/DSC system is useful as a potential tool not only to investigate the degradation mechanism of drugs in the solid state but also to directly predict the bond energy of the reaction.

Safety and pharmacokinetics of veliparib extended-release in patients with advanced solid tumors: a phase I study.

PubMed

Werner, Theresa L; Sachdev, Jasgit; Swisher, Elizabeth M; Gutierrez, Martin; Kittaneh, Muaiad; Stein, Mark N; Xiong, Hao; Dunbar, Martin; Sullivan, Danielle; Komarnitsky, Philip; McKee, Mark; Tan, Antoinette R

2018-05-07

The poly(ADP-ribose) polymerase-1/2 inhibitor veliparib is active against tumors deficient in homologous DNA damage repair. The pharmacokinetics and safety of veliparib extended-release (ER) were evaluated in patients with advanced solid tumors. This phase I study assessed veliparib-ER up to 800 mg once daily or 600 mg twice daily. Dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), and maximum tolerated dose (MTD) were assessed in cycle 1 and safety/tolerability during continuous administration (28-day cycles). Seventy-one patients (n = 53 ovarian, n = 17 breast, n = 1 prostate carcinoma) received veliparib; 50 had deleterious breast cancer susceptibility (BRCA) gene mutations. Single-dose veliparib-ER 200 mg (fasting) led to 58% lower peak concentration and similar area under the concentration-time curve compared with veliparib immediate-release (IR). Three patients experienced DLTs (grade 2: asthenia; grade 3: nausea/vomiting, seizure). RP2D and MTD for veliparib-ER were 400 mg BID. The most frequent adverse events (AEs) were nausea (78.9%) and vomiting (50.7%). The most common grade 3/4 treatment-related AEs were as follows: thrombocytopenia (7.0%), nausea, and anemia (4.2% each). Overall, 12 (27.3%) patients with ovarian and 10 (62.5%) patients with breast carcinoma had a partial response. Veliparib-ER, versus veliparib-IR, exhibited an improved pharmacokinetic profile and was well tolerated in patients with ovarian and BRCA-mutated breast cancers. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Preparation and characterization of novel anion phase change heat storage materials.

PubMed

Hong, Wei; Lil, Qingshan; Sun, Jing; Di, Youbo; Zhao, Zhou; Yu, Wei'an; Qu, Yuan; Jiao, TiFeng; Wang, Guowei; Xing, Guangzhong

2013-10-01

In this paper, polyurethane phase change material was successfully prepared with TDI with BDO for hard segments and PEG for soft segments. Moreover, based on this the solid-solid phase change material, A-PCM1030 which can release anions was prepared with the successful addition of anion additives A1030 for the first time. Then the test of the above material was conducted utilizing FT-IR, DSC, TEM, WAXD and Air Ion Detector. The Results indicated that the polyurethane phase change material possesses excellent thermal stability since there was no appearance of liquid leakage and phase separation after 50 times warming-cooling thermal cycles. It also presented reversibility on absorbing and releasing heat. In addition, adding a little A1030 can increase the thermal stability and reduce phase transition temperatures, as well as reduce the undercooling of the polyurethane phase change material. In addition, the anion test results suggested that the supreme amount of anion released by A-PCM1030 could reach 2510 anions/cm3 under dynamic conditions, which is beneficial for human health.

Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems.

PubMed

Thenmozhi, Kathavarayan; Yoo, Young Je

2017-09-01

Piperine alkaloid, an important constituent of black pepper, exhibits numerous therapeutic properties, whereas its usage as a drug is limited due to its poor solubility in aqueous medium, which leads to poor bioavailability. Herein, a new method has been developed to improve the solubility of this drug based on the development of solid dispersions with improved dissolution rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG) and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of piperine and carriers were also prepared for comparison. The physicochemical properties of the prepared solid dispersions were examined using SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid dispersions was recorded and compared with that of the pure piperine and physical mixtures. The effect of these carriers on the aqueous solubility of piperine has been investigated. The solid dispersions of piperine with Sor, PEG and PVP exhibited superior performance for the dissolution of piperine with a drug release of 70%, 76% and 89%, respectively after 2 h compared to physical mixtures and pure piperine, which could be due to its transformation from crystalline to amorphous form as well as the attachment of hydrophilic carriers to the surface of poorly water-soluble piperine. Results suggest that the piperine solid dispersions prepared with improved in vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement.

Nanoprobes, nanostructured materials and solid state materials

NASA Astrophysics Data System (ADS)

Yin, Houping

2005-07-01

Novel templates have been developed to prepare nanostructured porous materials through nonsurfactant templated pathway. And new applications of these materials, such as drug delivery and molecular imprinting, have been explored. The relationship between template content and pore structure has been investigated. The composition and pore structures were studied in detail using IR, TGA, SEM, TEM, BET and XRD. The obtained mesoporous materials have tunable diameters in the range of 2--12 nm. Due to the many advantages of this nonsurfactant templated pathway, such as environment friendly and biocompatibility, controlled release of antibiotics in the nanoporous materials were studied. The in vitro release properties were found to depend on the silica structures which were well tuned by varying the template content. A controlled long-term release pattern of vancomycin was achieved when the template content was 30 wt% or lower. Nanoscale electrochemical probes with dimensions as small as 50 nm in diameter and 1--2 mum in length were fabricated using electron beam deposition on the apex of conventional micron size electrodes. The electroactive region was limited to the extreme tip of the nanoprobe by coating with an insulating polymer and re-opening of the coating at the extreme tip. The novel nanoelectrodes thus prepared were employed to probe neurons in mouse brain slice and the results suggest that the nanoprobes were capable of recording neuronal excitatory postsynaptic potential signals. Interesting solid state chemistry was found in oxygenated iron phthalocyanine. Their Mossbauer spectra show the formation of four oxygenated species apart from the unoxygenated parent compound. The oxygen-bridged compounds formed in the solid matrix bear no resemblance to the one formed by solution chemistry. Tentative assignment of species has been made with the help of Mossbauer and IR spectroscopy. An effort to modify aniline trimer for potential nanoelectronics applications and to investigate the formation of "nano-pancake" shape aggregation was also reported.

Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology.

PubMed

Liu, Dongfei; Chen, Li; Jiang, Sunmin; Zhu, Shuning; Qian, Yong; Wang, Fengzhen; Li, Rui; Xu, Qunwei

2014-03-01

To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT-IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs.

Hypothalamic interactions between neuropeptide Y, agouti-related protein, cocaine- and amphetamine-regulated transcript and alpha-melanocyte-stimulating hormone in vitro in male rats.

PubMed

Dhillo, W S; Small, C J; Stanley, S A; Jethwa, P H; Seal, L J; Murphy, K G; Ghatei, M A; Bloom, S R

2002-09-01

A number of neuropeptides implicated in the hypothalamic regulation of appetite are synthesized in the arcuate nucleus (Arc). Neuropeptide Y (NPY) and agouti-related protein (Agrp) are orexigenic. The pro-opiomelanocortin (POMC) product alpha-melanocyte-stimulating hormone (alpha-MSH) is anorectic. Intracerebroventricular administration of cocaine- and amphetamine-regulated transcript (CART) decreases food intake. However, recent results show that CART is orexigenic when injected into discrete hypothalamic nuclei. There is almost complete coexpression of NPY and Agrp mRNA in Arc neurones, and the majority of CART-containing neurones in the Arc also contain POMC mRNA. We investigated possible interactions between these neuropeptides in vitro using a rat hypothalamic explant system. Administration of 1, 10 and 100 nm of NPY to hypothalamic explants significantly increased release of Agrp(83-132)-immunoreactivity (IR). NPY (10 and 100 nm) significantly increased the release of CART(55-102)-IR and alpha-MSH-IR from hypothalamic explants. Agrp(83-132) (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. Agrp(83-132) (10 and 100 nm) significantly decreased the release of CART(55-102)-IR from hypothalamic explants. Administration of 1, 10 and 100 nm CART(55-102) to hypothalamic explants resulted in a significant increase in NPY-IR release. Administration of 10 nm CART(55-102) to hypothalamic explants significantly increased the release of Agrp(83-132)-IR. NDP-MSH (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. NDP-MSH (10 and 100 nm) significantly increased the release of Agrp(83-132)-IR from hypothalamic explants. These data suggest that orexigenic neuropeptides in the arcuate nucleus stimulate the release of each other, perhaps reinforcing orexigenic behaviour via a positive-feedback loop. Our results are also in keeping with the possibility that the melanocortin-3 receptor in the arcuate nucleus may influence the release of arcuate neuropeptides.

Preparation of resveratrol-loaded nanoporous silica materials with different structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popova, Margarita, E-mail: mpopova@orgchem.bas.bg; Szegedi, Agnes; Mavrodinova, Vesselina

2014-11-15

Solid, nanoporous silica-based spherical mesoporous MCM-41 and KIL-2 with interparticle mesoporosity as well as nanosized zeolite BEA materials differing in morphology and pore size distribution, were used as carriers for the preparation of resveratrol-loaded delivery systems. Two preparation methods have been applied: (i) loading by mixing of resveratrol and mesoporous carrier in solid state and (ii) deposition in ethanol solution. The parent and the resveratrol loaded carriers were characterized by XRD, TEM, N2 physisorption, thermal analysis, and FT-IR spectroscopy. The influence of the support structure on the adsorption capacity and the release kinetics of this poorly soluble compound were investigated.more » Our results indicated that the chosen nanoporous silica supports are suitable for stabilization of trans-resveratrol and reveal controlled release and ability to protect the supported compound against degradation regardless of loading method. The solid-state dry mixing appears very effective for preparation of drug formulations composed of poorly soluble compound. - Graphical abstract: trans-Resveratrol was stabilized in the pores of BEA zeolite, MCM-41and KIL2 mesoporous silicas. - Highlights: • BEA, KIL-2 and MCM-41 materials were used as carriers for resveratrol loading. • Resveratrol encapsulation in ethanol solution and solid state procedure were applied. • The solid-state preparation appears very effective for stabilization of trans-resveratrol.« less

Biowaiver monographs for immediate release solid oral dosage forms: ibuprofen.

PubMed

Potthast, H; Dressman, J B; Junginger, H E; Midha, K K; Oeser, H; Shah, V P; Vogelpoel, H; Barends, D M

2005-10-01

Literature data are reviewed on the properties of ibuprofen related to the biopharmaceutics classification system (BCS). Ibuprofen was assessed to be a BCS class II drug. Differences in composition and/or manufacturing procedures were reported to have an effect on the rate, but not the extent of absorption; such differences are likely to be detectable by comparative in vitro dissolution tests. Also in view of its therapeutic use, its wide therapeutic index and uncomplicated pharmacokinetic properties, a biowaiver for immediate release (IR) ibuprofen solid oral drug products is scientifically justified, provided that the test product contains only those excipients reported in this paper in their usual amounts, the dosage form is rapidly dissolving (85% in 30 min or less) in buffer pH 6.8 and the test product also exhibits similar dissolution profiles to the reference product in buffer pH 1.2, 4.5, and 6.8. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Designing an extended release waxy matrix tablet containing nicardipine–hydroxy propyl β cyclodextrin complex

PubMed Central

Al-Zein, Hind; Sakeer, Khalil; Alanazi, Fars K.

2011-01-01

Aim The current study aimed to prepare a sustained release tablet for a drug which has poor solubility in alkaline medium using complexation with cyclodextrin. Nicardipine hydrochloride (NC) a weak basic drug was chosen as a model drug for this study. Method Firstly the most suitable binary system NC-HPβCD was selected in order to improve drug solubility in the intestinal media and then embedding the complexed drug into a plastic matrix, by fusion method, consists of glycerol monostearate (GMS) as an inert waxy substance and polyethylene glycol 4000 (PEG4000) as a channeling agent, after that the final solid dispersion [(NC:HPβCD):GMS:PEG4000] which was prepared at different ratios was mixed with other excipients, avicel PH101, lactose, and talc, to get a tablet owning dissolution profile complying with the FDA and USP requirements for the extended release solid dosage forms. Results Infrared spectroscopy (IR), differential scanning colorimetry (DSC), polarized microscopy and X-ray diffractometry proved that the coevaporation technique was effective in preparing amorphous cyclodextrin complexes with NC and trapping of NC within the HPβCD cavity by dissolving both in ethanol and evaporate the solvent using a rotavapor at 65 °C. Dissolution profile of NC enhanced significantly in pH 6.8 from NC:HPβCD inclusion complex prepared by the rotavapor (t-test Student p < 0.05). The release of NC from tablet containing [(NC:HPβCD):GMS:PEG4000] [(1):0.75:0.5] (w/w/w) solid dispersion (F8) was complying with the FDA dissolution requirements for extended release dosage forms, and studying the kinetics of the release showed that the diffusional contribution is the major factor controlling the drug release from that formula. Conclusion The prepared waxy matrix tablet containing NC complexes with CD shows promising results as extended release tablets. PMID:23960765

Enhancement of solubility and antidiabetic effects of Repaglinide using spray drying technique in STZ-induced diabetic rats.

PubMed

Varshosaz, Jaleh; Minayian, Mohsen; Ahmadi, Mahdieh; Ghassami, Erfaneh

2017-09-01

The purpose of the study was to enhance the solubility of the poorly water-soluble drug, Repaglinide using spray drying based solid dispersion technique by different carriers including Eudragit E100, hydroxyl propyl cellulose Mw 80 000 and poly vinyl pyrollidone K30. Optimization of the best formulation was carried out according to drug solubility, release profile, particle size and angle of repose of the solid dispersions. The optimized sample was characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The morphology of the dispersions was studied by SEM. The blood glucose lowering effect of spray dried solid dispersions was studied in normal and streptozocin-induced diabetic rats. The results showed that Eudragit E100 in 1:3 ratio could enhance drug solubility by 100-fold. DSC studies indicated a marked change in melting point of the drug possibly due to strong hydrogen bonds between the drug and Eudragit, while FT-IR study did not show obvious interactions between them. According to XRPD results Repaglinide converted to an amorphous state in the spray dried dispersions. Spray dried Repaglinide reduced the blood glucose level significantly during the 8 h of obtaining blood samples in comparison with untreated drug (p < 0.05).

alpha2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y from perivascular nerve terminals.

PubMed

Donoso, M Veronica; Carvajal, Andrés; Paredes, Alfonso; Tomic, Alexander; Koenig, Cecilia S; Huidobro-Toro, J Pablo

2002-09-01

Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many sympathetic synapses, but it is not yet clear if their release is independently regulated. To address this question, we quantified the electrically evoked release of these co-transmitters from perivascular nerve terminals to the mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine reduced the tissue content and the electrically evoked release of ir-NPY and NA as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the content of ir-NPY and NA, but did not modify their release nor altered the rise in perfusion pressure elicited by the electrical stimuli. However, 0.1mg/kg reserpine reduced both the content and release of NA but decreased only the content but not the release of ir-NPY; the rise in perfusion pressure was halved. Clonidine did not affect the release of ir-NPY while it lowered the outflow of NA, not altering the rise in perfusion pressure elicited by the electrical stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA outflow, it antagonized the clonidine effect. Therefore, presynaptic alpha2-adrenoceptors modulate the release of NA but not NPY, implying separate regulatory mechanisms.

Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes.

PubMed

Duggan, A W; Schaible, H G; Hope, P J; Lang, C W

1992-05-08

Antibody microprobes bearing antibodies to the C-terminus of substance P (SP) were used to measure release of immunoreactive (ir) SP in the dorsal horn of barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve produced a relatively localised release of ir SP in the superficial dorsal horn. Prior microinjection of the peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in ir SP being detected over the whole of the dorsal horn and the overlying dorsal column. This pattern had previously been observed with evoked release of ir neurokinin A and supports the proposal that a slow degradation results in a neuropeptide accessing many sites remote from sites of release.

Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs.

PubMed

De Smet, Lieselotte; Saerens, Lien; De Beer, Thomas; Carleer, Robert; Adriaensens, Peter; Van Bocxlaer, Jan; Vervaet, Chris; Remon, Jean Paul

2014-05-01

The aim of the study is to increase the bioavailability of itraconazole (ITRA) using nanosized cocrystals prepared via wet milling of ITRA in combination with dicarboxylic acids. Wet milling was used in order to create a nanosuspension of ITRA in combination with dicarboxylic acids. After spray-drying and bead layering, solid state was characterized by MDSC, XRD, Raman and FT-IR. The release profiles and bioavailability of the nanococrystalline suspension, the spray-dried and bead layered formulation were evaluated. A monodisperse nanosuspension (549±51nm) of ITRA was developed using adipic acid and Tween®80. Solid state characterization indicated the formation of nanococrystals by hydrogen bounds between the triazole group of ITRA and the carboxyl group of adipic acid. A bioavailability study was performed in dogs. The faster drug release from the nanocrystal-based formulation was reflected in the in vivo results since Tmax of the formulations was obtained 3h after administration, while Tmax of the reference formulation was observed only 6h after administration. This fast release of ITRA was obtained by a dual concept: manufacturing of nanosized cocrystals of ITRA and adipic acid via wet milling. Formation of stable nanosized cocrystals via this approach seems a good alternative for amorphous systems to increase the solubility and obtain a fast drug release of BCS class II drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

CO2 removal by solid amine sorbents. 1: Experimental studies of amine resin IR-45 with regard to spacecraft applications. 2: Computer program for predicting the transient performance of solid amine sorbent systems

NASA Technical Reports Server (NTRS)

Wright, R. M.; Hwang, K. C.

1973-01-01

The sorbent behavior of solid amine resin IR-45 with regard to potential use in regenerative CO2-removal systems for manned spacecraft is considered. Measurements of equilibrium sorption capacity of IR-45 for water and for CO2 are reported, and the dynamic mass transfer behavior of IR-45 beds is studied under conditions representative of those expected in a manned spacecraft. A digital computer program was written for the transient performance prediction of CO2 removal systems comprised of solid amine beds. Also evaluated are systems employing inorganic molecular-sieve sorbents. Tests show that there is definitely an effect of water loading on the absorption rate.

Eddy Seeding in the Labrador Sea: a Submerged Autonomous Launching Platform (SALP) Application

NASA Astrophysics Data System (ADS)

Furey, Heather H.; Femke de Jong, M.; Bower, Amy S.

2013-04-01

A simplified Submerged Autonomous Launch Platform (SALP) was used to release profiling floats into warm-core Irminger Rings (IRs) in order to investigate their vertical structure and evolution in the Labrador Sea from September 2007 - September 2009. IRs are thought to play an important role in restratification after convection in the Labrador Sea. The SALP is designed to release surface drifters or subsurface floats serially from a traditional ocean mooring, using real-time ocean measurements as criteria for launch. The original prototype instrument used properties measured at multiple depths, with information relayed to the SALP controller via acoustic modems. In our application, two SALP carousels were attached at 500 meters onto a heavily-instrumented deep water mooring, in the path of recently-shed IRs off the west Greenland shelf. A release algorithm was designed to use temperature and pressure measured at the SALP depth only to release one or two APEX profiling drifters each time an IR passed the mooring, using limited historical observations to set release thresholds. Mechanically and electronically, the SALP worked well: out of eleven releases, there was only one malfunction when a float was caught in the cage after the burn-wire had triggered. However, getting floats trapped in eddies met with limited success due to problems with the release algorithm and float ballasting. Out of seven floats launched from the platform using oceanographic criteria, four were released during warm water events that were not related to passing IRs. Also, after float release, it took on average about 2.6 days for the APEX to adjust from its initial ballast depth, about 600 meters, to its park point of 300 meters, leaving the float below the trapped core of water in the IRs. The other mooring instruments (at depths of 100 to 3000 m), revealed that 12 IRs passed by the mooring in the 2-year monitoring period. With this independent information, we were able to assess and improve the release algorithm, still based on ocean conditions measured only at one depth. We found that much better performance could have been achieved with an algorithm that detected IRs based on a temperature difference from a long-term running mean rather than a fixed temperature threshold. This highlights the challenge of designing an appropriate release strategy with limited a priori information on the amplitude and time scales of the background variability.

Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

PubMed

Qiu, Yihong; Li, Xia; Duan, John Z

2014-02-01

The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Enhanced intestinal permeability and oral bioavailability of enalapril maleate upon complexation with the cationic polymethacrylate Eudragit E100.

PubMed

Ramírez-Rigo, María V; Olivera, María E; Rubio, Modesto; Manzo, Ruben H

2014-05-13

The low bioavailability of enalapril maleate associated to its instability in solid state motivated the development of a polyelectrolyte-drug complex between enalapril maleate and the cationic polymethacrylate Eudragit E100. The solid complexes were characterized by DSC-TG, FT-IR and X-ray diffraction. Their aqueous dispersions were evaluated for drug delivery in bicompartimental Franz cells and electrokinetic potentials. Stability in solid state was also evaluated using an HPLC-UV stability indicating method. Absorption of enalapril maleate was assessed thorough the rat everted gut sac model. In addition, urinary recovery after oral administration in rats was used as an indicator of systemic exposition. The solid materials are stable amorphous solids in which both moieties of enalapril maleate are ionically bonded to the polymer. Their aqueous dispersions exhibited controlled release over more than 7h in physiologic saline solution, being ionic exchange the fundamental mechanism that modified the extent and rate of drug release. Intestinal permeation of enalapril maleate was 1.7 times higher in the presence of the cationic polymer. This increase can be related with the capacity to adhere the mucosa due to the positive zeta potential of the complexes. As a consequence bioavailability was significantly improved (1.39 times) after oral administration of the complexes. In addition, no signs of chemical decomposition were observed after a 14months period. The results indicated that the products are new chemical entities that improve unfavorable properties of a useful drug. Copyright © 2014 Elsevier B.V. All rights reserved.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as an Analytical Method to Investigate the Secondary Structure of a Model Protein Embedded in Solid Lipid Matrices.

PubMed

Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene; Medlicott, Natalie J

2018-02-01

Protein drugs may encounter conformational perturbations during the formulation processing of lipid-based solid dosage forms. In aqueous protein solutions, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can investigate these conformational changes following the subtraction of spectral interference of solvent with protein amide I bands. However, in solid dosage forms, the possible spectral contribution of lipid carriers to protein amide I band may be an obstacle to determine conformational alterations. The objective of this study was to develop an ATR FT-IR spectroscopic method for the analysis of protein secondary structure embedded in solid lipid matrices. Bovine serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol palmitostearate, melting point 58 ℃) was employed as the model lipid matrix. Bovine serum albumin was incorporated into lipid using physical mixing, melting and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR spectroscopy and size exclusion chromatography (SEC) were performed for the analysis of BSA secondary structure and its dissolution in aqueous media, respectively. The results showed significant interference of Precirol ATO5 with BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally denatured BSA solid alone and in the presence of lipid matrix indicating its suitability for the detection of denatured protein solids in lipid matrices. Despite being in the solid state, conformational changes occurred to BSA upon incorporation into solid lipid matrices. However, the extent of these conformational alterations was found to be dependent on the mixing method employed as indicated by area overlap calculations. For instance, the melting and mixing method imparted negligible effect on BSA secondary structure, whereas the wet granulation mixing method promoted more changes. Size exclusion chromatography analysis depicted the complete dissolution of BSA in the aqueous media employed in the wet granulation method. In conclusion, an ATR FT-IR spectroscopic method was successfully developed to investigate BSA secondary structure in solid lipid matrices following the subtraction of lipid spectral interference. The ATR FT-IR spectroscopy could further be applied to investigate the secondary structure perturbations of therapeutic proteins during their formulation development.

Protonation of benzimidazoles and 1,2,3-benzotriazoles Solid-state linear dichroic infrared (IR-LD) spectral analysis and ab initio calculations

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka B.; Pindeva, Liliya I.

2006-09-01

IR-LD spectroscopic data obtained by the orientated solid samples as a suspension in a nematic liquid crystal of 1-hydroxy-1,2,3-benzotriazole, 2-methyl-, 2-acetonitrilebenzimidazoles and their protonated salts have been presented. The stereo-structures have been predicted and compared with theoretical ones. The IR-characteristic bands assignments of all molecule systems have been achieved.

A Randomized, Single-Blind, Substitution Study of OROS Methylphenidate (Concerta) in ADHD Adults Receiving Immediate Release Methylphenidate

ERIC Educational Resources Information Center

Spencer, Thomas J.; Mick, Eric; Surman, Craig B. H.; Hammerness, Paul; Doyle, Robert; Aleardi, Megan; Kotarski, Meghan; Williams, Courtney G.; Biederman, Joseph

2011-01-01

Objective: The main aim of this study was to examine the efficacy, tolerability, and compliance of an extended-release formulation of methylphenidate (OROS-MPH) in adults with ADHD receiving immediate-release methylphenidate (IR-MPH). Method: Participants were outpatient adults with ADHD who were stable on IR-MPH-administered TID. Participants…

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States

PubMed Central

Iwanicki, Janetta L.; Severtson, S. Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J.; Ellis, Matthew S.; Kurtz, Steven P.; Buttram, Mance E.; Dart, Richard C.

2016-01-01

Background Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Methods Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. Results From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Conclusions Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations. PMID:27936038

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

PubMed

Iwanicki, Janetta L; Severtson, S Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J; Ellis, Matthew S; Kurtz, Steven P; Buttram, Mance E; Dart, Richard C

2016-01-01

Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

Aromatic dipeptides and their salts—Solid-state linear-dichroic infrared (IR-LD) spectral analysis and ab initio calculations

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka B.

2008-07-01

Stereo-structural analysis and IR-bands assignment of the aromatic dipeptides L-tryrosyl- L-phenylalanine ( Tyr-Phe), L-phenylalanyl- L-tyrosine ( Phe-Tyr) and their hydrochloride salts have been carried out by means of IR-LD spectroscopy of oriented as nematic liquid crystal suspension solid samples. The experimental data are compared with known crystallographic ones and theoretical predicted geometries at RHF/ and UHF/6-31G**.

The Cheshire-cat-like Behavior of 2nu(sub 3) Overtone of Co2 near 2.134 micron: NIR Lab Spectra of Solid CO2 in H2O and CH3OH

NASA Technical Reports Server (NTRS)

Bernstein, Max; Sandford, Scott; Cruikshank, Dale

2005-01-01

Infrared (IR) spectra have demonstrated that solid H2O is very common in the outer Solar System, and solid carbon dioxide (CO2) has been detected on icy satellites, comets, and planetismals throughout the outer Solar System. In such environments, CO2 and H2O must sometimes be mixed at a molecular level, changing their IR absorption features. In fact, the IR spectra of CO2-H2O mixtures are not equivalent to a linear combination of the spectra of the pure materials. Laboratory IR spectra of pure CO2 and H2O have been published but a lack of near-IR spectra of CO2-H2O mixtures has made the interpretation of outer Solar System spectra more difficult. We present near infrared (IR) spectra of CO2 in H2O and in CH3OH compared to that of pure solid CO2 and find significant differences. Peaks not present in either pure H2O or pure CO2 spectra become evident. First, the CO2 (2nu(sub 3)) overtone near 2.134 micron (4685/ cm) that is not seen in pure solid CO2 is prominent in the spectrum of a CO2/H2O = 25 mixture. Second, a 2.74 micron (3650/ cm) dangling OH feature of water (and a potentially related peak at 1.89 micron) appear in the spectra of CO2-H2O ice mixtures, but may not be specific to the presence of CO2. Other CO2 peaks display shifts in position and increased width because of intermolecular interactions with water. Changes in CO2 peak positions and profiles on warming of a CO2/H2O = 5 mixture are consistent with 'segregation' of the ice into nearly pure separate components. Absolute strengths for absorptions of CO2 in solid H2O are estimated. Similar results are observed for CO2 in solid CH3OH. Since the CO2 ( 2nu(sub 3)) overtone near 2.134 micron (4685/ cm) is not present in pure CO2 but prominent in mixtures it may be a good observational indicator of whether solid CO2 is a pure material or intimately mixed with other molecules. Significant changes in the near IR spectrum of solid CO2 in the presence of H2O and CH3OH means that the abundance of solid CO2 in the outer Solar System may have been under-estimated in those environments where solid CO2 and H2O or CH3OH are mixed.

Preparation and Optimization of Immediate Release/Sustained Release Bilayered Tablets of Loxoprofen Using Box-Behnken Design.

PubMed

Tak, Jin Wook; Gupta, Biki; Thapa, Raj Kumar; Woo, Kyu Bong; Kim, Sung Yub; Go, Toe Gyeong; Choi, Yongjoo; Choi, Ju Yeon; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-05-01

The aim of our current study was to characterize and optimize loxoprofen immediate release (IR)/sustained release (SR) tablet utilizing a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors included ratio of drug in the IR layer to total drug (X 1 ), ratio of HPMC to drug in the SR layer (X 2 ), and ratio of Eudragit RL PO to drug in the SR layer (X 3 ). The dependent variables assessed were % drug released in distilled water at 30 min (Y 1 ), % drug released in pH 1.2 at 2 h (Y 2 ), and % drug released in pH 6.8 at 12 h (Y 3 ). The responses were fitted to suitable models and statistical validation was performed using analysis of variance. In addition, response surface graphs and contour plots were constructed to determine the effects of different factor level combinations on the responses. The optimized loxoprofen IR/SR tablets were successfully prepared with the determined amounts of ingredients that showed close agreement in the predicted and experimental values of tablet characterization and drug dissolution profile. Therefore, BBD can be utilized for successful optimization of loxoprofen IR/SR tablet, which can be regarded as a suitable substitute for the current marketed formulations.

Redox-responsive solid lipid microparticles composed of octadecyl acrylate and allyl disulfide.

PubMed

Kim, Tae Hoon; Kim, Jin-Chul

2018-04-01

Redox-responsive solid lipid microparticles were prepared by an emulsification photo-polymerization method. Octadecyl acrylate (ODA) and a cross-linker (i.e. allyl disulfide (ADS) and octadiene (ODE)) were dissolved in dichloromethane, it was emulsified in poly(vinyl alcohol) solution, and the resulting O/W emulsion was irradiated with UV light. On the scanning electron microscope micrographs, the microparticles were sphere-like and they were not markedly different from the oil droplets in size. Using the atomic compositions analyzed by energy dispersive X-ray spectroscopy, the ODA to cross-linker molar ratio of ODA/ADS microparticles and ODA/ODE ones were calculated to be 1:0.13 and 1:0.15, respectively. In the FT-IR spectra of the microparticles, the signal of the vinyl group was hardly detected, implying that the monomer and the cross-linkers participated in the photo-polymerization. In differential scanning calorimetry study, ODA/ADS microparticles and ODA/ODE ones exhibited their endothermic peaks around 42.9 and 41.3 °C, respectively, possibly due to the melting of polymeric ODA. Dithiothreitol (DTT, a reducing agent) concentration had little effect on the release degree of dye loaded in ODA/ODE microparticles. Whereas, DTT concentration had a significant effect on the release degree of dye loaded in ODA/ADS microparticles. The release degree at 26 °C was weakly affected by DTT concentration. When the temperature was 37 °C, DTT concentration had a strong effect on the release degree. The disulfide cross-linker (i.e. ADS) can be broken to thiol compounds by the reducing agent, resulting in an increase in the release degree.

Application of hot-melt extrusion technology in immediate-release abuse-deterrent formulations.

PubMed

Wening, Klaus; Schwier, Sebastian; Stahlberg, Hans-J; Galia, Eric

Hot-melt extrusion (HME) technology has been used for manufacturing extended-release abuse-deterrent formulations (ADFs) of opioid-type analgesics with improved tamper-resistant properties. Our objective was to describe application of this technology to immediate-release (IR) ADFs. For development of a sample IR ADF (hydrocodone 10 mg/acetaminophen 325 mg) based on HME, feasibility studies were performed using different excipients. The formulation selected for further development was evaluated via in vitro test battery. Moreover, in vivo performance of IR ADF technologies was investigated in an open-label, randomized, cross-over, phase 1, relative oral bioavailability study with another opioid (model compound). Single-center bioavailability trial. Twenty-four healthy white male subjects. ADF IR formulation of an opioid and marketed IR formulation. For feasibility and in vitro studies, dissolution profiles, syringeability, particle size distribution after physical manipulation, and extractability were evaluated. For the phase 1 study, pharmacokinetic parameters were evaluated and compared for ADF IR and a marketed IR formulation. After manipulation, the majority of particles from the ADF IR formulation were >500µm and, thus, not considered suitable for intranasal abuse, while the majority of particles for the reference marketed IR formulation were <500µm. The ADF IR formulation was resistant to syringing and preparation for potential intravenous injection. In healthy subjects, pharmacokinetics of an ADF and marketed IR formulation of an opioid were nearly identical. Application of HME to IR formulations led to development of products with improved mechanical resistance to manipulation for intranasal or intravenous preparation, but similar bioavailability.

Cloning of corticotropin-releasing hormone (CRH) precursor cDNA and immunohistochemical detection of CRH peptide in the brain of the Japanese eel, paying special attention to gonadotropin-releasing hormone.

PubMed

Amano, Masafumi; Mizusawa, Nanami; Okubo, Kataaki; Amiya, Noriko; Mizusawa, Kanta; Chiba, Hiroaki; Yamamoto, Naoyuki; Takahashi, Akiyoshi

2014-04-01

The stress-related corticotropin-releasing hormone (CRH) was first identified by isolation of its cDNA from the brain of the Japanese eel Anguilla japonica. CRH cDNA encodes a signal peptide, a cryptic peptide and CRH (41 amino acids). The sequence homology to mammalian CRH is high. Next, the distribution of CRH-immunoreactive (ir) cell bodies and fibers in the brain and pituitary were examined by immunohistochemistry. CRH-ir cell bodies were detected in several brain regions, e.g., nucleus preopticus pars magnocellularis, nucleus preopticus pars gigantocellularis and formatio reticularis superius. In the brain, CRH-ir fibers were distributed not only in the hypothalamus but also in various regions. Some CRH-ir fibers projected to adrenocorticotropic hormone (ACTH) cells in the rostral pars distalis of the pituitary and also the α-melanocyte-stimulating hormone (α-MSH) cells in the pars intermedia of the pituitary. Finally, the neuroanatomical relationship between the CRH neurons and gonadotropin-releasing hormone (GnRH) neurons was examined by dual-label immunohistochemistry. CRH-ir fibers were found to be in close contact with GnRH-ir cell bodies in the hypothalamus and in the midbrain tegmentum and GnRH-ir fibers were in close contact with CRH-ir cell bodies in the nucleus preopticus pars magnocellularis. These results suggest that CRH has some physiological functions other than the stimulation of ACTH and α-MSH secretion and that reciprocal connections may exist between the CRH neurons and GnRH neurons in the brain of the Japanese eel.

A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study.

PubMed

Karlson, Björn W; Dellborg, Mikael; Gullestad, Lars; Aberg, Jan; Sugg, Jennifer; Herlitz, Johan

2014-01-01

Previous metoprolol studies in myocardial infarction patients were performed with immediate-release (IR) metoprolol. This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar β-blockade over 24 h compared to multiple dosing of metoprolol IR. After 2 days of routine metoprolol treatment, 27 patients with suspected acute myocardial infarction were randomized to open-label treatment with metoprolol IR (50 mg four times daily or 100 mg twice daily) or metoprolol CR/XL 200 mg once daily for 3 days. Metoprolol CR/XL 200 mg once daily gave more pronounced suppression of peak heart rate, with lower peak and less variation in peak to trough plasma levels. There were no differences in AUC between the CR/XL and IR formulations, although the trough plasma metoprolol levels were comparable for metoprolol CR/XL 200 mg once daily and metoprolol IR 50 mg four times daily, but lower for metoprolol IR 100 mg twice daily. Both treatments were well tolerated. Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC. This was accompanied by a more uniform β-blockade over time, which was reflected by heart rate, and a more pronounced suppression of peak heart rate with similar tolerability. This suggests metoprolol CR/XL may be used as an alternative to metoprolol IR in patients with myocardial infarction. © 2013 S. Karger AG, Basel.

Evaluation of the feasibility of switching from immediate release quetiapine to extended release quetiapine fumarate in stable outpatients with schizophrenia.

PubMed

Möller, Hans-Jürgen; Johnson, Sunny; Mateva, Temenuzhka; Brecher, Martin; Svensson, Ola; Miller, Frank; Meulien, Didier

2008-03-01

This double-blind, double-dummy study (D1444C00146) evaluated the efficacy and safety of switching patients with clinically stable schizophrenia from quetiapine immediate release (IR) to the same dose of once-daily extended release quetiapine fumarate (quetiapine XR). Patients received quetiapine IR 400-800 mg/day twice daily for 4 weeks, and were then randomized (2 : 1) to a once-daily equivalent dose of quetiapine XR or maintained on IR for 6 weeks. The primary variable was the proportion of patients who discontinued treatment owing to lack of efficacy or whose Positive and Negative Syndrome Scale scores increased by at least 20% from randomization to any visit. In total, 497 patients were randomized to quetiapine XR (n=331) or IR (n=166). Noninferiority (6% margin; one-sided test, 2.5% significance level) was narrowly missed for the primary efficacy variable for the modified intention-to-treat population (9.1%, quetiapine XR; 7.2%, quetiapine IR; difference 1.86%; 95% confidence interval: -3.78, 6.57; P=0.0431), but was shown for the per-protocol population (5.3%, quetiapine XR; 6.2%, quetiapine IR; difference: -0.83%; 95% confidence interval: -6.75, 3.71; P=0.0017). Serious adverse event incidence was low for quetiapine XR and IR; there were no unexpected adverse events. In conclusion, efficacy was maintained without compromising safety/tolerability when switching patients with stable schizophrenia from twice-daily quetiapine IR to once-daily quetiapine XR (400-800 mg/day).

Controllable light filters using an all-solid-state switchable mirror with a Mg-Ir thin film for preterm infant incubators

NASA Astrophysics Data System (ADS)

Tajima, Kazuki; Shimoike, Mika; Li, Heng; Inagaki, Masumi; Izumi, Hitomi; Akiyama, Misaki; Matsushima, Yukiko; Ohta, Hidenobu

2013-04-01

We have fabricated a controllable light filter using an all-solid-state switchable mirror incorporating a Mg-Ir thin film for use in preterm infant incubators. The solid-state switchable mirror device was fabricated by depositing a multilayer on a glass substrate. The mixed hydride of MgH2 and Mg6Ir2H11 created from the Mg-Ir thin film is red in the transparent state. The optical switching speeds between the reflective and transparent red states depended on applied voltage. The device showed three states, namely, reflective, black, and transparent red, due to the properties of the switchable mirror material. These results suggest that the material could be used as a controllable light filter for preterm infant incubators, since it eliminates the light wavelength that disturbs regular sleep-wake cycles of preterm infants.

Cyclodextrin inclusion complex formation and solid-state characterization of the natural antioxidants alpha-tocopherol and quercetin.

PubMed

Koontz, John L; Marcy, Joseph E; O'Keefe, Sean F; Duncan, Susan E

2009-02-25

Cyclodextrin (CD) complexation procedures are relatively simple processes, but these techniques often require very specific conditions for each individual guest molecule. Variations of the coprecipitation from aqueous solution technique were optimized for the CD complexation of the natural antioxidants alpha-tocopherol and quercetin. Solid inclusion complex products of alpha-tocopherol/beta-CD and quercetin/gamma-CD had molar ratios of 1.7:1, which were equivalent to 18.1% (w/w) alpha-tocopherol and 13.0% (w/w) quercetin. The molar reactant ratios of CD/antioxidant were optimized at 8:1 to improve the yield of complexation. The product yields of alpha-tocopherol/beta-CD and quercetin/gamma-CD complexes from their individual reactants were calculated as 24 and 21% (w/w), respectively. ATR/FT-IR, 13C CP/MAS NMR, TGA, and DSC provided evidence of antioxidant interaction with CD at the molecular level, which indicated true CD inclusion complexation in the solid state. Natural antioxidant/CD inclusion complexes may serve as novel additives in controlled-release active packaging to extend the oxidative stability of foods.

Pharmacokinetic profile of extended-release versus immediate-release oral naproxen sodium after single and multiple dosing under fed and fasting conditions: two randomized, open-label trials.

PubMed

Laurora, Irene; Wang, Yuan

2016-10-01

Extended-release (ER) naproxen sodium provides pain relief for up to 24 hours with a single dose (660 mg/day). Its pharmacokinetic profile after single and multiple dosing was compared to immediate release (IR) naproxen sodium in two randomized, open-label, crossover studies, under fasting and fed conditions. Eligible healthy subjects were randomized to ER naproxen sodium 660-mg tablet once daily or IR naproxen sodium 220-mg tablet twice daily (440 mg initially, followed by 220 mg 12 hours later). Primary variables: pharmacokinetic parameters after singleday administration (day 1) and at steady state after multiple-day administration (day 6). Total exposure was comparable for both treatments under fasting and fed conditions. After fasting: peak naproxen concentrations were slightly lower with ER naproxen sodium than with IR naproxen sodium but were reached at a similar time. Fed conditions: mean peak concentrations were comparable but reached after a longer time with ER vs. IR naproxen sodium. ER naproxen sodium was well tolerated, with a similar safety profile to IR naproxen sodium. The total exposure of ER naproxen sodium (660 mg) is comparable to IR naproxen sodium (220 mg) when administered at the maximum over the counter (OTC) dose of 660-mg daily dose on a single day and over multiple days. The rate of absorption is delayed under fed conditions.

Bilayer Tablet Formulation of Metformin HCl and Acarbose: A Novel Approach To Control Diabetes.

PubMed

Tiwari, Ruchi; Gupta, Ankita; Joshi, Meenakshi; Tiwari, Gaurav

2014-01-01

The present investigation studied a novel bilayer tablet having an extended release system of metformin HCl with Eudragit RS 100 and RL 100 and an immediate release system of acarbose with polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) in different ratios using solvent evaporation and cogrinding techniques. Solid dispersions (SDs) were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder x-ray diffractometry (XRD), scanning electron microscopy (SEM), as well as by content uniformity, in vitro dissolution studies, and release kinetics. The selected SD system was subjected to bilayer tablet preparation by direct compression. Compressed tablets were evaluated for drug content, weight variation, friability, hardness, and thickness, and they underwent in vitro dissolution studies. The progressive disappearance of IR, x-ray, and thermotropic drug signals in SDs and physical mixtures were related to increasing amount of polymer. SEM studies suggested the homogenous dispersion of drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between drug and polymer. All tablet formulations showed compliance with pharmacopoeial standards. The formulations gave an initial burst effect to provide the loading dose of the drug followed by extended release for 12 h (Higuchi model via a non-Fickian diffusion controlled release mechanism). Stability studies conducted for the optimized formulation did not show any change in physical properties, drug content, or in vitro drug release. The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of elevated blood glucose levels. Oral therapeutic options for the treatment of type 2 diabetes mellitus, until recently, have been severely limited. Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting hepatic glucose production and enhancing peripheral glucose uptake and thereby reducing insulin resistance; acarbose reversibly bind to pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes inhibit hydrolysis of complex starches to oligosaccharides in the lumen of the small intestine and hydrolysis of oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. The two agents were found to have a remarkable effect on glycemic control. In the present investigation a bilayer tablet was prepared in which one layer gives instant action against diabetes and another layer maintain concentration of drug in plasma for longer periods.

Solidify, An LLVM pass to compile LLVM IR into Solidity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kothapalli, Abhiram

The software currently compiles LLVM IR into Solidity (Ethereum’s dominant programming language) using LLVM’s pass library. Specifically, his compiler allows us to convert an arbitrary DSL into Solidity. We focus specifically on converting Domain Specific Languages into Solidity due to their ease of use, and provable properties. By creating a toolchain to compile lightweight domain-specific languages into Ethereum's dominant language, Solidity, we allow non-specialists to effectively develop safe and useful smart contracts. For example lawyers from a certain firm can have a proprietary DSL that codifies basic laws safely converted to Solidity to be securely executed on the blockchain. Inmore » another example, a simple provenance tracking language can be compiled and securely executed on the blockchain.« less

Preliminary Numerical Simulation of IR Structure Development in a Hypothetical Uranium Release.

DTIC Science & Technology

1981-11-16

art Identify by block nAsb.’) IR Structure Power spectrum Uranium release Parallax effects Numerical simulation PHARO code Isophots LWIR 20. _PSTRACT...release at 200 km altitude. Of interest is the LWIR emission from uranium oxide ions, induced by sunlight and earthshine. Assuming a one-level fluid...defense systems of long wave infrared ( LWIR ) emissions from metallic oxides in the debris from a high altitude nuclear explosion (HANE) is an

Sustained-release solid dispersion of pelubiprofen using the blended mixture of aminoclay and pH independent polymers: preparation and in vitro/in vivo characterization.

PubMed

Lee, Yeo-Song; Song, Jae Guen; Lee, Sang Hoon; Han, Hyo-Kyung

2017-11-01

The present study aimed to develop the sustained-release oral dosage form of pelubiprofen (PEL) by using the blended mixture of 3-aminopropyl functionalized-magnesium phyllosilicate (aminoclay) and pH-independent polymers. The sustained-release solid dispersion (SRSD) was prepared by the solvent evaporation method and the optimal composition of SRSD was determined as the weight ratio of drug: Eudragit® RL PO: Eudragit® RS PO of 1:1:2 in the presence of 1% of aminoclay (SRSD(F6)). The dissolution profiles of SRSD(F6) were examined at different pHs and in the simulated intestinal fluids. The drug release from SRSD(F6) was limited at pH 1.2 and gradually increased at pH 6.8, resulting in the best fit to Higuchi equation. The sustained drug release from SRSD(F6) was also maintained in simulated intestinal fluid at fasted-state (FaSSIF) and fed-state (FeSSIF). The structural characteristics of SRSD(F6) were examined by using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), indicating the change of drug crystallinity to an amorphous form. After oral administration in rats, SRSD(F6) exhibited the prolonged drug exposure in plasma. For both PEL and PEL-transOH (active metabolite), once a day dosing of SRSD(F6) achieved oral exposure (AUC) comparable to those from the multiple dosing (3 times a day) of untreated drug. In addition, the in vivo absorption of SRSD(F6) was well-correlated with the in vitro dissolution data, establishing a good level A in vitro/in vivo correlation. These results suggest that SRSD(F6) should be promising for the sustained-release of PEL, thereby reducing the dosing frequency.

Size and Site Dependence of the Catalytic Activity of Iridium Clusters toward Ethane Dehydrogenation.

PubMed

Ge, Yingbin; Jiang, Hao; Kato, Russell; Gummagatta, Prasuna

2016-12-01

This research focuses on optimizing transition metal nanocatalyst immobilization and activity to enhance ethane dehydrogenation. Ethane dehydrogenation, catalyzed by thermally stable Ir n (n = 8, 12, 18) atomic clusters that exhibit a cuboid structure, was studied using the B3LYP method with triple-ζ basis sets. Relativistic effects and dispersion corrections were included in the calculations. In the dehydrogenation reaction Ir n + C 2 H 6 → H-Ir n -C 2 H 5 → (H) 2 -Ir n -C 2 H 4 , the first H-elimination is the rate-limiting step, primarily because the reaction releases sufficient heat to facilitate the second H-elimination. The catalytic activity of the Ir clusters strongly depends on the Ir cluster size and the specific catalytic site. Cubic Ir 8 is the least reactive toward H-elimination in ethane: Ir 8 + C 2 H 6 → H-Ir 8 -C 2 H 5 has a large (65 kJ/mol) energy barrier, whereas Ir 12 (3 × 2 × 2 cuboid) and Ir 18 (3 × 3 × 2 cuboid) lower this energy barrier to 22 and 3 kJ/mol, respectively. The site dependence is as prominent as the size effect. For example, the energy barrier for the Ir 18 + C 2 H 6 → H-Ir 18 -C 2 H 5 reaction is 3, 48, and 71 kJ/mol at the corner, edge, or face-center sites of the Ir 18 cuboid, respectively. Energy release due to Ir cluster insertion into an ethane C-H bond facilitates hydrogen migration on the Ir cluster surface, and the second H-elimination of ethane. In an oxygen-rich environment, oxygen molecules may be absorbed on the Ir cluster surface. The oxygen atoms bonded to the Ir cluster surface may slightly increase the energy barrier for H-elimination in ethane. However, the adsorption of oxygen and its reaction with H atoms on the Ir cluster releases sufficient heat to yield an overall thermodynamically favored reaction: Ir n + C 2 H 6 + 1 / 2 O 2 → Ir n + C 2 H 4 + H 2 O. These results will be useful toward reducing the energy cost of ethane dehydrogenation in industry.

Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

PubMed

Ni, Lixiao; Li, Danye; Hu, Shuzhen; Wang, Peifang; Li, Shiyin; Li, Yiping; Li, Yong; Acharya, Kumud

2015-12-01

To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

Formulation studies on ibuprofen sodium-cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola

2016-01-01

The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid-solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.

Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion

PubMed Central

Yazdani, Hamza O.; Sud, Vikas; Goswami, Julie; Loughran, Patricia; Huang, Hai; Simmons, Richard L.; Tsung, Allan

2017-01-01

Introduction Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. Methods Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. Results After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines. Conclusions DRPs significantly attenuated metastatic tumor development and growth. DRPs warrant further investigation as a potential treatment for liver I/R injury in the clinical setting to improve cancer-specific outcomes. PMID:28938688

Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder.

PubMed

Sugrue, David; Bogner, Robin; Ehret, Megan J

2014-07-15

Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric attention-deficit/hyperactivity disorder (ADHD) is reviewed. The efficacy of methylphenidate in controlling ADHD symptoms is firmly established. Given the drug's relatively short half-life in pediatric patients (about 2.5 hours), a number of intermediate- and long-acting products have been developed; these extended-release methylphenidate products provide the same efficacy as immediate-release (IR) formulations, with the convenience of less frequent dosing. Intermediate-acting methylphenidate preparations have effects lasting as long as 8 hours, but peak concentrations are not attained for up to 5 hours, and many patients may require twice-daily dosing. Long-acting methylphenidate products developed to address these challenges include a controlled-release tablet and bimodal-delivery capsules containing mixtures of IR and extended-release beads (durations of effect, 8-12 hours). Options for patients with difficulty swallowing tablets or capsules include a once-daily transdermal delivery system and a once-daily liquid formulation. Dexmethylphenidate (the more pharmacologically active d-isomer of racemic methylphenidate) can provide efficacy comparable to that of IR methylphenidate at half the dose; an extended-release form of dexmethylphenidate can provide less fluctuation in peak and trough concentrations than the IR form. Methylphenidate and dexmethylphenidate products in capsule form can be opened and sprinkled on applesauce. The various formulations of IR and intermediate- and extended-release methylphenidate and dexmethylphenidate can be useful options in satisfying patients' individual needs in the management of ADHD. All are equally efficacious in controlling ADHD symptoms. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Pulsed Infrared Releases Ca2+ from the Endoplasmic Reticulum of Cultured Spiral Ganglion Neurons.

PubMed

Barrett, John N; Rincon, Samantha; Singh, Jayanti; Matthewman, Cristina; Pasos, Julio; Barrett, Ellen F; Rajguru, Suhrud M

2018-04-18

We investigated the effects of pulsed infrared radiation (IR, 1863 nm) stimulation on cytosolic [Ca 2+ ] in inner ear spiral ganglion neurons cultured from day 4 postnatal mice and loaded with a fluorescent Ca 2+ indicator (fluo-4, -5F or -5N). IR pulse trains (200 µs, 200-250 Hz, 2-5 s) delivered via an optical fiber coupled to IR source produced a rapid, transient temperature increase of 6-11ºC (above a baseline of 24-30 ºC) and evoked transient increases in both nuclear and cytosolic [Ca 2+ ] of 0.20 - 1.4 µM, with a simultaneous reduction of [Ca 2+ ] in regions containing endoplasmic reticulum (ER). IR-induced increases in cytosolic [Ca 2+ ] continued in medium containing no added Ca 2+ ({plus minus} Ca 2+ buffers) and low [Na + ], indicating that the [Ca 2+ ] increase was mediated by release from intracellular stores. Consistent with this hypothesis, the IR-induced [Ca 2+ ] response was prolonged and eventually blocked by inhibition of ER Ca-ATPase with cyclopiazonic acid, and was also inhibited by a high concentration of ryanodine and by inhibitors of IP 3 -mediated Ca 2+ release (xestospongin C and 2-APB). The thermal sensitivity of the response suggested involvement of warm-sensitive transient receptor potential (TRP) receptors. Immunostaining of the spiral ganglion demonstrated the presence of intracellular TRPV4 and TRPM2, and the IR-induced [Ca 2+ ] increase was inhibited by TRPV4 inhibitors (HC067047 and GSK2193874). These results suggest that the temperature-sensitivity of IR-induced [Ca 2+ ] elevations is conferred by TRP channels on ER membranes, which facilitate Ca 2+ efflux into the cytosol and initiate Ca 2+ -induced Ca 2+ -release via IP 3 and ryanodine receptors.

Salt formation improved the properties of a candidate drug during early formulation development.

PubMed

Sigfridsson, Kalle; Ahlqvist, Matti; Lindsjö, Martin; Paulsson, Stefan

2018-07-30

The purpose of this study was to investigate if AZD5329, a dual neurokinin NK1/2 receptor antagonist, is a suitable candidate for further development as an oral immediate release (IR) solid dosage form as a final product. The neutral form of AZD5329 has only been isolated as amorphous material. In order to search for a solid material with improved physical and chemical stability and more suitable solid-state properties, a salt screen was performed. Crystalline material of a maleic acid salt and a fumaric acid salt of AZD5329 were obtained. X-ray powder diffractiometry, thermogravimetric analysis, differential scanning calorimetry and dynamic vapor sorption were used to investigate the physicochemical characteristics of the two salts. The fumarate salt of AZD5329 is anhydrous, the crystallization is reproducible and the hygroscopicity is acceptable. Early polymorphism assessment work using slurry technique did not reveal any better crystal modification or crystallinity for the fumarate salt. For the maleate salt, the form isolated originally was found to be a solvate, but an anhydrous form was found in later experiments; by suspension in water or acetone, by drying of the solvate to 100-120 °C or by subjecting the solvate form to conditions of 40 °C/75%RH for 3 months. The dissolution behavior and the chemical stability (in aqueous solutions, formulations and solid-state) of both salts were also studied and found to be satisfactory. The compound displays sensitivity to low pH, and the salt of the maleic acid, which is the stronger acid, shows more degradation during stability studies, in line with this observation. The presented data indicate that the substance fulfils basic requirements for further development of an IR dosage form, based on the characterization on crystalline salts of AZD5329. Copyright © 2018 Elsevier B.V. All rights reserved.

Nanostructured lipid carriers: effect of solid phase fraction and distribution on the release of encapsulated materials.

PubMed

Dan, Nily

2014-11-25

Emulsions, solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC) containing a mix of liquid and solid domains are of interest as encapsulation vehicles for hydrophobic compounds. Studies of the release rate from these particles yield contradictory results: Some find that increasing the fraction of solid phase increases the rate of release and others the opposite. In this paper we study the release of encapsulated materials from lipid-based nanoparticles using Monte Carlo simulations. We find that, quite surprisingly, the release rate is largely insensitive to the size of solid domains or the fraction of solid phase. However, the distribution of the domains significantly affects the rate of release: Solid domains located at the interface with the surrounding solution inhibit transport, while nanoparticles where the solid domains are concentrated in the center enhance it. The latter can lead to release rates in NLCs that are faster than in the equivalent emulsions. We conclude that controlling the release rate from NLCs requires the ability to determine the location and distribution of the solid phase, which may be achieved through choice of the surfactants stabilizing the particles, incorporation of nucleation sites, and/or the cooling rates and temperatures.

Proinflammatory Actions of Visfatin/Nicotinamide Phosphoribosyltransferase (Nampt) Involve Regulation of Insulin Signaling Pathway and Nampt Enzymatic Activity*

PubMed Central

Jacques, Claire; Holzenberger, Martin; Mladenovic, Zvezdana; Salvat, Colette; Pecchi, Emilie; Berenbaum, Francis; Gosset, Marjolaine

2012-01-01

Visfatin (also termed pre-B-cell colony-enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (Nampt)) is a pleiotropic mediator acting on many inflammatory processes including osteoarthritis. Visfatin exhibits both an intracellular enzymatic activity (nicotinamide phosphoribosyltransferase, Nampt) leading to NAD synthesis and a cytokine function via the binding to its hypothetical receptor. We recently reported the role of visfatin in prostaglandin E2 (PGE2) synthesis in chondrocytes. Here, our aim was to characterize the signaling pathways involved in this response in exploring both the insulin receptor (IR) signaling pathway and Nampt activity. IR was expressed in human and murine chondrocytes, and visfatin triggered Akt phosphorylation in murine chondrocytes. Blocking IR expression with siRNA or activity using the hydroxy-2-naphthalenyl methyl phosphonic acid tris acetoxymethyl ester (HNMPA-(AM)3) inhibitor diminished visfatin-induced PGE2 release in chondrocytes. Moreover, visfatin-induced IGF-1R−/− chondrocytes released higher concentration of PGE2 than IGF-1R+/+ cells, a finding confirmed with an antibody that blocked IGF-1R. Using RT-PCR, we found that visfatin did not regulate IR expression and that an increased insulin release was also unlikely to be involved because insulin was unable to increase PGE2 release. Inhibition of Nampt activity using the APO866 inhibitor gradually decreased PGE2 release, whereas the addition of exogenous nicotinamide increased it. We conclude that the proinflammatory actions of visfatin in chondrocytes involve regulation of IR signaling pathways, possibly through the control of Nampt enzymatic activity. PMID:22399297

Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release Tablet.

PubMed

Christopher, Ronald; Morgan, Mike; Ferry, Jim; Rege, Bhaskar; Tang, Yong; Kristensen, Allan; Shanahan, William

2016-10-01

Lorcaserin is a serotonin 2C receptor agonist indicated for chronic weight management as an adjunct to diet and exercise. The initial approved formulation is a 10-mg, immediate-release (IR) tablet for administration BID. These studies investigated the single- and multiple-dose pharmacokinetic properties of a new, recently US Food and Drug Administration-approved, extended-release, 20-mg once-daily formulation. We performed 2 separate 2-period, 2-sequence crossover studies in 36 healthy adults: a study comparing the IR formulation to the extended-release formulation under fasting conditions and a study comparing the extended-release formulation under fed and fasted conditions. Compared with lorcaserin IR, the T max after a single dose of lorcaserin extended-release was greater (median, 12 vs 3 hours), and the C max was 26% lower (38.8 vs 52.3 ng/mL). AUC data were bioequivalent for the 2 formulations in both single- and multiple-dose regimens, confirming no formulation effect on lorcaserin bioavailability. In fasted and fed conditions, T max after a single dose was identical (median, 12 hours), but C max was approximately 45% higher in the fed state (mean, 38.5 ng/mL fasted vs 56.1 ng/mL fed). However, at steady state, C max and AUC were determined to be bioequivalent between the fasted and fed states, indicating no clinically relevant food effect on the pharmacokinetic properties of lorcaserin extended-release. The safety profile was consistent between the 2 formulations. Overall, the results indicate that lorcaserin extended-release is a suitable once-daily alternative to the approved IR BID formulation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes.

PubMed

Guo, Fang; Yu, Meng; Wang, Jinping; Tan, Fengping; Li, Nan

2015-09-23

The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.

Measuring Collimator Infrared (IR) Spectral Transmission

DTIC Science & Technology

2016-05-01

TECHNICAL REPORT RDMR-WD-16-15 MEASURING COLLIMATOR INFRARED (IR) SPECTRAL TRANSMISSION Christopher L. Dobbins Weapons...AND DATES COVERED Final 4. TITLE AND SUBTITLE Measuring Collimator Infrared (IR) Spectral Transmission 5. FUNDING NUMBERS 6. AUTHOR(S) Christopher L...release; distribution is unlimited. 12b. DISTRIBUTION CODE A 13. ABSTRACT (Maximum 200 Words) Several Infrared (IR) imaging systems have been measured

Comparative study on the in vitro performance of blister molded and conventional lornoxicam immediate release liquitablets: accelerated stability study and anti-inflammatory and ulcerogenic effects.

PubMed

El-Setouhy, Doaa Ahmed; Gamiel, Alaa Abdel-Rahman; Badawi, Alia Abd El-Latif; Osman, Afaf Sayed; Labib, Dina Ahmed

2017-03-01

Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID). It shows limited solubility in the gastric pH, delayed bioavailability and pharmacodynamic effects with aggravated gastric side effects (due to longer residence in the stomach wall). To enhance dissolution of lornoxicam in the gastric fluid and expectedly absorption and pharmacological action, with less ulcerogenic effects. Formulation of immediate release (IR) lornoxicam liquitablets containing both liquid and solid release modulators (wetting agent, solubilizers and microenvironmental pH modifiers). Beside the traditional direct compression technique employed for the preparation of liquitablets a new technique, blister molding, was also used. The effect of the two different manufacturing methods on the fast release characteristics (rapid disintegration and dissolution) was studied. Stability and pharmacological activity of the optimum formula were also explored. Similarity factor pointed out the superiority of molding technique in enhancing dissolution of lornoxicam owing to significant crystallinity reduction (XRD). Optimum formula showed negligible change in drug content and dissolution profiles over 12 weeks, significantly improved anti-inflammatory activity and significantly reduced gastric ulcerative effect over pure lornoxicam and commercial formula. Blister molded lornoxicam liquitablet of improved dissolution and pharmacological activity and less gastric erosion was successfully prepared.

Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS.

PubMed

Atkinson, L; Batten, T F C; Moores, T S; Varoqui, H; Erickson, J D; Deuchars, J

2004-01-01

Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR depended on the CNS region examined. In the spinal cord, P2X(7)R-IR co-localised with VGLUT2-IR. In the brainstem, co-localisation of P2X(7)R-IR with VGLUT2-IR was widespread, but co-localisation with VGLUT1-IR was seen only in the external cuneate nucleus and spinocerebellar tract region of the ventral medulla. In the cerebellum, P2X(7)R-IR co-localised with both VGLUT1 and VGLUT2-IR in the granular layer. In the hippocampus it was co-localised only with VGLUT1-IR, including in the polymorphic layer of the dentate gyrus and the substantia radiatum of the CA3 region. In other forebrain areas, P2X(7)R-IR co-localised with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate nucleus, amygdala and hypothalamus. Dual labelling studies performed using markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals. These data support our previous hypothesis that the P2X(7)R may play a role in modulating glutamate release in functionally different systems throughout the CNS but further suggest a role in modulating release of inhibitory transmitters in some regions.

Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

PubMed

Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

2015-01-01

This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

Activation of mitochondrial calpain and increased cardiac injury: beyond AIF release

PubMed Central

Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J.

2015-01-01

Calpain 1 (CPN1) is a ubiquitous cysteine protease that exists in both cytosol and cardiac mitochondria. Mitochondrial CPN1 (mit-CPN1) is located in the intermembrane space and matrix. Activation of mit-CPN1 within the intermembrane space increases cardiac injury by releasing apoptosis-inducing factor from mitochondria during ischemia-reperfusion (IR). We asked if activation of mit-CPN1 is involved in mitochondrial injury during IR. MDL-28170 (MDL) was used to inhibit CPN1 in buffer-perfused hearts following 25-min ischemia and 30-min reperfusion. MDL treatment decreased the release of lactate dehydrogenase into coronary effluent compared with untreated hearts, indicating that inhibition of CPN1 decreases cardiac injury. MDL also prevented the cleavage of spectrin (a substrate of CPN1) in cytosol during IR, supporting that MDL treatment decreased cytosolic calpain activation. In addition, MDL markedly improved calcium retention capacity compared with untreated heart, suggesting that MDL treatment decreases mitochondrial permeability transition pore opening. In addition, we found that IR led to decreased complex I activity, whereas inhibition of mit-CPN1 using MDL protected complex I. Pyruvate dehydrogenase content was decreased following IR. However, pyruvate dehydrogenase content was preserved in MDL-treated mitochondria. Taken together, MDL treatment decreased cardiac injury during IR by inhibiting both cytosolic and mit-CPN1. Activation of mit-CPN1 increases cardiac injury during IR by sensitizing mitochondrial permeability transition pore opening and impairing mitochondrial metabolism through damage of complex I. PMID:26637561

Investigation of the effectiveness of nutrient release from sludge foam after hybrid pretreatment processes by IR analysis and EDX Quantification.

PubMed

Machnicka, Alicja; Grübel, Klaudiusz

2016-12-01

One of the problems in wastewater treatment technologies is the formation of foam/scum. It is thought that filamentous microorganisms are responsible for foam formation and foam elimination/destruction can be carried out by various methods, among which disintegration is included. Hybrid disintegration (chemical decomposition and hydrodynamic cavitation) of foam microorganisms results in the transfer of phosphates, ammonium nitrogen, magnesium and potassium from the foam solids into the liquid phase. Application of both methods as a hybrid pretreatment process caused an increase in the concentration of phosphates of about 650 mg [Formula: see text] L(-1) and ammonium nitrogen of about 30 mg [Formula: see text] L(-1). The concentration of Mg(2+) and K(+) in the solution increased from 6.8 and 26.1 mg Mg(2+) L(-1) to 32.2 and 82.2 mg K(+) L(-1), respectively. The presence of nutrients and metal cations in the solid phase of foam was acknowledged by EDX Quantification. The confirmation of physico-chemical changes and release of cellular matter as a result of cellular lysis (hybrid disintegration) was done by infrared analysis. It was demonstrated that the disintegration of foam permits the removal of a part of nutrients in the form of struvite.

Fluorine substituted (Mn,Ir)O 2:F high performance solid solution oxygen evolution reaction electro-catalysts for PEM water electrolysis

DOE PAGES

Ghadge, Shrinath Dattatray; Patel, Prasad Prakash; Datta, Moni Kanchan; ...

2017-03-20

Identification and development of high performance with reduced overpotential (i.e. reduced operating electricity cost) oxygen evolution reaction (OER) electrocatalysts for proton exchange membrane (PEM) based water electrolysis with ultra-low noble metal content (i.e. reduced materials cost) is of significant interest for economic hydrogen production, thus increasing the commercialization potential of PEM water electrolysis. Accordingly, a novel electrocatalyst should exhibit low overpotential, excellent electrochemical activity and durability superior to state of the art noble metal based electro-catalysts (e.g. Pt, IrO 2, RuO 2). Here in this paper, for the very first time to the best of our knowledge, exploiting first-principles theoreticalmore » calculations of the total energies and electronic structures, we have identified a reduced noble metal content fluorine doped solid solution of MnO 2 and IrO 2, denoted as (Mn 1-xIr x)O 2:F (x = 0.2, 0.3, 0.4), OER electrocatalyst system exhibiting lower overpotential and higher current density than the state of the art IrO 2 and other previously reported systems for PEM water electrolysis. The doped solid solution displays an excellent electrochemical performance with a lowest reported onset potential to date of ~1.35 V (vs. RHE), ~80 mV lower than that of IrO 2 (~1.43 V vs. RHE) and ~15 fold (x = 0.3 and 0.4) higher electrochemical activity compared to pure IrO 2. In addition, the system displays excellent long term electrochemical durability, similar to that of IrO 2 in harsh acidic OER operating conditions. Our study therefore demonstrates remarkable, ~60–80% reduction in noble metal content along with lower overpotential and excellent electrochemical performance clearly demonstrating the potential of the (Mn 1-xIr x)O 2:F system as an OER electro-catalyst for PEM water electrolysis.« less

Fluorine substituted (Mn,Ir)O 2:F high performance solid solution oxygen evolution reaction electro-catalysts for PEM water electrolysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghadge, Shrinath Dattatray; Patel, Prasad Prakash; Datta, Moni Kanchan

Identification and development of high performance with reduced overpotential (i.e. reduced operating electricity cost) oxygen evolution reaction (OER) electrocatalysts for proton exchange membrane (PEM) based water electrolysis with ultra-low noble metal content (i.e. reduced materials cost) is of significant interest for economic hydrogen production, thus increasing the commercialization potential of PEM water electrolysis. Accordingly, a novel electrocatalyst should exhibit low overpotential, excellent electrochemical activity and durability superior to state of the art noble metal based electro-catalysts (e.g. Pt, IrO 2, RuO 2). Here in this paper, for the very first time to the best of our knowledge, exploiting first-principles theoreticalmore » calculations of the total energies and electronic structures, we have identified a reduced noble metal content fluorine doped solid solution of MnO 2 and IrO 2, denoted as (Mn 1-xIr x)O 2:F (x = 0.2, 0.3, 0.4), OER electrocatalyst system exhibiting lower overpotential and higher current density than the state of the art IrO 2 and other previously reported systems for PEM water electrolysis. The doped solid solution displays an excellent electrochemical performance with a lowest reported onset potential to date of ~1.35 V (vs. RHE), ~80 mV lower than that of IrO 2 (~1.43 V vs. RHE) and ~15 fold (x = 0.3 and 0.4) higher electrochemical activity compared to pure IrO 2. In addition, the system displays excellent long term electrochemical durability, similar to that of IrO 2 in harsh acidic OER operating conditions. Our study therefore demonstrates remarkable, ~60–80% reduction in noble metal content along with lower overpotential and excellent electrochemical performance clearly demonstrating the potential of the (Mn 1-xIr x)O 2:F system as an OER electro-catalyst for PEM water electrolysis.« less

Single-dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate-release and hydrophilic matrix extended-release tablets in healthy Japanese subjects without co-administration of an opioid antagonist.

PubMed

Toyama, Kaoru; Uchida, Naoki; Ishizuka, Hitoshi; Sambe, Takehiko; Kobayashi, Shinichi

2015-09-01

This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0 h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24 h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing. © 2015, The American College of Clinical Pharmacology.

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

PubMed

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Photo-Redox Activated Drug Delivery Systems Operating Under Two Photon Excitation in the Near-IR

PubMed Central

Guardado-Alvarez, Tania M.; Devi, Lekshmi Sudha; Vabre, Jean-Marie; Pecorelli, Travis; Schwartz, Benjamin J.; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille; Zink, Jeffrey I.

2014-01-01

We report the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by “snap-top” caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes inter-molecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. We describe the operation of the “snap-top” release mechanism by both one- and two-photon activation. This system presents a proof of concept of a near-IR photoredox-induced nanoparticle delivery system that may lead to a new type of photodynamic drug release therapy. PMID:24647752

Photo-redox activated drug delivery systems operating under two photon excitation in the near-IR.

PubMed

Guardado-Alvarez, Tania M; Devi, Lekshmi Sudha; Vabre, Jean-Marie; Pecorelli, Travis A; Schwartz, Benjamin J; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille; Zink, Jeffrey I

2014-05-07

We report the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by "snap-top" caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes inter-molecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. We describe the operation of the "snap-top" release mechanism by both one- and two-photon activation. This system presents a proof of concept of a near-IR photoredox-induced nanoparticle delivery system that may lead to a new type of photodynamic drug release therapy.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

PubMed

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

Compact near-IR and mid-IR cavity ring down spectroscopy device

NASA Technical Reports Server (NTRS)

Miller, J. Houston (Inventor)

2011-01-01

This invention relates to a compact cavity ring down spectrometer for detection and measurement of trace species in a sample gas using a tunable solid-state continuous-wave mid-infrared PPLN OPO laser or a tunable low-power solid-state continuous wave near-infrared diode laser with an algorithm for reducing the periodic noise in the voltage decay signal which subjects the data to cluster analysis or by averaging of the interquartile range of the data.

Macronutrient Composition and Food Form Affect Glucose and Insulin Responses in Humans

PubMed Central

Shafaeizadeh, Shila; Muhardi, Leilani; van de Heijning, Bert J. M.; van der Beek, Eline M.

2018-01-01

Glycaemic index (GI) is used as an indicator to guide consumers in making healthier food choices. We compared the GI, insulin index (II), and the area under the curve for blood glucose and insulin as glucose (GR) and insulin responses (IR) of a newly developed liquid nutritional formula with one commercially available liquid product with different types of carbohydrates. We then evaluated the glucose and insulin responses of two test foods with comparable energy density and protein percentage but presented in different food forms (liquid vs. solid). Fourteen healthy women participated in the study. GI, II, GR, and IR were assessed after (independent) consumption of two liquid products and a solid breakfast meal. The two liquid foods showed comparable GI, whilst the liquid form appeared to produce lower median GI (25 vs. 54), and II (52 vs. 98) values compared to the solid breakfast (p < 0.02). The median GR and IR for solid breakfast were respectively 44% and 45% higher compared to the liquid product (p < 0.02). Liquid formulas with different carbohydrate qualities produced comparable glucose responses, while foods with comparable energy density and protein percentage but different food form elicited differential effects on GI, II, GR, and IR. Nutrient quality and food form need to be taken into consideration when developing low GI products to manage glycaemic responses. PMID:29419785

Vibrational spectroscopic investigation of polymorphs and cocrystals of indomethacin.

PubMed

Ali, Hassan Refat H; Alhalaweh, Amjad; Velaga, Sitaram P

2013-05-01

Identification of optimal solid form of an active pharmaceutical ingredient and form control are very important in drug development. Thus, the structural information of these forms and in-depth insight on the modes of molecular interactions are necessary, and vibrational spectroscopic methods are well suited for this purpose. In-depth structural analysis of different solid forms of indomethacin (IND) using Raman and infrared (IR) spectroscopy is the objective. We have investigated the modes of molecular interactions in polymorphs (α and γ), amorphous and discovered cocrystals of IND with nicotinamide (NIC) and trans-cinnamic acid (CIN) coformers. The solid forms of IND have been prepared; their purity has been verified by differential scanning calorimetry and powder X-ray diffractometry and then studied in the solid-state by Raman and IR spectroscopy. The modes of the interactions were closely investigated from the vibrational data. The key vibrational features of IND solid forms have been specified. The IR (C=O) band at 1713 cm(-1) attributed to cyclic acid dimer of γ IND has disappeared in IND-NIC/CIN whilst retained in IND-SAC cocrystal. IND cocrystallizes in different conformations and crystal lattices with different coformers. The cyclic acid dimer of IND has been kept on its cocrystallization with saccharin and it could have been broken with NIC and CIN. The complementary nature of Raman and IR spectroscopy allowed unambiguous investigation of the chemical composition of pharmaceutical materials which is of particular importance in the absence of detailed structural information, as in the case of IND-NIC and IND-CIN.

Comparing the Immediate Effects of a Total Motion Release Warm-up and a Dynamic Warm-up Protocol on the Dominant Shoulder in Baseball Athletes.

PubMed

Gamma, Stephen C; Baker, Russell; May, James; Seegmiller, Jeff G; Nasypany, Alan; Iorio, Steven M

2018-04-10

Gamma, SC, Baker, R, May, J, Seegmiller, JG, Nasypany, A, and Iorio, SM. Comparing the immediate effects of a total motion release warm-up and a dynamic warm-up protocol on the dominant shoulder in baseball athletes. J Strength Cond Res XX(X): 000-000, 2017-A decrease in total range of motion (ROM) of the dominant shoulder may predispose baseball athletes to increased shoulder injury risk; the most effective technique for improving ROM is unknown. The purpose of this study was to compare the immediate effects of Total Motion Release (TMR) to a generic dynamic warm-up program in baseball athletes. Baseball athletes (n = 20) were randomly assigned to an intervention group: TMR group (TMRG; n = 10) or traditional warm-up group (TWG; n = 10). Shoulder ROM measurements were recorded for internal rotation (IR) and external rotation (ER), the intervention was applied, and postmeasurements were recorded. Each group then received the other intervention and postmeasurements were again recorded. The time main effect (p ≤ 0.001) and the time × group interaction effect were significant (p ≤ 0.001) for IR and ER. Post hoc analysis revealed that TMR produced significant increases in mean IR (p ≤ 0.005, d = 1.52) and ER (p ≤ 0.018, d = 1.22) of the dominant shoulder initially. When groups crossed-over, the TMRG experienced a decrease in mean IR and ER after the dynamic warm-up, whereas the TWG experienced a significant increase in mean IR (p ≤ 0.001, d = 3.08) and ER (p ≤ 0.001, d = 2.56) after TMR intervention. Total Motion Release increased IR and ER of the dominant shoulder more than a dynamic warm-up. Dynamic warm-up after TMR also resulted in decreased IR and ER; however, TMR after dynamic warm-up significantly improved IR and ER. Based on these results, TMR is more effective than a generic dynamic warm-up for improving dominant shoulder ROM in baseball players.

RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-α in cardiac ischaemia/reperfusion injury.

PubMed

Cabrera-Fuentes, H A; Ruiz-Meana, M; Simsekyilmaz, S; Kostin, S; Inserte, J; Saffarzadeh, M; Galuska, S P; Vijayan, V; Barba, I; Barreto, G; Fischer, S; Lochnit, G; Ilinskaya, O N; Baumgart-Vogt, E; Böning, A; Lecour, S; Hausenloy, D J; Liehn, E A; Garcia-Dorado, D; Schlüter, K-D; Preissner, K T

2014-12-01

Despite optimal therapy, the morbidity and mortality of patients presenting with an acute myocardial infarction (MI) remain significant, and the initial mechanistic trigger of myocardial "ischaemia/reperfusion (I/R) injury" remains greatly unexplained. Here we show that factors released from the damaged cardiac tissue itself, in particular extracellular RNA (eRNA) and tumour-necrosis-factor α (TNF-α), may dictate I/R injury. In an experimental in vivo mouse model of myocardial I/R as well as in the isolated I/R Langendorff-perfused rat heart, cardiomyocyte death was induced by eRNA and TNF-α. Moreover, TNF-α promoted further eRNA release especially under hypoxia, feeding a vicious cell damaging cycle during I/R with the massive production of oxygen radicals, mitochondrial obstruction, decrease in antioxidant enzymes and decline of cardiomyocyte functions. The administration of RNase1 significantly decreased myocardial infarction in both experimental models. This regimen allowed the reduction in cytokine release, normalisation of antioxidant enzymes as well as preservation of cardiac tissue. Thus, RNase1 administration provides a novel therapeutic regimen to interfere with the adverse eRNA-TNF-α interplay and significantly reduces or prevents the pathological outcome of ischaemic heart disease.

Infrared Spectroscopy as a Chemical Fingerprinting Tool

NASA Technical Reports Server (NTRS)

Huff, Tim; Munafo, Paul M. (Technical Monitor)

2002-01-01

Infrared (IR) spectroscopy is a powerful analytical tool in the chemical fingerprinting of materials. The technique is rapid, reproducible and usually non-invasive. With the appropriate accessories, the technique can be used to examine samples in either a solid, liquid or gas phase. Solid samples of varying sizes and shapes may be used, and with the addition of microscopic IR (microspectroscopy) capabilities, minute materials such as single fibers and threads may be examined. With the addition of appropriate software, microspectroscopy can be used for automated discrete point or compositional surface area mapping, with the latter providing a means to record changes in the chemical composition of a material surface over a defined area. Both aqueous and non-aqueous free-flowing solutions can be analyzed using appropriate IR techniques, as can viscous liquids such as heavy oils and greases. Due to the ability to characterize gaseous samples, IR spectroscopy can also be coupled with thermal processes such as thermogravimetric (TG) analyses to provide both thermal and chemical data in a single run. In this configuration, solids (or liquids) heated in a TG analyzer undergo decomposition, with the evolving gases directed into the IR spectrometer. Thus, information is provided on the thermal properties of a material and the order in which its chemical constituents are broken down during incremental heating. Specific examples of these varied applications will be cited, with data interpretation and method limitations further discussed.

The nervus terminalis in amphibians: anatomy, chemistry and relationship with the hypothalamic gonadotropin-releasing hormone system.

PubMed

Muske, L E; Moore, F L

1988-01-01

The nervus terminalis (TN), a component of the olfactory system, is found in most vertebrates. The TN of some fishes and mammals contains neurons immunoreactive (ir) to gonadotropin-releasing hormone (LHRH), and to several other neuropeptides and neurotransmitter systems, but there is little information on TN chemistry in other vertebrate taxa. Using immunocytochemical techniques, we found LHRH-ir neurons in amphibian TNs. In anurans, but not in a urodele, the TN was also found to contain Phe-Met-Arg-Phe-NH2 (FMRFamide) immunoreactivity. LHRH-ir neurons of the TN and those of the septal-hypothalamic system are morphologically homogeneous and form a distinct anatomical continuum in amphibians. Based upon topographical and cytological criteria, we hypothesize that LHRH-ir systems in vertebrates might derive embryonically from the TN.

Dehydrogenation of n-Alkanes by Solid-Phase Molecular Pincer-Iridium Catalysts. High Yields of α-Olefin Product.

PubMed

Kumar, Akshai; Zhou, Tian; Emge, Thomas J; Mironov, Oleg; Saxton, Robert J; Krogh-Jespersen, Karsten; Goldman, Alan S

2015-08-12

We report the transfer-dehydrogenation of gas-phase alkanes catalyzed by solid-phase, molecular, pincer-ligated iridium catalysts, using ethylene or propene as hydrogen acceptor. Iridium complexes of sterically unhindered pincer ligands such as (iPr4)PCP, in the solid phase, are found to give extremely high rates and turnover numbers for n-alkane dehydrogenation, and yields of terminal dehydrogenation product (α-olefin) that are much higher than those previously reported for solution-phase experiments. These results are explained by mechanistic studies and DFT calculations which jointly lead to the conclusion that olefin isomerization, which limits yields of α-olefin from pincer-Ir catalyzed alkane dehydrogenation, proceeds via two mechanistically distinct pathways in the case of ((iPr4)PCP)Ir. The more conventional pathway involves 2,1-insertion of the α-olefin into an Ir-H bond of ((iPr4)PCP)IrH2, followed by 3,2-β-H elimination. The use of ethylene as hydrogen acceptor, or high pressures of propene, precludes this pathway by rapid hydrogenation of these small olefins by the dihydride. The second isomerization pathway proceeds via α-olefin C-H addition to (pincer)Ir to give an allyl intermediate as was previously reported for ((tBu4)PCP)Ir. The improved understanding of the factors controlling rates and selectivity has led to solution-phase systems that afford improved yields of α-olefin, and provides a framework required for the future development of more active and selective catalytic systems.

Extended‐Release Once‐Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate‐Release Tofacitinib and Impact of Food

PubMed Central

Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C.

2016-01-01

Abstract Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended‐release (XR) formulation has been designed to provide a once‐daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice‐daily immediate‐release (IR) formulation. We conducted 2 randomized, open‐label, phase 1 studies in healthy volunteers. Study A characterized single‐dose and steady‐state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single‐dose and steady‐state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high‐fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half‐life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax) after single‐ and multiple‐dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. Cmax increased by 27% under the fed state. On repeat administration, negligible accumulation (<20%) of systemic exposures was observed for both formulations. Steady state was achieved within 48 hours of dosing with the XR formulation. Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. PMID:26970526

Preparation, Characterization and Application of a Molecularly Imprinted Polymer for Selective Recognition of Sulpiride

PubMed Central

Zhang, Wei; She, Xuhui; Wang, Liping; Fan, Huajun; Zhou, Qing; Huang, Xiaowen; Tang, James Z.

2017-01-01

A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio of sulpiride-ITA-EGDMA of 1:4:15 by single-factor experiments. The MIP showed good adsorption property with imprinting factor α of 5.36 and maximum adsorption capacity of 61.13 μmol/g, and was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and surface area analysis. With the structural analogs (amisulpride, tiapride, lidocaine and cisapride) and small molecules containing a mono-functional group (p-toluenesulfonamide, formamide and 1-methylpyrrolidine) as substrates, static adsorption, kinetic adsorption, and rebinding experiments were also performed to investigate the selective adsorption ability, kinetic characteristic, and recognition mechanism of the MIP. A serial study suggested that the highly selective recognition ability of the MIP mainly depended on binding sites provided by N-functional groups of amide and amine. Moreover, the MIP as solid-phase extractant was successfully applied to extraction of sulpiride from the mixed solution (consisted of p-toluenesulfonamide, sulfamethoxazole, sulfanilamide, p-nitroaniline, acetanilide and trimethoprim) and serum sample, and extraction recoveries ranged from 81.57% to 86.63%. The tentative tests of drug release in stimulated intestinal fluid (pH 6.8) demonstrated that the tablet with the MIP–sulpiride could obviously inhibit sulpiride release rate. Thus, ITA-based MIP is an efficient and promising alternative to solid-phase adsorbent for extraction of sulpiride and removal of interferences in biosample analysis, and could be used as a potential carrier for controlled drug release. PMID:28772831

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs

PubMed Central

Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

2016-01-01

Objective DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. Method In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. Results Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm3) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. Conclusion Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance. PMID:27354765

Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord.

PubMed

Zhu, J; Jhamandas, K; Yang, H Y

1992-10-02

Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs.

PubMed

Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

2016-01-01

DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm(3)) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance.

Modification of primordial ices by cosmic rays as simulated by cyclotron irradiation

NASA Technical Reports Server (NTRS)

Kaiser, R. I.; Roessler, K.

1992-01-01

Frozen CH4 and CH4/Ar mixtures closed into metal cuvettes and open to the vacuum were irradiated at 15 and 77 K with 10 - 20 MeV p and He-3(2+) ions in order to simulate the effect of cosmic rays on solid organic matter in space. Ices exposed to vacuum represent surfaces of icy systems whereas closed systems stand for bulk ices. The products were analyzed by MS, SEM, RBS, ERDA, H-1-NMR, HPLC, GC-MS, NEXAFS, and FT-IR. Volatile products consisted of a mixture of low molecular species, e.g., C2H2, C2H4, C2H6, and long linear aliphatic and olefinic compounds. The formation of polycyclic aromatic hydrocarbons (PAH's) and related species in solid CH4 is due to a multi-center reaction within one collision cascade and is governed by energy density effects with critical linear energy transfer values L(sub T) between 2 and 10 keV/micron. Open ices exhibit preferential hydrogen release resulting in an increased carbonization as compared to more hydrogen rich molecules protected inside large icy bodies.

Preparation of a novel breviscapine-loaded halloysite nanotubes complex for controlled release of breviscapine

NASA Astrophysics Data System (ADS)

Gao, Min; Lu, Liqian; Wang, Xiaoyue; Lin, Houke; Zhou, Qingsong

2017-11-01

For sustain the release rate and prolong half-life of breviscapine in vivo, the breviscapine-loaded halloysite nanotubes complex was prepared. The breviscapine was encapsulated into halloysite nanotubes (HNTs) using a vacuum process. The complex were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy(FT-IR). The formation of breviscapine-loaded HNTs complex was proved by the test results of SEM, DSC, TEM and IR analysise. The results confirmed that breviscapine was successfully loaded in the halloysite nanotubes. Additionally, the in vitro drug release of breviscapine from breviscapine-loaded HNTs complex was investigated, the result indicated this complex has apparent sustained-release effect.

Predicting biopharmaceutical performance of oral drug candidates - Extending the volume to dissolve applied dose concept.

PubMed

Muenster, Uwe; Mueck, Wolfgang; van der Mey, Dorina; Schlemmer, Karl-Heinz; Greschat-Schade, Susanne; Haerter, Michael; Pelzetter, Christian; Pruemper, Christian; Verlage, Joerg; Göller, Andreas H; Ohm, Andreas

2016-05-01

The purpose of the study was to experimentally deduce pH-dependent critical volumes to dissolve applied dose (VDAD) that determine whether a drug candidate can be developed as immediate release (IR) tablet containing crystalline API, or if solubilization technology is needed to allow for sufficient oral bioavailability. pH-dependent VDADs of 22 and 83 compounds were plotted vs. the relative oral bioavailability (AUC solid vs. AUC solution formulation, Frel) in humans and rats, respectively. Furthermore, in order to investigate to what extent Frel rat may predict issues with solubility limited absorption in human, Frel rat was plotted vs. Frel human. Additionally, the impact of bile salts and lecithin on in vitro dissolution of poorly soluble compounds was tested and data compared to Frel rat and human. Respective in vitro - in vivo and in vivo - in vivo correlations were generated and used to build developability criteria. As a result, based on pH-dependent VDAD, Frel rat and in vitro dissolution in simulated intestinal fluid the IR formulation strategy within Pharmaceutical Research and Development organizations can be already set at late stage of drug discovery. Copyright © 2016 Elsevier B.V. All rights reserved.

Solid-state chelation of metal ions by ethylenediaminetetraacetate intercalated in a layered double hydroxide.

PubMed

Tarasov, Konstantin A; O'Hare, Dermot; Isupov, Vitaly P

2003-03-24

The solid-state chelation of transition metal ions (Co(2+), Ni(2+), and Cu(2+)) from aqueous solutions into the lithium aluminum layered double hydroxide ([LiAl(2)(OH)(6)]Cl x 0.5H(2)O or LDH) which has been pre-intercalated with EDTA (ethylenediaminetetraacetate) ligand has been investigated. The intercalated metal cations form [M(edta)](2)(-) complexes between the LDH layers as indicated by elemental analysis, powder X-ray diffraction, and IR and UV-vis spectroscopies. If metal chloride or nitrate salts are used in the reaction with the LDH then co-intercalation of either the Cl(-) or NO(3)(-) anions is observed. In the case of metal acetate salts the cations intercalate without the accompanying anion. This can be explained by the different intercalation selectivity of the anions in relation to the LDH. In the latter case the introduction of the positive charge into LDH structure was compensated for by the release from the solid of the equivalent quantity of lithium and hydrogen cations. Time-resolved in-situ X-ray diffraction measurements have revealed that the chelation/intercalation reactions proceed very quickly. The rate of the reaction found for nickel acetate depends on concentration as approximately k[Ni(Ac)(2)](3).

Development of a Novel Simplified PBPK Absorption Model to Explain the Higher Relative Bioavailability of the OROS® Formulation of Oxybutynin.

PubMed

Olivares-Morales, Andrés; Ghosh, Avijit; Aarons, Leon; Rostami-Hodjegan, Amin

2016-11-01

A new minimal Segmented Transit and Absorption model (mSAT) model has been recently proposed and combined with intrinsic intestinal effective permeability (P eff,int ) to predict the regional gastrointestinal (GI) absorption (f abs ) of several drugs. Herein, this model was extended and applied for the prediction of oral bioavailability and pharmacokinetics of oxybutynin and its enantiomers to provide a mechanistic explanation of the higher relative bioavailability observed for oxybutynin's modified-release OROS® formulation compared to its immediate-release (IR) counterpart. The expansion of the model involved the incorporation of mechanistic equations for the prediction of release, transit, dissolution, permeation and first-pass metabolism. The predicted pharmacokinetics of oxybutynin enantiomers after oral administration for both the IR and OROS® formulations were in close agreement with the observed data. The predicted absolute bioavailability for the IR formulation was within 5% of the observed value, and the model adequately predicted the higher relative bioavailability observed for the OROS® formulation vs. the IR counterpart. From the model predictions, it can be noticed that the higher bioavailability observed for the OROS® formulation was mainly attributable to differences in the intestinal availability (F G ) rather than due to a higher colonic f abs , thus confirming previous hypotheses. The predicted f abs was almost 70% lower for the OROS® formulation compared to the IR formulation, whereas the F G was almost eightfold higher than in the IR formulation. These results provide further support to the hypothesis of an increased F G as the main factor responsible for the higher bioavailability of oxybutynin's OROS® formulation vs. the IR.

Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region.

PubMed

Hrabovszky, Erik; Borsay, Beáta Á; Rácz, Kálmán; Herczeg, László; Ciofi, Philippe; Bloom, Stephen R; Ghatei, Mohammad A; Dhillo, Waljit S; Liposits, Zsolt

2013-01-01

Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy samples from men (21-78 years) and postmenopausal (53-83 years) women. Significantly higher numbers of SP-immunoreactive (IR) neurons and darker labeling were observed in the Inf of postmenopausal women than in age-matched men. Triple-immunofluorescent studies localized SP immunoreactivity to considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled. Triple-, double- and single-labeled SP-IR axons innervated densely the portal capillaries of the infundibular stalk. In quadruple-labeled sections, these axons formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP neurons increases the functional complexity of the putative pulse generator network. First, it is possible that SP modulates the effects of KP and NKB in axo-somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect the activity and/or neuropeptide release of NKB and KP neurons via autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP and NKB secretory output via additional autocrine/paracrine mechanisms or regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP and NKB into the portal circulation could underlie further actions on adenohypophysial gonadotrophs.

Social Environment and Hospitalisation after Release from Prison: A Prospective Cohort Study

PubMed Central

2017-01-01

This study examined the association between remoteness and area disadvantage, and the rate of subsequent hospitalisation, in a cohort of adults released from prisons in Queensland. A baseline survey of 1267 adult prisoners within 6 weeks of expected release was prospectively linked with hospital, mortality and reincarceration records. Postcodes were used to assign remoteness and area disadvantage categories. Multivariate Andersen–Gill regression models were fitted to test for associations between remoteness, area disadvantage and hospitalisation after release from prison. Over a total of 3090.9 person-years of follow-up, the highest crude incidence rates were observed in areas characterised by remoteness and area disadvantage (crude incidence rate (IR) = 649; 95%CI: 526–791), followed by remoteness only (IR = 420; 95%CI: 349–501), severe area disadvantage only (IR = 403; 95%CI: 351–461), and neither of these factors (IR = 361; 95%CI: 336–388). Unadjusted analyses indicated that remoteness (hazard ratio (HR) = 1.32; 95%CI: 1.04–1.69; p = 0.024) was associated with increased risk of hospitalisation; however, this attenuated to the null after adjustment for covariate factors. The incidence of hospitalisation for those who live in remote or socio-economically disadvantaged areas is increased compared to their counterparts in more urban and less socio-economically disadvantaged areas. Experiencing both these factors together may compound the hospitalisation in the community. PMID:29149091

Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

PubMed

Yue, Yong; Collaku, Agron; Liu, Dongzhou J

2018-01-01

Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

PubMed

Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

2016-11-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (<20%) of systemic exposures was observed for both formulations. Steady state was achieved within 48 hours of dosing with the XR formulation. Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Concentration-effect relationship of levodopa in patients with Parkinson's disease after oral administration of an immediate release and a controlled release formulation.

PubMed Central

Harder, S; Baas, H; Bergemann, N; Demisch, L; Rietbrock, S

1995-01-01

1. The relationship between plasma concentration of levodopa and motor-response was investigated in 12 patients with Parkinson's disease who showed marked response fluctuations, after a single oral dose of an immediate release (IR) formulation (100 mg levodopa/25 mg genserazide) and a controlled release (CR) formulation (300 mg levodopa/75 mg benserazide), using a double-blind, randomized, cross-over design. 2. The sum score of the Columbia University Rating Scale (CURS sigma) was used for pharmacodynamic assessment. A sigmoidal Emax-model was fitted to the data using a semiparametric pharmacokinetic/dynamic approach. 3. The dose-corrected AUC of levodopa after the IR-formulation was 27.5 (+/- 9.1 s.d.) ng ml-1 h per mg and 23.2 (+/- 4.6 s.d.) ng ml-1 h per mg after the CR-formulation. Cmax was 1714 (+/- 1027 s.d.) ng ml-1 after the IR-formulation and 1494 (+/- 383 s.d.) ng ml-1 after the CR-formulation. 4. With both preparations, the maximal response to levodopa (Emax) was a decrease in the CURS sigma rating of about 27 scores. Estimates of the EC50 of levodopa were 495 (+/- 144 s.d.) ng ml-1 (IR) and 1024 (+/- 502 s.d.) ng ml-1 (CR), respectively (95%-CI: 1.51-2.66, point estimator 1.95). The mean duration of the motor response was 1.9 (+/- 0.5 s.d.) h (IR) and 2.8 (+/- 0.7 s.d.) h (CR), respectively (95%-CI: 1.12-2.04, point estimator 1.53).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7756097

Dust release rates and dust-to-gas mass ratios of eight comets

NASA Technical Reports Server (NTRS)

Singh, P. D.; De Almeida, A. A.; Huebner, W. F.

1992-01-01

Mass release rates of dust and mass ratios of dust-to-gas release rates of Comets Thiele (1985m), Wilson (1986l), P/Borrelly (1987p), Liller (1988a), Bradfield (1987s), Hartley-Good (1985l), P/Giacobini-Zinner (1984e), and P/Halley (1982i) are estimated from the analysis of continuum flux measurements at optical wavelengths. An attempt is made to estimate the size of each comet nucleus on the basis of water-ice sublimation (vaporization), assuming that the nucleus is spherical and only a fraction of its surface area is active. Where possible, the dust mass release rates are compared with those obtained by other investigators in the optical and IR wavelength regions. Good agreement with results based on IR observations is found.

Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

PubMed

Fegade, Harshal A; Umathe, Sudhir N

2016-04-01

Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal ganglia, the regions respectively responsible for neuroleptic and cataleptic effects; and as GnRH antagonist eliminated the effects of haloperidol without affecting GnRH-ir, it appears that GnRH released by haloperidol mediates its neuroleptic and cataleptic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Solid-phase extraction of iridium from soil and water samples by using activated carbon cloth prior to its spectrophotometric determination.

PubMed

Ozkantar, Nebiye; Yilmaz, Erkan; Soylak, Mustafa; Tuzen, Mustafa

2015-08-01

A solid-phase extraction method for separation and preconcentration of Ir(IV) ion by using activated carbon cloth (ACC) has been presented. Ir(IV) as their 1-(2-pyridylazo) 2-naphtol (PAN) chelate was adsorbed on ACC at pH 2.0 and was eluted from ACC with acidic dimethylformamide (DMF). The Ir(IV) concentration was determined at 536 nm as Ir(IV)-PAN complex by using UV-vis spectrophotometer. The analytical parameters including pH, sample and eluent flow rates, amount of PAN, eluent type, concentration, and sample volume were optimized. The effects of foreign ions on the recoveries of iridium were also investigated. The preconcentration factor was calculated as 60. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were found as 0.039 and 0.129 μg L(-1), respectively. The method was applied to soil and water samples for iridium determination.

Polyfluorides and Neat Fluorine as Host Material in Matrix-Isolation Experiments.

PubMed

Brosi, Felix; Vent-Schmidt, Thomas; Kieninger, Stefanie; Schlöder, Tobias; Beckers, Helmut; Riedel, Sebastian

2015-11-09

The use of neat fluorine in matrix isolation is reported, as well as the formation of polyfluoride monoanions under cryogenic conditions. Purification procedures and spectroscopic data of fluorine are described, and matrix shifts of selected molecules and impurities in solid fluorine are compared to those of common matrix gases (Ar, Kr, N2 , Ne). The reaction of neat fluorine and IR-laser ablated metal atoms to yield fluorides of chromium (CrF5 ), palladium (PdF2 ), gold (AuF5 ), and praseodymium (PrF4 ) has been investigated. The fluorides have been characterized in solid fluorine by IR spectroscopy at 5 K. Also the fluorination of Kr and the photo-dismutation of XeO4 have been studied by using IR spectroscopy in neat fluorine. Formation of the [F5 ](-) ion was obtained by IR-laser ablation of platinum in the presence of fluorine and proven in a Ne matrix at 5 K by two characteristic vibrational bands of [F5 ](-) at $\\tilde \

Model‐Informed Development and Registration of a Once‐Daily Regimen of Extended‐Release Tofacitinib

PubMed Central

Lamba, M; Hutmacher, MM; Furst, DE; Dikranian, A; Dowty, ME; Conrado, D; Stock, T; Nduaka, C; Cook, J

2017-01-01

Extended‐release (XR) formulations enable less frequent dosing vs. conventional (e.g., immediate release (IR)) formulations. Regulatory registration of such formulations typically requires pharmacokinetic (PK) and clinical efficacy data. Here we illustrate a model‐informed, exposure–response (E‐R) approach to translate controlled trial data from one formulation to another without a phase III trial, using a tofacitinib case study. Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). E‐R analyses were conducted using validated clinical endpoints from phase II dose–response and nonclinical dose fractionation studies of the IR formulation. Consistent with the delay in clinical response dynamics relative to PK, average concentration was established as the relevant PK parameter for tofacitinib efficacy and supported pharmacodynamic similarity. These evaluations, alongside demonstrated equivalence in total systemic exposure between IR and XR formulations, provided the basis for the regulatory approval of tofacitinib XR once daily by the US Food and Drug Administration. PMID:27859030

Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease

PubMed Central

Seltzer, Ben

2010-01-01

An extended release form of the cholinesterase inhibitor (ChEI) drug galantamine (galantamine-ER) was developed, chiefly to increase adherence to medication regimes in patients with mild-to-moderate Alzheimer’s disease (AD). Except for predicted differences in (Cmax) and tmax, comparable doses of once daily galantamine-ER and regular, immediate release galantamine, (galantamine-IR), are pharmacologically equivalent. A 24-week randomized, double-blind, placebo-and active-controlled, multicenter phase III trial, which compared galantamine-IR, galantamine-ER and placebo in subjects with mild to moderate AD (mini-mental state examination [MMSE] score range, 10 to 24) showed that both formulations of galantamine were significantly better than placebo in terms of cognition, although not with regard to global change. There was no difference in drug-related adverse events between galantamine-ER and galantamine-IR. Since its release onto the market galantamine-ER has enjoyed wide popularity and a recent surveillance study suggests that it has the highest 1-year persistence rate of all the ChEIs. PMID:20169037

Profiles of alpha-melanocyte-stimulating hormone in the Japanese flounder as revealed by a newly developed time-resolved fluoroimmunoassay and immunohistochemistry.

PubMed

Amiya, Noriko; Amano, Masafumi; Takahashi, Akiyoshi; Yamanome, Takeshi; Yamamori, Kunio

2007-03-01

Profiles of alpha-melanocyte-stimulating hormone (alpha-MSH) in the Japanese flounder were examined by a newly developed time-resolved fluoroimmunoassay (TR-FIA) and immunohistochemistry. A TR-FIA for alpha-MSH was newly developed, and its levels in the pituitary gland and plasma of Japanese flounder reared in a white or black tank for 5 months were compared. A competitive assay using two antibodies was performed among secondary antibodies in the solid phase, alpha-MSH antibodies, samples, and europium-labeled Des-Ac-alpha-MSH. The sensitivity of the assay, defined as twice the standard deviation at a zero dose, was 0.98 ng/ml (49 pg/well). The intra- and interassay coefficients of variation of the assay were 8.8% (n=8) and 17.3% (n=5), respectively, at about 50% binding. Cross-reactivities of Des-Ac-alpha-MSH and Di-Ac-alpha-MSH were about 100%. Cross-reactivities of adrenocorticotropic hormone, salmon gonadotropin-releasing hormone (sGnRH), and chicken GnRH-II were less than 0.2%, and that of melanin-concentrating hormone was less than 2.0% at 50% binding. Displacement curves of serially twofold-diluted hypothalamus extract, pituitary gland extract, and plasma extract of Japanese flounder with the assay buffer were parallel to the alpha-MSH standard curve. Moreover, displacement curves of serially twofold-diluted hypothalamus and/or pituitary gland extract of masu salmon, goldfish, red seabream, Japanese eel, tiger puffer, and barfin flounder with the assay buffer were also parallel to the alpha-MSH standard. In Japanese flounder, total immunoreactive (ir)-alpha-MSH levels in the pituitary gland were lower in the black tank, whereas those in the plasma tended to be higher in the black tank, suggesting that the synthesis and release of alpha-MSH are higher in the black tank. alpha-MSH-ir cells were detected in the pars intermedia and a small part of the pars distalis of the pituitary gland. alpha-MSH-ir cell bodies were located in the basal hypothalamus and alpha-MSH-ir fibers were distributed not only in the hypothalamus but also in the telencephalon, midbrain, cerebellum, and medulla oblongata, suggesting that alpha-MSH functions as a neuromodulator in the brain.

Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate-release methylphenidate in the three ADHD subtypes.

PubMed

Chou, Wen-Jiun; Chou, Miao-Chun; Tzang, Ruu-Fen; Hsu, Ya-Chen; Gau, Susan Shur-Fen; Chen, Shin-Jaw; Wu, Yu-Yu; Huang, Ya-Fen; Liang, Hsin-Yi; Cheng, Helen

2009-04-01

To determine factors for switching to osmotic release oral system methylphenidate (OROS-MPH) among poor adherents to immediate-release methylphenidate (IR-MPH); and to compare the efficacy of OROS-MPH on the three attention-deficit/hyperactivity disorder (ADHD) subtypes in a multi-site prospective observational study in Taiwan. The sample included 240 children with ADHD, aged 6-16 years, who were poor adherents to IR-MPH, 137 of whom were switched to OROS-MPH. The child psychiatrists diagnosed the Diagnostic Statistical Manual of Mental Disorders (4th edition) ADHD subtypes and assessed the medical history, adherence, side-effects, global ADHD severity, and family/school effectiveness. Parents reported their child's behavioral symptoms. The determinants for an OROS-MPH switch were higher dosage, shorter treatment and thrice-daily administration of IR-MPH, and more severe inattention symptoms. Hyperactivity and oppositional symptoms were greater in the ADHD combined and hyperactive-impulsive subtypes than the inattentive subtype. Switching to OROS-MPH significantly improved behavioral symptoms and family/school measures, and this was most evident in the ADHD-combined group, followed by the ADHD-inattentive group. Inattention influenced not only academic performance, but also overall classroom behaviors and the parent-child relationship, with the latter two also influenced by oppositional symptoms. This study suggests better efficacy for the OROS-MPH among poor adherents to IR-MPH; however, its effectiveness varied across the three ADHD subtypes (ClinicalTrials.gov number NCT00460720).

A retrospective cohort study of long-term immediate-release hydrocodone/acetaminophen use and acetaminophen dosing above the Food and Drug Administration recommended maximum daily limit among commercially insured individuals in the United States (2008-2013).

PubMed

DeVeaugh-Geiss, Angela; Kadakia, Aditi; Chilcoat, Howard; Alexander, Louis; Coplan, Paul

2015-06-01

Immediate-release (IR) hydrocodone/acetaminophen is the most prescribed opioid in the United States; however, patterns of use, including long-term treatment and dose, are not well described. Duration of use, including the percentage of patients on long-term treatment (>90 days of continuous use), was assessed for patients newly prescribed IR hydrocodone/acetaminophen compared to other opioid analgesics in a national commercial insurance database (January 2008-September 2013). Though only a small percentage of IR hydrocodone/acetaminophen patients continued treatment long-term (1.7%), the number was large (104,839) and was nearly 5 times the number receiving extended-release (ER) morphine (n = 22,338) and nearly 4 times the number receiving ER oxycodone (n = 26,946) long-term. Using a less conservative allowable gap in treatment increased the number of patients meeting the criteria for long-term use (approximately 160,000 for IR hydrocodone/acetaminophen vs <30,000 for ER morphine and ER oxycodone). Most patients meeting these criteria received IR hydrocodone doses between >20 and ≤60 mg/d (n = 56,220, 53.6%) in month 4; 5.5% (n = 5,743) received doses >60 mg/d. Moreover, approximately 15% of IR hydrocodone/acetaminophen patients (n > 900,000) were prescribed total daily acetaminophen doses exceeding 4 g (the limit recommended by the U.S. Food and Drug Administration) at their initial IR hydrocodone/acetaminophen prescription or any time during therapy. Although most patients were prescribed IR hydrocodone/acetaminophen for acute pain, the number of patients prescribed long-term therapy exceeds the number of patients prescribed ER opioids. It is important to consider the benefits and risks inherent with long-term opioid therapy, whether with IR or ER opioids, to ensure safe use of these products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine

PubMed Central

Stout, Stephen M.; Nielsen, Jace; Welage, Lynda S.; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E.

2010-01-01

Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used β-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4 phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate release (IR) tartrate and extended release (ER) succinate metoprolol formulations. Ten healthy subjects received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol AUC0–24h by 4 and 5 fold, respectively for IR, and 3 and 4 fold, respectively for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol and stereoselective metabolism is lost. This could theoretically result in greater β-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses / drug input rates employed. PMID:20400652

Synthesis of Ti3AuC2, Ti3Au2C2 and Ti3IrC2 by noble metal substitution reaction in Ti3SiC2 for high-temperature-stable Ohmic contacts to SiC

NASA Astrophysics Data System (ADS)

Fashandi, Hossein; Dahlqvist, Martin; Lu, Jun; Palisaitis, Justinas; Simak, Sergei I.; Abrikosov, Igor A.; Rosen, Johanna; Hultman, Lars; Andersson, Mike; Lloyd Spetz, Anita; Eklund, Per

2017-08-01

The large class of layered ceramics encompasses both van der Waals (vdW) and non-vdW solids. While intercalation of noble metals in vdW solids is known, formation of compounds by incorporation of noble-metal layers in non-vdW layered solids is largely unexplored. Here, we show formation of Ti3AuC2 and Ti3Au2C2 phases with up to 31% lattice swelling by a substitutional solid-state reaction of Au into Ti3SiC2 single-crystal thin films with simultaneous out-diffusion of Si. Ti3IrC2 is subsequently produced by a substitution reaction of Ir for Au in Ti3Au2C2. These phases form Ohmic electrical contacts to SiC and remain stable after 1,000 h of ageing at 600 °C in air. The present results, by combined analytical electron microscopy and ab initio calculations, open avenues for processing of noble-metal-containing layered ceramics that have not been synthesized from elemental sources, along with tunable properties such as stable electrical contacts for high-temperature power electronics or gas sensors.

A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement.

PubMed

Park, Yong-Beom; Ha, Chul-Won; Cho, Sung-Do; Lee, Myung-Chul; Lee, Ju-Hong; Seo, Seung-Suk; Kang, Seung-Baik; Kyung, Hee-Soo; Choi, Choong-Hyeok; Chang, NaYoon; Rhim, Hyou Young Helen; Bin, Seong-Il

2015-01-01

To evaluate the relative efficacy and safety of extended-release tramadol HCl 75 mg/acetaminophen 650 mg (TA-ER) and immediate-release tramadol HCl 37.5 mg/acetaminophen 325 mg (TA-IR) for the treatment of moderate to severe acute pain following total knee replacement. This phase III, double-blind, placebo-controlled, parallel-group study randomized 320 patients with moderate to severe pain (≥4 intensity on an 11 point numeric rating scale) following total knee replacement arthroplasty to receive oral TA-ER (every 12 hours) or TA-IR (every 6 hours) over a period of 48 hours. In the primary analysis, TA-ER was evaluated for efficacy non-inferior to that of TA-IR based on the sum of pain intensity difference (SPID) at 48 hours after the first dose of study drug (SPID48). Secondary endpoints included SPID at additional time points, total pain relief at all on-therapy time points (TOTPAR), sum of SPID and TOTPAR at all on-therapy time points (SPID + TOTPAR), use of rescue medication, subjective pain assessment (PGIC, Patient Global Impression of Change), and adverse events (AEs). Analysis of the primary efficacy endpoint (SPID48) could not establish the non-inferiority of TA-ER to TA-IR. However, a post hoc analysis with a re-defined non-inferiority margin did demonstrate the non-inferiority of TA-ER to TA-IR. No statistically significant difference in SPID at 6, 12, or 24 hours was observed between the TA-ER and TA-IR groups. Similarly, analysis of TOTPAR showed that there were no significant differences between groups at any on-therapy time point, and SPID + TOTPAR at 6 and 48 hours were similar among groups. There was no difference in the mean frequency or dosage of rescue medication required by both groups, and the majority of patients in both the TA-ER and TA-IR groups rated their pain improvement as 'much' or 'somewhat better'. The overall incidence of ≥1 AEs was similar among the TA-ER (88.8%) and TA-IR (89.5%) groups. The most commonly reported AEs by patients treated with TA-ER and TA-IR included nausea (49.7% vs 44.4%), vomiting (28.0% vs 24.2%), and decreased hemoglobin (23.6% vs 26.1%). This study is limited by the lack of placebo control, and the invalidity of the initial non-inferiority margin. This study demonstrated that the analgesic effect of TA-ER is non-inferior to TA-IR, and supports TA-ER as an effective and safe treatment for moderate to severe acute pain post total knee replacement. Clinicaltrials.gov, NCT01814878.

On formation mechanism of Pd-Ir bimetallic nanoparticles through thermal decomposition of [Pd(NH3)4][IrCl6

NASA Astrophysics Data System (ADS)

Asanova, Tatyana I.; Asanov, Igor P.; Kim, Min-Gyu; Gerasimov, Evgeny Yu.; Zadesenets, Andrey V.; Plyusnin, Pavel E.; Korenev, Sergey V.

2013-10-01

The formation mechanism of Pd-Ir nanoparticles during thermal decomposition of double complex salt [Pd(NH3)4][IrCl6] has been studied by in situ X-ray absorption (XAFS) and photoelectron (XPS) spectroscopies. The changes in the structure of the Pd and Ir closest to the surroundings and chemical states of Pd, Ir, Cl, and N atoms were traced in the range from room temperature to 420 °C in inert atmosphere. It was established that the thermal decomposition process is carried out in 5 steps. The Pd-Ir nanoparticles are formed in pyramidal/rounded Pd-rich (10-200 nm) and dendrite Ir-rich (10-50 nm) solid solutions. A d charge depletion at Ir site and a gain at Pd, as well as the intra-atomic charge redistribution between the outer d and s and p electrons of both Ir and Pd in Pd-Ir nanoparticles, were found to occur.

Pharmacokinetic Studies in Healthy Subjects for the Development of an Extended-Release Tablet Formulation of Guaifenesin: A 505(b)(2) New Drug Application Approval.

PubMed

Vilson, Lineau; Owen, Joel S

2013-01-01

Guaifenesin is an expectorant used to improve mucociliary clearance (MCC) and relieve chest congestion from upper respiratory tract infections. Immediate-release (IR) guaifenesin requires dosing every 4 hours to maintain efficacy because of the drug's short half-life. Extended-release (ER) guaifenesin has been developed to prolong efficacy and reduce dosing frequency. As part of the 505(b)(2) new drug application (NDA), the pharmacokinetics (PK) of an ER bi-layer tablet formulation of guaifenesin (Mucinex®) and bioequivalence to an over-the-counter (OTC) monograph IR formulation were evaluated in healthy subjects. In one study, subjects received 1,200 mg ER guaifenesin every 12 hours or 400 mg IR guaifenesin every 4 hours for 6 days. Steady-state exposures were equivalent between the two products, as demonstrated by AUC and Cmax . In another study, subjects received a single dose of 600 mg (fasted) or 1,200 mg (fasted or fed) ER bi-layer tablet formulations. AUC and Cmax were equivalent between both states for the 1,200 mg ER dose. However, Tmax of 1,200 mg ER guaifenesin was later in the fed than the fasted state. ER guaifenesin is bioequivalent to corresponding OTC monograph doses of IR guaifenesin. ER guaifenesin offers a convenient 12-hour dosing alternative to 4-hour dosing of IR guaifenesin. © The Author(s) 2013.

Tyrosine hydroxylase-immunoreactivity and its relations with gonadotropin-releasing hormone and neuropeptide Y in the preoptic area of the guinea pig.

PubMed

Bogus-Nowakowska, Krystyna; Równiak, Maciej; Hermanowicz-Sobieraj, Beata; Wasilewska, Barbara; Najdzion, Janusz; Robak, Anna

2016-12-01

The present study examines the distribution of tyrosine hydroxylase (TH) immunoreactivity and its morphological relationships with neuropeptide Y (NPY)- and gonadoliberin (GnRH)-immunoreactive (IR) structures in the preoptic area (POA) of the male guinea pig. Tyrosine hydroxylase was expressed in relatively small population of perikarya and they were mostly observed in the periventricular preoptic nucleus and medial preoptic area. The tyrosine hydroxylase-immunoreactive (TH-IR) fibers were dispersed troughout the whole POA. The highest density of these fibers was observed in the median preoptic nucleus, however, in the periventricular preoptic nucleus and medial preoptic area they were only slightly less numerous. In the lateral preoptic area, the density of TH-IR fibers was moderate. Two morphological types of TH-IR fibers were distinguished: smooth and varicose. Double immunofluorescence staining showed that TH and GnRH overlapped in the guinea pig POA but they never coexisted in the same structures. TH-IR fibers often intersected with GnRH-IR structures and many of them touched the GnRH-IR perikarya or dendrites. NPY wchich was abundantly present in the POA only in fibers showed topographical proximity with TH-IR structures. Althoug TH-IR perikarya and fibers were often touched by NPY-IR fibers, colocalization of TH and NPY in the same structures was very rare. There was only a small population of fibers which contained both NPY and TH. In conclusion, the morphological evidence of contacts between TH- and GnRH-IR nerve structures may be the basis of catecholaminergic control of GnRH release in the preoptic area of the male guinea pig. Moreover, TH-IR neurons were conatcted by NPY-IR fibers and TH and NPY colocalized in some fibers, thus NPY may regulate catecholaminergic neurons in the POA. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury.

PubMed

Lee, Dongwon; Bae, Soochan; Ke, Qingen; Lee, Jiyoo; Song, Byungjoo; Karumanchi, S Ananth; Khang, Gilson; Choi, Hak Soo; Kang, Peter M

2013-12-28

The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the generation of high level of hydrogen peroxide (H2O2). In this study, we report a novel diagnostic and therapeutic strategy for I/R injury based on H2O2-activatable copolyoxalate nanoparticles using a murine model of hind limb I/R injury. The nanoparticles are composed of hydroxybenzyl alcohol (HBA)-incorporating copolyoxalate (HPOX) that, in the presence of H2O2, degrades completely into three known and safe compounds, cyclohexanedimethanol, HBA and CO2. HPOX effectively scavenges H2O2 in a dose-dependent manner and hydrolyzes to release HBA which exerts intrinsic antioxidant and anti-inflammatory activities both in vitro and in vivo models of hind limb I/R. HPOX nanoparticles loaded with fluorophore effectively and robustly image H2O2 generated in hind limb I/R injury, demonstrating their potential for bioimaging of H2O2-associated diseases. Furthermore, HPOX nanoparticles loaded with anti-apoptotic drug effectively release the drug payload after I/R injury, exhibiting their effectiveness for a targeted drug delivery system for I/R injury. We anticipate that multifunctional HPOX nanoparticles have great potential as H2O2 imaging agents, therapeutics and drug delivery systems for H2O2-associated diseases. © 2013.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Hui; Zou Kang; Guo Shaohuan

A nanostructural drug-inorganic clay composite involving a pharmaceutically active compound captopril (Cpl) intercalated Mg-Al-layered double hydroxides (Cpl-LDHs) with Mg/Al molar ratio of 2.06 has been assembled by coprecipitation method. Powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR) and Raman spectra analysis indicate a successful intercalation of Cpl between the layers with a vertical orientation of Cpl disulphide-containing S-S linkage. SEM photo indicates that as-synthesized Cpl-LDHs possess compact and non-porous structure with approximately and linked elliptical shape particles of ca. 50 nm. TG-DTA analyses suggest that the thermal stability of intercalated organic species is largely enhanced due to host-guest interactionmore » involving the hydrogen bond compared to pure form before intercalation. The in vitro release studies show that both the release rate and release percentages markedly decrease with increasing pH from 4.60 to 7.45 due to possible change of release mechanism during the release process. The kinetic simulation for the release data, and XRD and FT-IR analyses for samples recovered from release media indicate that the dissolution mechanism is mainly responsible for the release behaviour of Cpl-LDHs at pH 4.60, while the ion-exchange one is responsible for that at pH 7.45. - Graphical abstract: Based on XRD, FT-IR and Raman spectra analyses, it is suggested that captopril (Cpl) exists as its disulphide metabolites in the interlayer of Mg-Al-LDHs via hydrogen bonding between guest carboxylate function and hydroxyl group of the host layers. A schematic supramolecular structure of Cpl intercalates involving a vertical orientation of Cpl disulphide-containing S-S bond between the layers with carboxylate anions pointing to both hydroxide layers is presented.« less

Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

PubMed Central

Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

1990-01-01

1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open‐label ADS‐5102

PubMed Central

Fahn, Stanley; Pahwa, Rajesh; Tanner, Caroline M.; Espay, Alberto J.; Trenkwalder, Claudia; Adler, Charles H.; Patni, Rajiv; Johnson, Reed

2018-01-01

Abstract Background ADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility. Methods In an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study. Results Change in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102. Conclusion These open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

Electrochemical Catalyst-Support Effects and Their Stabilizing Role for IrOx Nanoparticle Catalysts during the Oxygen Evolution Reaction.

PubMed

Oh, Hyung-Suk; Nong, Hong Nhan; Reier, Tobias; Bergmann, Arno; Gliech, Manuel; Ferreira de Araújo, Jorge; Willinger, Elena; Schlögl, Robert; Teschner, Detre; Strasser, Peter

2016-09-28

Redox-active support materials can help reduce the noble-metal loading of a solid chemical catalyst while offering electronic catalyst-support interactions beneficial for catalyst durability. This is well known in heterogeneous gas-phase catalysis but much less discussed for electrocatalysis at electrified liquid-solid interfaces. Here, we demonstrate experimental evidence for electronic catalyst-support interactions in electrochemical environments and study their role and contribution to the corrosion stability of catalyst/support couples. Electrochemically oxidized Ir oxide nanoparticles, supported on high surface area carbons and oxides, were selected as model catalyst/support systems for the electrocatalytic oxygen evolution reaction (OER). First, the electronic, chemical, and structural state of the catalyst/support couple was compared using XANES, EXAFS, TEM, and depth-resolved XPS. While carbon-supported oxidized Ir particle showed exclusively the redox state (+4), the Ir/IrOx/ATO system exhibited evidence of metal/metal-oxide support interactions (MMOSI) that stabilized the metal particles on antimony-doped tin oxide (ATO) in sustained lower Ir oxidation states (Ir(3.2+)). At the same time, the growth of higher valent Ir oxide layers that compromise catalyst stability was suppressed. Then the electrochemical stability and the charge-transfer kinetics of the electrocatalysts were evaluated under constant current and constant potential conditions, where the analysis of the metal dissolution confirmed that the ATO support mitigates Ir(z+) dissolution thanks to a stronger MMOSI effect. Our findings raise the possibility that MMOSI effects in electrochemistry-largely neglected in the past-may be more important for a detailed understanding of the durability of oxide-supported nanoparticle OER catalysts than previously thought.

Cleanliness evaluation of rough surfaces with diffuse IR reflectance

NASA Technical Reports Server (NTRS)

Pearson, L. H.

1995-01-01

Contamination on bonding surfaces has been determined to be a primary cause for degraded bond strength in certain solid rocket motor bondlines. Hydrocarbon and silicone based organic contaminants that are airborne or directly introduced to a surface are a significant source of contamination. Diffuse infrared (IR) reflectance has historically been used as an effective technique for detection of organic contaminants, however, common laboratory methods involving the use of a Fourier transform IR spectrometer (FTIR) are impractical for inspecting the large bonding surface areas found on solid rocket motors. Optical methods involving the use of acousto-optic tunable filters and fixed bandpass optical filters are recommended for increased data acquisition speed. Testing and signal analysis methods are presented which provide for simultaneous measurement of contamination concentration and roughness level on rough metal surfaces contaminated with hydrocarbons.

An infrared study of the nitro—nitrito linkage isomerization in solid nitro- and nitritopentamminecobalt(III) chloride

NASA Astrophysics Data System (ADS)

Heyns, A. M.; de Waal, D.

1989-01-01

The photochemical isomerization reaction of [Co(NH 3) 5NO 2]Cl 2 to [Co(NH 3) 5ONO]Cl 2 has been studied in the solid state by means of i.r. spectroscopy. The reaction is first order with k = 2.53±0.05 × 10 -4s -1 and is much faster ( t1/2=49min) than the well-known spontaneous nitrito → nitro isomerization ( t1/2 = 6 days). The i.r. bands of both the NH 3 and ONO - -groups in the range 4000-50 cm -1 indicate minor differences between the structures of freshly and photochemically prepared [Co(NH 3) 5ONO]Cl 2. The far i.r. spectra indicate the disorder existing in the intermediate products during the isomerization processes.

Tunable solid-state lasers - An emerging technology for remote sensing of planetary atmospheres

NASA Technical Reports Server (NTRS)

Barnes, Norman P.; Allario, Frank

1988-01-01

The present development status and prospective (1990s) performance-improvement evaluation of tunable solid-state laser technology notes recent trends toward spectrum coverage over the 0.20-14.0 microns range, in addition to dramatic increases in efficiency, service life, and reliability. It is judged that the Ti:Al2O3 laser and the AgGaSe2 optical parametric oscillator pumped by a Ho:YAG laser could cover the near-IR and mid-IR regions of the spectrum. Laser diodes operating at 0.78 microns should provide an excellent pump for a Ho:YAG laser.

Near-IR Light-Cleavable Antibody Conjugates and Conjugate Precursors | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) developed novel groups of cyanine (Cy) based antibody-drug conjugate (ADC) chemical linkers that undergo photolytic cleavage upon irradiation with near-IR light. By using the fluorescent properties of the Cy linker to monitor localization of the ADC, and subsequent near-IR irradiation of cancerous tissue, drug release could be confined to the tumor microenvironment.

USNO CCD Astrograph Catalog (UCAC) - Naval Oceanography Portal

Science.gov Websites

are here: Home › USNO › Astrometry › Optical/IR Products › UCAC USNO Logo USNO Navigation Optical/IR Products NOMAD UCAC URAT USNO-B1.0 Double Stars Solar System Bodies USNO Image and Catalog 2MASS near-IR photometry (as in previous releases) UCAC4 now includes APASS 5-band photometry. The APASS

First report of vertically aligned (Sn,Ir)O2:F solid solution nanotubes: Highly efficient and robust oxygen evolution electrocatalysts for proton exchange membrane based water electrolysis

NASA Astrophysics Data System (ADS)

Ghadge, Shrinath Dattatray; Patel, Prasad P.; Datta, Moni K.; Velikokhatnyi, Oleg I.; Shanthi, Pavithra M.; Kumta, Prashant N.

2018-07-01

One dimensional (1D) vertically aligned nanotubes (VANTs) of (Sn0.8Ir0.2)O2:10F are synthesized for the first time by a sacrificial template assisted approach. The aim is to enhance the electrocatalytic activity of F doped (Sn,Ir)O2 solid solution electrocatalyst for oxygen evolution reaction (OER) in proton exchange membrane (PEM) based water electrolysis by generating (Sn0.8Ir0.2)O2:10F nanotubes (NTs). The 1D vertical channels and the high electrochemically active surface area (ECSA ∼38.46 m2g-1) provide for facile electron transport. This results in low surface charge transfer resistance (4.2 Ω cm2), low Tafel slope (58.8 mV dec-1) and excellent electrochemical OER performance with ∼2.3 and ∼2.6 fold higher electrocatalytic activity than 2D thin films of (Sn0.8Ir0.2)O2:10F and benchmark IrO2 electrocatalysts, respectively. Furthermore, (Sn0.8Ir0.2)O2:10F NTs exhibit excellent mass activity (21.67 A g-1), specific activity (0.0056 mAcm-2) and TOF (0.016 s-1), which is ∼2-2.6 fold higher than thin film electrocatalysts at an overpotential of 270 mV, with a total mass loading of 0.3 mg cm-2. In addition, (Sn0.8Ir0.2)O2:10F NTs demonstrate remarkable electrochemical durability - comparable to thin films of (Sn0.8Ir0.2)O2:10F and pure IrO2, operated under identical testing conditions in PEM water electrolysis. These results therefore indicate promise of (Sn0.8Ir0.2)O2:10F NTs as OER electrocatalysts for efficient and sustainable hydrogen production.

Bipyridine- and phenanthroline-based metal-organic frameworks for highly efficient and tandem catalytic organic transformations via directed C-H activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manna, Kuntal; Zhang, Teng; Greene, Francis X.

2015-02-16

We report here the synthesis of a series of robust and porous bipyridyl- and phenanthryl-based metal–organic frameworks (MOFs) of UiO topology (BPV-MOF, mBPV-MOF, and mPT-MOF) and their postsynthetic metalation to afford highly active single-site solid catalysts. While BPV-MOF was constructed from only bipyridyl-functionalized dicarboxylate linker, both mBPV- and mPT-MOF were built with a mixture of bipyridyl- or phenanthryl-functionalized and unfunctionalized dicarboxylate linkers. The postsynthetic metalation of these MOFs with [Ir(COD)(OMe)] 2 provided Ir-functionalized MOFs (BPV-MOF-Ir, mBPV-MOF-Ir, and mPT-MOF-Ir), which are highly active catalysts for tandem hydrosilylation of aryl ketones and aldehydes followed by dehydrogenative ortho-silylation of benzylicsilyl ethers as wellmore » as C–H borylation of arenes using B₂pin₂. Both mBPV-MOF-Ir and mPT-MOF-Ir catalysts displayed superior activities compared to BPV-MOF-Ir due to the presence of larger open channels in the mixed-linker MOFs. Impressively, mBPV-MOF-Ir exhibited high TONs of up to 17000 for C–H borylation reactions and was recycled more than 15 times. The mPT-MOF-Ir system is also active in catalyzing tandem dehydrosilylation/dehydrogenative cyclization of N-methylbenzyl amines to azasilolanes in the absence of a hydrogen acceptor. Importantly, MOF-Ir catalysts are significantly more active (up to 95 times) and stable than their homogeneous counterparts for all three reactions, strongly supporting the beneficial effects of active site isolation within MOFs. This work illustrates the ability to increase MOF open channel sizes by using the mixed linker approach and shows the enormous potential of developing highly active and robust single-site solid catalysts based on MOFs containing nitrogen-donor ligands for important organic transformations.« less

Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

PubMed

Karkossa, Frank; Klein, Sandra

2017-10-01

The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

Comparative evaluation of bioactivity of crystalline trypsin for drying by Fourier-transformed infrared spectroscopy.

PubMed

Otsuka, Makoto; Fukui, Yuya; Ozaki, Yukihiro

2009-03-01

The purpose of this study was to evaluate the enzymatic stability of colloidal trypsin powder during heating in a solid-state by using Fourier transform infrared (FT-IR) spectra with chemoinformatics and generalized two-dimensional (2D) correlation spectroscopy. Colloidal crystalline trypsin powders were heated using differential scanning calorimetry. The enzymatic activity of trypsin was assayed by the kinetic degradation method. Spectra of 10 calibration sample sets were recorded three times with a FT-IR spectrometer. The maximum intensity at 1634cm(-1) of FT-IR spectra and enzymatic activity of trypsin decreased as the temperature increased. The FT-IR spectra of trypsin samples were analyzed by a principal component regression analysis (PCR). A plot of the calibration data obtained was made between the actual and predicted trypsin activity based on a two-component model with gamma(2)=0.962. On the other hand, a 2D method was applied to FT-IR spectra of heat-treated trypsin. The result was consistent with that of the chemoinformetrical method. The results for deactivation of colloidal trypsin powder by heat-treatment indicated that nano-structure of crystalline trypsin changed by heating reflecting that the beta-sheet was mainly transformed, since the peak at 1634cm(-1) decreased with dehydration. The FT-IR chemoinformetrical method allows for a solid-state quantitative analysis of the bioactivity of the bulk powder of trypsin during drying.

Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet.

PubMed

Cho, Jung Hyun; Kim, Yong-Il; Kim, Dong-Wuk; Yousaf, Abid Mehmood; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

2014-04-11

The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule. Copyright © 2013 Elsevier B.V. All rights reserved.

Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

PubMed

Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

2015-01-01

Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

Evaluation of the effects of food on levodropropizine controlled-release tablet and its pharmacokinetic profile in comparison to that of immediate-release tablet.

PubMed

Lee, Soyoung; Nam, Kyu-Yeol; Oh, Jaeseong; Lee, SeungHwan; Cho, Sang-Min; Choi, Youn-Woong; Cho, Joo-Youn; Lee, Beom-Jin; Hong, Jang Hee

2018-01-01

Levodropropizine is a non-opioid antitussive agent that inhibits cough reflex by reducing the release of sensory peptide in the peripheral region. To improve patients' compliance, a controlled-release (CR) tablet is under development. The aim of this study was to compare the pharmacokinetic (PK) profiles of the CR and immediate-release (IR) tablets of levodropropizine. In addition, the effect of food on the PK properties of levodropropizine CR tablet in healthy subjects was evaluated. A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence, crossover study was conducted on 47 healthy subjects. All subjects were randomly assigned to one of the six sequences, which involve combinations of the following three treatments: levodropropizine IR 60 mg three times in the fasted state (R), levodropropizine CR 90 mg two times in the fasted state (T), and levodropropizine CR 90 mg two times in the fed state (TF). Serial blood samples were collected up to 24 h after the first dose. Tolerability was assessed based on the vital signs, adverse events (AEs), and clinical laboratory tests. Levodropropizine CR showed lower maximum drug concentration ( C max ) and similar total exposure compared to levodropropizine IR. The geometric mean ratios (GMRs) (90% confidence intervals [CIs]) of T to R for the C max and area under the concentration-time curve from the 0 to 24 h time points (AUC 0-24h ) were 0.80 (0.75-0.85) and 0.89 (0.86-0.93), respectively. In the fed group, levodropropizine CR showed exposure similar to that in the fasted group. The GMRs (90% CIs) of TF to T for the C max and AUC 0-24h were 0.90 (0.85-0.97) and 1.10 (1.05-1.14), respectively. No serious AEs occurred with both levodropropizine CR and IR tablets. Total systemic exposure for levodropropizine was similar in subjects receiving the CR and IR formulations in terms of the AUC. Although food delayed the absorption of levodropropizine CR, systemic exposure was not affected.

Modulating drug loading and release profile of beta-cyclodextrin polymers by means of cross-linked degree.

PubMed

Wang, Qi-fang; Li, San-ming; Zhang, Yu-yang; Zhang, Hong

2011-02-01

The purpose of the present study is to use beta-cyclodextrin polymers (beta-CDP) with different cross-linked degree (CLD) to form inclusion complexes with ibuprofen and examine the effects of structural and compositional factors of beta-CDP on its drug loading and release behaviors. A series of beta-CDP with different CLD were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and 13C NMR spectrum. The beta-CDP was systemically characterized for the relation between the CLD of beta-CDP and the drug loading and release as well. The results of FT-IR and 13C NMR showed that similar peak-shaped vibration of beta-CDP and beta-CD implies that the polymer keeps the original characteristic structure of beta-CD. The CLD of the beta-CDP played a critical role in the drug loading and release, increasing the CLD resulted in reduction of drug loading, but increase in drug release.

Infrared absorption of trans-1-chloromethylallyl and trans-1-methylallyl radicals produced in photochemical reactions of trans-1,3-butadiene and Cl2 in solid para-hydrogen.

PubMed

Bahou, Mohammed; Wu, Jen-Yu; Tanaka, Keiichi; Lee, Yuan-Pern

2012-08-28

The reactions of chlorine and hydrogen atoms with trans-1,3-butadiene in solid para-hydrogen (p-H(2)) were investigated with infrared (IR) absorption spectra. When a p-H(2) matrix containing Cl(2) and trans-1,3-butadiene was irradiated with ultraviolet light at 365 nm, intense lines at 650.3, 809.0, 962.2, 1240.6 cm(-1), and several weaker ones due to the trans-1-chloromethylallyl radical, ●(CH(2)CHCH)CH(2)Cl, appeared. Observed wavenumbers and relative intensities agree with the anharmonic vibrational wavenumbers and IR intensities predicted with the B3PW91/6-311++g(2d, 2p) method. That the Cl atom adds primarily to the terminal carbon atom of trans-1,3-butadiene is in agreement with the path of minimum energy predicted theoretically, but in contrast to the reaction of Cl + propene in solid p-H(2) [J. Amicangelo and Y.-P. Lee, J. Phys. Chem. Lett. 1, 2956 (2010)] in which the addition of Cl to the central C atom is favored, likely through steric effects in a p-H(2) matrix. A second set of lines, intense at 781.6, 957.9, 1433.6, 2968.8, 3023.5, 3107.3 cm(-1), were observed when the UV-irradiated Cl(2)/trans-1,3-butadiene/p-H(2) matrix was further irradiated with IR light from a SiC source. These lines are assigned to the trans-1-methylallyl radical, ●(CH(2)CHCH)CH(3), produced from reaction of 1,3-butadiene with a H atom resulted from the reaction of Cl atoms with solid p-H(2) exposed to IR radiation.

Quantification of umu genotoxicity level of urban river water.

PubMed

Kameya, T; Nagato, T; Nakagawa, K; Yamashita, D; Kobayashi, T; Fujie, K

2011-01-01

In recent years, the request of environmental safety management for carcinogenic substances, mutagenic substances and/or reproductive toxicity substances (CMR) has increased. This study focused on clarifying the genotoxicity level of environmental water and its release source by using the umu test provided in ISO13829. Although a genotoxicity index "induction ratio (IR)" is used in ISO13829, we normalised it to make it possible to compare various environmental water quantitatively to each other as a new index "genotoxic activity (GA=(IR-1)/Dose)". Sample water was collected and concentrated to 100 times or 1,000 times by a solid phase extraction method. As the test results, it was found that GA level in actual river water varied widely from less than the determination limit of 23 [1/L] to 1,100 [1/L] by quantitative comparison, and the value was also equivalent to more than 50 times the level of tap water. The GA level of household wastewater was not so high, but the levels of treated water from wastewater treatment plant (WTP) were from 220 [1/L] to 3,200 [1/L]. Raw sewage of some WTP shows high level genotoxicity. A part of genotoxicity substances, for example 50%, could be removed by conventional wastewater treatment, but it was not enough to reduce the water environmental load of genotoxicity.

Histamine H4-Receptors Inhibit Mast Cell Renin Release in Ischemia/Reperfusion via Protein Kinase Cε-Dependent Aldehyde Dehydrogenase Type-2 Activation

PubMed Central

Aldi, Silvia; Takano, Ken-ichi; Tomita, Kengo; Koda, Kenichiro; Chan, Noel Y.-K.; Marino, Alice; Salazar-Rodriguez, Mariselis; Thurmond, Robin L.

2014-01-01

Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being Gαi/o-coupled, might activate a protein kinase C isotype–ε (PKCε)–aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow–derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKCε and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKCε and ALDH2 activation, reduction of toxic aldehyde-induced MC renin release, prevention of RAS activation, reduction of norepinephrine release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure. PMID:24696042

Low-pressure clathrate-hydrate formation in amorphous astrophysical ice analogs

NASA Technical Reports Server (NTRS)

Blake, D. F.; Allamandola, L. J.; Sandford, S.; Hudgins, D.; Freund, F.

1991-01-01

In modeling cometary ice, the properties of clathrate hydrates were used to explain anomalous gas release at large radial distances from the Sun, and the retention of particular gas inventories at elevated temperatures. Clathrates may also have been important early in solar system history. However, there has never been a reasonable mechanism proposed for clathrate formation under the low pressures typical of these environments. For the first time, it was shown that clathrate hydrates can be formed by warming and annealing amorphous mixed molecular ices at low pressures. The complex microstructures which occur as a result of clathrate formation from the solid state may provide an explanation for a variety of unexplained phenomena. The vacuum and imaging systems of an Hitachi H-500H Analytical Electron Microscope was modified to study mixed molecular ices at temperatures between 12 and 373 K. The resulting ices are characterized by low-electron dose Transmission Electron Microscopy (TEM) and Selected Area Electron Diffraction (SAED). The implications of these results for the mechanical and gas release properties of comets are discussed. Laboratory IR data from similar ices are presented which suggest the possibility of remotely observing and identifying clathrates in astrophysical objects.

Post-polymerization C-H Borylation of Donor-Acceptor Materials Gives Highly Efficient Solid State Near-Infrared Emitters for Near-IR-OLEDs and Effective Biological Imaging.

PubMed

Crossley, Daniel L; Urbano, Laura; Neumann, Robert; Bourke, Struan; Jones, Jennifer; Dailey, Lea Ann; Green, Mark; Humphries, Martin J; King, Simon M; Turner, Michael L; Ingleson, Michael J

2017-08-30

Post-polymerization modification of the donor-acceptor polymer, poly(9,9-dioctylfluorene-alt-benzothiadiazole), PF8-BT, by electrophilic C-H borylation is a simple method to introduce controllable quantities of near-infrared (near-IR) emitting chromophore units into the backbone of a conjugated polymer. The highly stable borylated unit possesses a significantly lower LUMO energy than the pristine polymer resulting in a reduction in the band gap of the polymer by up to 0.63 eV and a red shift in emission of more than 150 nm. Extensively borylated polymers absorb strongly in the deep red/near-IR and are highly emissive in the near-IR region of the spectrum in solution and solid state. Photoluminescence quantum yield (PLQY) values are extremely high in the solid state for materials with emission maxima ≥ 700 nm with PLQY values of 44% at 700 nm and 11% at 757 nm for PF8-BT with different borylation levels. This high brightness enables efficient solution processed near-IR emitting OLEDs to be fabricated and highly emissive borylated polymer loaded conjugated polymer nanoparticles (CPNPs) to be prepared. The latter are bright, photostable, low toxicity bioimaging agents that in phantom mouse studies show higher signal to background ratios for emission at 820 nm than the ubiquitous near-IR emissive bioimaging agent indocyanine green. This methodology represents a general approach for the post-polymerization functionalization of donor-acceptor polymers to reduce the band gap as confirmed by the C-H borylation of poly((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(3-hexylthien-5-yl)-2,1,3-benzothiadiazole]-2c,2cc-diyl) (PF8TBT) resulting in a red shift in emission of >150 nm, thereby shifting the emission maximum to 810 nm.

Visualizing Chemistry with Infrared Imaging

ERIC Educational Resources Information Center

Xie, Charles

2011-01-01

Almost all chemical processes release or absorb heat. The heat flow in a chemical system reflects the process it is undergoing. By showing the temperature distribution dynamically, infrared (IR) imaging provides a salient visualization of the process. This paper presents a set of simple experiments based on IR imaging to demonstrate its enormous…

Multispectral Observations of Explosive Gas Emissions from Santiaguito, Guatemala

NASA Astrophysics Data System (ADS)

Carn, S. A.; Watson, M.; Thomas, H.; Rodriguez, L. A.; Campion, R.; Prata, F. J.

2016-12-01

Santiaguito volcano, Guatemala, has been persistently active for decades, producing frequent explosions from its actively growing lava dome. Repeated release of volcanic gases contains information about conduit processes during the cyclical explosions at Santiaguito, but the composition of the gas phase and the amount of volatiles released in each explosion remains poorly constrained. In addition to its persistent activity, Santiaguito offers an exceptional opportunity to investigate lava dome degassing processes since the upper surface of the active lava dome can be viewed from the summit of neighboring Santa Maria. In January 2016 we conducted multi-spectral observations of Santiaguito's explosive eruption plumes and passive degassing from multiple perspectives as part of the first NSF-sponsored `Workshop on Volcanoes' instrument deployment. Gas measurements included open-path Fourier-Transform infrared (OP-FTIR) spectroscopy from the Santa Maria summit, coincident with ultraviolet (UV) and infrared (IR) camera and UV Differential Optical Absorption Spectroscopy (DOAS) from the El Mirador site below Santiaguito's active Caliente lava dome. Using the OP-FTIR in passive mode with the Caliente lava dome as the source of IR radiation, we were able to collect IR spectra at high temporal resolution prior to and during two explosions of Santiaguito on 7-8 January, with volcanic SO2 and H2O emissions detected. UV and IR camera data provide constraints on the total SO2 burden in the emissions (and potentially the volcanic ash burden), which coupled with the FTIR gas ratios provides new constraints on the mass and composition of volatiles driving explosions at Santiaguito. All gas measurements indicate significant volatile release during explosions with limited degassing during repose periods. In this presentation we will present ongoing analysis of the unique Santiaguito gas dataset including estimation of the total volatile mass released in explosions and an intercomparison of SO2 amounts recorded by the UV and IR instruments.

Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

PubMed

Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

2014-01-01

This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

PubMed Central

Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

2014-01-01

Background This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were generally well tolerated. Conclusion At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability. PMID:24470753

Control of composition and crystallinity in hydroxyapatite films deposited by electron cyclotron resonance plasma sputtering

NASA Astrophysics Data System (ADS)

Akazawa, Housei; Ueno, Yuko

2014-01-01

Hydroxyapatite (HAp) films were deposited by electron cyclotron resonance plasma sputtering under a simultaneous flow of H2O vapor gas. Crystallization during sputter-deposition at elevated temperatures and solid-phase crystallization of amorphous films were compared in terms of film properties. When HAp films were deposited with Ar sputtering gas at temperatures above 460 °C, CaO byproducts precipitated with HAp crystallites. Using Xe instead of Ar resolved the compositional problem, yielding a single HAp phase. Preferentially c-axis-oriented HAp films were obtained at substrate temperatures between 460 and 500 °C and H2O pressures higher than 1×10-2 Pa. The absorption signal of the asymmetric stretching mode of the PO43- unit (ν3) in the Fourier-transform infrared absorption (FT-IR) spectra was the narrowest for films as-crystallized during deposition with Xe, but widest for solid-phase crystallized films. While the symmetric stretching mode of PO43- (ν1) is theoretically IR-inactive, this signal emerged in the FT-IR spectra of solid-phase crystallized films, but was absent for as-crystallized films, indicating superior crystallinity for the latter. The Raman scattering signal corresponding to ν1 PO43- sensitively reflected this crystallinity. The surface hardness of as-crystallized films evaluated by a pencil hardness test was higher than that of solid-phase crystallized films.

FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

NASA Astrophysics Data System (ADS)

Alcolea Palafox, M.; Kattan, D.; Afseth, N. K.

2018-04-01

A theoretical and experimental vibrational study of the anti-HIV d4T (stavudine or Zerit) nucleoside analogue was carried out. The predicted spectra in the three most stable conformers in the biological active anti-form of the isolated state were compared. Comparison of the conformers with those of the natural nucleoside thymidine was carried out. The calculated spectra were scaled by using different scaling procedures and three DFT methods. The TLSE procedure leads to the lowest error and is thus recommended for scaling. With the population of these conformers the IR gas-phase spectra were predicted. The crystal unit cell of the different polymorphism forms of d4T were simulated through dimer forms by using DFT methods. The scaled spectra of these dimer forms were compared. The FT-IR spectrum was recorded in the solid state in the 400-4000 cm-1 range. The respective vibrational bands were analyzed and assigned to different normal modes of vibration by comparison with the scaled vibrational values of the different dimer forms. Through this comparison, the polymorphous form of the solid state sample was identified. The study indicates that d4T exist only in the ketonic form in the solid state. The results obtained were in agreement with those determined in related anti-HIV nucleoside analogues.

Identification of Uranium Minerals in Natural U-Bearing Rocks Using Infrared Reflectance Spectroscopy.

PubMed

Beiswenger, Toya N; Gallagher, Neal B; Myers, Tanya L; Szecsody, James E; Tonkyn, Russell G; Su, Yin-Fong; Sweet, Lucas E; Lewallen, Tricia A; Johnson, Timothy J

2018-02-01

The identification of minerals, including uranium-bearing species, is often a labor-intensive process using X-ray diffraction (XRD), fluorescence, or other solid-phase or wet chemical techniques. While handheld XRD and fluorescence instruments can aid in field applications, handheld infrared (IR) reflectance spectrometers can now also be used in industrial or field environments, with rapid, nondestructive identification possible via analysis of the solid's reflectance spectrum providing information not found in other techniques. In this paper, we report the use of laboratory methods that measure the IR hemispherical reflectance of solids using an integrating sphere and have applied it to the identification of mineral mixtures (i.e., rocks), with widely varying percentages of uranium mineral content. We then apply classical least squares (CLS) and multivariate curve resolution (MCR) methods to better discriminate the minerals (along with two pure uranium chemicals U 3 O 8 and UO 2 ) against many common natural and anthropogenic background materials (e.g., silica sand, asphalt, calcite, K-feldspar) with good success. Ground truth as to mineral content was attained primarily by XRD. Identification is facile and specific, both for samples that are pure or are partially composed of uranium (e.g., boltwoodite, tyuyamunite, etc.) or non-uranium minerals. The characteristic IR bands generate unique (or class-specific) bands, typically arising from similar chemical moieties or functional groups in the minerals: uranyls, phosphates, silicates, etc. In some cases, the chemical groups that provide spectral discrimination in the longwave IR reflectance by generating upward-going (reststrahlen) bands can provide discrimination in the midwave and shortwave IR via downward-going absorption features, i.e., weaker overtone or combination bands arising from the same chemical moieties.

AMPA Receptors Mediate Acetylcholine Release from Starburst Amacrine Cells in the Rabbit Retina

PubMed Central

FIRTH, SALLY I.; LI, WEI; MASSEY, STEPHEN C.; MARSHAK, DAVID W.

2012-01-01

The light response of starburst amacrine cells is initiated by glutamate released from bipolar cells. To identify the receptors that mediate this response, we used a combination of anatomical and physiological techniques. An in vivo, rabbit eyecup was preloaded with [3H]-choline, and the [3H]-acetylcholine (ACh) released into the superfusate was monitored. A photopic, 3 Hz flashing light increased ACh release, and the selective AMPA receptor antagonist, GYKI 53655, blocked this light-evoked response. Nonselective AMPA/kainate agonists increased the release of ACh, but the specific kainate receptor agonist, SYM 2081, did not increase ACh release. Selective AMPA receptor antagonists, GYKI 53655 or GYKI 52466, also blocked the responses to agonists. We conclude that the predominant excitatory input to starburst amacrine cells is mediated by AMPA receptors. We also labeled lightly fixed rabbit retinas with antisera to choline acetyltransferase (ChAT), AMPA receptor subunits GluR1, GluR2/3, or GluR4, and kainate receptor subunits GluR6/7 and KA2. Labeled puncta were observed in the inner plexiform layer with each of these antisera to glutamate receptors, but only GluR2/3-IR puncta and GluR4-IR puncta were found on the ChAT-IR processes. The same was true of starburst cells injected intracellularly with Neurobiotin, and these AMPA receptor subunits were localized to two populations of puncta. The AMPA receptors are expected to desensitize rapidly, enhancing the sensitivity of starburst amacrine cells to moving or other rapidly changing stimuli. PMID:14515241

T-dependence of the vibrational dynamics of IBP/diME-β-CD in solid state: A FT-IR spectral and quantum chemical study

NASA Astrophysics Data System (ADS)

Crupi, V.; Guella, G.; Majolino, D.; Mancini, I.; Rossi, B.; Stancanelli, R.; Venuti, V.; Verrocchio, P.; Viliani, G.

2010-05-01

Solid inclusion complex of the non-steroidal anti-inflammatory drug Ibuprofen (IBP, (2-[4-(2-methylpropyl)phenyl]-propanoic acid) with (2,6-dimethyl)-β-cyclodextrin (diME-β-CD) has been investigated by Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR spectroscopy) and numerical simulation. The complexation-induced changes in the FTIR-ATR spectrum of IBP have been interpreted by comparison with the theoretical vibrational wavenumbers and IR intensities of dimeric structures of IBP, derived from symmetric hydrogen bonding of the two carboxylic groups, computed by using Density Functional Theory (DFT) calculations. From temperature-dependent studies, the enthalpy change ΔH associated with the binding of IBP with diME-β-CD for 1:1 stoichiometry, in solid phase, has been estimated.

Pharmaceutical properties of supramolecular assembly of co-loaded cardanol/triazole-halloysite systems.

PubMed

Massaro, Marina; Colletti, Carmelo G; Noto, Renato; Riela, Serena; Poma, Paola; Guernelli, Susanna; Parisi, Filippo; Milioto, Stefana; Lazzara, Giuseppe

2015-01-30

Halloysite nanotubes were explored as drug carrier for cardanol, which is considered as a promising natural anticancer active species. To this aim, besides the pristine nanoclay, a chemical modification of the nanocarrier was performed by attaching triazolium salts with different hydrophobicity at the outer surface of the hollow nanotubes. The interaction between cardanol and nanotubes was highlighted in solution by HPLC. This method proved the loading of the drug into the nanotubes. The solid dried complexes formed by pristine and modified halloysite with the cardanol were characterized by IR spectroscopy, thermogravimetric analysis as well as water contact angle to evidence the structure, thermal properties and wettability of the obtained materials. The kinetics of cardanol release as well as cell viability experiments provided promising results that put forward a new strategy for potential applications of cardanol as active antiproliferative molecule and clay nanotubes as drug carrier. Copyright © 2015. Published by Elsevier B.V.

Release profiles of phenytoin from new oral dosage form for the elderly.

PubMed

Watanabe, A; Hanawa, T; Sugihara, M; Yamamoto, K

1994-08-01

Utilization of the solid mass containing phenytoin, sodium caseinate and microcrystalline cellulose (MCC) as a new dosage form for the elderly was studied. The solid mass was prepared by treatment of the powder mixture with high pressure steam at 115 degrees C for 10 min. The stability of phenytoin in the solid mass was confirmed by infrared spectroscopy and high performance liquid chromatography. The extent of swelling of the solid mass containing phenytoin was investigated by water absorption test and gel strength test, and the swelling property was almost independent of the presence of phenytoin. The release profile of phenytoin from the solid mass was determined under various conditions, and was found to be influenced by the extent of swelling and the swollen state. It was observed that the protein adsorption to the phenytoin crystal surface and the addition of digestive enzyme also affected the release profile. In water, the solid mass prepared from a ground mixture of phenytoin and MCC showed remarkable improvement of release profile of phenytoin.

Optical fingerprints of solid-liquid interfaces: a joint ATR-IR and first principles investigation

NASA Astrophysics Data System (ADS)

Yang, L.; Niu, F.; Tecklenburg, S.; Pander, M.; Nayak, S.; Erbe, A.; Wippermann, S.; Gygi, F.; Galli, G.

Despite the importance of understanding the structural and bonding properties of solid-liquid interfaces for a wide range of (photo-)electrochemical applications, there are presently no experimental techniques available to directly probe the microscopic structure of solid-liquid interfaces. To develop robust strategies to interpret experiments and validate theory, we carried out attenuated total internal reflection (ATR-IR) spectroscopy measurements and ab initio molecular dynamics (AIMD) simulations of the vibrational properties of interfaces between liquid water and well-controlled prototypical semiconductor substrates. We show the Ge(100)/H2O interface to feature a reversible potential-dependent surface phase transition between Ge-H and Ge-OH termination. The Si(100)/H2O interface is proposed as a model system for corrosion and oxidation processes. We performed AIMD calculations under finite electric fields, revealing different pathways for initial oxidation. These pathways are predicted to exhibit unique spectral signatures. A significant increase in surface specificity can be achieved utilizing an angle-dependent ATR-IR experiment, which allows to detect such signatures at the interfacial layer and consequently changes in the hydrogen bond network. Funding from DOE-BES Grant No. DE-SS0008939 and the Deutsche Forschungsgemeinschaft (RESOLV, EXC 1069) are gratefully acknowledged.

Boronate ligands in materials: determining their local environment by using a combination of IR/solid-state NMR spectroscopies and DFT calculations.

PubMed

Sene, Saad; Reinholdt, Marc; Renaudin, Guillaume; Berthomieu, Dorothée; Zicovich-Wilson, Claudio M; Gervais, Christel; Gaveau, Philippe; Bonhomme, Christian; Filinchuk, Yaroslav; Smith, Mark E; Nedelec, Jean-Marie; Bégu, Sylvie; Mutin, P Hubert; Laurencin, Danielle

2013-01-14

Boronic acids (R-B(OH)(2)) are a family of molecules that have found a large number of applications in materials science. In contrast, boronate anions (R-B(OH)(3)(-)) have hardly been used so far for the preparation of novel materials. Here, a new crystalline phase involving a boronate ligand is described, Ca[C(4)H(9)-B(OH)(3)](2), which is then used as a basis for the establishment of the spectroscopic signatures of boronates in the solid state. The phase was characterized by IR and multinuclear solid-state NMR spectroscopy ((1)H, (13)C, (11)B and (43)Ca), and then modeled by periodic DFT calculations. Anharmonic OH vibration frequencies were calculated as well as NMR parameters (by using the Gauge Including Projector Augmented Wave--GIPAW--method). These data allow relationships between the geometry around the OH groups in boronates and the IR and (1)H NMR spectroscopic data to be established, which will be key to the future interpretation of the spectra of more complex organic-inorganic materials containing boronate building blocks. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prediction and Characterization of NaGaS2, A High Thermal Conductivity Mid-Infrared Nonlinear Optical Material for High-Power Laser Frequency Conversion.

PubMed

Hou, Dianwei; Nissimagoudar, Arun S; Bian, Qiang; Wu, Kui; Pan, Shilie; Li, Wu; Yang, Zhihua

2018-06-15

Infrared nonlinear optical (IR NLO) crystals are the major materials to widen the output range of solid-state lasers to mid- or far-infrared regions. The IR NLO crystals used in the middle IR region are still inadequate for high-power laser applications because of deleterious thermal effects (lensing and expansion), low laser-induced damage threshold, and two-photon absorption. Herein, the unbiased global minimum search method was used for the first time to search for IR NLO optical materials and ultimately found a new IR NLO material NaGaS 2 . It meets the stringent demands for IR NLO materials pumped by high-power laser with the highest thermal conductivity among common IR NLO materials able to avoid two-photon absorption, a classic nonlinear coefficient, and wide infrared transparency.

Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Mimura, Hisahi; Ozaki, Yukihiro; Reppas, Christos; Kitamura, Satoshi

2015-07-25

The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of various solid carriers and spray drying on pre/post compression properties of solid SNEDDS loaded with glimepiride: in vitro-ex vivo evaluation and cytotoxicity assessment.

PubMed

Rajesh, Sarvi Yadav; Singh, Sachin Kumar; Pandey, Narendra Kumar; Sharma, Parth; Bawa, Palak; Kumar, Bimlesh; Gulati, Monica; Jain, Subheet Kumar; Gowthamarajan, Kuppusamy; Singh, Saurabh

2018-07-01

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80, and ethanol were used as oil, surfactant, and co-surfactant, respectively as independent variables. The optimized composition of SNEDDS formulation (F1) was 10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.005% w/v glimepiride. Further, the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, dissolution, and diffusion. Both, liquid and solid-SNEDDS have shown release of more than 90% within 10 min. Results of permeation studies performed on Caco-2 cell showed that optimized SNEDDS exhibited 1.54 times higher drug permeation amount and 0.57 times lower drug excretion amount than that of market tablets at 4 hours (p < .01). Further, the cytotoxicity study performed on Caco-2 cell revealed that the cell viability was lower in SNEDDS (92.22% ± 4.18%) compared with the market tablets (95.54% ± 3.22%; p > .05, i.e. 0.74). The formulation was found stable with temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline glimepiride was observed in amorphous state in solid SNEDDS when characterized through DSC, PXRD, and FT-IR studies. The study revealed successful formulation of SNEDDS for glimepiride.

Rh6G released from solid and nanoporous SiO2 spheres prepared by sol-gel route

NASA Astrophysics Data System (ADS)

García-Macedo, J. A.; Francisco S., P.; Franco, A.

2015-10-01

Porous silica nanoparticles are considering good systems for drug cargo and liquid separation. In this work we studied the release of rhodamine 6G (Rh6G) from solid and porous silica nanoparticles. Solid and porous SiO2 spheres were prepared by sol-gel method. Nanoporous channels were produced by using a surfactant that was removed by chemical procedure. Rh6G was incorporated into the channels by impregnation. The hexagonal structure of the pores was detected by XRD and confirmed by HRTEM micrographs. Rh6G released from the particles by stirring them in water at controlled speed was studied as function of time by photoluminescence. Released ratio was faster in the solid nanoparticles than in the porous ones. In the last case, a second release mechanism was observed. It was related with rhodamine coming out from the porous.

Two-photon luminescence from polar bis-terpyridyl-stilbene derivatives of Ir(III) and Ru(II).

PubMed

Natrajan, Louise S; Toulmin, Anita; Chew, Alex; Magennis, Steven W

2010-12-07

Four structurally related iridium(III) and ruthenium(II) complexes bearing two polar terpyridyl-stilbene derived chromophores 4-(4-{2-[4-(methoxy)phenyl]ethenyl}phenyl)-2,2'-6',2''-terpyridine (ttpyeneanisole) and 4-(4-{2-[phenyl]ethenyl}phenyl)-2,2'-6',2''-terpyridine (tpystilbene) have been synthesised and characterised in the solid state and in solution. In the solid state, the dihedral angle subtending the pyridyl and tolyl groups of 27.1° in the Ir(III) complex [Ir(ttpyeneanisole)(2)]·3PF(6) is more acute than in the Ru(II) derivative [Ru(tpystilbene)(2)]·2PF(6) (35.5°), indicating the presence of a greater degree of π-delocalisation across the terpyridine unit in the former compound. Their luminescence properties in fluid solution have been investigated following both resonant and non-resonant excitation. We have shown that each of the complexes undergoes two-photon excitation when excited in the near infrared (740 to 820 nm), with two-photon absorption cross sections in the range 11-67 × 10(-50) cm(4) s photon(-1). The larger cross sections for the Ir(III) complexes reflect the differences observed in the solid state. This work therefore demonstrates that such complexes are promising as luminescent markers for 3D imaging and illustrates that simple functionalisation of the chromophores and the choice of metal can lead to marked enhancements in the two-photon cross sections (σ(2)) compared to those of simpler heteroleptic polypyridyl based derivatives.

Skutterudite Compounds For Power Semiconductor Devices

NASA Technical Reports Server (NTRS)

Fleurial, Jean-Pierre; Caillat, Thierry; Borshchevsky, Alexander; Vandersande, Jan

1996-01-01

New semiconducting materials with p-type carrier mobility values much higher than state-of-art semiconductors discovered. Nine compounds, antimonides CoSb(sub3), RhSb(sub3), IrSb(sub3), arsenides CoAs(sub3), RhAs(sub3), IrAs(sub3), and phosphides CoP(sub3), RhP(sub3) and IrP(sub3), exhibit same skutterudite crystallographic structure and form solid solutions of general composition Co(1-x-y)RH(x)Ir(y)P(1-w-z)As(w)Sb(z). Materials exhibit high hole mobilities, high doping levels, and high electronic figures of merit. Some compositions show great potential for application to thermoelectric devices.

Multiple Beam Optical Processing

DTIC Science & Technology

1989-12-01

the interference of multiple reflections between the two mirrors. The most promising optical bistable devices, at present, are very thin, solid Fabry...MEDIUM b) R - Ir ,, PMASE SHIFTr Figure 1.3 (a) Nonlinear Fabry-Perot etalon consisting of solid material with parallel surfaces with coatings of...instead of the solid planar structure [2.10]. Voids between columns cause an Inhomogeneous broadening and an exponential extension (Urbach tail) of the

Solid-state phosphorescence-to-fluorescence switching in a cyclometalated Ir(III) complex containing an acid-labile chromophoric ancillary ligand: implication for multimodal security printing.

PubMed

Whang, Dong Ryeol; You, Youngmin; Chae, Weon-Sik; Heo, Jeongyun; Kim, Sehoon; Park, Soo Young

2012-11-06

In this study, we have demonstrated the reconstruction of encrypted information by employing photoluminescence spectra and lifetimes of a phosphorescent Ir(III) complex (IrHBT). IrHBT was constructed on the basis of a heteroleptic structure comprising a fluorescent N^O ancillary ligand. From the viewpoint of information security, the transformation of the Ir(III) complex between phosphorescent and fluorescent states can be encoded with chemical/photoirradiation methods. Thin polymer films (poly(methylmethacrylate), PMMA) doped with IrHBT display long-lived emission typical of phosphorescence (λ(max) = 586 nm, τ(obs) = 2.90 μs). Meanwhile, exposure to HCl vapor switches the emission to fluorescence (λ(max) = 514 nm, τ(obs) = 1.53 ns) with drastic changes in both the photoluminescence color and lifetime. Security printing on paper impregnated with IrHBT or on a PMMA film containing IrHBT and photoacid generator (triphenylsulfonium triflate) enables the bimodal readout of photoluminescence color and lifetime.

Modelling a man-portable air-defence (MANPAD) system with a conical scan two-colour infrared (IR) seeker

NASA Astrophysics Data System (ADS)

Jackman, James; Richardson, Mark; Butters, Brian; Walmsley, Roy

2011-11-01

The use of flares of flares against 1st and 2nd generation man-portable air-defence (MANPAD) systems proved to be very effective. This naturally led to the development of counter-countermeasures (CCM) that could be incorporated into the MANPADs infrared (IR) seeker. One possible CCM is two-colour where the seeker detects in two separate IR bands. It is designed to exploit the different spectral characteristics of the target and flare. In this paper we describe the modelling process of a two-colour conical scan (conscan) IR seeker using CounterSim, a missile engagement and countermeasure simulation software tool developed by Chemring Countermeasures Ltd. It starts by explaining the signal processing needed to be able to reject the flare and track the target. The MANPAD model is then used in an engagement with a fast jet model and a transport aircraft model. Flares are first deployed reactively then released throughout an engagement to investigate the effect of flare release time and the viability of pre-emptive countermeasures.

Renoprotective Effects of AVE0991, a Nonpeptide Mas Receptor Agonist, in Experimental Acute Renal Injury

PubMed Central

Barroso, Lívia Corrêa; Silveira, Kátia Daniela; Lima, Cristiano Xavier; Borges, Valdinéria; Bader, Michael; Rachid, Milene; Santos, Robson Augusto Souza; Souza, Danielle Gloria; Simões e Silva, Ana Cristina; Teixeira, Mauro Martins

2012-01-01

Renal ischemia and reperfusion (I/R) is the major cause of acute kidney injury in hospitalized patients. Mechanisms underlying reperfusion-associated injury include recruitment and activation of leukocytes and release of inflammatory mediators. In this study, we investigated the renal effects of acute administration of AVE0991, an agonist of Mas, the angiotensin-(1–7) receptor, the angiotensin-(1–7) receptor, in a murine model of renal I/R. Male C57BL/6 wild-type or Mas−/− mice were subjected to 30 min of bilateral ischemia and 24 h of reperfusion. Administration of AVE0991 promoted renoprotective effects, as seen by improvement of function, decreased tissue injury, prevention of local and remote leucocyte infiltration, and release of the chemokine, CXCL1. I/R injury was similar in WT and Mas−/− mice, suggesting that endogenous activation of this receptor does not control renal damage under baseline conditions. In conclusion, pharmacological interventions using Mas receptor agonists may represent a therapeutic opportunity for the treatment of renal I/R injury. PMID:22319645

The Risk of Opioid Intoxications or Related Events and the Effect of Alcohol-Related Disorders: A Retrospective Cohort Study in German Patients Treated with High-Potency Opioid Analgesics.

PubMed

Jobski, K; Kollhorst, B; Schink, T; Garbe, Edeltraut

2015-09-01

Intoxications involving prescription opioids are a major public health problem in many countries. When taken with opioids, alcohol can enhance the effects of opioids, particularly in the central nervous system. However, data quantifying the impact of alcohol involvement in opioid-related intoxications are limited. Using claims data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a retrospective cohort study based on users of high-potency opioid (HPO) analgesics during the years 2005-2009. HPO use was classified as extended-release, immediate-release or both. We calculated incidence rates (IRs) for opioid intoxications or related events as well as adjusted IR ratios (aIRR) comparing HPO-treated patients with alcohol-related disorders (ARDs) to those without ARDs overall and within each HPO category. During the study period, 308,268 HPO users were identified with an overall IR of 340.4 per 100,000 person-years [95 % confidence interval (CI) 325.5-355.7]. The risk was highest when patients received concomitant treatment with extended- and immediate-release HPOs (IR 1093.8; 95 % CI 904.6-1310.9). ARDs increased the risk during HPO use by a factor of 1.7 and the highest aIRR was seen when comparing patients simultaneously exposed to extended- and immediate-release HPOs with ARDs to those without ARD also after excluding patients with potential improper/non-medical HPO use. Physicians should be aware of these elevated risks in HPO patients with ARDs. Active patient education by healthcare providers regarding the risk of opioid intoxications or related events due to alcohol in conjunction with HPOs is warranted.

Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction.

PubMed

Fariña, Juan Pablo; García, María Elisa; Alzamendi, Ana; Giovambattista, Andrés; Marra, Carlos Alberto; Spinedi, Eduardo; Gagliardino, Juan José

2013-07-01

In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

Tolerability of extended-release quetiapine fumarate compared with immediate-release quetiapine fumarate in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation: a randomised, double-blind, parallel-group study.

PubMed

De Deyn, Peter Paul; Eriksson, Hans; Svensson, Hanna

2012-03-01

The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR. Copyright © 2011 John Wiley & Sons, Ltd.

Ischemia Reperfusion Injury Triggers TNFα Induced-Necroptosis in Rat Retina.

PubMed

Kim, Cho Rong; Kim, Jie Hyun; Park, Hae-Young Lopilly; Park, Chan Kee

2017-05-01

A recent study revealed a novel form of cell death, termed necroptosis, or programmed necrosis. Previous research indicated that after ischemia-reperfusion (IR) injury to the retina, Tumor Necrosis Factor α (TNFα) is increased, which may activate necroptosis. This study observed macroglial cell activation, and in particular, astrocyte activation, after the release of TNFα and other necroptosis factors in the rat retina due to IR. IR was induced in the retinas of adult male Sprague-Dawley rats by increasing the intraocular pressure to 160 mmHg and then allowing reperfusion. In addition, to inhibit necroptosis, Nec-1 (necrostatin-1) was injected intravitreally after IR. Rats were sacrificed after reperfusion at 12 hours, 1, 3, and 5 days, and 1 and 2 weeks. Retinas from each time point were analyzed by immunohistochemistry (IHC) and Western blotting (WB) to identify the initiator of necroptosis, TNFα, the expression of necroptosis factors, such as receptor interacting protein (RIP) 1, 3, and inactive caspase 8, and Brn3a. Cell death in the IR-injured retinas was identified by cell counting. We found decreased retinal cell numbers in the inner and outer nuclear layers (INL and ONL), as well as in the ganglion cell layer (GCL). Increased glial cell activation was detected by using glial fibrillary acidic protein (GFAP) IHC. TNFα, RIP1, RIP3, and inactive caspase 8 were mainly expressed in the GCL after IR, as determined by IHC and WB. Nec-1 inhibited RIP1, a necroptosis factor, indicating protection against retinal cell loss after IR injury. We showed that IR injury triggered increases in both activation of astrocytes and the expression of TNFα. In addition, TNFα, which was activated by IR, triggered the release of necroptosis factors, particularly, in GCL. Inhibition of necroptosis using Nec-1 decreased the level of RIP1 and retinal cell loss in IR-injured retinas.

Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.

PubMed

Li, Xuechao; Peng, Huanhuan; Tian, Bin; Gou, Jingxin; Yao, Qing; Tao, Xiaoguang; He, Haibing; Zhang, Yu; Tang, Xing; Cai, Cuifang

2015-01-01

The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of Extracellular RNA and TLR3‐Trif Signaling in Myocardial Ischemia–Reperfusion Injury

PubMed Central

Chen, Chan; Feng, Yan; Zou, Lin; Wang, Larry; Chen, Howard H.; Cai, Jia‐Yan; Xu, Jun‐Mei; Sosnovik, David E.; Chao, Wei

2014-01-01

Background Toll‐like receptor 3 (TLR3) was originally identified as the receptor for viral RNA and represents a major host antiviral defense mechanism. TLR3 may also recognize extracellular RNA (exRNA) released from injured tissues under certain stress conditions. However, a role for exRNA and TLR3 in the pathogenesis of myocardial ischemic injury has not been tested. This study examined the role of exRNA and TLR3 signaling in myocardial infarction (MI), apoptosis, inflammation, and cardiac dysfunction during ischemia‐reperfusion (I/R) injury. Methods and Results Wild‐type (WT), TLR3−/−, Trif−/−, and interferon (IFN) α/β receptor‐1 deficient (IFNAR1−/−) mice were subjected to 45 minutes of coronary artery occlusion and 24 hours of reperfusion. Compared with WT, TLR3−/− or Trif−/− mice had smaller MI and better preserved cardiac function. Surprisingly, unlike TLR(2/4)‐MyD88 signaling, lack of TLR3‐Trif signaling had no impact on myocardial cytokines or neutrophil recruitment after I/R, but myocardial apoptosis was significantly attenuated in Trif−/− mice. Deletion of the downstream IFNAR1 had no effect on infarct size. Importantly, hypoxia and I/R led to release of RNA including microRNA from injured cardiomyocytes and ischemic heart, respectively. Necrotic cardiomyocytes induced a robust and dose‐dependent cytokine response in cultured cardiomyocytes, which was markedly reduced by RNase but not DNase, and partially blocked in TLR3‐deficient cardiomyocytes. In vivo, RNase administration reduced serum RNA level, attenuated myocardial cytokine production, leukocytes infiltration and apoptosis, and conferred cardiac protection against I/R injury. Conclusion TLR3‐Trif signaling represents an injurious pathway during I/R. Extracellular RNA released during I/R may contribute to myocardial inflammation and infarction. PMID:24390148

Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis.

PubMed

LeWitt, Peter A; Verhagen Metman, Leo; Rubens, Robert; Khanna, Sarita; Kell, Sherron; Gupta, Suneel

Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.

Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis

PubMed Central

LeWitt, Peter A.; Verhagen Metman, Leo; Rubens, Robert; Khanna, Sarita; Kell, Sherron; Gupta, Suneel

2018-01-01

Objectives Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in “off” time, “on” time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). Methods ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures (“off” time and “on” time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Results and Conclusions Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in “off” time and “on” time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of “good” on time. PMID:29432286

Post-marketing experience with nevirapine extended release (XR) tablets: effectiveness and tolerability in a population-based cohort in British Columbia, Canada.

PubMed

Lepik, Katherine J; Yip, Benita; McGovern, Rachel A; Ding, Erin; Nohpal, Adriana; Watson, Birgit E; Toy, Junine; Akagi, Linda; Harrigan, P Richard; Moore, David M; Hogg, Robert S; Montaner, Julio S G; Barrios, Rolando

2015-01-01

Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once-daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR). Study objectives were to describe the effectiveness and tolerability of nevirapine-XR in clinical practice and, for patients who switched from once daily 2×200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and plasma nevirapine concentrations during each treatment period. HIV-1-infected adults entered the study cohort if they initiated nevirapine-XR in British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were followed until 30 September 2013. Demographic and clinical variables were abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6 months pre- and post-switch with comparison of virological suppression (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon-Mann-Whitney test) in each period. The 536 nevirapine-XR-treated patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in their stools, this was not associated with adverse outcomes. Among the 305 patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690-6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (P<0.001), but there was no difference in virological suppression, 89% and 87% respectively (P=0.414). This post-marketing study affirms the effectiveness and tolerability of nevirapine-XR as an alternative to nevirapine-IR in adults.

Structure, optical and phonon properties of bulk and nanocrystalline Al2-xScx(WO4)3 solid solutions doped with Cr3+

NASA Astrophysics Data System (ADS)

Mączka, M.; Hermanowicz, K.; Pietraszko, A.; Yordanova, A.; Koseva, I.

2014-01-01

Pure and Cr3+ doped nanosized Al2-xScx(WO4)3 solid solutions were prepared by co-precipitation method as well as Al2-xScx(WO4)3 single crystals were grown by high-temperature flux method. The obtained samples were characterized by X-ray, Raman, IR, absorption and luminescence methods. Single crystal X-ray diffraction showed that AlSc(WO4)3 is orthorhombic at room temperature with space group Pnca and trivalent cations are statistically distributed. Raman and IR studies showed that Al2-xScx(WO4)3 solid solutions show "two mode" behavior. They also showed that vibrational properties of nanosized samples have been weakly modified in comparison with the bulk materials. The luminescence and absorption spectra revealed that chromium ions occupy two sites of weak and strong crystal field strength.

Structural Basis of Tonic Inhibition by Dimers of Dimers in Hyperpolarization-Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels.

PubMed

VanSchouwen, Bryan; Melacini, Giuseppe

2016-10-03

The hyperpolarization-activated cyclic-nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP (cAMP) modulates HCN activity through cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN. In the absence of cAMP, the IR cAMP-binding domain (CBD) mainly samples its inactive conformation, resulting in steric clashes that destabilize the IR tetramer. Although these clashes with the inactive CBD are released through tetramer dissociation into monomers, functional mutagenesis suggests that the apo IR is not fully monomeric. To investigate the inhibitory non-monomeric IR species, we performed molecular dynamics simulations starting from "hybrid" structures that are tetrameric, but contain inactive apo-state CBD conformations. The ensemble of simulated trajectories reveals that full dissociation of the tetramer into monomers is not necessary to release the steric hindrance with the inactive CBD. Specifically, we found that partial dissociation of the tetramer into dimers is sufficient to accommodate four inactive CBDs, while reduction of the quaternary symmetry of the non-dissociated tetramer from four- to two-fold permits accommodation of two inactive CBDs. Our findings not only rationalize available electrophysiological, fluorometry and sedimentation equilibrium data, but they also provide unprecedented structural insight into previously elusive non-monomeric auto-inhibitory HCN species.

Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin

PubMed Central

Meagher, Alison K.; Forrest, Alan; Dalhoff, Axel; Stass, Heino; Schentag, Jerome J.

2004-01-01

The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma. A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes. A “mixture model” was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment. Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively. The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios. PMID:15155200

Intranasal abuse potential of an abuse-deterrent oxycodone formulation compared to oxycodone immediate release and placebo in nondependent, recreational opioid users.

PubMed

Setnik, Beatrice; Schoedel, Kerri; Bartlett, Cindy; Dick, Chris; Hakim, Nasrat; Geoffroy, Pierre

To assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone. Randomized, double-blind, double-dummy, active and placebo-controlled, five-way crossover study. Pharmacodynamics, safety, and pharmacokinetics (PKs) were evaluated for up to 36 hours postdose. Single site in Canada (INC Research Toronto). Healthy male and female nondependent recreational opioid users underwent a naloxone challenge and drug discrimination qualification test. Single IN dose of ground ELI-200 (30-mg oxycodone hydrochloride [HCl]/3-mg naltrexone HCl), crushed 30-mg oxycodone HCl IR (Roxicodone®), placebo, fixed placebo, and single oral dose of intact ELI-200 (30mg/3mg). Peak effect (E max ) for bipolar Drug Liking (0-100 point visual analog scale). Of the 44 randomized subjects, 37 completed all five treatment periods. All active treatments showed significantly higher (p<0.001) median Drug Liking E max relative to placebo. Significant reductions (p<0.001) in median Drug Liking [E max ] were observed for IN ELI-200 [56.0] compared to IN oxycodone IR [100.0]. Secondary positive or objective measures (High, Good Drug Effects, Overall Drug Liking, Take Drug Again, and maximum pupil constriction) showed significantly lower E max for IN ELI-200 (p<0.001) compared to IN oxycodone IR. IN administration of ELI-200 demonstrated significantly decreased effects on subjective and physiologic measures, and greater nasal irritation, compared to IN oxycodone IR. These findings, along with the PK profile of naltrexone, demonstrated that when ELI-200 capsules were ground and administered intranasally, the naltrexone component was rapidly released and conferred meaningful abuse-deterrent properties.

Autologous Fat Transfer in Secondary Carpal Tunnel Release

PubMed Central

Noszczyk, Bartłomiej H.

2015-01-01

Background: Carpal tunnel release is the gold standard for the treatment of median nerve compression disease. Recurrent or persistent symptoms do not occur in most patients, although a small number of them have indicated that such a postoperative condition indeed exists. Some patients undergo repeated treatments. In the majority of the cases, the disease is associated with scarring in the carpal tunnel or even reformation of the carpal ligament. The authors propose the usage of autologous fat grafting during secondary carpal tunnel release to inhibit the scarring process. Methods: Ten patients with recurrent or persistent symptoms underwent autologous fat grafting at the time of their repeated carpal tunnel release. Fat was harvested from the lower abdomen and grafted into the scarred transverse carpal ligament and surrounding tissues. Each patient underwent pre- and postoperative examinations and completed the carpal tunnel questionnaire (Boston) to evaluate their sensory and motor functions. The patients underwent 1 year of follow-up. Results: There were 2 main reasons for continued symptoms: a technical mistake resulting in incomplete release (IR) during the first operation and abundant scarring (ABS) in the operated area. The beneficial effects of the interventions were confirmed by a clinical study and by administering the carpal tunnel questionnaire to all patients (functional severity score decreased from 4.38 to 1.88 in IR and 3.62 to 1.48 in ABS group, sensory severity score from 3.26 to 1.7 in IR and 3.04 to 1.48 in ABS group; P < 0.05) after 12 months of follow-up. Conclusion: Our initial observations suggest the possible efficacy of adipose tissue in secondary carpal tunnel release. PMID:26090291

Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

PubMed

Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

2015-01-01

A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included headache (26%) and nausea (18%). All three hydrocodone ER tablet prototypes (low-, intermediate-, and high-level polymer coating) demonstrated ER pharmacokinetic characteristics. The hydrocodone ER tablet prototype with the high-level coating was selected for development because of its comparable exposure to the hydrocodone IR/APAP formulation and potentially increased ability to resist rapid drug release upon product tampering because of a higher polymer coating level. All study medications were well tolerated in healthy naltrexone-blocked volunteers.

The effect of moisture on the release and enrichment of heavy metals during pyrolysis of municipal solid waste.

PubMed

Raclavská, Helena; Corsaro, Agnieszka; Hlavsová, Adéla; Juchelková, Dagmar; Zajonc, Ondřej

2015-03-01

The investigation of the effect of moisture on the release and enrichment of heavy metals during pyrolysis of municipal solid waste is essential. This is important owing to: (i) the increasing amount of metals in the solid product of pyrolysis beyond the normalised level; (ii) the effect of moisture on the overall cost of pyrolysis process; and (iii) the utilisation of pyrolysis products. Seven metals were selected for evaluation: arsenic, cadmium, chromium, mercury, nickel, lead, and vanadium. Pyrolysis experiments were conducted in a steel retort at 650 °C. The municipal solid waste samples with moisture contents of 0, 30, and 65 wt% were investigated. The relative enrichment index and release of heavy metals were evaluated individually for liquid and solid fractions. A consistent trend was observed for the majority of metals investigated. Reductions of relative enrichment index and release, i.e. an increase of volatility, were observed for arsenic, chromium, cadmium, nickel, and vanadium, with an increase of municipal solid waste moisture. Whereas divergent results were obtained for lead and mercury. The effect of moisture on the relative enrichment index and release was greater at 65 wt% moisture than at 30 wt% for lead, and more remarkable at 30 wt% than at 65 wt% for mercury. © The Author(s) 2015.

A novel solid solution LiGa(S1–x Se x )2 for generating coherent ultrafast mid-IR sources

NASA Astrophysics Data System (ADS)

Jer Huang, Jin; Zhang, Xin Lu; Feng, Qian; Dai, Jun Feng; Andreev, Yury M.; Lanskii, Grigory V.; Grechin, Sergei G.

2018-06-01

With renewed refractive indices, the potential of a solid solution () in optical frequency conversion—especially in phase matching and group velocity matching—is theoretically investigated, together with the composition ratio limitation. It is found that the solution has excellent features for generating coherent ultrafast mid-IR sources covering 8–11 μm, which can be realized by type II down-conversion in the ba-plane with perfect group velocity matching, or type I in the bc-plane with part group velocity matching. This will have broad applications in LiDAR monitoring and precision spectroscopy, as well as life and environmental sciences.

Development of solid dispersions of artemisinin for transdermal delivery.

PubMed

Shahzad, Yasser; Sohail, Sadia; Arshad, Muhammad Sohail; Hussain, Talib; Shah, Syed Nisar Hussain

2013-11-30

Solid dispersions of the poorly soluble drug artemisinin were developed using polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with the aim of enhancing solubility and in vitro permeation of artemisinin through skin. Formulations were characterised using a combination of molecular dynamics (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of artemisinin was determined in two solvents: de-ionised water and phosphate buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were carried out using rabbit skin as a model membrane. MD simulations revealed miscibility between the drug and polymers. DSC confirmed the molecular dispersion of the drug in the polymer blend. Decrease in crystallinity of artemisinin with respect to polymer content and the absence of specific drug-polymer interactions were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin was dramatically enhanced for the solid dispersions, as was the permeation of artemisinin from saturated solid-dispersion vehicles relative to that from saturated solutions of the pure drug. The study suggests that high energy solid forms of artemisinin could possibly enable transdermal delivery of artemisinin. Copyright © 2013 Elsevier B.V. All rights reserved.

Aromatic hydrazones derived from nicotinic acid hydrazide as fluorimetric pH sensing molecules: Structural analysis by computational and spectroscopic methods in solid phase and in solution

NASA Astrophysics Data System (ADS)

Benković, T.; Kenđel, A.; Parlov-Vuković, J.; Kontrec, D.; Chiş, V.; Miljanić, S.; Galić, N.

2018-02-01

Structural analyses of aroylhydrazones were performed by computational and spectroscopic methods (solid state NMR, 1 and 2D NMR spectroscopy, FT-IR (ATR) spectroscopy, Raman spectroscopy, UV-Vis spectrometry and spectrofluorimetry) in solid state and in solution. The studied compounds were N‧-(2,3-dihydroxyphenylmethylidene)-3-pyridinecarbohydrazide (1), N‧-(2,5-dihydroxyphenylmethylidene)-3-pyridinecarbohydrazide (2), N‧-(3-chloro-2-hydroxy-phenylmethylidene)-3-pyridinecarbohydrazide (3), and N‧-(2-hydroxy-4-methoxyphenyl-methylidene)-3-pyridinecarbohydrazide (4). Both in solid state and in solution, all compounds were in ketoamine form (form I, sbnd COsbnd NHsbnd Ndbnd Csbnd), stabilized by intramolecular H-bond between hydroxyl proton and nitrogen atom of the Cdbnd N group. In solid state, the Cdbnd O group of 1-4 were involved in additional intermolecular H-bond between closely packed molecules. Among hydrazones studied, the chloro- and methoxy-derivatives have shown pH dependent and reversible fluorescence emission connected to deprotonation/protonation of salicylidene part of the molecules. All findings acquired by experimental methods (NMR, IR, Raman, and UV-Vis spectra) were in excellent agreement with those obtained by computational methods.

Pharmacokinetic drug evaluation of extended release lorcaserin for the treatment of obesity.

PubMed

Hurren, Kathryn M; Dunham, Marissa W

2017-08-01

Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3 and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

Efficacy of single-dose, extended-release naproxen sodium 660 mg in postsurgical dental pain: two double-blind, randomized, placebo-controlled trials.

PubMed

Laurora, Irene; An, Robert

2016-01-01

To evaluate the efficacy of a novel formulation of extended-release/immediate-release (ER) naproxen sodium over 24 h in a dental pain model. Two randomized, double-blind, placebo-controlled trials in moderate to severe pain after extraction of one or two impacted third molars (at least one partial mandibular bony impaction). Treatment comprised oral ER naproxen sodium 660 mg (single dose), placebo (both studies) or immediate-release (IR) naproxen sodium 220 mg tid (study 2). Primary efficacy endpoint: 24-h summed pain intensity difference (SPID). Secondary variables included total pain relief (TOTPAR), use of rescue medication. All treatment-emergent adverse events were recorded. NCT00720057 (study 1), NCT01389284 (study 2). Primary efficacy analyses: pain intensity was significantly lower over 24 h with ER naproxen sodium vs. placebo (p < 0.001), with significant relief from 15 min (study 2). In study 2, ER naproxen sodium was non-inferior to IR naproxen sodium, reducing pain intensity to a comparable extent over 24 h. TOTPAR was significantly greater with ER and IR naproxen sodium vs. placebo at all time points, with generally comparable differences between active treatments. Significantly more placebo patients required rescue medication vs. ER and IR naproxen sodium from 2-24 h post-dose. Once daily ER naproxen sodium was generally safe and well tolerated, with a similar safety profile to IR naproxen sodium tid. The studies were single dose, with limited ability to assess efficacy or safety of multiple doses over time. As the imputed pain score meant that estimated treatment differences may have been biased in favor of ER naproxen sodium, a post hoc analysis evaluated the robustness of the results for pain relief. A single dose of ER naproxen sodium 660 mg significantly reduced moderate to severe dental pain vs. placebo and was comparable to IR naproxen sodium 220 mg tid. Significant pain relief was experienced from 15 min and sustained over 24 h, resulting in a reduced need for rescue medication. ER naproxen sodium 660 mg once daily is a convenient and effective therapy providing 24 h relief of pain.

Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.

PubMed

Rostaing, Lionel; Bunnapradist, Suphamai; Grinyó, Josep M; Ciechanowski, Kazimierz; Denny, Jason E; Silva, Helio Tedesco; Budde, Klemens

2016-04-01

1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT's improved bioavailability and absorption. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

IRS Releases Tax Questionnaire that Asks Colleges to Disclose More

ERIC Educational Resources Information Center

Kelderman, Eric

2008-01-01

Nearly 400 colleges across the United States are about to be asked to disclose intimate financial details of their operations to the Internal Revenue Service. This article reports on a highly detailed financial questionnaire designed by the IRS for the first phase of its Colleges and Universities Compliance Project, which is part of a continuing…

Waste Material of Propolis as a Film Forming Agent Intended to Modify the Metronidazole Release: Preparation and Characterization.

PubMed

de Toledo, Lucas de Alcântara Sica; Rosseto, Hélen Cássia; Ravani, Laura; Cortesi, Rita; Bruschi, Marcos Luciano

2016-01-01

Metronidazole is an antimicrobial agent utilized for the treatment of protozoa and anaerobic bacteria infections. Many times, it is necessary to modify the metronidazole release, and the development of modified release systems may be suggested. In this study, we are able to investigate the use of the residue normally thrown out from the preparation of propolis extracts (BP) as strategy to modify the metronidazole release. We prepared films containing polymeric adjuvant (gelatin or ethylcellulose) and metronidazole, by solvent casting method. Density, mechanical properties, water vapor permeability (WVP), moisture uptake capacity (MUC), thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and in vitro metronidazole release were investigated. Thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout. Mechanical properties were influenced by film composition. Films containing gelatin showed higher resistance to stress while those containing ethylcellulose presented greater flexibility. The greater the adjuvant concentrations lower the resistance to rupture and the elasticity, but higher MUC and WVP of formulations. FT-IR tests suggested interactions between BP and the adjuvants. Films were capable to protect the metronidazole and changed its release profile. BP films are of great practical importance constituting a novel strategy to modify the metronidazole release.

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

High wettability of liquid caesium iodine with solid uranium dioxide.

PubMed

Kurosaki, Ken; Suzuki, Masanori; Uno, Masayoshi; Ishii, Hiroto; Kumagai, Masaya; Anada, Keito; Murakami, Yukihiro; Ohishi, Yuji; Muta, Hiroaki; Tanaka, Toshihiro; Yamanaka, Shinsuke

2017-09-13

In March 2011, the Fukushima Daiichi Nuclear Power Plant accident caused nuclear fuel to melt and the release of high-volatility fission products into the environment. Caesium and iodine caused environmental contamination and public exposure. Certain fission-product behaviours remain unclear. We found experimentally that liquid CsI disperses extremely favourably toward solid UO 2 , exhibiting a contact angle approaching zero. We further observed the presence of CsI several tens of micrometres below the surface of the solid UO 2 sample, which would be caused by the infiltration of pores network by liquid CsI. Thus, volatile fission products released from molten nuclear fuels with complex internal composition and external structure migrate or evaporate to varying extents, depending on the nature of the solid-liquid interface and the fuel material surface, which becomes the pathway for the released fission products. Introducing the concept of the wettability of liquid chemical species of fission products in contact with solid fuels enabled developing accurate behavioural assessments of volatile fission products released by nuclear fuel.

Assessment of the abuse of tapentadol immediate release: the first 24 months.

PubMed

Dart, Richard C; Cicero, Theodore J; Surratt, Hilary L; Rosenblum, Andrew; Bartelson, Becki Bucher; Adams, Edgar H

2012-01-01

Prescription opioid analgesics play an important role in the management of moderate to severe pain. An unintended consequence of prescribing opioid analgesics is the abuse and diversion of these medications. The authors estimated abuse and diversion rates for tapentadol immediate release (IR) compared with oxycodone, hydrocodone, and tramadol during the first 24 months of tapentadol IR availability. The Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System measures rates of prescription opioid abuse and diversion throughout the United States. Quarterly data from the Poison Center, Drug Diversion, Opioid Treatment, and Survey of Key Informants' Patients (SKIP) programs were plotted to visually compare the rates of tapentadol IR abuse and diversion with those of other opioid analgesics from July 2009 through June 2011 using both cases per 100,000 population and per 1,000 unique recipients of dispensed drug (URDD) as denominators. Trends in abuse and diversion rates over time were determined using a linear regression model of rate versus time. During the 24 months following its introduction, tapentadol IR had very low population-based rates of abuse and diversion that were similar to rates for tramadol and lower than rates for oxycodone and hydrocodone. Rates of tapentadol IR abuse and diversion based on URDD were variable by program due to changes in market share and had not stabilized as of June 2011. Rates of tapentadol IR abuse and diversion have been low during the first 24 months after its launch. Continued monitoring of trends in these data is warranted.

Geometrically Thick Obscuration by Radiation-driven Outflow from Magnetized Tori of Active Galactic Nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Chi-Ho; Krolik, Julian H.

2017-07-01

Near-Eddington radiation from active galactic nuclei (AGNs) has significant dynamical influence on the surrounding dusty gas, plausibly furnishing AGNs with geometrically thick obscuration. We investigate this paradigm with radiative magnetohydrodynamics simulations. The simulations solve the magnetohydrodynamics equations simultaneously with the infrared (IR) and ultraviolet (UV) radiative transfer (RT) equations; no approximate closure is used for RT. We find that our torus, when given a suitable sub-Keplerian angular momentum profile, spontaneously evolves toward a state in which its opening angle, density distribution, and flow pattern change only slowly. This “steady” state lasts for as long as there is gas resupply towardmore » the inner edge. The torus is best described as a midplane inflow and a high-latitude outflow. The outflow is launched from the torus inner edge by UV radiation and expands in solid angle as it ascends; IR radiation continues to drive the wide-angle outflow outside the central hole. The dusty outflow obscures the central source in soft X-rays, the IR, and the UV over three-quarters of solid angle, and each decade in column density covers roughly equal solid angle around the central source; these obscuration properties are similar to what observations imply.« less

Four new polymorphic forms of suplatast tosilate.

PubMed

Nagai, Keiko; Ushio, Takanori; Miura, Hidenori; Nakamura, Takashi; Moribe, Kunikazu; Yamamoto, Keiji

2014-01-02

We found four new polymorphic forms (γ-, ε-, ζ-, and η-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (α-, β-, and δ-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the ε- and η-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the ε- and η-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid-state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The α-form was the most insoluble in 2-propanol at 35°C, and was thus concluded to be the most stable form. The ε-form was the most soluble, and a polymorphic transition from the ε- to the α-form was observed during solubility testing. Copyright © 2013 Elsevier B.V. All rights reserved.

A Facile Solvent-Free Cannizzaro Reaction: An Instructional Model for Introductory Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Phonchaiya, Sonthi; Panijpan, Bhinyo; Rajviroongit, Shuleewan; Wright, Tony; Blanchfield, Joanne T.

2009-01-01

Liquid 2-chlorobenzaldehyde was converted, by grinding with potassium hydroxide pellets, into equimolar quantities of solid 2-chlorobenzoic acid and solid 2-chlorobenzyl alcohol in a Cannizzaro reaction. TLC, IR, and NMR experiments, using authentic samples for comparison, confirmed the identity and purity of the two products. Guided-inquiry…

76 FR 67209 - Notice of Lodging of Consent Decree Under the Comprehensive Environmental Response, Compensation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... Response, Compensation, and Liability Act and the Texas Solid Waste Disposal Act Notice is hereby given... Texas Solid Waste Disposal Act, Texas Health & Safety Code Ann. Sec. Sec. 361.001 to 361.966 (hereafter... responding to the releases and threatened releases of solid wastes and hazardous substances at and from the...

Computer-aided detection of artificial pulmonary nodules using an ex vivo lung phantom: influence of exposure parameters and iterative reconstruction.

PubMed

Wielpütz, Mark O; Wroblewski, Jacek; Lederlin, Mathieu; Dinkel, Julien; Eichinger, Monika; Koenigkam-Santos, M; Biederer, Jürgen; Kauczor, Hans-Ulrich; Puderbach, Michael U; Jobst, Bertram J

2015-05-01

To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the performance of computer-aided detection (CAD) of pulmonary nodules on chest multidetector computed tomography (MDCT). Seven porcine lung explants were inflated in a dedicated ex vivo phantom shell and prepared with n=162 artificial nodules of a clinically relevant volume and maximum diameter (46-1063 μl, and 6.2-21.5 mm). n=118 nodules were solid and n=44 part-solid. MDCT was performed with different combinations of 120 and 80 kV with 120, 60, 30 and 12 mA*s, and reconstructed with both filtered back projection (FBP) and IR. Subsequently, 16 datasets per lung were subjected to dedicated CAD software. The rate of true positive, false negative and false positive CAD marks was measured for each reconstruction. The rate of true positive findings ranged between 88.9-91.4% for FBP and 88.3-90.1% for IR (n.s.) with most exposure settings, but was significantly lower with the combination of 80 kV and 12 mA*s (80.9% and 81.5%, respectively, p<0.05). False positive findings ranged between 2.3-8.1 annotations per lung. For nodule volumes <200 μl the rate of true positives was significantly lower than for >300 μl (p<0.05). Similarly, it was significantly lower for diameters <12 mm compared to ≥12 mm (p<0.05). The rate of true positives for solid and part-solid nodules was similar. Nodule CAD on chest MDCT is robust over a wide range of exposure settings. Noise reduction by IR is not detrimental for CAD, and may be used to improve image quality in the setting of low-dose MDCT for lung cancer screening. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An investigation of acetylcholine released in skeletal muscle and protein unbound drug released in blood based on the pyridostigmine bromide (pretreatment drug) sustained-release pellets by microdialysis technique in the rabbit model.

PubMed

Huang, Yuh-Tyng; Cheng, Chun-Jen; Lai, Tsun-Fwu; Tsai, Tong-Rong; Tsai, Tung-Hu; Chuo, Wen-Ho; Cham, Thau-Ming

2007-04-18

Pyridostigmine bromide (PB) is a reversible acetylcholinesterase inhibitor that has been used as a pretreatment drug for "Soman" nerve gas poisoning in combat to increase survival. The once-daily PB-sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods in our laboratory, which was followed by zero-order release mechanism. The results showed that the released concentration of acetylcholine (ACh) in skeletal muscle and the released concentration of protein unbound drug in blood were determined by microdialysis technique to have significant differences (P<0.05) among the three dosage forms (IV injection, commercial IR tablets and the PB-SR pellet). The released concentrations of ACh and protein unbound drug for PB-SR pellets were slower than IV injection and commercial IR tablets; this phenomenon indicating that the retention period of drug efficacy in vivo for PB-SR pellet was longer than the others, that is to say, the PB-SR pellets provided with SR effect in vivo as well. We believe that once-daily administered PB-SR pellets would improve limitations of post-exposure antidotes, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in wars or terrorist attacks in the future.

New insights on poly(vinyl acetate)-based coated floating tablets: characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength.

PubMed

Strübing, Sandra; Abboud, Tâmara; Contri, Renata Vidor; Metz, Hendrik; Mäder, Karsten

2008-06-01

The purpose of this study was to investigate the mechanism of floating and drug release behaviour of poly(vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon SR as an excipient for direct compression and different Kollicoat SR 30 D/Kollicoat IR coats varying from 10 to 20mg polymer/cm2 were investigated regarding drug release in 0.1N HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10mg polymer/cm2 SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics. Poly(vinyl acetate) proved to be an appropriate excipient to ensure safe and reliable drug release. Floating strength measurements offered the possibility to quantify the floating ability of the developed systems and thus to compare different formulations more efficiently. Benchtop MRI studies allowed a deeper insight into drug release and floating mechanisms noninvasively and continuously.

Laser-activated nano-biomaterials for tissue repair and controlled drug release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matteini, P; Ratto, F; Rossi, F

2014-07-31

We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia–reperfusion

PubMed Central

Wu, Bin; Qiu, Wei; Wang, Peng; Yu, Hui; Cheng, Tao; Zambetti, Gerard P; Zhang, Lin; Yu, Jian

2007-01-01

Background The small intestine is highly sensitive to ischaemia–reperfusion (I/R) induced injury which is associated with high morbidity and mortality. Apoptosis, or programmed cell death, is a major mode of cell death occurring during I/R induced injury. However, the mechanisms by which I/R cause apoptosis in the small intestine are poorly understood. p53 upregulated modulator of apoptosis (PUMA) is a p53 downstream target and a member of the BH3‐only group of Bcl‐2 family proteins. It has been shown that PUMA plays an essential role in apoptosis induced by a variety of stimuli in different tissues through a mitochondrial pathway. Aims The role of PUMA in I/R induced injury and apoptosis in the small intestine was investigated. The mechanisms by which PUMA is regulated in I/R induced intestinal apoptosis were also studied. Methods Ischaemia was induced by superior mesenteric artery occlusion in the mouse small intestine. Induction of PUMA in response to ischaemia alone, or ischaemia followed by reperfusion (I/R), was examined. I/R induced intestinal apoptosis and injury were compared between PUMA knockout and wild‐type mice. The mechanisms of I/R induced and PUMA mediated apoptosis were investigated through analysis of caspase activation, cytosolic release of mitochondrial cytochrome c and alterations of the proapoptotic Bcl‐2 family proteins Bax and Bak. To determine whether PUMA is induced by reactive oxygen species and/or reactive nitrogen species generated by I/R, superoxide dismutase (SOD) and N‐nitro‐L‐arginine methyl ester (L‐NAME) were used to treat animals before I/R. To determine whether p53 is involved in regulating PUMA during I/R induced apoptosis, PUMA induction and apoptosis in response to I/R were examined in p53 knockout mice. Results PUMA was markedly induced following I/R in the mucosa of the mouse small intestine. I/R induced intestinal apoptosis was significantly attenuated in PUMA knockout mice compared with that in wild‐type mice. I/R induced caspase 3 activation, cytochrome c release, Bax mitochondrial translocation and Bak multimerisation were also inhibited in PUMA knockout mice. SOD or L‐NAME significantly blunted I/R induced PUMA expression and apoptosis. Furthermore, I/R induced PUMA expression and apoptosis in the small intestine were not affected in the p53 knockout mice. Conclusions Our data demonstrated that PUMA is activated by oxidative stress in response to I/R to promote p53 independent apoptosis in the small intestine through the mitochondrial pathway. Inhibition of PUMA is potentially useful for protecting against I/R induced intestinal injury and apoptosis. PMID:17127703

High-pressure synthesis and structural, physical properties of CaIr1-xPtxO3 and CaIr1-xRhxO3

NASA Astrophysics Data System (ADS)

Hirai, S.; Bromiley, G. D.; Klemme, S.; Irifune, T.; Ohfuji, H.; Attfield, P.; Nishiyama, N.

2010-12-01

Since the discovery of the perovskite to post-perovskite transition in MgSiO3 in a laser-heated DAC, wide attention has been focussed on the post-perovskite phase of MgSiO3. This is because the post-perovskite phase is likely to play a key role in Earth’s lowermost mantle, and because the perovskite to post-perovskite transition can explain many features of the D” seismic discontinuity. While it is meaningful to conduct further studies of MgSiO3, the post-perovskite phase of MgSiO3 cannot be quenched to ambient pressure/temperature conditions. Thus, further studies must be conducted using analogue compounds of MgSiO3 post-perovskite, which are quenchable to ambient pressure/temperature conditions. The post-perovskite phase of MgSiO3 crystallizes in a layered structure with CaIrO3-structure. Therefore, it is useful to investigate compounds with CaIrO3-structure. There are only four quenchable oxides with CaIrO3-structure reported to date: CaIrO3, CaPtO3, CaRhO3 and CaRuO3. CaIrO3 can be synthesized at ambient pressure, whilst the other three oxides can only be obtained at high pressure/temperature conditions using a multi-anvil apparatus. Further studies on these materials have revealed structural phase transitions at high P-T and a metal-insulator transition by hole doping. In the case of CaIrO3, The post-perovskite phase of CaIrO3 synthesized at 2GPa, 1373K transforms into a perovskite phase at 2GPa, 1673K. In other words, the perovskite phase can be synthesized at temperatures higher than those needed for synthesizing the post-perovskite phase. This is also the case for CaRhO3 (6GPa, 1873K) and CaRuO3 (23GPa, 1343K), while CaPtO3 remained post-perovskite at higher temperatures. We have succeeded in synthesizing solid solutions between CaIrO3, CaPtO3 and CaRhO3. We have found the systematic change in structural and physical properties of post-perovskite oxides, with composition and P-T, which broadens the future opportunity for studying post-perovskite systems in terms of materials science applications. To our knowledge, this will be the first report on structural, magnetic and charge-transport properties of B-site substituted solid solutions of post-perovskite oxides with 4d/5d transition metals. High-quality polycrystalline samples of CaIr1-xPtxO3 and CaIr1-xRhxO3 have been obtained at high pressures, and structural, magnetic and charge-transport properties of the compounds will be reported. ODF analysis reveals that solutions of CaIrO3, CaPtO3 and CaRhO3 exhibit similar grain growth features to the mother compound, although growth in [0 1 0] plays a more dominant role than the growth in [0 0 1] for the solid solutions. CaIrO3 is a characteristic hard magnet suitable for applications such as magnetic recording, with TN = 108K. A new phase of CaIr1-xPtxO3 synthesized at a high P/T condition has Raman modes which resemble those of CaIrO3 perovskite, suggesting this phase has a perovskite structure.The instability of the perovskite phase of CaIr1-xPtxO3 reveals why the post-perovskite to peovskite phase transition has not been observed for CaPtO3 unlike the case for CaIrO3, CaRhO3 and CaRuO3.

3D printing of tablets using inkjet with UV photoinitiation.

PubMed

Clark, Elizabeth A; Alexander, Morgan R; Irvine, Derek J; Roberts, Clive J; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Hague, Richard J M; Tuck, Chris J; Wildman, Ricky D

2017-08-30

Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector. Copyright © 2017. Published by Elsevier B.V.

A straightforward graphical user interface for basic and advanced signal processing of thermographic infrared sequences

NASA Astrophysics Data System (ADS)

Klein, Matthieu T.; Ibarra-Castanedo, Clemente; Maldague, Xavier P.; Bendada, Abdelhakim

2008-03-01

IR-View, is a free and open source Matlab software that was released in 1998 at the Computer Vision and Systems Laboratory (CVSL) at Université Laval, Canada, as an answer to many common and recurrent needs in Infrared thermography. IR-View has proven to be a useful tool at CVSL for the past 10 years. The software by itself and/or its concept and functions may be of interest for other laboratories and companies working in research in the IR NDT field. This article describes the functions and processing techniques integrated to IR-View, freely downloadable under the GNU license at http://mivim.gel.ulaval.ca. Demonstration of IR-View functionalities will also be done during the DSS08 SPIE Defense and Security Symposium.

Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release.

PubMed

Geng, Hongjian; Zhao, Yating; Liu, Jia; Cui, Yu; Wang, Ying; Zhao, Qinfu; Wang, Siling

2016-08-20

The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system and pharmaceutic adjuvant. Copyright © 2016 Elsevier B.V. All rights reserved.

Highly versatile heteroditopic ligand scaffolds for accommodating group 8, 9 & 11 heterobimetallic complexes.

PubMed

Gatus, Mark R D; Bhadbhade, Mohan; Messerle, Barbara A

2017-10-24

Two highly versatile xanthene scaffolds containing pairs of heteroditopic ligands were found to be capable of accommodating a range of transition metal ions, including Au(i), Ir(i), Ir(iii), Rh(i), and Ru(ii) to generate an array of heterobimetallic complexes. The metal complexes were fully characterised and proved to be stable in the solid and solution state, with no observed metal-metal scrambling. Heterobimetallic complexes containing the Rh(i)/Ir(i) combinations were tested as catalysts for the two-step dihydroalkoxylation reaction of alkynediols and sequential hydroamination/hydrosilylation reaction of alkynamines.

Silent and higher-order vibrations of C 60 and its compounds

NASA Astrophysics Data System (ADS)

Graja, Andrzej; Łapiński, Andrzej; Król, Sylwia

1997-02-01

We present rich IR spectra of solid samples of C 60 and its derivatives. Most of the IR lines are identified as the activated silent modes of the C 60 or second-order combination modes. The method of preparation of a complex of C 60 and chloro(triphenyl-phosphine) gold grown from toluene solution is described. Basic physical properties, in particular IR transmission of the single crystals of the complex, are studied as a function of temperature. Anomalies in the temperature dependences of the linewidths, their frequencies and intensities are observed and discussed.

Physicochemical characterization and an injection formulation study of water insoluble ZCVI₄-2, a novel NO-donor anticancer compound.

PubMed

Gao, Yuan; Li, Li; Zhang, Jianjun; Su, Feng; Gong, Zhenhua; Lai, Yisheng; Zhang, Yihua

2012-07-01

ZCVI(4)-2 was a novel nitric oxide-releasing glycosyl derivative of oleanolic acid that displayed strong cytotoxicity selectively against human hepatocellular carcinoma in vitro and in vivo. In this study, ZCVI(4)-2 was characterized by FT-IR spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, Raman spectroscopy, hygroscopicity and stability. A high performance liquid chromatography method was also established for the quantitative determination of solubility and additional stability profile of ZCVI(4)-2. ZCVI(4)-2 was found to be an amorphous and stable solid with low solubility of less than 10 μg/mL. Based on the solubilization tests that included methods of cosolvency and micellization, the solution mixture of 5% Solutol HS-15, 5% 1, 2-propylene glycol and 5% anhydrous ethanol was determined to be the system for the preparation of the ZCVI(4)-2 early injection solution. The effect of pH, temperature, light and injectable isotonic glucose or NaCl solution on ZCVI(4)-2 injection was also investigated. Good stability was observed at all testing conditions. Under the conditions studied, the NO-releasing rate and amount of ZCVI(4)-2 from the early injection solution in rat plasma demonstrated a promising therapeutic efficacy while maintaining a good safety profile.

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

PubMed

Kim, Jeong Tae; Barua, Sonia; Kim, Hyeongmin; Hong, Seong-Chul; Yoo, Seung-Yup; Jeon, Hyojin; Cho, Yeongjin; Gil, Sangwon; Oh, Kyungsoo; Lee, Jaehwi

2017-07-01

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

PARTITION INFRARED METHOD FOR TOTAL GASOLINE RANGE ORGANICS IN WATER BASED ON SOLID PHASE MICROEXTRACTION. (R825343)

EPA Science Inventory

A new method is described for determining total gasoline-range organics
(TGRO) in water that combines solid-phase microextraction (SPME) and infrared
(IR) spectroscopy. In this method, the organic compounds are extracted from
250-mL of water into a small square (3....

SCREENING METHOD FOR NITROAROMATIC COMPOUNDS IN WATER BASED ON SOLID-PHASE MICROEXTRACTION AND INFRARED SPECTROSCOPY. (R825343)

EPA Science Inventory

A new method is described for determining nitroaromatic compounds in water
that combines solid-phase microextraction (SPME) and infrared (IR) spectroscopy. In this method, the compounds are extracted from a 250-mL volume of water into a small square (3.2 cm ? 3.2 cm ? 61.2...

A chimeric switch-receptor targeting PD1 augments the efficacy of second generation CAR T-Cells in advanced solid tumors

PubMed Central

Liu, Xiaojun; Ranganathan, Raghuveer; Jiang, Shuguang; Fang, Chongyun; Sun, Jing; Kim, Soyeon; Newick, Kheng; Lo, Albert; June, Carl H.; Zhao, Yangbing; Moon, Edmund K.

2015-01-01

Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy (ATC) has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally-occurring and genetically-modified tumor infiltrating lymphocytes (TILs) by inhibitory receptors (IRs), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T cell activity against solid tumors. To address this possibility, we introduced a genetically-engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T-cells. We tested the effect of this supplement, “PD1CD28”, on human CAR T-cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T-cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared to treatments with CAR T-cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality. PMID:26979791

Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca(2+) Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.

PubMed

Iwasaki, Yusaku; Shimomura, Kenju; Kohno, Daisuke; Dezaki, Katsuya; Ayush, Enkh-Amar; Nakabayashi, Hajime; Kubota, Naoto; Kadowaki, Takashi; Kakei, Masafumi; Nakata, Masanori; Yada, Toshihiko

2013-01-01

Some of insulin's functions, including glucose/lipid metabolism, satiety and neuroprotection, involve the alteration of brain activities. Insulin could signal to the brain via penetrating through the blood-brain barrier and acting on the vagal afferents, while the latter remains unproved. This study aimed to clarify whether insulin directly regulates the nodose ganglion neurons (NGNs) of vagal afferents in mice. NGs expressed insulin receptor (IR) and insulin receptor substrate-2 (IRS2) mRNA, and some of NGNs were immunoreactive to IR. In patch-clamp and fura-2 microfluorometric studies, insulin (10(-12)∼10(-6) M) depolarized and increased cytosolic Ca(2+) concentration ([Ca(2+)]i) in single NGNs. The insulin-induced [Ca(2+)]i increases were attenuated by L- and N-type Ca(2+) channel blockers, by phosphatidylinositol 3 kinase (PI3K) inhibitor, and in NGNs from IRS2 knockout mice. Half of the insulin-responsive NGNs contained cocaine- and amphetamine-regulated transcript. Neuronal fibers expressing IRs were distributed in/around pancreatic islets. The NGNs innervating the pancreas, identified by injecting retrograde tracer into the pancreas, responded to insulin with much greater incidence than unlabeled NGNs. Insulin concentrations measured in pancreatic vein was 64-fold higher than that in circulation. Elevation of insulin to 10(-7) M recruited a remarkably greater population of NGNs to [Ca(2+)]i increases. Systemic injection of glibenclamide rapidly released insulin and phosphorylated AKT in NGs. Furthermore, in IRS2 knockout mice, insulin action to suppress [Ca(2+)]i in orexigenic ghrelin-responsive neurons in hypothalamic arcuate nucleus was intact while insulin action on NGN was markedly attenuated, suggesting a possible link between impaired insulin sensing by NGNs and hyperphagic obese phenotype in IRS2 knockout mice These data demonstrate that insulin directly activates NGNs via IR-IRS2-PI3K-AKT-cascade and depolarization-gated Ca(2+) influx. Pancreas-innervating NGNs may effectively sense dynamic changes of insulin released in response to nutritional states. These interactions could serve to convey the changes in pancreatic and systemic insulin to the brain.

A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu Fengyu; Chemistry and Pharmaceutical College, Jiamusi University, Jiamusi 154007; Zhu Guangshan

2006-07-15

A series of mesoporous silica materials with similar pore sizes, different morphologies and variable pore geometries were prepared systematically. In order to control drug release, ibuprofen was employed as a model drug and the influence of morphology and pore geometry of mesoporous silica on drug release profiles was extensively studied. The mesoporous silica and drug-loaded samples were characterized by X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. It was found that the drug-loading amount was directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drugmore » release profiles could be controlled by tailoring the morphologies of mesoporous silica carriers. - Graphical abstract: The release of ibuprofen is controlled by tailoring the morphologies of mesoporous silica. The mesoporous silica and drug-loaded samples are characterized by powder X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. The drug-loading amount is directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drug release profiles can be controlled by tailoring the morphologies of mesoporous silica carriers.« less

[Preparation of curcumin-EC sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Bai, Wei-li; Yan, Ting-yuan; Wang, Zhi-xiang; Huang, De-chun; Yan, Ting-xuan; Li, Ping

2015-01-01

Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes, on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading, yield, particle size distribution, electron microscope analysis (SEM) , infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 45 degrees C, crystallization pressure 10 MPa, curcumin concentration 8 g x L(-1), solvent flow rate 0.9 mL x min(-1), and CO2 velocity 4 L x min(-1). Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%, and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies.

PubMed

Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

2014-09-01

The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (24-28 participants/study). Caloric and fat content of meals were varied and treatments were administered in the morning, at midday, or in the evening. Blood samples were collected up to 48 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies. One hundred and twenty-eight healthy participants (19-54 years of age) received pregabalin. Peak plasma concentrations (C max) were lower for CR than the respective pregabalin IR doses, and time to C max occurred later. When pregabalin CR was administered with food at midday or in the evening, total exposures [area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC∞)] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content. When pregabalin CR was administered with an 800-1,000 calorie medium-fat breakfast, AUC∞ was equivalent for pregabalin CR and IR. Bioequivalence criteria for comparison of pregabalin CR after a low- or medium-calorie breakfast relative to pregabalin IR were not met; however, bioavailability of the pregabalin CR vs. IR formulation was relatively high (75-86 %). When pregabalin CR was administered fasted, the AUC∞ was 70-78 % of the AUC∞ of pregabalin CR administered with food and bioequivalence criteria were not met. Additionally, the AUC∞ of the pregabalin CR formulation administered fasted was 62-69 % of that of pregabalin IR administered fasted and bioequivalence criteria were not met. Single-dose pregabalin CR and IR were well tolerated in all studies, with no serious or severe adverse events reported. Time of day of administration and the fat and caloric content of the accompanying meal had minimal overall effect on the pharmacokinetic properties and bioavailability of the pregabalin CR formulation.

Clean Photothermal Heating and Controlled Release from Near-Infrared Dye Doped Nanoparticles without Oxygen Photosensitization.

PubMed

Guha, Samit; Shaw, Scott K; Spence, Graeme T; Roland, Felicia M; Smith, Bradley D

2015-07-21

The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of (1)O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive (1)O2, leading to bleaching of the dye and also decomposition of coencapsulated payload such as the drug doxorubicin. Croc dye was especially useful as a photothermal agent for laser-controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water-soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications.

Clean Photothermal Heating and Controlled Release From Near Infrared Dye Doped Nanoparticles Without Oxygen Photosensitization

PubMed Central

Guha, Samit; Shaw, Scott K.; Spence, Graeme T.; Roland, Felicia M.; Smith, Bradley D.

2015-01-01

The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer-hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of 1O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive 1O2 leading to bleaching of the dye and also decomposition of co-encapsulated payload such as the drug Doxorubicin. Croc dye was especially useful as a photothermal agent for laser controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications. PMID:26149326

Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release.

PubMed

Farhadnejad, Hassan; Mortazavi, Seyed Alireza; Erfan, Mohammad; Darbasizadeh, Behzad; Motasadizadeh, Hamidreza; Fatahi, Yousef

2018-05-01

The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN-as a model drug-was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis, structural, conformational and pharmacological study of some amides derived from 3 -methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine

NASA Astrophysics Data System (ADS)

Iriepa, I.; Bellanato, J.; Gálvez, E.; Gil-Alberdi, B.

2010-07-01

Some mono-substituted amides ( 2- 5) derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine were synthesized and studied by IR, 1H and 13C NMR spectroscopy. The crystal structure of 3-methyl-2,4-diphenyl-9α-(3,5-dichlorobenzamido)-3-azabicyclo[3.3.1]nonane ( 3) was determined by X-ray diffraction. NMR data showed that all compounds adopt in CDCl 3 a preferred flattened chair-chair conformation with the N-CH 3 group in equatorial disposition. X-ray data agreed with this conformation in the case of compound 3. IR data revealed that compounds 2 and 3 present a C dbnd O⋯HN intermolecular bond in the solid state. This conclusion was also confirmed by X-ray data of compound 3. In the case of compound 5, IR results suggested intermolecular NH⋯N-heterocyclic bonding. On the contrary, in the pyrazine derivative ( 4), IR, 1H and 13C NMR data showed the presence of an intramolecular NH⋯N1″-heterocyclic hydrogen bond in the solid state and solution. Moreover, NMR and IR data showed a preferred trans disposition for the NH-C dbnd O group. NMR also revealed free rotation of the -NH-CO-R group around C9-NH bond. Pharmacological assays on mice were drawn to evaluate analgesic activity.

CPTAC Develops Fit-for-Purpose Multiplex Immuno-MRM Assay for Profiling the DNA Damage Response Pathway | Office of Cancer Clinical Proteomics Research

Cancer.gov

Ionizing radiation (IR) is a commonly employed cancer treatment that kills cancer cells by damaging their DNA. While the DNA damage response (DDR) pathway may be key to determining tumor responses, radiochemical damage due to IR can target the patients’ healthy dividing cells, leading to the formation of secondary hematologic and solid tumors after DNA-damaging therapy.

Formation and infrared absorption of protonated naphthalenes (1-C10H9+ and 2-C10H9+) and their neutral counterparts in solid para-hydrogen.

PubMed

Bahou, Mohammed; Wu, Yu-Jong; Lee, Yuan-Pern

2013-02-14

Protonated naphthalene (C(10)H(9)(+)) and its neutral counterparts (hydronaphthyl radicals, C(10)H(9)) are important intermediates in the reactions of aromatic compounds and in understanding the unidentified infrared (IR) emissions from interstellar media. We report the IR spectra of 1-C(10)H(9)(+), 2-C(10)H(9)(+), 1-C(10)H(9), and 2-C(10)H(9) trapped in solid para-hydrogen (p-H(2)); the latter three are new. These species were produced upon electron bombardment of a mixture of naphthalene (C(10)H(8)) and p-H(2) during matrix deposition. The intensities of IR features of 1-C(10)H(9)(+) decreased after the matrix was maintained in darkness for 19 h, whereas those of 1-C(10)H(9) and 2-C(10)H(9) increased. Irradiation of this matrix sample with light at 365 nm diminished lines of 1-C(10)H(9)(+) and 2-C(10)H(9) and enhanced lines of 1-C(10)H(9) and 2-C(10)H(9)(+); the latter species was unstable and converted to 1-C(10)H(9)(+) in less than 30 min and 2-C(10)H(9) was converted to 1-C(10)H(9) at 365 nm. Observed wavenumbers and relative intensities of these species agree satisfactorily with the anharmonic vibrational wavenumbers and IR intensities predicted with the B3PW91/6-311++G(2d,2p) method. Compared with spectra recorded previously with IR photodissociation of Ar-tagged C(10)H(9)(+) or IR multiphoton dissociation of C(10)H(9)(+), our method has the advantages of producing high-resolution IR spectra with a wide spectral coverage, true IR intensity and excellent ratio of signal to noise; both protonated species and their neutral counterparts are produced with little interference from other fragments. With these advantages, the IR spectra of 1-C(10)H(9)(+), 2-C(10)H(9)(+), 1-C(10)H(9), and 2-C(10)H(9) are here clearly characterized.

Protective effect of mitochondrial-targeted antioxidant MitoQ against iron ion 56Fe radiation induced brain injury in mice.

PubMed

Gan, Lu; Wang, Zhenhua; Si, Jing; Zhou, Rong; Sun, Chao; Liu, Yang; Ye, Yancheng; Zhang, Yanshan; Liu, Zhiyuan; Zhang, Hong

2018-02-15

Exposure to iron ion 56 Fe radiation (IR) during space missions poses a significant risk to the central nervous system and radiation exposure is intimately linked to the production of reactive oxygen species (ROS). MitoQ is a mitochondria-targeted antioxidant that has been shown to decrease oxidative damage and lower mitochondrial ROS in a number of animal models. Therefore, the present study aimed to investigate role of the mitochondrial targeted antioxidant MitoQ against 56 Fe particle irradiation-induced oxidative damage and mitochondria dysfunction in the mouse brains. Increased ROS levels were observed in mouse brains after IR compared with the control group. Enhanced ROS production leads to disruption of cellular antioxidant defense systems, mitochondrial respiration dysfunction, altered mitochondria dynamics and increased release of cytochrome c (cyto c) from mitochondria into cytosol resulting in apoptotic cell death. MitoQ reduced IR-induced oxidative stress (decreased ROS production and increased SOD, CAT activities) with decreased lipid peroxidation as well as reduced protein and DNA oxidation. MitoQ also protected mitochondrial respiration after IR. In addition, MitoQ increased the expression of mitofusin2 (Mfn2) and optic atrophy gene1 (OPA1), and decreased the expression of dynamic-like protein (Drp1). MitoQ also suppressed mitochondrial DNA damage, cyto c release, and caspase-3 activity in IR-treated mice compared to the control group. These results demonstrate that MitoQ may protect against IR-induced brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

PubMed Central

Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

2015-01-01

A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

PubMed Central

Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

2016-01-01

Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

Irma 5.2 multi-sensor signature prediction model

NASA Astrophysics Data System (ADS)

Savage, James; Coker, Charles; Thai, Bea; Aboutalib, Omar; Chow, Anthony; Yamaoka, Neil; Kim, Charles

2007-04-01

The Irma synthetic signature prediction code is being developed by the Munitions Directorate of the Air Force Research Laboratory (AFRL/MN) to facilitate the research and development of multi-sensor systems. There are over 130 users within the Department of Defense, NASA, Department of Transportation, academia, and industry. Irma began as a high-resolution, physics-based Infrared (IR) target and background signature model for tactical weapon applications and has grown to include: a laser (or active) channel (1990), improved scene generator to support correlated frame-to-frame imagery (1992), and passive IR/millimeter wave (MMW) channel for a co-registered active/passive IR/MMW model (1994). Irma version 5.0 was released in 2000 and encompassed several upgrades to both the physical models and software; host support was expanded to Windows, Linux, Solaris, and SGI Irix platforms. In 2005, version 5.1 was released after an extensive verification and validation of an upgraded and reengineered active channel. Since 2005, the reengineering effort has focused on the Irma passive channel. Field measurements for the validation effort include the unpolarized data collection. Irma 5.2 is scheduled for release in the summer of 2007. This paper will report the validation test results of the Irma passive models and discuss the new features in Irma 5.2.

FT-IR and FT-Raman spectra of 5-chlorocytosine: Solid state simulation and tautomerism. Effect of the chlorine substitution in the Watson-Crick base pair 5-chlorodeoxycytidine-deoxyguanosine

NASA Astrophysics Data System (ADS)

Alcolea Palafox, M.; Rastogi, V. K.; Singh, S. P.

2018-01-01

The laser Raman and IR spectra of 5-chlorocytosine have been recorded and accurately assigned in the solid state using Density functional calculations (DFT) together with the linear scaling equation procedure (LSE) and the solid state simulation of the crystal unit cell through a tetramer form. These results remarkably improve those reported previously by other authors. Several new scaling equations were proposed to be used in related molecules. The six main tautomers of the biomolecule 5-chlorocytosine were determined and optimized at the MP2 and CCSD levels, using different basis sets. The relative stabilities were compared with those obtained in cytosine and their 5-halo derivatives. Several relationships between energies, geometric parameters and NBO atomic charges were established. The effect of the chlorine substitution in the fifth position was evaluated through the stability of the Watson-Crick (WC) base pair of 5-chlorodeoxycytidine with deoxyguanosine, and through their vibrational spectra.

All-Solid-State UV Transmitter Development for Ozone Sensing Applications

NASA Technical Reports Server (NTRS)

Prasad, Narasimha S.; Singh, Upendra N.; Armstrong, Darrell Jr.

2009-01-01

In this paper, recent progress made in the development of an all-solid-state UV transmitter suitable for ozone sensing applications from space based platforms is discussed. A nonlinear optics based UV setup based on Rotated Image Singly Resonant Twisted Rectangle (RISTRA) optical parametric oscillator (OPO) module was effectively coupled to a diode pumped, single longitudinal mode, conductively cooled, short-pulsed, high-energy Nd:YAG laser operating at 1064 nm with 50 Hz PRF. An estimated 10 mJ/pulse with 10% conversion efficiency at 320 nm has been demonstrated limited only by the pump pulse spatial profile. The current arrangement has the potential for obtaining greater than 200 mJ/pulse. Previously, using a flash-lamp pumped Nd:YAG laser with round, top-hat profile, up to 24% IR-UV conversion efficiency was achieved with the same UV module. Efforts are underway to increase the IR-UV conversion efficiency of the all solid-state setup by modifying the pump laser spatial profile along with incorporating improved OPO crystals.

Enhancing nonlinear energy deposition into transparent solids with an elliptically polarized and mid-IR heating laser pulse under two-color femtosecond impact

NASA Astrophysics Data System (ADS)

Potemkin, F. V.; Mareev, E. I.; Bezsudnova, Yu I.; Platonenko, V. T.; Bravy, B. G.; Gordienko, V. M.

2017-06-01

We report on an enhancement of deposited energy density of up to 10 kJ cm-3 inside transparent solids (fused silica and quartz) from using two-color µJ energy level tightly focused (NA  =  0.5) co-propagating linearly polarized seeding (visible, 0.62 µm) and elliptically polarized heating (near-IR, 1.24 µm) femtosecond laser pulses. The rise in temperature under constant volume causes pressure of up to 12 GPa. It has been shown experimentally and theoretically that the production of seeding electrons through multiphoton ionization by visible laser pulse paves the way for controllability of the energy deposition and laser-induced micromodification via carrier heating by delayed infrared laser pulses inside the material. The developed theoretical approach predicts that the deposited energy density will be enhanced by up to 14 kJ cm-3 when using longer (up to 5 µm) wavelengths for heating laser pulses inside transparent solids.

Perspectives on Strategies Using Swellable Polymers in Solid Dispersions for Controlled Drug Release.

PubMed

Tran, Thao T D; Tran, Phuong H L

2017-01-01

Poorly water-soluble drugs, which commonly face the issue of poor absorption and low bioavailability, have been under ongoing research of many formulation scientists for the past few decades. Solid dispersion is one of the most effective strategies in concerns for improving bioavailability of poorly water-soluble drugs. Either application of solid dispersions in dissolution enhancement of poorly water-soluble drugs or the use of swellable polymers in controlled drug release has been reported in pharmaceutical designs widely. However, a review of strategies of using swellable polymers in solid dispersion to take a full advantage of these polymers as a current perspective in facilitating drug bioavailability enhancement is still missing. In this review, we aim to provide a summary of techniques used to formulate a swellable polymer in solid dispersion especially a description of a suitable fabrication method in design of a controlled release solid dispersion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Utilization of spray drying technique for improvement of dissolution and anti-inflammatory effect of Meloxicam.

PubMed

Shazly, Gamal; Badran, Mohamed; Zoheir, Khairy; Alomrani, Abdullah

2015-01-01

Meloxicam (MLX) is a poorly water-soluble non steroidal anti-inflammatory drug (NSAID). The main objective of the present work was to enhance the dissolution of MLX and thus its bioavailability by the aid of additives. The novelty of this work rises from the utilization of spray drying technology to produce micro particulates solid dispersion systems containing MLX in the presence of small amount of additives. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and Scan Electron Microscope (SEM) were used for studying the physico-chemical and morphological properties of MLX samples. The dissolution of MLX samples was investigated in two different pH media. The morphology of MLX solid dispersion micro-particles was spherical in shape according to SEM. FT-IR profiles indicated that a complex was formed between MLX and the additives. DSC patterns of the MLX micro-particles suggested a reduction in the crystallinity of MLX and probability of presence of an interaction between MLX and the additives. The rate of dissolution of the spray-dried MLX enhanced as compared with the unprocessed MLX in both acidic and neutral media. It was found that 100% of the added MLX released within 5 min in phosphate buffer dissolution medium (pH 7.4) compared to that of the unprocessed MLX (15% in 60 min). Such increase rate in the dissolution of the spray dried MLX could be attributed to the increase in wettability of MLX particles and the hydrophilic nature of the additives. The anti-inflammatory effect of the spray dried MLX was explored using formalin induced rat paw edema model. The spray-dried samples showed an increase in the anti-inflammatory activity of MLX as compared to the unprocessed MLX. This work reveals that the spray drying technique is suitable for preparation of micro-particles with improved dissolution and anti-inflammatory effect of MLX.

Infrared Spectroscopy as a Chemical Fingerprinting Tool

NASA Technical Reports Server (NTRS)

Huff, Timothy L.

2003-01-01

Infrared (IR) spectroscopy is a powerful analytical tool in the chemical fingerprinting of materials. Any sample material that will interact with infrared light produces a spectrum and, although normally associated with organic materials, inorganic compounds may also be infrared active. The technique is rapid, reproducible and usually non-invasive to the sample. That it is non-invasive allows for additional characterization of the original material using other analytical techniques including thermal analysis and RAMAN spectroscopic techniques. With the appropriate accessories, the technique can be used to examine samples in liquid, solid or gas phase. Both aqueous and non-aqueous free-flowing solutions can be analyzed, as can viscous liquids such as heavy oils and greases. Solid samples of varying sizes and shapes may also be examined and with the addition of microscopic IR (microspectroscopy) capabilities, minute materials such as single fibers and threads may be analyzed. With the addition of appropriate software, microspectroscopy can be used for automated discrete point or compositional surface area mapping, with the latter providing a means to record changes in the chemical composition of a material surface over a defined area. Due to the ability to characterize gaseous samples, IR spectroscopy can also be coupled with thermal processes such as thermogravimetric (TG) analyses to provide both thermal and chemical data in a single run. In this configuration, solids (or liquids) heated in a TG analyzer undergo decomposition, with the evolving gases directed into the IR spectrometer. Thus, information is provided on the thermal properties of a material and the order in which its chemical constituents are broken down during incremental heating. Specific examples of these varied applications will be cited, with data interpretation and method limitations further discussed.

Artificial neural networks in evaluation and optimization of modified release solid dosage forms.

PubMed

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-10-18

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

PubMed Central

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-01-01

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms. PMID:24300369

Hot and cold gas toward young stellar objects

NASA Technical Reports Server (NTRS)

Mitchell, George F.; Maillard, Jean-Pierre; Allen, Mark; Beer, Reinhard; Belcourt, Kenneth

1990-01-01

High-resolution M band spectra are presented for the seven embedded IR sources W3 IRS 5, S140 IRS1, NGC 7538 IRS 1, NGC 7538 IRS 9, GL 2136, LkH-alpha 101, and MWC 349A, and the data are combined with previously published work for W33A and GL 2591. Cold CO is seen toward all nine sources, with temperatures from 11 K to 66 K. Column densities of cold CO are presented. Hot gas is seen toward eight of the nine objects with temperatures from 120 K to 1010 K. New lower limits to the hot gas density are obtained. The hot gas toward GL 2591, GL 2136, W3 IRS 5, and S140 IRS 1 is probably very near the central source and heated via gas-grain collisions. The optical depth in the silicate feature is strongly correlated with the (C-13)O column density, confirming that silicate optical depth is a useful measure of gas column density. The ratio of solid-to-gaseous CO is obtained for seven sources.

Experimental and modeling studies showing the effect of lipid type and level on flavor release from milk-based liquid emulsions.

PubMed

Roberts, Deborah D; Pollien, Philippe; Watzke, Brigitte

2003-01-01

The purpose of this work was to study two key parameters of the lipid phase that influence flavor release-lipid level and lipid type-and to relate the results to a mass balance partition coefficient-based mathematical model. Release of 10 volatile compounds from milk-based emulsions at 10, 25, and 50 degrees C was monitored by 1-min headspace sampling with a solid-phase microextraction fiber, followed by GC-MS analysis. As compared to the observations for milk fat, changing to a lipophilic lipid (medium-chain triglycerides, MCT) and adding a monoglyceride-based surfactant did not influence the volatiles release. However, increasing the solid fat content was found to increase the release. At 25 degrees C, and even more so at 10 degrees C, concurrent with an increase in their solid fat content, hydrogenated palm fat emulsions showed increased flavor release over that observed for emulsions made with coconut oil, coconut oil with surfactant, milk fat, and MCT. However, at 50 degrees C, when hydrogenated palm fat emulsions had zero solid fat content, there was no difference in flavor release from that observed for milk fat emulsions. Varying milk fat at nine levels between 0 and 4.5% showed a systematic dependence of the release on the lipid level, dependent on compound lipophilicity. Close correlations were found between the experimental and model predictions with lipid level and percent liquid lipid as variables.

Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

PubMed Central

XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

2016-01-01

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

Risk of emergent bradycardia associated with initiation of immediate- or slow-release metoprolol.

PubMed

Shin, Jaekyu; Gonzales, Marco; Pletcher, Mark J

2013-12-01

To estimate and compare the risk of emergent bradycardia associated with starting immediate-release (IR) and slow-release (SR) formulations of metoprolol. Retrospective analysis of administrative claims data. State of California Medicaid program (Medi-Cal) claims database. A total of 31,574 adults beginning metoprolol between May 1, 2004, and November 1, 2009, without a pharmacy claim for a β blocker within the previous 6 months of metoprolol initiation; patients with a primary or secondary diagnosis of symptomatic bradycardia, pacemaker, or implantable cardioverter-defibrillator placement before metoprolol initiation were excluded. The study outcome was the time to first occurrence of emergent bradycardia, measured at an emergency department visit or hospitalization due to diagnosis of symptomatic bradycardia, after metoprolol initiation. We calculated the incidence and compared the risk of emergent bradycardia by using a proportional hazards model that included the metoprolol formulation with adjustment for total daily metoprolol dose and the use of other drugs as time-varying covariates, as well as demographics and comorbidities. Among 31,574 patients starting metoprolol, 18,516 (58.6%) used the IR formulation. The incidence of emergent bradycardia was 19.1/1000 person-years overall but was nearly twice as common in patients using the IR versus the SR formulation (24.1/1000 person-yrs in the IR group versus 12.9/1000 person-yrs in the SR group, unadjusted hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.28-2.56). Adjustment for other drugs also associated with symptomatic bradycardia (cytochrome P450 2D6 inhibitors, class I or III antiarrhythmics, and atrioventricular node-blocking agents), metoprolol dose, and other participant characteristics somewhat attenuated the association (adjusted HR 1.48, 95% CI 1.03-2.13). The risk of emergent bradycardia associated with metoprolol initiation was higher with the IR formulation than the SR formulation, although the absolute risk was low. © 2013 Pharmacotherapy Publications, Inc.

Risk of Emergent Bradycardia Associated with Initiation of Immediate- or Slow-Release Metoprolol

PubMed Central

Shin, Jaekyu; Gonzales, Marco; Pletcher, Mark J

2013-01-01

Objectives To estimate and compare the risk of emergent bradycardia associated with initiation of immediate-release (IR) and slow-release (SR) formulations of metoprolol. Design Retrospective analysis of administrative claims data. Data Source State of California Medicaid program (Medi-Cal) claims database. Patients A total of 31,574 adults initiating metoprolol between May 1, 2004, and November 1, 2009, without a pharmacy claim for a beta blocker within the previous 6 months of metoprolol initiation; patients with a primary or secondary diagnosis of symptomatic bradycardia, pacemaker, or implantable cardioverter-defibrillator placement before metoprolol initiation were excluded. Measurements and Main Results The study outcome was the time to first occurrence of emergent bradycardia, measured at an emergency department visit or hospitalization due to diagnosis of symptomatic bradycardia, after metoprolol initiation. We calculated the incidence and compared the risk of emergent bradycardia by using a proportional hazards model that included the metoprolol formulation with adjustment for total daily metoprolol dose and the use of other medications as time-varying covariates, as well as demographics and comorbidities. Among 31,574 patients initiating metoprolol, 18,516 (58.6%) initiated the IR formulation. The incidence of emergent bradycardia was 19.1 per 1000 person-years overall but was nearly twice as common in patients using the IR versus the SR formulation (24.1 per 1000 person-years in the IR group vs. 12.9 per 1000 person-years in the SR group; unadjusted hazard ratio [HR] 1.81; 95% CI 1.28-2.56). Adjustment for other medications also associated with symptomatic bradycardia (cytochrome P450 2D6 inhibitors, class I or III antiarrhythmics, and atrioventricular node–blocking agents), metoprolol dose, and other participant characteristics somewhat attenuated the association (adjusted HR 1.48, 95% CI 1.03-2.13). Conclusion The risk of emergent bradycardia associated with metoprolol initiation was higher with the IR formulation than the SR formulation, although the absolute risk was low. PMID:23813768

A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

PubMed Central

Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

2016-01-01

Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury.

PubMed

Xiao, Bing; Chai, Yi; Lv, Shigang; Ye, Minhua; Wu, Miaojing; Xie, Liyuan; Fan, Yanghua; Zhu, Xingen; Gao, Ziyun

2017-10-01

Cerebral ischemia is a leading cause of death and disability. A previous study indicated that remote ischemic postconditioning (RIP) in the treatment of cerebral ischemia reduces ischemia/reperfusion (I/R) injury. However, the underlying mechanism is not well understood. In the present study, the authors hypothesized that the protective effect of RIP on neurological damage is mediated by exosomes that are released by endothelial cells in femoral arteries. To test this, right middle cerebral artery occlusion/reperfusion with RIP was performed in rats. In addition, an I/R injury cell model was tested that included human umbilical vein endothelial cells (HUVECs) and SH-SY5Y cells. Both the in vivo and in vitro models were examined for injury. Markers of exosomes (CD63, HSP70 and TSG101) were assessed by immunohistochemistry, western blot analysis and flow cytometry. Exosomes were extracted from both animal serum and HUVEC culture medium and identified by electron microscopy. They investigated the role of endothelial cell-derived exosomes in the proliferation, apoptosis, cell cycle, migration and invasion of I/R-injured SH-SY5Y cells. In addition, apoptosis-related molecules caspase-3, Bax and Bcl-2 were detected. RIP was determined to increase the number of exosomes and the expression levels of CD63, HSP70 and TSG101 in plasma, but not in brain hippocampal tissue. The size of exosomes released after I/R in HUVECs was similar to the size of exosomes released in rats subjected to RIP. Endothelial cell-derived exosomes partly suppressed the I/R-induced cell cycle arrest and apoptosis, and inhibited cell proliferation, migration and invasion in SH-SY5Y nerve cells. Endothelial cell-derived exosomes directly protect nerve cells against I/R injury, and are responsible for the protective role of RIP in I/R.

Mild and Low-Pressure fac-Ir(ppy)3 -Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis.

PubMed

Chow, Shiao Y; Stevens, Marc Y; Åkerbladh, Linda; Bergman, Sara; Odell, Luke R

2016-06-27

A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3 -catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3 , amines, reductants, and CO gas (released ex situ from Mo(CO)6 ), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective IR multiphoton dissociation of molecules in a pulsed gas-dynamically cooled molecular flow interacting with a solid surface as an alternative to low-energy methods of molecular laser isotope separation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makarov, G N; Petin, A N

2016-03-31

We report the results of studies on the isotope-selective infrared multiphoton dissociation (IR MFD) of SF{sub 6} and CF{sub 3}I molecules in a pulsed, gas-dynamically cooled molecular flow interacting with a solid surface. The productivity of this method in the conditions of a specific experiment (by the example of SF{sub 6} molecules) is evaluated. A number of low-energy methods of molecular laser isotope separation based on the use of infrared lasers for selective excitation of molecules are analysed and their productivity is estimated. The methods are compared with those of selective dissociation of molecules in the flow interacting with amore » surface. The advantages of this method compared to the low-energy methods of molecular laser isotope separation and the IR MPD method in the unperturbed jets and flows are shown. It is concluded that this method could be a promising alternative to the low-energy methods of molecular laser isotope separation. (laser separation of isotopes)« less

Preparation and reactivity of the heterobimetallic ReIr face-shared bioctahedral compounds Cp*Ir(mu-Cl)(3)Re(CO)(3) and Cp*Ir(mu-SC6H4Me-4)(3)Re(CO)(3): X-ray diffraction structures and redox behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiaoping; Hammons, Casey; Richmond, Michael G.

2009-01-01

Thermolysis of the dinuclear compound [Cp*IrCl2](2) (1) with ClRe(CO)(5) (2) leads to the formation of the confacial bioctahedral compound Cp*Ir(mu-Cl)(3)Re(CO)(3) (3) in high yield. Whereas the substitution of the chloride ligands in 3 is observed on treatment with excess p-methylbenzenethiol to furnish the sulfido-bridged compound Cp*Ir(mu-SC6H4Me-4)(3)Re(CO)(3) (4), 3 undergoes fragmentation upon reaction with tertiary phosphines [PPh3 and P(OMe)(3)] to furnish the mononuclear compounds CP*IrCl2P and fac-ClRe-(CO3)P-2. Both 3 and 4 have been isolated and fully characterized in solution by IR and H-1 NMR spectroscopies, and their solid-state structures have been established by X-ray crystallography. The redox properties of 3 andmore » 4 have been explored by cyclic voltammetry, and the results are discussed relative to extended Huckel MO calculations.« less

High-Temperature Oxidation Behavior of Iridium-Rhenium Alloys

NASA Technical Reports Server (NTRS)

Reed, Brian D.

1995-01-01

The life-limiting mechanism for radiation-cooled rockets made from iridium-coated rhenium (Ir/Re) is the diffusion of Re into the Ir layer and the subsequent oxidation of the resulting Ir-Re alloy from the inner surface. In a previous study, a life model for Ir/Re rockets was developed. It incorporated Ir-Re diffusion and oxidation data to predict chamber lifetimes as a function of temperature and oxygen partial pressure. Oxidation testing at 1540 deg C suggested that a 20-wt percent Re concentration at the inner wall surface should be established as the failure criterion. The present study was performed to better define Ir-oxidation behavior as a function of Re concentration and to supplement the data base for the life model. Samples ranging from pure Ir to Ir-40 wt percent Re (Ir-40Re) were tested at 1500 deg C, in two different oxygen environments. There were indications that the oxidation rate of the Ir-Re alloy increased significantly when it went from a single-phase solid solution to a two-phase mixture, as was suggested in previous work. However, because of testing anomalies in this study, there were not enough dependable oxidation data to definitively raise the Ir/Re rocket failure criterion from 20-wt percent Re to a Re concentration corresponding to entry into the two-phase region.

High-Performance Thermoelectric Semiconductors

NASA Technical Reports Server (NTRS)

Fleurial, Jean-Pierre; Caillat, Thierry; Borshchevsky, Alexander

1994-01-01

Figures of merit almost double current state-of-art thermoelectric materials. IrSb3 is semiconductor found to exhibit exceptional thermoelectric properties. CoSb3 and RhSb3 have same skutterudite crystallographic structure as IrSb3, and exhibit exceptional transport properties expected to contribute to high thermoelectric performance. These three compounds form solid solutions. Combination of properties offers potential for development of new high-performance thermoelectric materials for more efficient thermoelectric power generators, coolers, and detectors.

The infrared luminosity function of AKARI 90 μm galaxies in the local Universe

NASA Astrophysics Data System (ADS)

Kilerci Eser, Ece; Goto, Tomotsugu

2018-03-01

Local infrared (IR) luminosity functions (LFs) are necessary benchmarks for high-redshift IR galaxy evolution studies. Any accurate IR LF evolution studies require accordingly accurate local IR LFs. We present IR galaxy LFs at redshifts of z ≤ 0.3 from AKARI space telescope, which performed an all-sky survey in six IR bands (9, 18, 65, 90, 140, and 160 μm) with 10 times better sensitivity than its precursor Infrared Astronomical Satellite. Availability of 160 μm filter is critically important in accurately measuring total IR luminosity of galaxies, covering across the peak of the dust emission. By combining data from Wide-field Infrared Survey Explorer (WISE), Sloan Digital Sky Survey (SDSS) Data Release 13 (DR 13), six-degree Field Galaxy Survey and the 2MASS Redshift Survey, we created a sample of 15 638 local IR galaxies with spectroscopic redshifts, factor of 7 larger compared to previously studied AKARI-SDSS sample. After carefully correcting for volume effects in both IR and optical, the obtained IR LFs agree well with previous studies, but comes with much smaller errors. Measured local IR luminosity density is ΩIR = 1.19 ± 0.05 × 108L⊙ Mpc-3. The contributions from luminous IR galaxies and ultraluminous IR galaxies to ΩIR are very small, 9.3 per cent and 0.9 per cent, respectively. There exists no future all-sky survey in far-IR wavelengths in the foreseeable future. The IR LFs obtained in this work will therefore remain an important benchmark for high-redshift studies for decades.

A Novel Infrared Gas Monitor

NASA Astrophysics Data System (ADS)

Wang, Yingding; Zhong, Hongjie

2000-03-01

In the paper a novel non-dispersive infrared(IR) gas monitor is described.It is based on the principle that certain gases absorb IR radiation at specific(and often unique) wavelengths.Conventional devices typically include several primary components:a broadband source, usually an incandescent filament,a rotating chopper shutter,a narrow-band filter,a sample tube and a detector. We have developed a number of IR light emitting diodes(LED) having narrow optical bandwidths and which can be intensity modulated by electrical means,for example InAsSbP(4.2 micron)LED.The IR LED can thus replace the thermal source,narrow-band filter and chopper assembly of the conventional IR gas monitor,yielding a solid state,low- powered,compact and almost maintenance-free instrument with high sensitivity and stability and which free of the effects of mechanical vibration too. The detector used in the IR gas monitor is the solid-state detector,such as PbS,PbSe, InSb,HgCdTe,TGS,LT and PZT detector etc. The different configuration of the IR gas monitor is designed.For example,two-path version for measuring methane concentration by monitoring the 3.31 micron absorption band,it can eliminate the interference effects,such as to compensate for LED intensity changes caused by power and temperature variations,and for signal fluctuations due to changes in detector bias. we also have designed portable single-beam version without the sample tube.Its most primary advantage is very cheap(about cost USD 30 ).It measures carbon dioxide concentration by monitoring the 4.25 micron absorption band.Thought its precisions is low,it is used to control carbon dioxide concentration in the air in the green houses and plastic houses(there are about twenty millon one in the China).Because more carbon dioxide will increase the quanity of vegetable and flower production to a greatextent. It also is used in medical,sanitary and antiepidemic applications,such as hospital, store,hotel,cabin and ballroom etc. Key words:infrared gas monitor LED

Kinetics of lisinopril intramolecular cyclization in solid phase monitored by Fourier transform infrared microscopy.

PubMed

Widjaja, Effendi; Tan, Wei Jian

2008-08-01

The solid-state intramolecular cyclization of lisinopril to diketopiperazine was investigated by in situ Fourier transform infrared (FT-IR) microscopy. Using a controllable heating cell, the isothermal transformation was monitored in situ at 147.5, 150, 152.5, 155, and 157.5 degrees C. The collected time-dependent FT-IR spectra at each isothermal temperature were preprocessed and analyzed using a multivariate chemometric approach. The pure component spectra of the observable component (lisinopril and diketopiperazine) were resolved and their time-dependent relative contributions were also determined. Model-free and various model fitting methods were implemented in the kinetic analysis to estimate the activation energy of the intramolecular cyclization reaction. Arrhenius plots indicate that the activation energy is circa 327 kJ/mol.

“Beyond saving lives”: Current perspectives of interventional radiology in trauma

PubMed Central

Singh, Anuradha; Kumar, Atin; Kumar, Pawan; Kumar, Subodh; Gamanagatti, Shivanand

2017-01-01

Interventional radiology (IR) has become an integral part in the management of traumatic injuries. There is an ever-increasing role of IR in traumatic injuries of solid abdominal organs, pelvic and peripheral arteries to control active bleeding by therapeutic embolization or vascular reconstruction using stent grafts. Traditionally, these endovascular treatments have been offered to hemodynamically stable patients. However, in recent times endovascular approach has become preferable to surgery even in hemodynamically unstable patients with injury of surgically difficult-to-access sites. With shifting trends towards non operative management coupled with availability of the current state-of-the-art equipments, hardware and technical expertise, IR has gained an impeccable role in trauma management. However, due to lack of awareness and widespread acceptance, IR continues to remain an ocean of unexplored potentialities. PMID:28529680

Dual-responsive carbon dot for pH/redox triggered fluorescence imaging with controllable photothermal ablation therapy of cancer.

PubMed

Choi, Cheong A; Lee, Jung Eun; Mazrad, Zihnil Adha Islamy; Kim, Young Kwang; In, Insik; Jeong, Ji Hoon; Park, Sung Young

2018-05-18

We described fluorescence resonance energy transfer for pH/redox-activatable fluorescent carbon dot (FNP) to realize "off-on" switched imaging-guided controllable photothermal therapy (PTT). The FNP is a carbonized self-crosslinked polymer that allows IR825 loading (FNP[IR825]) via hydrophobic interactions in cancer therapy. The capability for fluorescence bioimaging was achieved via the internalization of FNP(IR825) into tumor cells, wherein glutathione (GSH) disulfide bonds were reduced and benzoic imine were cleaved under acidic conditions. The release of IR825 from FNP core in this system can may be used to efficiently control PTT-mediated cancer therapy via its photothermal conversion after near-infrared (NIR) irradiation. The in vitro and in vivo cellular uptake studies revealed the efficient uptake of FNP(IR825) by tumor cells to treat the disease site. Therefore, we demonstrated in mice that our smart nanocarrier could effectively kill tumor cells under exposure to a NIR laser and the particles were biocompatible with various organs. This platform responds sensitively to the exogenous environment inside the cancer cells and may selectively induce the release of PTT-mediated cytotoxicity. Furthermore, this platform may be useful for monitoring the elimination of cancer cells through the fluorescence on/off switch, which can be used for various applications in the field of cancer cell therapy and diagnosis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Particulate Arsenic Release in a Drinking Water Distribution System

EPA Science Inventory

Trace contaminants, such as arsenic, have been shown to accumulate in solids found in drinking water distribution systems. The obvious concern is that the contaminants in these solids could be released back into the water resulting in elevated levels in a consumer’s tap water. Th...

Exploring the Thermal Limits of IR-Based Automatic Whale Detection (ETAW)

DTIC Science & Technology

2015-09-30

1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Exploring the thermal limits of IR-based automatic whale ...marine mammals are entering a predefined exclusion zone. Marine mammal observers usually scan the ship’s environs for whales using binoculars or the...Hence, in combination with the whales ’ prolonged dives, sighting opportunities are rare, which, in addition to the limited field of view and finite

Notice of Changes to the Weekly Natural Gas Storage Report

EIA Publications

2015-01-01

On November 19, 2015, EIA will release the Weekly Natural Gas Storage Report (WNGSR) with new data breakouts for five regions of the Lower 48 states, converting from the current three-region structure. On Monday, November 16, 2015, EIA will re-release the data that will be published on Friday, November 13 (for the week ending Friday, November 6) in the new five-region format. The release will be conducted through the same timed countdown procedures used for normal releases on the same WNGSR web page: http://ir.eia.gov/ngs/ngs.html.

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Encapsulation and release of the hypnotic agent zolpidem from biodegradable polymer microparticles containing hydroxypropyl-beta-cyclodextrin.

PubMed

Trapani, Giuseppe; Lopedota, Angela; Boghetich, Giancarlo; Latrofa, Andrea; Franco, Massimo; Sanna, Enrico; Liso, Gaetano

2003-12-11

The goal of this study was to design a prolonged release system of the hypnotic agent zolpidem (ZP) useful for the treatment of insomnia. In this work, ZP alone or in the presence of HP-beta-CD was encapsulated in microparticles constituted by poly(DL-lactide) (PDLLA) and poly(DL-lactide-co-glycolide) (PLGA) and the drug release from these systems was evaluated. ZP alone-loaded microparticles were prepared by the classical O/W emulsion-solvent evaporation method. Conversely, ZP/HP-beta-CD containing microparticles were prepared by the W/O/W emulsion-solvent evaporation method following two different procedures (i.e. A and B). Following procedure A, the previously produced ZP/HP-beta-CD solid complex was added to the water phase of primary emulsion. In the procedure B, HP-beta-CD was added to the aqueous phase and ZP to the organic phase. The resulting microparticles were characterized about morphology, size, encapsulation efficiency and release rates. FT-IR, X-ray, and DSC results suggest the drug is in an essentially amorphous state within the microparticles. The release profiles of ZP from microparticles were in general biphasic, being characterized by an initial burst effect and a subsequent slow ZP release. It resulted that co-encapsulating ZP with or without HP-beta-CD in PDLLA and PLGA the drug release from the corresponding microparticles was protracted. Moreover, in a preliminary pharmacological screening, the ataxic activity in rats was investigated and it was found that intragastric administration of the ZP/HP-beta-CD/PLGA microparticles prepared according to procedure B produced the same ataxic induction time as the one induced by the currently used formulation Stilnox. Interestingly moreover, there was a longer ataxic lasting and a lower intensity of ataxia produced by the ZP/HP-beta-CD/PLGA-B-formulation already after 60 min following the administration. However, a need for further pharmacokinetic and pharmacodynamic studies resulted to fully evaluate the utility of this last formulation for the sustained delivery of ZP.

Efficacy and Safety of Immediate-Release Methylphenidate Treatment for Preschoolers with ADHD

ERIC Educational Resources Information Center

Greenhill, Laurence; Kollins, Scott; Abikoff, Howard; McCracken, James; Riddle, Mark; Swanson, James; McGough, James; Wigal, Sharon; Wigal, Tim; Vitiello, Benedetto; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Cunningham, Charles; Davies, Mark; Chuang, Shirley; Cooper, Tom

2006-01-01

Objective: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included…

Immediate-Release Methylphenidate for ADHD in Children with Comorbid Chronic Multiple Tic Disorder

ERIC Educational Resources Information Center

Gadow, Kenneth D.; Sverd, Jeffrey; Nolan, Edith E.; Sprafkin, Joyce; Schneider, Jayne

2007-01-01

Objective: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). Method: Two cohorts of prepubertal children (N = 71) received placebo and three doses of…

Simultaneous probing of bulk liquid phase and catalytic gas-liquid-solid interface under working conditions using attenuated total reflection infrared spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meemken, Fabian; Müller, Philipp; Hungerbühler, Konrad

Design and performance of a reactor set-up for attenuated total reflection infrared (ATR-IR) spectroscopy suitable for simultaneous reaction monitoring of bulk liquid and catalytic solid-liquid-gas interfaces under working conditions are presented. As advancement of in situ spectroscopy an operando methodology for gas-liquid-solid reaction monitoring was developed that simultaneously combines catalytic activity and molecular level detection at the catalytically active site of the same sample. Semi-batch reactor conditions are achieved with the analytical set-up by implementing the ATR-IR flow-through cell in a recycle reactor system and integrating a specifically designed gas feeding system coupled with a bubble trap. By the usemore » of only one spectrometer the design of the new ATR-IR reactor cell allows for simultaneous detection of the bulk liquid and the catalytic interface during the working reaction. Holding two internal reflection elements (IRE) the sample compartments of the horizontally movable cell are consecutively flushed with reaction solution and pneumatically actuated, rapid switching of the cell (<1 s) enables to quasi simultaneously follow the heterogeneously catalysed reaction at the catalytic interface on a catalyst-coated IRE and in the bulk liquid on a blank IRE. For a complex heterogeneous reaction, the asymmetric hydrogenation of 2,2,2-trifluoroacetophenone on chirally modified Pt catalyst the elucidation of catalytic activity/enantioselectivity coupled with simultaneous monitoring of the catalytic solid-liquid-gas interface is shown. Both catalytic activity and enantioselectivity are strongly dependent on the experimental conditions. The opportunity to gain improved understanding by coupling measurements of catalytic performance and spectroscopic detection is presented. In addition, the applicability of modulation excitation spectroscopy and phase-sensitive detection are demonstrated.« less

Comparison of the efficacy and safety profile of morning administration of controlled-release simvastatin versus evening administration of immediate-release simvastatin in chronic kidney disease patients with dyslipidemia.

PubMed

Yi, Yong Jin; Kim, Hyo Jin; Jo, Sang Kyung; Kim, Sung Gyun; Song, Young Rim; Chung, Wookyung; Han, Kum Hyun; Lee, Chang Hwa; Hwang, Young-Hwan; Oh, Kook-Hwan

2014-08-01

Evening administration of the conventional immediate-release (IR) formulation of simvastatin is recommended because of its short half-life (1.9 hours). In a healthy population, morning administration of a controlled-release (CR) formulation of simvastatin was shown to have equivalent lipid-lowering efficacy and a safety profile similar to that of evening doses of IR simvastatin. The present study aimed to verify noninferiority and to compare the safety of morning administration of CR simvastatin with that of evening administration of IR simvastatin in patients with chronic kidney disease (CKD) who have dyslipidemia. The present study was a prospective, multicenter, double-blind, Phase IV trial with an active comparator. We randomly assigned 122 patients with CKD and dyslipidemia to 1 of 2 drug administration groups: morning administration of CR simvastatin 20 mg (test group) and evening administration of IR simvastatin 20 mg (control group). After 8 weeks, the treatment outcomes and adverse effects of the 2 treatments were compared. The mean (SD) percentage of change in serum LDL-C at the end of treatment was -35.1% (15.7%) for the test group and -35.6% (14.6%) for the control group. The difference between the 2 groups was not significant (P = 0.858). The 95% CI of the difference in the percentage of change of LDL-C between the test and control groups was -6.0 to 5.0. There was no difference in the percentage of change of total cholesterol (-24.3% [12.5%] vs -26.5% [12.0%], P = 0.317), triglyceride (-10.6% [35.1%] vs -12.4% [33.2%], P = 0.575) and HDL-C (10.2% [20.7%] vs 4.5% [11.4%], P = 0.064). Treatment-related adverse events were similar in both groups (10 events in the test group vs 8 events in the control group, P = 0.691). The efficacy of morning administration of CR simvastatin was noninferior to evening administration of IR simvastatin in patients with CKD. Furthermore, the safety profile analysis showed no significant difference between the 2 treatments. Morning administration of CR simvastatin is expected to increase patient compliance and therefore better control of dyslipidemia in CKD patients. Copyright © 2014 The Authors. Published by EM Inc USA.. All rights reserved.

Single-Dose Pharmacokinetics of Methylphenidate Extended-Release Multiple Layer Beads Administered as Intact Capsule or Sprinkles Versus Methylphenidate Immediate-Release Tablets (Ritalin®) in Healthy Adult Volunteers

PubMed Central

Teuscher, Nathan S.; Kupper, Robert J.; Chang, Wei-Wei; Greenhill, Laurence; Newcorn, Jeffrey H.; Connor, Daniel F.; Wigal, Sharon

2014-01-01

Abstract Objectives: The purpose of this study was to evaluate the relative bioavailability and safety of a multilayer extended-release bead methylphenidate (MPH) hydrochloride 80 mg (MPH-MLR) capsule or sprinkles (37% immediate-release [IR]) versus MPH hydrochloride IR(Ritalin®) tablets, and to develop a pharmacokinetic (PK) model simulating MPH concentration-time data for different MPH-MLR dosage strengths. Methods: This was a single-center, randomized, open-label, three-period crossover study conducted in 26 fasted healthy adults (mean weight±standard deviation, 70.4±11.7 kg) assigned to single-dose oral MPH-MLR 80 mg capsule or sprinkles with applesauce, or Ritalin IR 25 mg (1×5 mg and 1×20 mg tablet) administered at 0, 4, and 8 hours. Results: MPH-MLR 80 mg capsule and sprinkles were bioequivalent; ratios for maximum concentration (Cmax), area under plasma drug concentration versus time curve (AUC)0-t, and AUC0-inf were 1.04 (95% confidence interval [CI], 96.3–112.4), 0.99 (95% CI, 95.3–102.8), and 0.99 (95% CI, 95.4–103.0), respectively. MPH-MLR capsule/sprinkles produced highly comparable, biphasic profiles of plasma MPH concentrations characterized by rapid initial peak, followed by moderate decline until 5 hours postdose, and gradual increase until 7 hours postdose, culminating in an attenuated second peak. Based on 90% CIs, total systemic exposure to MPH-MLR 80 mg capsule/sprinkles was similar to that for Ritalin IR 25 mg three times daily, but marked differences in Cmax values indicated that MPH-MLR regimens were not bioequivalent to Ritalin. MPH Cmax and total systemic exposure over the first 4 hours postdose with MPH-MLR capsule/sprinkles was markedly higher than that associated with the first dose of Ritalin. All study drugs were safe and well tolerated. The PK modeling in adults suggested that differences in MPH pharmacokinetics between MPH-MLR and Ritalin are the result of dosage form design attributes and the associated absorption profiles of MPH. Conclusions: MPH-MLR 80 mg provides a long-acting biphasic pattern of plasma MPH concentrations with one less peak and trough than Ritalin IR. PMID:25514542

Single-dose pharmacokinetics of methylphenidate extended-release multiple layer beads administered as intact capsule or sprinkles versus methylphenidate immediate-release tablets (Ritalin(®)) in healthy adult volunteers.

PubMed

Adjei, Akwete; Teuscher, Nathan S; Kupper, Robert J; Chang, Wei-Wei; Greenhill, Laurence; Newcorn, Jeffrey H; Connor, Daniel F; Wigal, Sharon

2014-12-01

The purpose of this study was to evaluate the relative bioavailability and safety of a multilayer extended-release bead methylphenidate (MPH) hydrochloride 80 mg (MPH-MLR) capsule or sprinkles (37% immediate-release [IR]) versus MPH hydrochloride IR(Ritalin(®)) tablets, and to develop a pharmacokinetic (PK) model simulating MPH concentration-time data for different MPH-MLR dosage strengths. This was a single-center, randomized, open-label, three-period crossover study conducted in 26 fasted healthy adults (mean weight±standard deviation, 70.4±11.7 kg) assigned to single-dose oral MPH-MLR 80 mg capsule or sprinkles with applesauce, or Ritalin IR 25 mg (1×5 mg and 1×20 mg tablet) administered at 0, 4, and 8 hours. MPH-MLR 80 mg capsule and sprinkles were bioequivalent; ratios for maximum concentration (Cmax), area under plasma drug concentration versus time curve (AUC)0-t, and AUC0-inf were 1.04 (95% confidence interval [CI], 96.3-112.4), 0.99 (95% CI, 95.3-102.8), and 0.99 (95% CI, 95.4-103.0), respectively. MPH-MLR capsule/sprinkles produced highly comparable, biphasic profiles of plasma MPH concentrations characterized by rapid initial peak, followed by moderate decline until 5 hours postdose, and gradual increase until 7 hours postdose, culminating in an attenuated second peak. Based on 90% CIs, total systemic exposure to MPH-MLR 80 mg capsule/sprinkles was similar to that for Ritalin IR 25 mg three times daily, but marked differences in Cmax values indicated that MPH-MLR regimens were not bioequivalent to Ritalin. MPH Cmax and total systemic exposure over the first 4 hours postdose with MPH-MLR capsule/sprinkles was markedly higher than that associated with the first dose of Ritalin. All study drugs were safe and well tolerated. The PK modeling in adults suggested that differences in MPH pharmacokinetics between MPH-MLR and Ritalin are the result of dosage form design attributes and the associated absorption profiles of MPH. MPH-MLR 80 mg provides a long-acting biphasic pattern of plasma MPH concentrations with one less peak and trough than Ritalin IR.

Preparation and characterization of solid dispersion freeze-dried efavirenz - polyvinylpyrrolidone K-30.

PubMed

Fitriani, Lili; Haqi, Alianshar; Zaini, Erizal

2016-01-01

The aim of this research is to prepare and characterize solid dispersion of efavirenz - polyvinylpyrrolidone (PVP) K-30 by freeze drying to increase its solubility. Solid dispersion of efavirenz - PVP K-30 was prepared by solvent evaporation method with ratio 2:1, 1:1, and 1:2 and dried using a freeze dryer. Characterizations were done by scanning electron microscopy (SEM), powder X-ray diffraction analysis, differential thermal analysis (DTA), and Fourier transform infrared (FT-IR) spectroscopy. Solubility test was carried out in CO2-free distilled water, and efavirenz assay was conducted using high-performance liquid chromatography with acetonitrile:acetic acid (80:20) as the mobile phases. Powder X-ray diffractogram showed a decrease in the peak intensity, which indicated the crystalline altered to amorphous phase. DTA thermal analysis showed a decrease in the melting point of the solid dispersion compared to intact efavirenz. SEM results indicated the changes in the morphology of the crystal into an amorphous form compared to pure components. FT-IR spectroscopy analysis showed a shift wavenumber of the spectrum efavirenz and PVP K-30. The solubility of solid dispersion at ratio 2:1, 1:1, and 1:2 was 6.777 μg/mL, 6.936 μg/mL, and 14,672 μg/mL, respectively, whereas the solubility of intact efavirenz was 0.250 μg/mL. In conclusion, the solubility of solid dispersion increased significantly (P < 0.05).

Identification, Expression, and Physiological Functions of Siberian Hamster Gonadotropin-Inhibitory Hormone

PubMed Central

Ubuka, Takayoshi; Inoue, Kazuhiko; Fukuda, Yujiro; Mizuno, Takanobu; Ukena, Kazuyoshi; Kriegsfeld, Lance J.

2012-01-01

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds and mammals. To further understand its physiological roles in mammalian reproduction, we identified its precursor cDNA and endogenous mature peptides in the Siberian hamster brain. The Siberian hamster GnIH precursor cDNA encoded two RFamide-related peptide (RFRP) sequences. SPAPANKVPHSAANLPLRF-NH2 (Siberian hamster RFRP-1) and TLSRVPSLPQRF-NH2 (Siberian hamster RFRP-3) were confirmed as mature endogenous peptides by mass spectrometry from brain samples purified by immunoaffinity chromatography. GnIH mRNA expression was higher in long days (LD) compared with short days (SD). GnIH mRNA was also highly expressed in SD plus pinealectomized animals, whereas expression was suppressed by melatonin, a nocturnal pineal hormone, administration. GnIH-immunoreactive (-ir) neurons were localized to the dorsomedial region of the hypothalamus, and GnIH-ir fibers projected to hypothalamic and limbic structures. The density of GnIH-ir perikarya and fibers were higher in LD and SD plus pinealectomized hamsters than in LD plus melatonin or SD animals. The percentage of GnRH neurons receiving close appositions from GnIH-ir fiber terminals was also higher in LD than SD, and GnIH receptor was expressed in GnRH-ir neurons. Finally, central administration of hamster RFRP-1 or RFRP-3 inhibited LH release 5 and 30 min after administration in LD. In sharp contrast, both peptides stimulated LH release 30 min after administration in SD. These results suggest that GnIH peptides fine tune LH levels via its receptor expressed in GnRH-ir neurons in an opposing fashion across the seasons in Siberian hamsters. PMID:22045661

Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study.

PubMed

Adler, Lenard A; Lynch, Lauren R; Shaw, David M; Wallace, Samantha P; Ciranni, Michael A; Briggie, Alexis M; Kulaga, Agatha; O'Donnell, Katherine E; Faraone, Stephen V

2011-09-01

The study objectives were to 1) evaluate medication adherence for adults with attention-deficit/hyperactivity disorder (ADHD) treated with 3 times daily (TID) mixed amphetamine salts immediate release (MAS IR) versus once-daily (qAM) MAS extended release (MAS XR) in a randomized, crossover study; and 2) to examine the associations between adherence and efficacy for MAS IR and MAS XR. Sixty-two adults with ADHD were enrolled and 49 completed the study. The treatment condition order (TID-qAM or qAM-TID) was counterbalanced across participants, with an intervening washout period of ≥ 7 days. Adherence was assessed via 3 measures: 1) self-report, 2) pill count, and 3) the Medication Event Monitoring System (MEMS(®)). The primary efficacy measure was the ADHD Rating Scale (ADHD-RS); secondary measures included the Time-Sensitive ADHD Symptom Scale (TASS) and Clinical Global Impressions-Severity of Illness (CGI-S) scale. Adherence to treatment as measured by self-report and pill count was not significantly different between MAS XR and MAS IR. Adherence was significantly better for MAS XR than MAS IR for all of the MEMS(®) measures. The mean change in ADHD-RS, TASS, and CGI-S scores at endpoint was significantly improved for both MAS IR and MAS XR and did not differ significantly between groups. There was not a significant adherence by efficacy interaction. Adults with ADHD adhered equally well with MAS IR as with MAS XR when assessed by pill count and self-report, but not by the MEMS(®) measures. Both treatments significantly reduced ADHD symptoms, and efficacy was not significantly different between groups. Adherence was not associated with treatment outcome.

Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.

PubMed

Meador, Kimford J; Loring, David W; Boyd, Alan; Echauz, Javier; LaRoche, Suzette; Velez-Ruiz, Naymee; Korb, Pearce; Byrnes, William; Dilley, Deanne; Borghs, Simon; De Backer, Marc; Story, Tyler; Dedeken, Peter; Webster, Elizabeth

2016-09-01

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) as a drug carrier for controlled release of tramadol hydrochloride

PubMed Central

Subramanian, Kaliappa gounder; Vijayakumar, Vediappan

2011-01-01

Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic acid and characterized by FT-IR, thermogravimetry and swelling in simulated biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug–polymer interaction. But differential scanning calorimetric studies indicated a probable drug–polymer interaction at a scale >100 nm level. The observed Korsmeyer–Peppas’s power law exponents (0.19–1.21) for the in vitro release profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an anomalous drug release mechanism. The decreased release rates for the grafted chitosan and the enhanced release rate for the grafts with increasing itaconic acid content in the feed were more likely attributed to the enhanced drug–matrix interaction and polymer–SBF interactions, respectively. The different release profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the different chemical structures of drugs. The above features suggest the graft copolymer’s candidature for use as a promising oral drug delivery system. PMID:23960799

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

USGS Publications Warehouse

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.; Knaeble, Alan R.; Marcus, Matthew A.; Lynch, Joshua K.; Toner, Brandy M.

2017-01-01

e of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (lXAS) approach is developed and applied to rotosonic drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s lXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity observed in the distribution of elevated-As wells.

Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.

PubMed

Barilla, Denise; Prasad, Pratapa; Hubert, Martine; Gumbhir-Shah, Kavita

2004-03-01

This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright 2004 John Wiley & Sons, Ltd.

A Family of A-Site Cation-Deficient Double-Perovskite-Related Iridates: Ln9Sr2Ir4O24 (Ln = La, Pr, Nd, Sm).

PubMed

Ferreira, Timothy; Smith, Mark D; Zur Loye, Hans-Conrad

2018-06-21

The compositions of the general formula Ln 11- x Sr x Ir 4 O 24 (Ln = La, Pr, Nd, Sm; 1.37 ≥ x ≥ 2) belonging to a family of A-site cation-deficient double-perovskite-related oxide iridates were grown as highly faceted single crystals from a molten strontium chloride flux. Their structures were determined by single-crystal X-ray diffraction. On the basis of the single-crystal results, additional compositions, Ln 9 Sr 2 Ir 4 O 24 (Ln = La, Pr, Nd, Sm), were prepared as polycrystalline powders via solid-state reactions and structurally characterized by Rietveld refinement. The compositions Ln 9 Sr 2 Ir 4 O 24 (Ln = La, Pr, Nd, Sm) contain Ir(V) and Ir(IV) in a 1:3 ratio with an average iridium oxidation state of 4.25. The single-crystal compositions La 9.15 Sr 1.85 Ir 4 O 24 and Pr 9.63 Sr 1.37 Ir 4 O 24 contain relatively less Ir(V), with the average iridium oxidation states being 4.21 and 4.09, respectively. The magnetic properties of Ln 9 Sr 2 Ir 4 O 24 (Ln = La, Pr, Nd, Sm) were measured, and complex magnetic behavior was observed in all cases at temperatures below 30 K.

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100.

PubMed

El Maghraby, Gamal Mohamed; Elzayat, Ehab Mostafa; Alanazi, Fars Kaed

2014-03-01

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels.

Novel star-type methoxy-poly(ethylene glycol) (PEG)-poly(ɛ-caprolactone) (PCL) copolymeric nanoparticles for controlled release of curcumin

NASA Astrophysics Data System (ADS)

Feng, Runliang; Zhu, Wenxia; Song, Zhimei; Zhao, Liyan; Zhai, Guangxi

2013-06-01

To improve curcumin's (CURs) water solubility and release property, a novel star methoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with MPEG, epichlorohydrin, and ɛ-caprolactone as raw materials. The structure of the novel copolymer was characterized by 1H NMR, FT-IR, and GPC. The results of FT-IR and differential scanning calorimeter of CUR-loaded nanoparticles (NPs) prepared by dialysis method showed that CUR was successfully encapsulated into the SMP12 copolymeric NPs with 98.2 % of entrapment efficiency, 10.91 % of drug loading, and 88.4 ± 11.2 nm of mean particle diameter in amorphous forms. The dissolubility of nanoparticulate CUR was increased by 1.38 × 105 times over CUR in water. The obtained blank copolymer showed no hemolysis. A sustained CUR release to a total of approximately 56.13 % was discovered from CUR-NPs in 40 % of ethanol saline solution within 72 h on the use of dialysis method. The release behavior fitted the ambiexponent and biphasic kinetics equation. In conclusion, the copolymeric NPs loading CUR might serve as a potential nanocarrier to improve the solubility and release property of CUR.

Investigation of triacetin effect on indomethacin release from poly(methyl methacrylate) microspheres: evaluation of interactions using FT-IR and NMR spectroscopies.

PubMed

Yuksel, Nilufer; Baykara, Meltem; Shirinzade, Hanif; Suzen, Sibel

2011-02-14

The purpose of this study was to form indomethacin (IND)-loaded poly(methyl methacrylate) (PMMA) microspheres having an extended drug release profile over a period of 24h. Microspheres were prepared by solvent evaporation method using sucrose stearate as a droplet stabilizer. When PMMA was used alone for the preparation of microspheres, only 44% of IND could be released at the end of 8h. Triacetin was added to PMMA, as a minor phase, and the obtained microspheres showed a high yield process with recovery of 89.82% and incorporation efficiency of 102.3%. A desired release profile lasting 24h was achieved. Differential scanning calorimetry (DSC) analysis showed that IND was found to be in an amorphous state in the microspheres. Fourier transform infrared (FT-IR) and nuclear magnetic resonance ((1)H NMR) spectra suggested that there might be a hydrogen bond present between the IND hydroxyl group and PMMA. No interaction between triacetin and IND or PMMA as the formation of secondary bonds was observed. The release enhancement of IND from microspheres was attributed to the physical plasticization effect of triacetin on PMMA and, to some extent, the amorphous state of the drug. Copyright © 2010 Elsevier B.V. All rights reserved.

FTIR and 1H MAS NMR investigations on the correlation between the frequency of stretching vibration and the chemical shift of surface OH groups of solids

NASA Astrophysics Data System (ADS)

Brunner, Eike; Karge, H. G.; Pfeifer, H.

1992-03-01

The study of surface hydroxyl groups of solids, especially of zeolites, belongs to the 'classical' topics of IR spectroscopy since physico-chemical information may be derived from the wavenumber (nu) OH of the stretching vibration of the different hydroxyls. On the other hand, the last decade has seen the development of high resolution solid-state NMR spectroscopy and through the use of the so-called magic-angle-spinning technique (MAS) the signals of different hydroxyl species can be resolved in the 1H NMR spectra of solids. The chemical shift (delta) H describing the position of these lines may be used as well as (nu) OH to characterize quantitatively the strength of acidity of surface OH groups of solids. In a first comparison of (nu) OH with (delta) H for several types of surface OH groups, a linear correlation between them could be found. The aim of this paper was to prove the validity of this correlation for a wide variety of hydroxyls. The IR measurements were carried out on a Perkin-Elmer FTIR spectrometer 1800 at the Fritz Haber Institute of the Max Planck Society, Berlin, and the 1H MAS NMR spectra were recorded on a Bruker MSL- 300 at the University of Leipzig.

Pyromellitamide aggregates and their response to anion stimuli.

PubMed

Webb, James E A; Crossley, Maxwell J; Turner, Peter; Thordarson, Pall

2007-06-06

The N,N',N'',N'''-1,2,4,5-tetra(ethylhexanoate) pyromellitamide is found to be capable of both intermolecular aggregation and binding to small anions. It is synthesized by aminolysis of pyromellitic anhydride with ethanolamine, followed by a reaction with hexanoyl chloride. The single-crystal X-ray structure of the pyromellitamide shows that it forms one-dimensional columnar stacks through an intermolecular hydrogen-bonding network. It also forms self-assembled gels in nonpolar solvents, presumably by a hydrogen-bonding network similar to the solid-state structure as shown by IR and XRD studies. Aggregation by intermolecular hydrogen bonding of the pyromellitamide is also observed by NMR and IR in solution. Fitting of NMR dilution data for pyromellitamide in d6-acetone to a cooperative aggregation model gave KE=232 M-1 and positive cooperativity of aggregation (rho=0.22). The pyromellitamide binds to a range of small anions with the binding strength decreasing in the order chloride>acetate>bromide>nitrate approximately iodide. The data indicate that the pyromellitamide binds two anions and that it displays negative cooperativity. The intermolecular aggregation of the pyromellitamide can also be altered using small anion stimuli; anion addition to preformed self-assembled pyromellitamide gels causes their collapse. The kinetics of anion-induced gel collapse are qualitatively correlated to the binding affinities of the same anions in solution. The cooperative anion binding properties and the sensitivity of the self-assembled gels formed by pyromellitamide toward anions could be useful in the development of sensors and switching/releasing devices.

The mechanisms of drug release from solid dispersions in water-soluble polymers.

PubMed

Craig, Duncan Q M

2002-01-14

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. However, despite the publication of numerous original papers and reviews on the subject, the mechanisms underpinning the observed improvements in dissolution rate are not yet understood. In this review the current consensus with regard to the solid-state structure and dissolution properties of solid dispersions is critically assessed. In particular the theories of carrier- and drug-controlled dissolution are highlighted. A model is proposed whereby the release behaviour from the dispersions may be understood in terms of the dissolution or otherwise of the drug into the concentrated aqueous polymer layer adjacent to the solid surface, including a derivation of an expression to describe the release of intact particles from the dispersions. The implications of a deeper understanding of the dissolution mechanisms are discussed, with particular emphasis on optimising the choice of carrier and manufacturing method and the prediction of stability problems.

Xanthe Terra Landslide in IR

NASA Technical Reports Server (NTRS)

2005-01-01

[figure removed for brevity, see original site]

This is a daytime IR image of a chaos region within Xanthe Terra. As with earlier images, the landslide in this image is caused by the failure of steep slopes releasing material to form the landslide deposit.

Image information: IR instrument. Latitude 3.1, Longitude 309.7 East (50.3 West). 100 meter/pixel resolution.

Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

The advantage of hollow mesoporous carbon as a near-infrared absorbing drug carrier in chemo-photothermal therapy compared with IR-820.

PubMed

Zhao, Qinfu; Wang, Xiudan; Yan, Yue; Wang, Da; Zhang, Ying; Jiang, Tongying; Wang, Siling

2017-03-01

In this study, we synthesized a kind of hollow mesoporous carbon (HMC) as near-infrared (NIR) nanomaterial and made a comparison between HMC and IR-820 commercially available in terms of heat generation properties and thermal stability exposed under NIR laser irradiation. The NIR-induced photothermal tests indicated that HMC had excellent heat generating capacity and remained stable after exposed to NIR laser irradiation for several times. On the contrary, the IR-820 was thermal unstable and degraded completely after exposed to NIR laser irradiation for only one time. The anticancer drug DOX was chosen as a model drug to evaluate the loading capacity and release properties of carboxylated HMC (HMC-COOH). The drug loading efficiency of HMC-COOH could reach to 39.7%. In vitro release results indicated that the release rate of DOX was markedly increased under NIR laser irradiation both in pH5.0 and pH7.4 PBS. Cell viability experiments indicated that HMC-COOH/DOX has a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This present research demonstrated that HMC could be employed as NIR-adsorbing agents as well as drug carriers to load lots of drug, realizing the synergistic treatment of chemotherapy and photothermal therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Decoy receptor 3 analogous supplement protects steatotic rat liver from ischemia-reperfusion injury.

PubMed

Li, Tzu-Hao; Liu, Chih-Wei; Lee, Pei-Chang; Huang, Chia-Chang; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Yang, Ying-Ying; Hsieh, Shie-Liang; Lin, Han-Chieh; Tsai, Chang-Youh

2017-07-01

For steatotic livers, pharmacological approaches to minimize the hepatic neutrophil and macrophage infiltration, and cytokine and chemokine release in ischemia-reperfusion (IR) injury are still limited. Tumor necrosis factor (TNF)-α superfamily-stimulated pathogenic cascades and M1 macrophage/Kupffer cells (KC) polarization from Th1 cytokines are important in the pathogenesis of IR liver injury with hepatic steatosis (HS). Conversely, anti-inflammatory M2 macrophages produce Th2 cytokine (interleukin-4), which reciprocally enhances M2 polarization. Toll-like receptor 4-activated KCs can release proinflammatory mediators, skew M1 polarization and escalate liver IR injury. Decoy receptor 3 (DcR 3 ) could be potential agents simultaneously blocking the IR liver injury-related pathogenic changes and extend the survival of steatotic graft. Rats were fed with methionine and choline-deficient high-fat diet (MCD HFD) for 6 weeks to induce HS. Preliminary experiments with HS group and IR group were conducted, and either immunoglobulin G Fc protein or DcR3 analogue was treated for 14 days in all groups to evaluate the severity. In the Zucker rat-focused experiments, various serum and hepatic substances, M1 polarization, and hepatic microcirculation were assessed. We found that serum/hepatic DcR 3 levels were lower in nonalcoholic fatty liver disease patients with HS. DcR 3 a protected Zucker rats with HS from IR liver injury. The beneficial effects of DcR 3 a supplement were mediated by inhibiting hepatic M1 polarization of KCs, decreasing serum/hepatic TNFα, nitric oxide, nitrotyrosine, soluble TNF-like cytokine 1A, Fas ligand, and interferon-γ levels, neutrophil infiltration, and improving hepatic microcirculatory failure among rats with IR-injured steatotic livers. Additionally, downregulated hepatic TNF-like cytokine 1A/Fas-ligand and toll-like receptor 4/nuclear factor-κB signals were found to mediate the DcR 3 a-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR 3 a analogue was a potential agent to protect steatotic liver against IR injury by simultaneous blockade of the multiple IR injury-related pathogenic changes. Copyright © 2017. Published by Elsevier Taiwan LLC.

Influence of the Stefan Flow on Heat Transfer in the System "Gas-Solid Particle" in Thermochemical Conversion of a Solid Fuel

NASA Astrophysics Data System (ADS)

Pechenegov, Yu. Ya.; Mrakin, A. N.

2017-09-01

Recommendations are presented on calculating interphase heat transfer in gas-disperse systems of plants for thermochemical conversion of ground solid fuel. An analysis is made of the influence of the gas release of fuel particles on the heat transfer during their heating. It is shown that in the processes of thermal treatment of oil shales, the presence of gas release reduces substantially the intensity of interphase heat transfer compared to the heat transfer in the absence of thermochemical decomposition of the solid phase.

Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human

PubMed Central

Skrapits, Katalin; Kanti, Vivien; Savanyú, Zsófia; Maurnyi, Csilla; Szenci, Ottó; Horváth, András; Borsay, Beáta Á.; Herczeg, László; Liposits, Zsolt; Hrabovszky, Erik

2015-01-01

Hypophysiotropic projections of gonadotropin-releasing hormone (GnRH)-synthesizing neurons form the final common output way of the hypothalamus in the neuroendocrine control of reproduction. Several peptidergic neuronal systems of the medial hypothalamus innervate human GnRH cells and mediate crucially important hormonal and metabolic signals to the reproductive axis, whereas much less is known about the contribution of the lateral hypothalamic area to the afferent control of human GnRH neurons. Orexin (ORX)- and melanin-concentrating hormone (MCH)-synthesizing neurons of this region have been implicated in diverse behavioral and autonomic processes, including sleep and wakefulness, feeding and other functions. In the present immunohistochemical study, we addressed the anatomical connectivity of these neurons to human GnRH cells in post-mortem hypothalamic samples obtained from autopsies. We found that 38.9 ± 10.3% and 17.7 ± 3.3% of GnRH-immunoreactive (IR) perikarya in the infundibular nucleus of human male subjects received ORX-IR and MCH-IR contacts, respectively. On average, each 1 mm segment of GnRH dendrites received 7.3 ± 1.1 ORX-IR and 3.7 ± 0.5 MCH-IR axo-dendritic appositions. Overall, the axo-dendritic contacts dominated over the axo-somatic contacts and represented 80.5 ± 6.4% of ORX-IR and 76.7 ± 4.6% of MCH-IR inputs to GnRH cells. Based on functional evidence from studies of laboratory animals, the direct axo-somatic and axo-dendritic input from ORX and MCH neurons to the human GnRH neuronal system may convey critical metabolic and other homeostatic signals to the reproducive axis. In this study, we also report the generation and characterization of new antibodies for immunohistochemical detection of GnRH neurons in histological sections. PMID:26388735

Trapped Melt in IIIAB Irons: Solid/Liquid Elemental Partitioning During the Fractionation of the IIIAB Magma

NASA Technical Reports Server (NTRS)

Wasson, John T.

1999-01-01

Group IIIAB, the largest iron-meteorite group, shows compositional trends (including a three-order-of-magnitude It concentration range) indicating that it formed by fractional crystallization of a metallic magma. Because about 200 irons are available, and all degrees of crystallization are well represented, IIIAB offers an excellent set of samples for the study of crystallization at all depths of the asteroidal core. On log-log Ir-Au, and Ir-As diagrams IIIAB forms a broad band; the breadth represents real meteorite-to-meteorite variations, far outside experimental or sampling uncertainties. A successful model must explain the width of this band; I suggest that it mainly resulted from the trapping of parental magma within the crystallizing solid. Because S is essentially insoluble in metal, the abundance of FeS is a measure of the fraction of trapped liquid. The trapped-melt model is supported by the observation that irons having higher S contents plot closer to the inferred composition of the magmatic parental liquid. The lowest S values are found in the irons occupying the left envelope of the IIIAB Ir-Au or Ir-As compositional fields, thus it is this set of irons that should be interpreted as the solid products of a fractionating magma. This simplifies the modeling of the crystallization process and allows inferences regarding the distribution ratios for other elements in the evolved IIIAB system. The large (multiton) Cape York irons show wide variations in their trapped-melt fractions; their compositions seem best understood in terms of a low initial S content of the IIIAB magma, about 20 mg/g. The inferred initial IIIAB distribution coefficient for Ir, 4.6, is much higher than published values based on laboratory studies of low-S systems; I suggest that low-S (and low-P) partition-ratio measurements tend to err in the direction of unity. In IIIAB distribution coefficients for Au, As, and Ni were still < 1 when the most evolved IIIAB irons formed, another indication of a low initial S content.

SNMP Over Wi-Fi Wireless Networks

DTIC Science & Technology

2003-03-01

headphone, 1 x microphone, 1 x AC adapter 73 Wireless connectivity IrDA, Wi-Fi (IEEE 802.11b) Power Battery installed (max) 1 x Lithium Ion battery ...headphone, 1 x microphone, 1 x AC adapter Wireless connectivity Bluetooth, IrDA, Wi-Fi Power Battery installed (max) 1 x Lithium Ion battery ...is required. However Microsoft released the new version of Embedded Visual Tool that integrated Pocket PC 2002 SDK and Smartphone 2002 SDK on

Approaching the limits of cationic and anionic electrochemical activity with the Li-rich layered rocksalt Li3IrO4

NASA Astrophysics Data System (ADS)

Perez, Arnaud J.; Jacquet, Quentin; Batuk, Dmitry; Iadecola, Antonella; Saubanère, Matthieu; Rousse, Gwenaëlle; Larcher, Dominique; Vezin, Hervé; Doublet, Marie-Liesse; Tarascon, Jean-Marie

2017-12-01

The Li-rich rocksalt oxides Li2MO3 (M = 3d/4d/5d transition metal) are promising positive-electrode materials for Li-ion batteries, displaying capacities exceeding 300 mAh g-1 thanks to the participation of the oxygen non-bonding O(2p) orbitals in the redox process. Understanding the oxygen redox limitations and the role of the O/M ratio is therefore crucial for the rational design of materials with improved electrochemical performances. Here we push oxygen redox to its limits with the discovery of a Li3IrO4 compound (O/M = 4) that can reversibly take up and release 3.5 electrons per Ir and possesses the highest capacity ever reported for any positive insertion electrode. By quantitatively monitoring the oxidation process, we demonstrate the material's instability against O2 release on removal of all Li. Our results show that the O/M parameter delineates the boundary between the material's maximum capacity and its stability, hence providing valuable insights for further development of high-capacity materials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finnegan, D.L.; Miller, T.L.; Zoller, W.H.

Particle and gas samples were collected at Mauna Loa volcano during and after its eruption in March and April, 1984 and at Kilauea volcano in 1983, 1984, and 1985 during various phases of its ongoing activity. In the last two Kilauea sampling missions, samples were collected during eruptive activity. The samples were analyzed by INAA for over 40 elements. We have found Ir in samples collected at Kilauea and Mauna Loa during fountaining activity as well as after eruptive activity. Os was also seen in the Mauna Loa samples. Enrichment factors for Ir in the volcanic fumes range from 10/supmore » 4/ to 10/sup 5/ relative to BHVO. Flux calculations for Ir at Mauna Loa and Kilauea had ranges of 80 to 3000 and 10 to 315 g/d respectively. The percentage of Ir released from the magma into the fumes ranged from 1% to 12% for both volcanoes. Calculations assuming the Deccan as the source of Ir for the K/T boundary layer show that the concentration of Ir left in the basalts may be too low to account for all of the K/T Ir. It would require a very high fraction (> 30%) of the Ir to be purged from the basalt to account for all the Ir, which cannot be supported by the Hawaiian data. 26 refs., 1 fig., 4 tabs.« less

The application of electrocoagulation for the conversion of MSWI fly ash into nonhazardous materials.

PubMed

Liao, Wing-Ping; Yang, Renbo; Kuo, Wei-Ting; Huang, Jui-Yuan

2014-05-01

This research investigated the electrocoagulation of municipal solid waste incineration (MSWI) fly ash at a liquid-to-solid ratio (L/S) of 20:1. The leachate that was obtained from this treatment was recovered for reutilization. Two different anodic electrodes were investigated, and two unit runs were conducted. In Unit I, the optimum anode was chosen, and in Unit II, the optimum anode and the recovered leachate were used to replace deionized water for repeating the same electrocoagulation experiments. The results indicate that the aluminum (Al) anode performed better than the iridium oxide (IrO2) anode. The electrocoagulation technique includes washing with water, changing the composition of the fly ash, and stabilizing the heavy metals in the ash. Washing with water can remove the soluble salts from fly ash, and the fly ash can be converted into Friedel's salt (3CaO·Al2O3·CaCl2·10H2O) under an uniform electric field and the sacrificial release of Al(+3) ions, which stabilizes the toxic heavy metals and brings the composition of the fly ash to within the regulatory limits of the toxicity characteristic leaching procedure (TCLP). Use of the Al anode to manage the MSWI fly ash and the leachate obtained from the electrocoagulation treatment is therefore feasible. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gonadotropin-Releasing hormones in the brain and pituitary of the white sucker

USGS Publications Warehouse

Robinson, T. Craig; Tobet, Stuart A.; Chase, Cindy; Waldron, Travis; Sower, Stacia A.

2000-01-01

The present study investigated GnRH forms within the brain of a representative of the order Cypriniformes, the white sucker, Catostomus commersoni, using HPLC, RIA, andimmunocytochemistry. Several immunoreactive (ir) GnRH forms were identified in the brain of the white sucker by chromatography and radioimmunoassay, including ir-salmon GnRH, ir-lamprey GnRH-I and -III, and ir-chicken GnRH-II. Results from immunocytochemical studies were consistent with multiple GnRH forms distributed in different patterns, particularly for fibers. Neuronal perikarya containing ir-salmon GnRH and ir-lamprey-like GnRH were found laterally within the preoptic area and rostralhypothalamus. Cells containing exclusively ir-salmon GnRH appeared slightly more rostrally, but in the same region. Fibers containing ir-salmon GnRH and ir-lamprey-like GnRH were seen throughout the caudal telencephalon and extended into thediencephalon, toward the pituitary. Fibers containing ir-chicken-II-like GnRH were also seen in the caudal telencephalon, but were concentrated more dorsally in the diencephalon. Within the pituitary, fibers containing ir-salmon GnRH and ir-lamprey-like GnRH entered the neurohypophysis, but differed in their destinations. Fibers containing ir-salmon GnRH remained within the neurohypophysis, while fibers containing ir-lamprey-like GnRH targeted adenohypophyseal tissue. These findings are consistent with the hypothesis that multiple GnRH forms with multiple functions exist within the brain and pituitary of teleosts and provide further evidence of a lamprey-like GnRH within an early evolved teleost species.

Understanding The Interfacial Structure Of Aqueous Phospholipid Monolayer Films Via External Reflection FT-IR Spectroscopy.

NASA Astrophysics Data System (ADS)

Mitchell, Melody L.; Dluhy, Richard A.

1989-12-01

Monolayer films of dimyristoyl-phosphatidic-acid (DMPA) at neutral and basic pH exhibit first-order phase transitions in their pressure-area curves. In situ external reflection FT-IR studies in the CH, stretching bands over this phase transition region exhibit a --6 cm-1 shift similar to that observed in previous studies of dipalmitoyl-phosphotidylcholine (DPPC)1. The acid form of DMPA at pH 3.0 does not exhibit the first order phase transition, but a ~1cm-1 frequency shift is observed in the liquid condensed phase and is also present in the neutral pH form. A solid-solid phase transition is proposed. Examination of the polar headgroup region (1300-960 cm-1)for acidic, neutral, and basic forms of DMPA give characteristic bands of each protonation state of PO3.

Formation and identification of borane radical anions isolated in solid argon

NASA Astrophysics Data System (ADS)

Lin, Meng-Yeh; Huang, Tzu-Ping; Chin, Chih-Hao; Wu, Yu-Jong

2018-02-01

The infrared (IR) spectrum of borane(3) anions (BH3-) isolated in solid Ar was recorded; two vibrational modes were observed at 2259.4 and 606.6 cm-1, which were assigned to the BH2 stretching (ν3) and out-of-plane large-amplitude (ν2) modes, respectively. These anions were produced by the electron bombardment of an Ar matrix sample containing a small proportion of B2H6 and H2 during matrix deposition or by the photolysis of single-bridged-B2H5- in an Ar matrix with the selected ultraviolet light. The band positions, relative intensity ratios, isotopic splitting pattern, and isotopic shift ratios of the observed IR features of BH3- are generally in good agreement with those predicted by the B2PLYP/aug-cc-pVTZ method.

High Energy Materials. New Preparation Approaches to Nitro and Nitroso Derivatives.

DTIC Science & Technology

1981-06-01

hexane as the pyridazinofuroxan 2, a yellow solid, 67% mp 118-1190C (dec); satisfactory analysis for C, H and N; ir(KBr): 3460 (m), 3370 (m) and 1600 cm-l...la (tlc) left a clear yellow solution. The re- action mixture was concentrated at a temperature below 45°C until a crystalline solid 2 appeared...Dilution with ice-water brought further separation of the per- oxide 2a as a light yellow solid which was filtered and dried at room temperature, 7.2g(75

Detection of solid C(triple bond)N bearing materials on solar system bodies

NASA Technical Reports Server (NTRS)

Cruikshank, Dale P.; Hartmann, W. K.; Tholen, David J.; Allamandola, L. J.; Brown, R. H.; Matthews, C. N.; Bell, J. F.

1991-01-01

We found observational evidence for the presence of C(triple bond)N-bearing solid materials on four classes of Solar System bodies: comets, asteroids, the rings of Uranus, and Saturn's satellite Iapetus. Gaseous CN was known in comet spectra, and the IR spectra of Comet P/Halley show emission of the CN fundamental at 4.5 microns interpreted as solids containing CN- group in the grains of the inner coma. The presented data offer the first evidence for chemically related material on the other objects.

Structural modifications of polymethacrylates: impact on thermal behavior and release characteristics of glassy solid solutions.

PubMed

Claeys, Bart; De Coen, Ruben; De Geest, Bruno G; de la Rosa, Victor R; Hoogenboom, Richard; Carleer, Robert; Adriaensens, Peter; Remon, Jean Paul; Vervaet, Chris

2013-11-01

Polymethacrylates such as Eudragit® polymers are well established as drug delivery matrix. Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization. These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets. Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit. These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties. The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics. Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

PubMed

Zhai, Qing-Zhou

2013-01-01

This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

Memantine-induced chorea and dystonia.

PubMed

Borges, Letizia Goncalves; Bonakdarpour, Borna

2017-04-01

Memantine is an uncompetitive N -methyl-d-aspartate receptor antagonist and probably also has an indirect dopaminergic action at high concentrations. We describe a person with Alzheimer's disease who developed chorea and dystonia after inadvertently doubling of her daily dose by taking extended-release (XR) memantine twice daily, rather than once daily (planned dose memantine XR, 21 mg once daily), after the drug was switched from immediate release (IR, 10 mg twice daily). Memantine is rarely associated with movement disorders, but this case emphasises the need for awareness of potential problems when switching from memantine IR to XR. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Cai, Jin-Yuan; Huang, De-Chun; Wang, Zhi-Xiang; Dang, Bei-Lei; Wang, Qiu-Ling; Su, Xin-Guang

2012-06-01

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Visible and shortwave infrared focal planes for remote sensing instruments

NASA Astrophysics Data System (ADS)

Tower, J. R.; McCarthy, B. M.; Pellon, L. E.; Strong, R. T.; Elabd, H.

1984-01-01

The development of solid-state sensor technology for multispectral linear array (MLA) instruments is described. A buttable four-spectral-band linear-format CCD and a buttable two-spectral band linear-format short-wave IR CCD have been designed, and first samples have been demonstrated. In addition, first-sample four-band interference filters have been fabricated, and hybrid packaging technology is being developed. Based on this development work, the design and construction of focal planes for a Shuttle sortie MLA instrument have begun. This work involves a visible and near-IR focal plane with 2048 pixels x 4 spectral bands and a short-wave IR focal plane with 1024 pixels x 2 spectral bands.

Differential effects of buffer pH on Ca2+-induced ROS emission with inhibited mitochondrial complexes I and III

PubMed Central

Lindsay, Daniel P.; Camara, Amadou K. S.; Stowe, David F.; Lubbe, Ryan; Aldakkak, Mohammed

2015-01-01

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca2+, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rotenone, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore (mPTP). These results indicate that ROS production by complex I and by complex III is differently affected by buffer pH and Ca2+ loading with mPTP opening. The study suggests that changes in the levels of cytosolic Ca2+ and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III. PMID:25805998

Preparation and evaluation of BSA-based hydrosol nanoparticles cross-linked with genipin for oral administration of poorly water-soluble curcumin.

PubMed

Shahgholian, Narges; Rajabzadeh, Ghadir; Malaekeh-Nikouei, Bizhan

2017-11-01

One of the most interesting functions of albumin is the ability to interact with bioactive compounds. This study describes preparation of protein-based nanoparticles (NPs) for the preparation of solid dispersion of curcumin (CN). Fabrication of hydrosol system of dispersed CN in bovine serum albumin (BSA) was approached, followed by cross-linking with glutaraldehyde (Gta). Response surface methodology (RSM) was used to investigate the influence of input factors (pH, CN content and organic phase ratio (r)), on the particle size and CN entrapment efficiency (EE). Particle size, EE and CN loading efficiency (LE) at optimum condition (pH 7, r 10% and 3.4mg of CN content), were found to be in the range of 153-184.4nm, 72.54%, and 14.508μg/mg, respectively. In the optimum formulation, genipin (Gnp) was used at three different levels (0.1-0.2 and 0.3% w/w of BSA), as a safe, natural cross-linker instead of toxic Gta, to address the limitation of oral delivery purpose. AFM and SEM analysis revealed the spherical and smooth surface of Nps. Ninhydrin (NHD) assay and FT-IR analysis confirmed the cross-linking between BSA and Gnp. In vitro release studies ensure the efficiency of the formulation for sustained release of soluble CN. Copyright © 2017 Elsevier B.V. All rights reserved.

New Therapeutic Agent against Arterial Thrombosis: An Iridium(III)-Derived Organometallic Compound.

PubMed

Hsia, Chih-Wei; Velusamy, Marappan; Tsao, Jeng-Ting; Hsia, Chih-Hsuan; Chou, Duen-Suey; Jayakumar, Thanasekaran; Lee, Lin-Wen; Li, Jiun-Yi; Sheu, Joen-Rong

2017-12-05

Platelet activation plays a major role in cardio and cerebrovascular diseases, and cancer progression. Disruption of platelet activation represents an attractive therapeutic target for reducing the bidirectional cross talk between platelets and tumor cells. Platinum (Pt) compounds have been used for treating cancer. Hence, replacing Pt with iridium (Ir) is considered a potential alternative. We recently developed an Ir(III)-derived complex, [Ir(Cp*)1-(2-pyridyl)-3-(2-hydroxyphenyl)imidazo[1,5-a]pyridine Cl]BF₄ (Ir-11), which exhibited strong antiplatelet activity; hence, we assessed the therapeutic potential of Ir-11 against arterial thrombosis. In collagen-activated platelets, Ir-11 inhibited platelet aggregation, adenosine triphosphate (ATP) release, intracellular Ca 2+ mobilization, P-selectin expression, and OH · formation, as well as the phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt. Neither the adenylate cyclase inhibitor nor the guanylate cyclase inhibitor reversed the Ir-11-mediated antiplatelet effects. In experimental mice, Ir-11 prolonged the bleeding time and reduced mortality associated with acute pulmonary thromboembolism. Ir-11 plays a crucial role by inhibiting platelet activation through the inhibition of the PLCγ2-PKC cascade, and the subsequent suppression of Akt and MAPK activation, ultimately inhibiting platelet aggregation. Therefore, Ir-11 can be considered a new therapeutic agent against either arterial thrombosis or the bidirectional cross talk between platelets and tumor cells.

Drug delivery properties of macroporous polystyrene solid foams.

PubMed

Canal, Cristina; Aparicio, Rosa Maria; Vilchez, Alejandro; Esquena, Jordi; García-Celma, Maria José

2012-01-01

Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-time.

Solid lipid microparticles containing loratadine prepared using a Micromixer.

PubMed

Milak, Spomenka; Medlicott, Natalie; Tucker, Ian G

2006-12-01

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

DOE PAGES

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.; ...

2017-05-19

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonicmore » drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity seen in the distribution of elevated-As wells.« less

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonicmore » drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity seen in the distribution of elevated-As wells.« less

Stimulation of the hypothalamo-pituitary-adrenal axis in the rat by three selective type-4 phosphodiesterase inhibitors: in vitro and in vivo studies

PubMed Central

Kumari, Meena; Cover, Patricia O; Poyser, Robert H; Buckingham, Julia C

1997-01-01

Previous studies in our laboratory have shown that the synthetic xanthine analogue denbufylline, a selective type 4 phosphodiesterase (PDE-4) inhibitor, is a potent activator of the hypothalamo-pituitary-adrenal (HPA) axis when given orally or intraperitoneally (i.p.) to adult male rats. This paper describes the results of experiments in which well established in vivo and in vitro methods were used to compare the effects of denbufylline on HPA function with those of two other selective PDE-4 inhibitors, rolipram and BRL 61063 (1,3-dicyclopropylmethyl-8-amino-xanthine). For comparison, parallel measurements of the immunoreactive- (ir-) luteinising hormone (LH) were made where appropriate. When injected intraperitoneally, rolipram (40 and 200 μg kg−1, P<0.005), denbufylline (0.07–0.6 μg kg−1, P<0.05) and BRL 61063 (30 μg kg−1, P<0.005) each produced marked rises in the serum ir-corticosterone concentrations. However, lower doses of rolipram (1.6 and 8 μg kg−1) and BRL 61063 (0.25–6 μg kg−1) were without effect (P>0.05). By contrast, intracerebroventricular (i.c.v.) injection of rolipram (8 ng–1 μg kg−1) or denbufylline (50 ng–1 μg kg−1) failed to influence the serum ir-corticosterone concentration. BRL 61063 (8–120 ng kg−1, i.c.v.) was also ineffective in this regard although at a higher dose (1 μg kg−1, i.c.v.) it produced a small but significant (P<0.05) increase in ir-corticosterone release. Denbufylline also increased the serum ir-LH concentration when given peripherally (0.2–0.6 μg kg−1, i.p., P<0.05) or centrally (100 ng kg−1, i.c.v., P<0.05) but rolipram (1.6–200 μg kg−1, i.p. or 8 ng–1 μg kg−1, i.c.v.) and BRL 61063 (0.25–30 μg kg−1, i.p. or 1 ng–1 μg kg−1, i.c.v.) did not (P>0.05). In vitro rolipram (10 μM, P<0.01), denbufylline (1 mM, P<0.001) and BRL 61063 (1 and 10 μM, P<0.05) stimulated the release of corticotrophin releasing hormone (ir-CRH-41) but lower concentrations of the drugs were without effect as also was BRL 61063 at 100 μM (P>0.05); the rank order of potency was thus BRL 61063>rolipram>denbufylline. The adenylyl cyclase activator forskolin (100 μM, P<0.01) also stimulated the release of ir-CRH-41, producing effects which were additive with those of rolipram and denbufylline but not with those of BRL 61063. The secretory responses to forskolin (100 μM) were accompanied by a highly significant increase in the cyclic AMP content of the hypothalamic tissue (P<0.005). Rolipram (10 μM) also significantly (P<0.05) elevated the hypothalamic cyclic AMP but denbufylline (10 mM) and BRL 61063 (10 μM) did not. However, all three PDE-inhibitors potentiated the rise in cyclic AMP induced by forskolin (P<0.05). None of the drugs tested, alone or in combination, modified the release of arginine vasopressin (ir-AVP) from the hypothalamus. Rolipram (100 μM), denbufylline (100 μM) and BRL 61063 (100 μM) stimulated the release of corticotrophin (ir-ACTH) from pituitary tissue in vitro (P<0.05) but in lower concentrations they were without significant effect. In addition, rolipram (10 μM, P<0.05), denbufylline (0.1 μM, P<0.05) and BRL 61063 (10 μM, P<0.05) potentiated the significant (P<0.05) rises in ir-ACTH secretion induced by forskolin (100 μM). Forskolin (100 μM) also produced a highly significant increase (P<0.01) in the tissue cyclic AMP content which was further potentiated by rolipram (10 μM), denbufylline (10 μM) and BRL 61063 (10 μM) which, alone did not affect the cyclic AMP content of the tissue. Since both denbufylline and BRL 61063 possess significant adenosine A1 receptor blocking activity, further studies examined the potential influence of these receptors on the secretion in vitro of CRH-41, AVP and ACTH. The release of ir-CRH-41 was increased significantly by adenosine deaminase (ADA, 5 u ml−1, P<0.05) and the A1-receptor antagonist, 1,3-dicyclopropyl-8-cyclopentylxanthine (DPCPX, 0.1–10 nM, P<0.05). The responses to ADA were abolished by the A1 receptor agonist N6-cyclo-hexyladenosine (CHA, 100 nM, P<0.05) which alone had no significant effect on ir-CRH-41 release. ADA (0.1–10 u ml−1) and DPCPX (1 nM) had weak stimulant and inhibitory effects, respectively, on the release of ir-ACTH from the pituitary gland while CHA (0.1–10 nM) was without effect. Ligand binding studies with [3H]-DPCPX as a probe demonstrated the presence of specific high affinity A1 binding sites in the hypothalamus (Kd=0.7 nM; Bmax=367±32 fmol mg−1 protein) and in the hippocampus (Kd=1 nM; Bmax=1165±145 fmol mg−1 protein). In both tissues binding of the ligand was displaced by CHA (IC50=1 nM (hypothalamus) and 2 nM (hippocampus)), BRL 61063 (IC50=80 nM (hypothalamus) and 100 nM (hippocampus)) and denbufylline (IC50=5 μM (hypothalamus) and 9 μM (hippocampus)) but not by rolipram. The results suggest that rolipram, denblufylline and BRL 61063 stimulate the HPA axis in the rat, acting at the levels of both the hypothalamus and the pituitary gland. Their actions may be explained, at least in part, by inhibition of PDE-4 but additional actions including blockade of hypothalamic adenosine A1 receptors by denbufylline and BRL 61063 cannot be excluded. PMID:9179387

[Study on solid dispersion of precipitated calcium carbonate-based oleanolic acid].

PubMed

Yan, Hong-mei; Zhang, Zhen-hai; Jia, Xiao-bin; Jiang, Yan-rong; Sun, E

2015-05-01

Oleanolic acid-precipitated calcium carbonate solid dispersion was prepared by using solvent evaporation method. The microscopic structure and physicochemical properties of solid dispersion were analyzed using differential scanning calorimetry and scanning electron microscopy (SEM). And its in vitro release also was investigated. The properties of the precipitated calcium carbonate was studied which was as a carrier of oleanolic acid solid dispersion. Differential scanning calorimetry analysis suggested that oleanolic acid may be present in solid dispersion as amorphous substance. The in vitro release determination results of oleanolic acid-precipitated calcium carbonate (1: 5) solid dispersion showed accumulated dissolution rate of.oleanolic acid was up to 90% at 45 min. Accelerating experiment showed that content and in vitro dissolution of oleanolic acid solid dispersion did not change after storing over 6 months. The results indicated that in vitro dissolution of oleanolic acid was improved greatly by the solid dispersion with precipitated calcium carbonate as a carrier. The solid dispersion is a stabilizing system which has actual applied value.

C-H activations at iridium(I) square-planar complexes promoted by a fifth ligand.

PubMed

Martín, Marta; Torres, Olga; Oñate, Enrique; Sola, Eduardo; Oro, Luis A

2005-12-28

In the presence of ligands such as acetonitrile, ethylene, or propylene, the Ir(I) complex [Ir(1,2,5,6-eta-C8H12)(NCMe)(PMe3)]BF4 (1) transforms into the Ir(III) derivatives [Ir(1-kappa-4,5,6-eta-C8H12)(NCMe)(L)(PMe3)]BF4 (L = NCMe, 2; eta2-C2H4, 3; eta2-C3H6, 4), respectively, through a sequence of C-H oxidative addition and insertion elementary steps. The rate of this transformation depends on the nature of L and, in the case of NCMe, the pseudo-first-order rate constants display a dependence upon ligand concentration suggesting the formation of five-coordinate reaction intermediates. A similar reaction between 1 and vinyl acetate affords the Ir(III) complex [Ir(1-kappa-4,5,6-eta-C8H12){kappa-O-eta2-OC(Me)OC2H3}(PMe3)]BF4 (7) via the isolable five-coordinate Ir(I) compound [Ir(1,2,5,6-eta-C8H12){kappa-O-eta2-OC(Me)OC2H3}(PMe3)]BF4 (6). DFT (B3LYP) calculations in model complexes show that reactions initiated by acetonitrile or ethylene five-coordinate adducts involve C-H oxidative addition transition states of lower energy than that found in the absence of these ligands. Key species in these ligand-assisted transformations are the distorted (nonsquare-planar) intermediates preceding the intramolecular C-H oxidative addition step, which are generated after release of one cyclooctadiene double bond from the five-coordinate species. The feasibility of this mechanism is also investigated for complexes [IrCl(L)(PiPr3)2] (L = eta2-C2H4, 27; eta2-C3H6, 28). In the presence of NCMe, these complexes afford the C-H activation products [IrClH(CH=CHR)(NCMe)(PiPr3)2] (R = H, 29; Me, 30) via the common cyclometalated intermediate [IrClH{kappa-P,C-P(iPr)2CH(CH3)CH2}(NCMe)(PiPr3)] (31). The most effective C-H oxidative addition mechanism seems to involve three-coordinate intermediates generated by photochemical release of the alkene ligand. However, in the absence of light, the reaction rates display dependences upon NCMe concentration again indicating the intermediacy of five-coordinate acetonitrile adducts.

Radiological Environmental Protection for PEP-II Ring High Luminosity Operation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, James C.; Nakao, Noriaki; /SLAC

2006-08-16

Stanford Linear Accelerator Center (SLAC) is located in northern California, USA. Radiological environmental protection is one of the main elements of the radiation protection program. One of SLAC's accelerator facilities is B-Factory, whose PEP-II accelerator ring has been operating since 1997 and is being upgraded to higher luminosity operation. Four radiological issues associated with high luminosity operation up to CY2008 are re-evaluated: (1) annual doses in IR halls, (2) annual skyshine doses at site boundaries, (3) potential radioactive air releases, and (4) potential groundwater activation. This paper presents the skyshine doses and air emission doses to the Maximally Exposed Individualmore » (MEI) at SLAC site boundaries. The normal beam loss scenarios around PEP-II ring are presented first. In CY2008, the luminosity is 2 x 10{sup 34} cm{sup -2} s{sup -1}, and the stored current is 4.0-A for low-energy ring (LER ) and 2.2-A for high-energy ring (HER). The beam losses around PEP-II ring include those near injection region in IR10 and IR8 and those at collimators (e.g., HER collimators in IR12, LER collimators in IR4 and IR6). The beam losses in IR8 and IR10 (where injection into ring occurs) are further divided into septum, BAD (beam abort dump) and TD (tune-up dump), as well as apertures. The skyshine prompt dose rate distributions as a function of distance from an IR hall at four directions were calculated using the MARS15 Monte Carlo code. For skyshine dose to the MEI, the annual dose (7200 h/y occupancy) is calculated to be 2.9 mrem/y at Sand Hill Road (from e{sup -} losses in IR12 HER collimators) and 1.2 mrem/y at Horse Track Offices near IR6 (from e{sup +} losses in IR8, IR6 and IR4). These are lower than the SLAC skyshine limit of 5 mrem/y for any single facility within SLAC. Radionuclide productions in the air at the PEP-II IR10 were calculated using MARS15. Beam losses of 9-GeV electrons were assumed in three target cases: the copper TD, septum and BAD. Energy spectra of secondary particles of photons, neutrons, protons and pions in the IR10 air region were calculated. Radionuclide yields of {sup 11}C, {sup 13}N, {sup 15}O, {sup 3}H, {sup 7}Be and {sup 41}Ar were estimated using the obtained particle energy spectra, folded with the reaction cross sections. With certain operation and ventilation conditions, the annual air emission dose to the MEI at Sand Hill Road from e{sup -} losses in IR10 is calculated to be 0.004 mrem/y (7200 h/y occupancy). The annual dose to the MEI at Horse Track Offices is 0.002 mrem/y from e{sup +} losses in IR8, 0.003 mrem/y from IR6, and 0.025 mrem/y from IR4. The doses are dominated by {sup 13}N. Therefore, the EPA annual dose limit of 10 mrem/y for SLAC and the continuous ventilation monitoring limit of 0.1 mrem/y for each release point are not exceeded.« less

Insulin-Like Growth Factor-I Regulates LH Release by Modulation of Kisspeptin and NMDA-Mediated Neurotransmission in Young and Middle-Aged Female Rats

PubMed Central

Yao, Dachun; Shu, Jun; Sun, Yan; Etgen, Anne M.

2014-01-01

This study investigated potential mechanisms by which age and IGF-I receptor (IGF-Ir) signaling in the neuroendocrine hypothalamus affect estradiol-positive feedback effects on GnRH neuronal activation and on kisspeptin and N-methyl-D-aspartate (NMDA)-induced LH release and on the abundance of NMDA receptor subunits Nr1 and Nr2b and Kiss1r transcript and protein in the hypothalamus of young and middle-aged female rats. We infused vehicle, IGF-I, or JB-1, a selective antagonist of IGF-Ir, into the third ventricle of ovariectomized female rats primed with estradiol or vehicle and injected with vehicle, kisspeptin (3 or 30 nmol/kg), or NMDA (15 or 30 mg/kg). Regardless of dose, NMDA and kisspeptin resulted in significantly more LH release, GnRH/c-Fos colabeling, and c-Fos immunoreative cells in young than in middle-aged females. Estradiol priming significantly increased Kiss1r, Nr1, and Nr2b receptor transcript and protein abundance in young but not middle-aged female hypothalamus. JB-1 attenuated kisspeptin and NMDA-induced LH release, numbers of GnRH/c-Fos and c-Fos cells, and Kiss1r, Nr1, and Nr2b transcript and protein abundance in young females to levels observed in middle-aged females. IGF-I significantly enhanced NMDA and kisspeptin-induced LH release in middle-aged females without increasing numbers of GnRH/c-Fos or c-Fos immunoreactive cells. IGF-I infusion in middle-aged females also increased Kiss1r, Nr1, and Nr2b protein and transcript to levels that were equivalent to young estradiol-primed females. These findings indicate that age-related changes in estradiol-regulated responsiveness to excitatory input from glutamate and kisspeptin reflect reduced IGF-Ir signaling. PMID:24617524

Annual Surveillance Summary: Bacterial Infections in the Military Health System (MHS), 2016

DTIC Science & Technology

2017-06-01

Approved for public release. Distribution is unlimited. The views expressed in this document are those of the authors and do not necessarily reflect...historic IR to the IR of the current analysis year. c Results are presented by two decimal places to account for low incidence rates. Data Source...NMCPHC HL7-formatted CHCS microbiology and M2 databases. Prepared by the EpiData Center Department, Navy and Marine Corps Public Health Center, on 21

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder.

PubMed

Findling, Robert L; Quinn, Declan; Hatch, Simon J; Cameron, Sara J; DeCory, Heleen H; McDowell, Michael

2006-12-01

To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.

Successful synthesis and thermal stability of immiscible metal Au-Rh, Au-Ir andAu-Ir-Rh nanoalloys

NASA Astrophysics Data System (ADS)

Shubin, Yury; Plyusnin, Pavel; Sharafutdinov, Marat; Makotchenko, Evgenia; Korenev, Sergey

2017-05-01

We successfully prepared face-centred cubic nanoalloys in systems of Au-Ir, Au-Rh and Au-Ir-Rh, with large bulk miscibility gaps, in one-run reactions under thermal decomposition of specially synthesised single-source precursors, namely, [AuEn2][Ir(NO2)6], [AuEn2][Ir(NO2)6] х [Rh(NO2)6]1-х and [AuEn2][Rh(NO2)6]. The precursors employed contain all desired metals ‘mixed’ at the atomic level, thus providing significant advantages for obtaining alloys. The observations using high-resolution transmission electron microscopy show that the nanoalloy structures are composed of well-dispersed aggregates of crystalline domains with a mean size of 5 ± 3 nm. Еnergy dispersive x-ray spectroscopy and x-ray powder diffraction (XRD) measurements confirm the formation of AuIr, AuRh, AuIr0.75Rh0.25, AuIr0.50Rh0.50 and AuIr0.25Rh0.75 metastable solid solutions. In situ high-temperature synchrotron XRD (HTXRD) was used to study the formation mechanism of nanoalloys. The observed transformations are described by the ‘conversion chemistry’ mechanism characterised by the primary development of particles comprising atoms of only one type, followed by a chemical reaction resulting in the final formation of a nanoalloy. The obtained metastable nanoalloys exhibit essential thermal stability. Exposure to 180 °C for 30 h does not cause any dealloying process.

Successful synthesis and thermal stability of immiscible metal Au-Rh, Au-Ir andAu-Ir-Rh nanoalloys.

PubMed

Shubin, Yury; Plyusnin, Pavel; Sharafutdinov, Marat; Makotchenko, Evgenia; Korenev, Sergey

2017-05-19

We successfully prepared face-centred cubic nanoalloys in systems of Au-Ir, Au-Rh and Au-Ir-Rh, with large bulk miscibility gaps, in one-run reactions under thermal decomposition of specially synthesised single-source precursors, namely, [AuEn 2 ][Ir(NO 2 ) 6 ], [AuEn 2 ][Ir(NO 2 ) 6 ] х [Rh(NO 2 ) 6 ] 1-х and [AuEn 2 ][Rh(NO 2 ) 6 ]. The precursors employed contain all desired metals 'mixed' at the atomic level, thus providing significant advantages for obtaining alloys. The observations using high-resolution transmission electron microscopy show that the nanoalloy structures are composed of well-dispersed aggregates of crystalline domains with a mean size of 5 ± 3 nm. Еnergy dispersive x-ray spectroscopy and x-ray powder diffraction (XRD) measurements confirm the formation of AuIr, AuRh, AuIr 0.75 Rh 0.25 , AuIr 0.50 Rh 0.50 and AuIr 0.25 Rh 0.75 metastable solid solutions. In situ high-temperature synchrotron XRD (HTXRD) was used to study the formation mechanism of nanoalloys. The observed transformations are described by the 'conversion chemistry' mechanism characterised by the primary development of particles comprising atoms of only one type, followed by a chemical reaction resulting in the final formation of a nanoalloy. The obtained metastable nanoalloys exhibit essential thermal stability. Exposure to 180 °C for 30 h does not cause any dealloying process.

Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

PubMed

Blaesi, Aron H; Saka, Nannaji

2017-11-01

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug in the walls. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of aeolian erosion on microbial release from solids.

NASA Technical Reports Server (NTRS)

Gustan, E. A.; Olson, R. L.; Taylor, D. M.; Green, R. H.

1972-01-01

This study was initiated to determine the percentage of spores that would be expected to be released from the interior of solid materials by aeolian erosion on a planetary surface. Methyl methacrylate and Eccobond disks were fabricated so that each disk contained approximately 40,000 Bacillus subtilis var. niger spores. The disks were placed in a specially designed sandblasting device and eroded. Exposure periods of 0.5, 2 and 24 hours were investigated using filtered air to accelerate the sand. A series of tests was also conducted for a 0.5 hour period using carbon dioxide. Examination of the erosion products showed that less than 1% of the spores originally contained in the solids was released by aeolian erosion.

A comparative study on the effects of amphiphilic and hydrophilic polymers on the release profiles of a poorly water-soluble drug.

PubMed

Irwan, Anastasia W; Berania, Jacqueline E; Liu, Xueming

2016-03-01

This paper reports the use of two crystalline polymers, an amphiphilic Pluronic® F-127 (PF-127) and a hydrophilic poly(ethylene glycol) (PEG6000) as drug delivery carriers for improving the drug release of a poorly water-soluble drug, fenofibrate (FEN), via micelle formation and formation of a solid dispersion (SD). In 10% PF-127 (aq.), FEN showed an equilibrium solubility of ca. 0.6 mg/mL, due to micelle formation. In contrast, in 10% PEG6000 (aq.), FEN only exhibited an equilibrium solubility of 0.0037 mg/mL. FEN-loaded micelles in PF-127 were prepared by direct dissolution and membrane dialysis. Both methods only yielded a highest drug loading (DL) of 0.5%. SDs of FEN in PF-127 and PEG6000, at DLs of 5-80%, were prepared by solvent evaporation. In-vitro dissolution testing showed that both micelles and SDs significantly improved FEN's release rate. The SDs of FEN in PF-127 showed significantly faster release than crystalline FEN, when the DL was as high as 50%, whereas SDs of PEG6000 showed similar enhancement in the release rate when the DL was not more than 20%. The DSC thermograms of SDs of PF-127 exhibited a single phase transition peak at ca. 55-57 °C when the DL was not more than 50%, whereas those in PEG6000 exhibited a similar peak at ca. 61-63 °C when the DL was not more than 35%. When the DL exceeded 50% for SDs of PF-127 and 35% for SDs of PEG6000, DSC thermograms showed two melting peaks for the carrier polymer and FEN, respectively. FT-IR studies revealed that PF-127 has a stronger hydrophobic-hydrophobic interaction with FEN than PEG6000. It is likely that both dispersion and micelle formation contributed to the stronger effect of PF-127 on enhancing the release rate of FEN in its SDs.

Passive infrared ice detection for helicopter applications

NASA Technical Reports Server (NTRS)

Dershowitz, Adam L.; Hansman, R. John, Jr.

1990-01-01

A technique is proposed to remotely detect rotor icing on helicopters by using passive IR thermometry to detect the warming caused by latent heat release as supercooled water freezes. During icing, the ice accretion region will be warmer than the uniced trailing edge, resulting in a characteristic chordwise temperature profile. Preliminary tests were conducted on a static model in the NASA Icing Research Tunnel for a variety of wet (glaze) and dry (rime) ice conditions. The chordwise temperature profiles were confirmed by observation with an IR thermal video system and thermocouple observations. The IR observations were consistent with predictions of the LEWICE ice accretion code, which was used to extrapolate the observations to rotor icing conditions. Based on the static observations, the passive IR ice detection technique appears promising; however, further testing or rotating blades is required.

Compound simulator IR radiation characteristics test and calibration

NASA Astrophysics Data System (ADS)

Li, Yanhong; Zhang, Li; Li, Fan; Tian, Yi; Yang, Yang; Li, Zhuo; Shi, Rui

2015-10-01

The Hardware-in-the-loop simulation can establish the target/interference physical radiation and interception of product flight process in the testing room. In particular, the simulation of environment is more difficult for high radiation energy and complicated interference model. Here the development in IR scene generation produced by a fiber array imaging transducer with circumferential lamp spot sources is introduced. The IR simulation capability includes effective simulation of aircraft signatures and point-source IR countermeasures. Two point-sources as interference can move in two-dimension random directions. For simulation the process of interference release, the radiation and motion characteristic is tested. Through the zero calibration for optical axis of simulator, the radiation can be well projected to the product detector. The test and calibration results show the new type compound simulator can be used in the hardware-in-the-loop simulation trial.

Combined IR-Raman vs vibrational sum-frequency heterospectral correlation spectroscopy

NASA Astrophysics Data System (ADS)

Roy, Sandra; Beutier, Clémentine; Hore, Dennis K.

2018-06-01

Vibrational sum-frequency generation spectroscopy is a valuable probe of surface structure, particularly when the same molecules are present in one of the adjacent bulk solid or solution phases. As a result of the non-centrosymmetric requirement of SFG, the signal generated is a marker of the extent to which the molecules are ordered in an arrangement that breaks the up-down symmetry at the surface. In cases where the accompanying changes in the bulk are of interest in understanding and interpreting the surface structure, simultaneous analysis of the bulk IR absorption or bulk Raman scattering is helpful, and may be used in heterospectral surface-bulk two-dimensional correlation. We demonstrate that, in such cases, generating a new type of bulk spectrum that combines the IR and Raman amplitudes is a better candidate than the individual IR and Raman spectra for the purpose of correlation with the SFG signal.

Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

PubMed

Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

2008-08-07

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

Identity of sensory and motor systems that are critical to the immobility reflex ("animal hypnosis").

PubMed

Klemm, W R

1976-01-01

This review presents an analysis of the sensory and motor mechanisms as they are now understood that cause the immobility reflex (IR). Of the sensory systems that conceivably could trigger and sustain the IR, as commonly induced experimentally by inversion and manual restraint, evidence has been presented to eliminate some senses (vestibular, vision, sound, many visceral sensations, olfaction, taste, temperature), while incriminating tactile and proprioceptive influences. Of the motor systems which could cause the profound immobility during IR, neurosurgical and electrophysiological evidence identifies the locus of the inhibitory neurons in the brain stem and/or spinal cord. The evidence reviewed leads to a unified working hypothesis of IR mechanisms. IR is considered to be caused by a group of neurons in the brain stem which inhibit spinal motoneurons, either directly or indirectly, when those inhibitory neurons are activated by a specific pattern of tactile and proprioceptive input. Modulation of the IR control system appears to come from the limbic system, which under fear-producing conditions, potentiates the IR in part by release of epinephrine. Inhibition of the IR control system appears to come from the neocortex, as well as the brain stem reticulum, when it is activated by nonspecific, arousing somaesthetic sensations that produce generalized activation of the neocortex and skeletal muscle.

Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design.

PubMed

Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

2011-01-01

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X(1)), surfactant (X(2)), and drug/lipid ratio (X(3)) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was -8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas-Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release.

Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

PubMed Central

Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

2011-01-01

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X1), surfactant (X2), and drug/lipid ratio (X3) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was −8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas–Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release. PMID:21556343

Synthesis and properties of greenish-blue-emitting iridium dendrimers with N-phenylcarbazole-based polyether dendrons by a post-dendronization route.

PubMed

Wang, Yang; Wang, Shumeng; Shao, Shiyang; Ding, Junqiao; Wang, Lixiang; Jing, Xiabin; Wang, Fosong

2015-01-21

A series of solution processible greenish-blue-emitting Ir dendrimers with polyether dendrons that consist of N-phenylcarbazole (NPC) are developed via a convenient post-dendronization method. It involves two steps: (i) the successful preparation of a reactive Ir core, namely m-HO-dfppyIr, only when the hydroxyl group is located at the meta position relative to the N atom in the C^N ligand so as to eliminate the possible resonance structure between enol and keto; and (ii) the subsequent functionalization with NPC-based polyether dendrons to afford the first, second and third generation Ir dendrimers (Ir-G1B, Ir-G2B and Ir-G3B) with ease and high yields over 60%. All these dendritic complexes possess good thermal stability with decomposition temperatures higher than 380 °C and glass transition temperatures higher than 200 °C. In addition, with the growing generation number, the intermolecular interactions between emissive Ir cores are expected to be effectively inhibited to avoid the luminescence quenching, which is confirmed from the blue-shifted emission peak and the enhanced lifetime of Ir-G3B in the solid state. As a result, on going from Ir-G1B to Ir-G3B, the maximum luminous efficiency rises upward from 4.7 to 9.2 cd A(-1) for nondoped electrophosphorescent devices. Further optimization by doping them into a dendritic H2 host leads to the improved luminous efficiencies as high as 20.0-25.2 cd A(-1).

Development of fast-release solid catchers for rare isotopes

NASA Astrophysics Data System (ADS)

Nolen, Jerry; Greene, John; Elam, Jeffrey; Mane, Anil; Sampathkumaran, Uma; Winter, Raymond; Hess, David; Mushfiq, Mohammad; Stracener, Daniel; Wiendenhoever, Ingo

2015-04-01

Porous solid catchers of rare isotopes are being developed for use at high power heavy ion accelerator facilities such as RIKEN, FRIB, and RISP. Compact solid catchers are complementary to helium gas catchers for parasitic harvesting of rare isotopes in the in-flight separators. They are useful for short lived isotopes for basic nuclear physics research and longer-lived isotopes for off-line applications. Solid catchers can operate effectively with high intensity secondary beams, e.g. >> 1E10 atoms/s with release times as short as 10-100 milliseconds. A new method using a very sensitive and efficient RGA has been commissioned off-line at Argonne and is currently being shipped to Florida State University for in-beam measurements of the release curves using stable beams. The same porous solid catcher technology is also being evaluated for use in targets for the production of medical isotopes such as 211-At. Research supported by the U.S. DOE Office of Nuclear Physics under the SBIR Program and Contract # DE-AC02-06CH11357 and a University of Chicago Comprehensive Cancer Center/ANL Pilot Project.

Biocompatible interpolymer complex matrix tablets - an oral sustained release class-III antidiabetic drug

NASA Astrophysics Data System (ADS)

Ershadul Haque, S. K.; Sheela, A.

2017-11-01

Development of sustained release formulations of Metformin hydrochloride (Met) having low bioavailability and short half-life is one of the frontier areas of research towards achieving novel drug delivery systems. Towards the same, we have prepared interpolymer complexes (IPCs) of chitosan (CH) and two different viscosity grades of hydroxypropyl methylcellulose - HPMC (K4M and K100M) in various ratios, say, 4:6, 2:8, 1:9, respectively. The IPCs are characterized by Fourier transform infrared spectroscopy (FT-IR) and Thermo gravimetric analysis (TGA) techniques. Drug compatibility study is carried out by FT-IR and powder X-ray diffraction (XRD) techniques. The physical properties and drug content of formulated tablets are evaluated and found to be optimum. In addition, in vitro drug release kinetics is carried out at two different pH, say, 1.2 and 6.8. The release pattern from different polymeric matrices is shown in figure below: a) Chitosan, HPMC K4M and HPMC K100M b) IPCs of CH/HPMC K4M in [2:3, 1:4 and 1:9 ratios] c) IPCs of CH/HPMC K100M in [2:3, 1:4 and 1:9 ratios]. From the study, it has been observed that the drug release is sustained for a period of 12h in 1:9 ratio of CH: K100M IPC due to the formation of complex network matrix.

{sup 45}Sc Solid State NMR studies of the silicides ScTSi (T=Co, Ni, Cu, Ru, Rh, Pd, Ir, Pt)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmening, Thomas; Eckert, Hellmut, E-mail: eckerth@uni-muenster.de; Fehse, Constanze M.

The silicides ScTSi (T=Fe, Co, Ni, Cu, Ru, Rh, Pd, Ir, Pt) were synthesized by arc-melting and characterized by X-ray powder diffraction. The structures of ScCoSi, ScRuSi, ScPdSi, and ScIrSi were refined from single crystal diffractometer data. These silicides crystallize with the TiNiSi type, space group Pnma. No systematic influences of the {sup 45}Sc isotropic magnetic shift and nuclear electric quadrupolar coupling parameters on various structural distortion parameters calculated from the crystal structure data can be detected. {sup 45}Sc MAS-NMR data suggest systematic trends in the local electronic structure probed by the scandium atoms: both the electric field gradients andmore » the isotropic magnetic shifts relative to a 0.2 M aqueous Sc(NO{sub 3}){sub 3} solution decrease with increasing valence electron concentration and within each T group the isotropic magnetic shift decreases monotonically with increasing atomic number. The {sup 45}Sc nuclear electric quadrupolar coupling constants are generally well reproduced by quantum mechanical electric field gradient calculations using the WIEN2k code. Highlights: Black-Right-Pointing-Pointer Arc-melting synthesis of silicides ScTSi. Black-Right-Pointing-Pointer Single crystal X-ray data of ScCoSi, ScRuSi, ScPdSi, and ScIrSi. Black-Right-Pointing-Pointer {sup 45}Sc solid state NMR of silicides ScTSi.« less

Water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) amorphous solid dispersions: Insights with confocal fluorescence microscopy.

PubMed

Saboo, Sugandha; Taylor, Lynne S

2017-08-30

The aim of this study was to evaluate the utility of confocal fluorescence microscopy (CFM) to study the water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) (mico-PVPVA) amorphous solid dispersions (ASDs), induced during preparation, upon storage at high relative humidity (RH) and during dissolution. Different fluorescent dyes were added to drug-polymer films and the location of the dyes was evaluated using CFM. Orthogonal techniques, in particular atomic force microscopy (AFM) coupled with nanoscale infrared spectroscopy (AFM-nanoIR), were used to provide additional analysis of the drug-polymer blends. The initial miscibility of mico-PVPVA ASDs prepared under low humidity conditions was confirmed by AFM-nanoIR. CFM enabled rapid identification of drug-rich and polymer-rich phases in phase separated films prepared under high humidity conditions. The identity of drug- and polymer-rich domains was confirmed using AFM-nanoIR imaging and localized IR spectroscopy, together with Lorentz contact resonance (LCR) measurements. The CFM technique was then utilized successfully to further investigate phase separation in mico-PVPVA films exposed to high RH storage and to visualize phase separation dynamics following film immersion in buffer. CFM is thus a promising new approach to study the phase behavior of ASDs, utilizing drug and polymer specific dyes to visualize the evolution of heterogeneity in films exposed to water. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental investigation of passive infrared ice detection for helicopter applications

NASA Technical Reports Server (NTRS)

Dershowitz, Adam; Hansman, R. John, Jr.

1991-01-01

A technique is proposed to remotely detect rotor icing on helicopters. Using passive infrared (IR) thermometry it is possible to detect the warming caused by latent heat released as supercooled water freezes. During icing, the ice accretion region on the blade leading edge will be warmer than the uniced trailing edge resulting in a chordwise temperature profile characteristic of icing. Preliminary tests were conducted on a static model in the NASA Icing Research Tunnel for a variety of wet (glaze) and dry (rime) ice conditions. The characteristic chordwise temperature profiles were observed with an IR thermal video system and confirmed with thermocouple measurements. A prototype detector system was built consisting of a single point IR pyrometer, and experiments were run on a small scale rotor model. Again the characteristic chordwise temperature profiles were observed during icing, and the IR system was able to remotely detect icing. Based on the static and subscale rotor tests the passive IR technique is promising for rotor ice detection.

Experimental investigation of passive infrared ice detection for helicopter applications

NASA Technical Reports Server (NTRS)

Dershowitz, Adam; Hansman, R. John, Jr.

1991-01-01

A technique is proposed to remotely detect rotor icing on helicopters. Using passive infrared (IR) thermometry, it is possible to detect the warming caused by latent heat released as supercooled water freezes. During icing, the ice accretion region on the blade leading edge will be warmer than the uniced trailing edge, resulting in a chordwise temperature profile characteristic of icing. Preliminary tests were conducted on a static model in the NASA Icing Research Tunnel for a variety of wet (glaze) and dry (rime) ice conditions. The characteristic chordwise temperature profiles were observed with an IR thermal video system and confirmed with thermocouple measurements. A prototype detector system was built consisting of a single point IR pyrometer. Experiments were run on a small scale rotor model. Again, the characteristic chordwise temperature profiles were observed during icing, and the IR system was able to remotely detect icing. Based on the static and subscale rotor tests, the passive IR technique is promising for rotor ice detection.

H2O2-responsive molecularly engineered polymer nanoparticles as ischemia/reperfusion-targeted nanotherapeutic agents

NASA Astrophysics Data System (ADS)

Lee, Dongwon; Bae, Soochan; Hong, Donghyun; Lim, Hyungsuk; Yoon, Joo Heung; Hwang, On; Park, Seunggyu; Ke, Qingen; Khang, Gilson; Kang, Peter M.

2013-07-01

The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the most abundant form of ROS produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. Here, we report H2O2-responsive antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA) (PVAX) as a novel I/R-targeted nanotherapeutic agent. PVAX was designed to incorporate VA and H2O2-responsive peroxalate ester linkages covalently in its backbone. PVAX nanoparticles therefore degrade and release VA, which is able to reduce the generation of ROS, and exert anti-inflammatory and anti-apoptotic activity. In hind-limb I/R and liver I/R models in mice, PVAX nanoparticles specifically reacted with overproduced H2O2 and exerted highly potent anti-inflammatory and anti-apoptotic activities that reduced cellular damages. Therefore, PVAX nanoparticles have tremendous potential as nanotherapeutic agents for I/R injury and H2O2-associated diseases.

Synthesis and photocatalytic degradation study of methylene blue dye under visible light irradiation by Fe1-xBixVO4 solid solutions (0 ≤ x ≤ 1.0)

NASA Astrophysics Data System (ADS)

Bera, Ganesh; Reddy, V. R.; Mal, Priyanath; Das, Pradip; Turpu, G. R.

2018-05-01

The novel hetero-structures Fe1-xBixVO4 solid solutions (0 ≤ x ≤ 1.0) with the two dissimilar end member of FeVO4 - BiVO4, were successfully synthesized by the standard solid state reaction method. The structural and chemical properties of as prepared photo-catalyst samples were characterized by X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and UV-visible absorption spectroscopy techniques. It is confirmed from the results of XRD, Raman and FT-IR that FeVO4 and BiVO4 are in triclinic (space group P-1 (2)) and monoclinic (space group I2/b (15)) phases respectively. The Bi incorporation into Fe site of FeVO4 emerges as hetero-structures of both the end members of the solid solutions. In addition, the photocatalytic activity in the degradation of methylene blue (MB) dye under visible light irradiation was carried out through UV-visible spectroscopy measurement of photo-catalysts FeVO4, BiVO4 and mixed phases of both photo-catalyst. The results indicate that under visible light irradiation the photocatalytic activity of mixed phases were very effective and higher than the both single phases of the solid solutions. The composition x= 0.25 exhibits an excellent photocatalytic property for the degradation of MB solution under visible light irradiation rather than other.

Phase Behavior of Binary Mixture of Heptaethylene Glycol Decyl Ether and Water: Formation of Phase Compound in Solid Phase

PubMed

Nibu; Suemori; Inoue

1997-07-01

Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were used to construct and characterize the phase diagram for a binary mixture of heptaethylene glycol decyl ether (C10 E7 ) and water in the temperature range from -60 to 80°C. Plots of the endothermic peak temperatures obtained by DSC measurements against compositions provided eutectic solid-liquid phase boundaries with a eutectic composition of 34 wt% of H2 O. On the other hand, heat of fusion per unit weight of the mixture changed discretely at the composition corresponding to the "eutectic" composition. Furthermore, the IR spectra obtained for the mixture in the solid phase were well reproduced as a superposition of those for the mixture of 34 wt% H2 O and pure components but were not reproduced by superimposing the spectra obtained for the solid surfactant and ice. These observations indicate that a solid phase compound is formed between C10 E7 and water with a stoichiometry of 1:14 and that the compound and pure components exist as separate phases, rather than the phases separating into surfactant and ice, which would be expected if the C10 E7 /water mixture formed a true eutectic mixture system. It is estimated from the composition corresponding to the phase compounds that two molecules of water per oxyethylene unit are bound to hydrophilic polyoxyethylene chain of C10 E7 to form a hydrated compound.

Lone-pair interactions and photodissociation of compressed nitrogen trifluoride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurzydłowski, D., E-mail: dkurzydlowski@uw.edu.pl; Department of Biogeochemistry, Max Planck Institute for Chemistry, 55128 Mainz; Wang, H. B.

2014-08-14

High-pressure behavior of nitrogen trifluoride (NF{sub 3}) was investigated by Raman and IR spectroscopy at pressures up to 55 GPa and room temperature, as well as by periodic calculations up to 100 GPa. Experimentally, we find three solid-solid phase transitions at 9, 18, and 39.5 GPa. Vibrational spectroscopy indicates that in all observed phases NF{sub 3} remains in the molecular form, in contrast to the behavior of compressed ammonia. This finding is confirmed by density functional theory calculations, which also indicate that the phase transitions of compressed NF{sub 3} are governed by the interplay between lone‑pair interactions and efficient moleculemore » packing. Although nitrogen trifluoride is molecular in the whole pressure range studied, we show that it can be photodissociated by mid-IR laser radiation. This finding paves the way for the use of NF{sub 3} as an oxidizing and fluorinating agent in high-pressure reactions.« less

Pressure-induced polymerization of P(CN) 3

DOE PAGES

Gou, Huiyang; Yonke, Brendan L.; Epshteyn, Albert; ...

2015-05-21

Motivated to explore the formation of novel extended carbon-nitrogen solids via well-defined molecular precursor pathways, we studied the chemical reactivity of highly pure phosphorous tricyanide, P(CN) 3, under conditions of high pressure at room temperature. Raman and infrared (IR) spectroscopic measurements reveal a series of phase transformations below 10 GPa, and several low-frequency vibrational modes are reported for the first time. Synchrotron powder Xray diffraction (PXRD) measurements taken during compression show that molecular P(CN) 3 is highly compressible with a bulk modulus of 10.0±0.3 GPa and polymerizes into an amorphous solid above ~10.0 GPa. Raman and infrared (IR) spectra, togethermore » with first-principles molecular-dynamics simulations, show that the amorphization transition is associated with polymerization of the cyanide groups into CN bonds with predominantly sp 2 character, similar to known carbon nitrides, resulting in a novel PCN polymeric phase, which is recoverable to ambient pressure.« less

Quantum-chemical calculations and IR spectra of the (F2)MF2 molecules (M = B, Al, Ga, In, Tl) in solid matrices: a new class of very high electron affinity neutral molecules.

PubMed

Wang, Xuefeng; Andrews, Lester

2011-03-23

Electron-deficient group 13 metals react with F(2) to give the compounds MF(2) (M = B, Al, Ga, In, Tl), which combine with F(2) to form a new class of very high electron affinity neutral molecules, (F(2))MF(2), in solid argon and neon. These (F(2))MF(2) fluorine metal difluoride molecules were identified through matrix IR spectra containing new antisymmetric and symmetric M-F stretching modes. The assignments were confirmed through close comparisons with frequency calculations using DFT methods, which were calibrated against the MF(3) molecules observed in all of the spectra. Electron affinities calculated at the CCSD(T) level fall between 7.0 and 7.8 eV, which are in the range of the highest known electron affinities.

Thermal analysis of combinatorial solid geometry models using SINDA

NASA Technical Reports Server (NTRS)

Gerencser, Diane; Radke, George; Introne, Rob; Klosterman, John; Miklosovic, Dave

1993-01-01

Algorithms have been developed using Monte Carlo techniques to determine the thermal network parameters necessary to perform a finite difference analysis on Combinatorial Solid Geometry (CSG) models. Orbital and laser fluxes as well as internal heat generation are modeled to facilitate satellite modeling. The results of the thermal calculations are used to model the infrared (IR) images of targets and assess target vulnerability. Sample analyses and validation are presented which demonstrate code products.

Preparation of Spray-Dried Soy Isoflavone-Loaded Gelatin Microspheres for Enhancement of Dissolution: Formulation, Characterization and in Vitro Evaluation

PubMed Central

Panizzon, Gean Pier; Bueno, Fernanda Giacomini; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; Dias Filho, Benedito Prado

2014-01-01

The most bioactive soy isoflavones (SI), daidzein (DAI) and genistein (GEN) have poor water solubility, which reduces their bioavailability and health benefits and limits their use in industry. The goal of this study was to develop and characterize a new gelatin matrix to microencapsulate DAI and GEN from soy extract (SE) by spray drying, in order to obtain solid dispersions to overcome solubility problems and to allow controlled release. The influences of 1:2 (MP2) and 1:3 (MP3) SE/polymer ratios on the solid state, yield, morphology, encapsulation efficiency, particle size distribution, release kinetics and cumulative release were evaluated. Analyses showed integral microparticles and high drug content. MP3 and MP2 yield were 43.6% and 55.9%, respectively, with similar mean size (p > 0.05), respectively. X-ray diffraction revealed the amorphous solid state of SE. In vitro release tests showed that dissolution was drastically increased. The results indicated that SE microencapsulation might offer a good system to control SI release, as an alternative to improve bioavailability and industrial applications. PMID:25494200

Methylphenidate Induced Lip and Tongue Biting.

PubMed

Gokcen, Cem; Karadag, Mehmet; Aksoy, Ihsan

2018-05-31

Attention deficit hyperactivity disorder (ADHD) is a life-long neurodevelopmental disorder and treatment depends on pharmacotherapy because of its biological origin. Stimulant drugs are the most commonly used treatment for ADHD and they have various side effects. Herein, we report a case who bit off the tip of her tongue with Osmotic Release Oral System methylphenidate (OROS MPH) 36 mg/day, bit the tip of her lower lip with immediate release (IR) MPH 10 mg/day and lateral part of her tongue with IR MPH 20 mg/day. A diagnosis of epilepsy was unlikely because of the normal neurological examination and electroencephalography findings. This case was considered as an atypical side effect of MPH such as perseverative/compulsive behaviours and movement disorders. Clinicians should be aware of that stimulant medications may cause lip and tongue biting behavior and this may effect treatment compliance tremendously.

[Preparation and in vitro dissolution of magnolol solid dispersion].

PubMed

Tang, Lan; Qiu, Shuai-Bo; Wu, Lan; Lv, Long-Fei; Lv, Hui-Xia; Shan, Wei-Guang

2016-02-01

In this study, solid dispersion system of magnolol in croscarmellose sodium was prepared by using the solvent evaporation method, in order to increase the drug dissolution. And its dissolution behavior, stability and physical characteristics were studied. The solid dispersion was prepared with magnolol and croscarmellose sodium, with the proportion of 1∶5, the in vitro dissolution of magnolol solid dispersion was up to 80.66% at 120 min, which was 6.9 times of magnolol. The results of DSC (differential scanning calorimetry), IR (infra-red) spectrum and SEM (scanning electron microscopy) showed that magnolol existed in solid dispersion in an amorphous form. After an accelerated stability test for six months, the drug dissolution and content in magnolol solid dispersion showed no significant change. So the solid dispersion prepared with croscarmellose sodium as the carrier can remarkably improve the stability and dissolution of magnolol. Copyright© by the Chinese Pharmaceutical Association.

Effects of Shock-Breakout Pressure on Ejection of Micron-Scale Material from Shocked Tin Surfaces

NASA Astrophysics Data System (ADS)

Zellner, Michael; Hammerberg, James; Hixson, Robert; Morley, Kevin; Obst, Andrew; Olson, Russell; Payton, Jeremy; Rigg, Paulo; Buttler, William; Grover, Michael; Iverson, Adam; Macrum, Gregory; Stevens, Gerald; Turley, William; Veeser, Lynn; Routley, Nathan

2007-06-01

Los Alamos National Lab (LANL) is actively engaged in the development of a model to predict the formation of micron-scale fragments ejected (ejecta) from shocked metal surfaces. The LANL ejecta model considers that the amount of ejecta is mainly related to the material's phase on shock release at the free-surface. This effort investigates the relation between ejecta production and shock-breakout pressure for Sn shocked with high explosives to pressures near the solid-on-release/partial-liquid-on-release phase transition region. We found that the amount of ejecta produced for shock-breakout pressures that resulted in partial-liquid-on-release increased significantly compared to that which resulted in solid-on-release. Additionally, we found that the amount of ejecta remained relatively constant within the partial-liquid-on-release, regardless of shock-breakout pressure.

Pressure Effects on the Ejection of Material from Shocked Tin Surfaces

NASA Astrophysics Data System (ADS)

Zellner, M. B.; Grover, M.; Hammerberg, J. E.; Hixson, R. S.; Iverson, A. J.; Macrum, G. S.; Morley, K. B.; Obst, A. W.; Olson, R. T.; Payton, J. R.; Rigg, P. A.; Routley, N.; Stevens, G. D.; Turley, W. D.; Veeser, L.; Buttler, W. T.

2007-12-01

Los Alamos National Lab (LANL) is actively engaged in the development of a model to predict the formation of micron-scale fragments ejected (ejecta) from shocked metals that have surface defects. The LANL ejecta model considers that the amount of ejecta is mainly related to the material's phase on shock release at the free-surface. This effort investigates the relation between ejecta production and shock-breakout pressure for Sn shocked with high explosives to pressures near the solid-on-release/partial-liquid-on-release phase transition region. We found that the amount of ejecta produced for shock-breakout pressures that resulted in partial-liquid-on-release increased significantly compared to that which resulted in solid-on-release. Additionally, we found that the amount of ejecta remained relatively constant within the partial-liquid-on-release, regardless of shock-breakout pressure.

Solid-state NMR and IR for the analysis of pharmaceutical solids: polymorphs of fosinopril sodium.

PubMed

Brittain, H G; Morris, K R; Bugay, D E; Thakur, A B; Serajuddin, A T

1993-01-01

The two polymorphic modifications of fosinopril sodium have been characterized as to their differences in melting behaviour, powder X-ray diffraction patterns, Fourier transform infrared spectra (FTIR), and solid-state 31P- and 13C-NMR spectra. The polymorphs were found to be enantiotropically related based upon melting point, heat of fusion, and solution mediated transformation data. Analysis of the solid-state FTIR and 13C-NMR data indicated that the environment of the acetal side chain of fosinopril sodium differed in two polymorphs, and that there might be cis-trans isomerization about the C6-N peptide bond. These conformational differences are postulated as the origin of the observed polymorphism.

Distribution of Hydroxyl Groups in Kukersite Shale Oil: Quantitative Determination Using Fourier Transform Infrared (FT-IR) Spectroscopy.

PubMed

Baird, Zachariah Steven; Oja, Vahur; Järvik, Oliver

2015-05-01

This article describes the use of Fourier transform infrared (FT-IR) spectroscopy to quantitatively measure the hydroxyl concentrations among narrow boiling shale oil cuts. Shale oil samples were from an industrial solid heat carrier retort. Reference values were measured by titration and were used to create a partial least squares regression model from FT-IR data. The model had a root mean squared error (RMSE) of 0.44 wt% OH. This method was then used to study the distribution of hydroxyl groups among more than 100 shale oil cuts, which showed that hydroxyl content increased with the average boiling point of the cut up to about 350 °C and then leveled off and decreased.

Lasers '81

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, C.B.

1982-01-01

Progress in lasers is discussed. The subjects addressed include: excimer lasers, surface spectroscopy, modern laser spectroscopy, free electron lasers, cavities and propagation, lasers in medicine, X-ray and gamma ray lasers, laser spectroscopy of small molecules and clusters, optical bistability, excitons, nonlinear optics in the X-ray and gamma ray regions, collective atomic phenomena, tunable IR lasers, far IR/submillimeter lasers, and laser-assisted collisions. Also treated are: special applications, multiphoton processes in atoms and small molecules, nuclear pumped lasers, material processing and applications, polarization, high energy lasers, laser chemistry, IR molecular lasers, laser applications of collision and dissociation phenomena, solid state laser materials,more » phase conjugation, advances in laser technology for fusion, metal vapor lasers, picosecond phenomena, laser ranging and geodesy, and laser photochemistry of complex molecules.« less

NanoRelease: Pilot interlaboratory comparison of a weathering protocol applied to resilient and labile polymers with and without embedded carbon nanotubes

EPA Science Inventory

A major use of multi-walled carbon nanotubes (MWCNTs) is as functional fillers embedded in a solid matrix, such as plastics or coatings. Weathering and abrasion of the solid matrix during use can lead to environmental releases of the MWCNTs. Here we focus on a protocol to identif...

77 FR 13145 - Notice of Realty Action: Direct Sale of Public Land in Esmeralda County, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-05

... which solids or hazardous substances or wastes, as defined by Federal and State environmental laws are..., publication in the Federal Register of a termination of the segregation, or on March 5, 2014, unless extended..., or damages of any kind incurred by the United States; (4) Releases or threatened releases of solid or...

Microwave-assisted solid phase conversion study of Meldrum's acid to ethylenetetracarboxylic dianhydride (C 6O 6)

NASA Astrophysics Data System (ADS)

Taherpour, Avat (Arman)

2010-01-01

Utilization of microwave irradiation provides an effective method for fast synthesizing of some important compounds. Microwave-assisted solid phase is an especial class in chemical synthesis. By the use of MW-irradiation on chemicals, sometimes interesting results can be seen. The synthesis of the interesting molecule ethylenetetracarboxylic dianhydride (C 6O 6) was attempted with a few different methods. In this study, the microwave-assisted solid phase conversion of Meldrum's acid to ethylenetetracarboxylic dianhydride was reported. This conversion was characterized by FT-IR, GC/MS and NMR spectroscopy results.

Preparation of a deuterated polymer: Simulating to produce a solid tritium radioactive source

NASA Astrophysics Data System (ADS)

Hu, Rui; Kan, Wentao; Xiong, Xiaoling; Wei, Hongyuan

2017-08-01

The preparation of a deuterated polymer was performed in order to simulate the production of the corresponding tritiated polymer as a solid tritium radioactive source. Substitution and addition reaction were used to introduce deuterium into the polymer. Proton nuclear magnetic resonance and FT-IR spectroscopy were used to investigate the extent and location of deuterium in the polymer, indicating an effectively deuterated polymer was produced. The thermal analysis showed that the final polymer product could tolerate the environmental temperature below 125 °C in its application. This research provides a prosperous method to prepare solid tritium radioactive source.

A solid solution series of atacamite type Ni{sub 2x}Mg{sub 2−2x}Cl(OH){sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bette, Sebastian; Dinnebier, Robert E.; Röder, Christian

2015-08-15

For the first time a complete solid solution series Ni{sub 2x}Mg{sub 2−2x}Cl(OH){sub 3} of an atacamite type alkaline main group metal chloride, Mg{sub 2}Cl(OH){sub 3}, and a transition group metal chloride, Ni{sub 2}Cl(OH){sub 3}, was prepared and characterized by chemical and thermal analysis as well as by Raman and IR spectroscopy, and high resolution laboratory X-ray powder diffraction. All members of the solid solution series crystallize in space group Pnam (62). The main building units of these crystal structures are distorted, edge-linked Ni/MgO{sub 4}Cl{sub 2} and Ni/MgO{sub 5}Cl octahedra. The distribution of Ni{sup 2+}- and Mg{sup 2+}-ions among these twomore » metal-sites within the solid solution series is discussed in detail. The crystallization of the solid solution phases occurs via an intermediate solid solution series, (Ni/Mg)Cl{sub 2x}(OH){sub 2−2x}, with variable Cl: OH ratio up to the 1:3 ratio according to the formula Ni{sub 2x}Mg{sub 2−2x} Cl(OH){sub 3}. For one isolated intermediate solid solution member, Ni{sub 0.70}Mg{sub 0.30}Cl{sub 0.58}(OH){sub 1.42}, the formation and crystal structure is presented as well. - Graphical abstract: For the first time a complete solid solution series, Ni{sub 2x}Mg{sub 2−2x} Cl(OH){sub 3}, was synthesized and characterized. Structure solution by revealed that Ni{sup 2+} prefers to occupy the Jahn–Teller-like distorted hole, out of two available cation sites. Substitution of Ni{sup 2+} by Mg{sup 2+} in atacamite type Ni{sub 2}Cl(OH){sub 3} results in systematic band shifts in Raman and IR spectra as well as in systematic changes in thermal properties. The α-polymorphs M{sub 2}Cl(OH){sub 3} with M=Mg{sup 2+}, Ni{sup 2+} and other divalent transition metal ions, as described in literature, were identified as separate compounds. - Highlights: • First synthesis of solid solution series between main and transition metal chloride. • Ni{sup 2+} prefers to occupy Jahn–Teller-like distorted octahedral holes. • Substitution of Ni{sup 2+} by Mg{sup 2+} results in systematic Raman and IR band shifts. • α-Polymorphs M{sub 2}Cl(OH){sub 3} with M=Mg{sup 2+}, Ni{sup 2+}, … as described in literature do not exist.« less

Phosphorescent binuclear iridium complexes based on terpyridine-carboxylate: an experimental and theoretical study.

PubMed

Andreiadis, Eugen S; Imbert, Daniel; Pécaut, Jacques; Calborean, Adrian; Ciofini, Ilaria; Adamo, Carlo; Demadrille, Renaud; Mazzanti, Marinella

2011-09-05

The phosphorescent binuclear iridium(III) complexes tetrakis(2-phenylpyridine)μ-(2,2':6',2''-terpyridine-6,6''-dicarboxylic acid)diiridium (Ir1) and tetrakis(2-(2,4-difluorophenyl) pyridine))μ-(2,2':6',2''-terpyridine-6,6''-dicarboxylic acid)diiridium (Ir2) were synthesized in a straightforward manner and characterized using X-ray diffraction, NMR, UV-vis absorption, and emission spectroscopy. The complexes have similar solution structures in which the two iridium centers are equivalent. This is further confirmed by the solid state structure of Ir2. The newly reported complexes display intense luminescence in dichloromethane solutions with maxima at 538 (Ir1) and 477 nm (Ir2) at 298 K (496 and 468 nm at 77 K, respectively) and emission quantum yields reaching ~18% for Ir1. The emission quantum yield for Ir1 is among the highest values reported for dinuclear iridium complexes. It shows only a 11% decrease with respect to the emission quantum yield reported for its mononuclear analogue, while the molar extinction coefficient is roughly doubled. This suggests that such architectures are of potential interest for the development of polymetallic assemblies showing improved optical properties. DFT and time-dependent-DFT calculations were performed on the ground and excited states of the complexes to provide insights into their structural, electronic, and photophysical properties.

IRS ruling makes patient power a reality for all employers.

PubMed

Scandlen, Greg

2002-01-01

In June, 2002, the Internal Revenue Service released guidance on the use of Health Reimbursement Arrangements (HRAs) by employers. This action added another important tool to the effort to restore patient power to a financing system that has become ever more dysfunctional over the years. HRAs are far more flexible in design than earlier efforts such as Medical Savings Accounts or Flexible Spending Accounts. Ironically, because of the IRS, innovation is likely to continue in the area of employee benefits.

COBE looks back to the Big Bang

NASA Technical Reports Server (NTRS)

Mather, John C.

1993-01-01

An overview is presented of NASA-Goddard's Cosmic Background Explorer (COBE), the first NASA satellite designed to observe the primeval explosion of the universe. The spacecraft carries three extremely sensitive IR and microwave instruments designed to measure the faint residual radiation from the Big Bang and to search for the formation of the first galaxies. COBE's far IR absolute spectrophotometer has shown that the Big Bang radiation has a blackbody spectrum, proving that there was no large energy release after the explosion.

Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

PubMed

Blaesi, Aron H; Saka, Nannaji

2016-07-25

At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

The use of response surface methodology in the evaluation of captopril microparticles manufactured using an oil in oil solvent evaporation technique.

PubMed

Khamanga, Sandile Maswazi; Walker, Roderick B

2012-01-01

Captopril (CPT) microparticles were manufactured by solvent evaporation using acetone (dispersion phase) and liquid paraffin (manufacturing phase) with Eudragit® and Methocel® as coat materials. Design of experiments and response surface methodology (RSM) approaches were used to optimize the process. The microparticles were characterized based on the percent of drug released and yield, microcapsule size, entrapment efficiency and Hausner ratio. Differential scanning calorimetry (DSC), Infrared (IR) spectroscopy, scanning electron microscopy (SEM) and in vitro dissolution studies were conducted. The microcapsules were spherical, free-flowing and IR and DSC thermograms revealed that CPT was stable. The percent drug released was investigated with respect to Eudragit® RS and Methocel® K100M, Methocel® K15M concentrations and homogenizing speed. The optimal conditions for microencapsulation were 1.12 g Eudragit® RS, 0.67 g Methocel® K100M and 0.39 g Methocel® K15M at a homogenizing speed of 1643 rpm and 89% CPT was released. The value of RSM-mediated microencapsulation of CPT was elucidated.

Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.

PubMed

Djuris, Jelena; Ioannis, Nikolakakis; Ibric, Svetlana; Djuric, Zorica; Kachrimanis, Kyriakos

2014-02-01

This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate. Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate. © 2013 Royal Pharmaceutical Society.

Integrated gas analyzer for complete monitoring of turbine engine test cells.

PubMed

Markham, James R; Bush, Patrick M; Bonzani, Peter J; Scire, James J; Zaccardi, Vincent A; Jalbert, Paul A; Bryant, M Denise; Gardner, Donald G

2004-01-01

Fourier transform infrared (FT-IR) spectroscopy is proving to be reliable and economical for the quantification of many gas-phase species during testing and development of gas turbine engines in ground-based facilities such as sea-level test cells and altitude test cells. FT-IR measurement applications include engine-generated exhaust gases, facility air provided as input to engines, and ambient air in and around test cells. Potentially, the traditionally used assembly of many gas-specific single gas analyzers will be eliminated. However, the quest for a single instrument capable of complete gas-phase monitoring at turbine engine test cells has previously suffered since the FT-IR method cannot measure infrared-inactive oxygen molecules, a key operational gas to both air-breathing propulsion systems and test cell personnel. To further the quest, the FT-IR sensor used for the measurements presented in this article was modified by integration of a miniature, solid-state electrochemical oxygen sensor. Embedded in the FT-IR unit at a location near the long-effective-optical-path-length gas sampling cell, the amperometric oxygen sensor provides simultaneous, complementary information to the wealth of spectroscopic data provided by the FT-IR method.

Solid lipid particles for oral delivery of peptide and protein drugs II--the digestion of trilaurin protects desmopressin from proteolytic degradation.

PubMed

Christophersen, Philip Carsten; Zhang, Long; Müllertz, Anette; Nielsen, Hanne Mørck; Yang, Mingshi; Mu, Huiling

2014-09-01

To investigate the in vitro release and degradation of desmopressin from saturated triglyceride microparticles under both lipolytic and proteolytic conditions. The release of desmopressin from different solid lipid microparticles in the absence and presence of a microbial lipase and protease was determined. Trilaurin (TG12), trimyristin (TG14), tripalmitin (TG16), and tristearin (TG18) were used as lipid excipients to produce solid lipid microparticles. In the presence of lipase, the rate of drug release from different lipid particles was in the order of TG14 > TG16 > TG18, which is the same rank order as the lipid degradation rate. A reverse rank order was found for the protection of desmopressin from enzymatic degradation due to spatial separation of desmopressin from the protease. TG12 accelerated the release of desmopressin from all lipid particles when added as either drug-free microparticles to the lipolysis medium or incorporated in TG16 particles. Additionally, TG12 particles protected desmopressin from degradation when present in the lipolysis medium with the other lipid microparticles. TG12 is a very interesting lipid for oral lipid formulations containing peptides and proteins as it alters release and degradation of the incorporated desmopressin. The present study demonstrates the possibility of bio-relevant in vitro evaluation of lipid-based solid particles.

Heat-mediated activation of affinity-immobilized Taq DNA polymerase.

PubMed

Nilsson, J; Bosnes, M; Larsen, F; Nygren, P A; Uhlén, M; Lundeberg, J

1997-04-01

A novel strategy for heat-mediated activation of recombinant Taq DNA polymerase is described. A serum albumin binding protein tag is used to affinity-immobilize an E. coli-expressed Taq DNA polymerase fusion protein onto a solid support coated with human serum albumin (HSA). Analysis of heat-mediated elution showed that elevated temperatures (> 70 degrees C) were required to significantly release the fusion protein from the solid support. A primer-extension assay showed that immobilization of the fusion protein resulted in little or no extension product. In contrast, fusion protein released from the HSA ligand by heat showed high polymerase activity. Thus, a heat-mediated release and reactivation of the Taq DNA polymerase fusion protein from the solid support can be obtained to allow for hot-start PCR with improved amplification performance.

76 FR 21299 - Emergency Planning and Notification; Emergency Planning and List of Extremely Hazardous...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

...EPA is proposing to revise the manner by which the regulated community would apply the threshold planning quantities (TPQs) for those extremely hazardous substances (EHSs) that are non-reactive solid chemicals in solution form. Specifically, facilities with a solid EHS in solution would be subject to the Emergency Planning requirements if the amount of the solid chemical on-site, when multiplied by 0.2, equaled or exceeded the lower published TPQ, based on data that shows less potential for the solid chemical in solution to remain airborne in the event of an accidental release. Previously, EPA assumed that 100% of the chemical could become airborne in the event of an accidental release.

40 CFR 264.101 - Corrective action for solid waste management units.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Corrective action for solid waste... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Releases From Solid Waste Management Units § 264.101 Corrective action for...

40 CFR 264.101 - Corrective action for solid waste management units.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Corrective action for solid waste... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Releases From Solid Waste Management Units § 264.101 Corrective action for...

Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

PubMed

Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

2016-12-14

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

Gas Supersaturation May Reduce the Survival of Yearling Chinook Salmon in the Lower Columbia River and Ocean Plume

NASA Technical Reports Server (NTRS)

Brosnan, Ian; Welch, David; Scott, Melinda Jacobs

2015-01-01

Unusually high flows in the Columbia River in 2011 raised total dissolved gas (TDG) levels in the river above the 120 percent legal limit imposed to prevent harmful impacts to aquatic organisms. This provided a unique opportunity to evaluate the effect on smolt survival. In-river (IR) migrating juvenile yearling Chinook released at Bonneville Dam with acoustic tags during periods when TDG exceeded 120 percent received estimated maximum exposures of 134 TDG. Subsequent daily survival rates in the lower river and plume were reduced by 0.06 per day (SE equals 0.01) and 0.15 per day (SE equals 0.05) relative to IR migrant fish released when TDG was less than 120 percent. Transported smolts (T) released 10-13 kilometers below Bonneville Dam had lower maximum exposure levels (126 percent) and experienced no difference in daily survival rates relative to unexposed smolts. River temperature levels and trends in turbidity and disease prevalence between releases of high and low exposure smolts were not consistent with the observed effects on survival rates. We conclude that smolts may suffer from chronic effects of elevated TDG exposure while migrating through the Columbia River and plume. Consideration should be given to measuring these survival losses in an explicit experimental framework that isolates possible confounding factors.

IR spectra and properties of solid acetone, an interstellar and cometary molecule

NASA Astrophysics Data System (ADS)

Hudson, Reggie L.; Gerakines, Perry A.; Ferrante, Robert F.

2018-03-01

Mid-infrared spectra of amorphous and crystalline acetone are presented along with measurements of the refractive index and density for both forms of the compound. Infrared band strengths are reported for the first time for amorphous and crystalline acetone, along with IR optical constants. Vapor pressures and a sublimation enthalpy for crystalline acetone also are reported. Positions of 13C-labeled acetone are measured. Band strengths are compared to gas-phase values and to the results of a density-functional calculation. A 73% error in previous work is identified and corrected.

A lithium oxygen secondary battery

NASA Technical Reports Server (NTRS)

Semkow, Krystyna W.; Sammells, Anthony F.

1987-01-01

Some recent work on a lithium-oxygen secondary battery is reported in which stabilized zirconia oxygen vacancy conducting solid electrolytes were used for the effective separation of respective half-cell reactions. The electroactive material consisted of alloys possessing the general composition Li(x)FeSi2 immersed in a ternary molten salt comprising LiF, LiCl, and Li2O. The manufacture of the cell is described, and discharge-current voltage curves for partially charged cells are shown and discussed. A galvanostatic IR free-changing curve and an IR-free charge-discharge curve are also shown.

III-V semiconductor solid solution single crystal growth

NASA Technical Reports Server (NTRS)

Gertner, E. R.

1982-01-01

The feasibility and desirability of space growth of bulk IR semiconductor crystals for use as substrates for epitaxial IR detector material were researched. A III-V ternary compound (GaInSb) and a II-VI binary compound were considered. Vapor epitaxy and quaternary epitaxy techniques were found to be sufficient to permit the use of ground based binary III-V crystals for all major device applications. Float zoning of CdTe was found to be a potentially successful approach to obtaining high quality substrate material, but further experiments were required.

Space Flight Ionizing Radiation Environments

NASA Technical Reports Server (NTRS)

Koontz, Steve

2017-01-01

The space-flight ionizing radiation (IR) environment is dominated by very high-kinetic energy-charged particles with relatively smaller contributions from X-rays and gamma rays. The Earth's surface IR environment is not dominated by the natural radioisotope decay processes. Dr. Steven Koontz's lecture will provide a solid foundation in the basic engineering physics of space radiation environments, beginning with the space radiation environment on the International Space Station and moving outward through the Van Allen belts to cislunar space. The benefits and limitations of radiation shielding materials will also be summarized.

99 W mid-IR operation of a ZGP OPO at 25% duty cycle.

PubMed

Hemming, Alexander; Richards, Jim; Davidson, Alan; Carmody, Neil; Bennetts, Shayne; Simakov, Nikita; Haub, John

2013-04-22

We have demonstrated the highest reported output power from a mid-IR ZGP OPO. The laser is a cascaded hybrid system consisting of a thulium fibre laser, Ho:YAG solid state laser and a Zinc Germanium Phosphide parametric oscillator. The system produces 27 W of output power in the 3-5 μm wavelength range with an M(2) = 4.0 when operating in a repetitively q-switched mode, and a modulated peak output power of 99 W at a reduced duty cycle of 25%.

Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design.

PubMed

Mease, Kirsten M; Kimzey, Amy L; Lansita, Janice A

2017-06-01

The observation of an infusion reaction (IR) in a nonclinical study can cause concern among investigators and regulators in the development of biotherapeutics. Biomarkers can be informative to determine whether the reactions are immune-mediated or test-article related and if there is a potential risk to human subjects. IRs encompass a broad range of adverse events with a variety of triggers; the focus of this paper is IRs due to cytokine release syndrome or immune complex formation and the associated biomarkers. Such reactions generally do not preclude clinical development or marketing approval, because it is widely accepted that immune-mediated reactions in nonclinical species are not predictive of human outcomes. Several US approved products (from 2004 to 2016) have documented IRs in nonclinical species. This review article discusses recent examples, the biomarkers evaluated, and implications for study design and conduct.

Application of FT-IR Classification Method in Silica-Plant Extracts Composites Quality Testing

NASA Astrophysics Data System (ADS)

Bicu, A.; Drumea, V.; Mihaiescu, D. E.; Purcareanu, B.; Florea, M. A.; Trică, B.; Vasilievici, G.; Draga, S.; Buse, E.; Olariu, L.

2018-06-01

Our present work is concerned with the validation and quality testing efforts of mesoporous silica - plant extracts composites, in order to sustain the standardization process of plant-based pharmaceutical products. The synthesis of the silica support were performed by using a TEOS based synthetic route and CTAB as a template, at room temperature and normal pressure. The silica support was analyzed by advanced characterization methods (SEM, TEM, BET, DLS and FT-IR), and loaded with Calendula officinalis and Salvia officinalis standardized extracts. Further desorption studies were performed in order to prove the sustained release properties of the final materials. Intermediate and final product identification was performed by a FT-IR classification method, using the MID-range of the IR spectra, and statistical representative samples from repetitive synthetic stages. The obtained results recommend this analytical method as a fast and cost effective alternative to the classic identification methods.

The chemistry and preparation of tantalum complexes with 2,3-dihydroxy benzoic acid: Experimental and theoretical investigation

NASA Astrophysics Data System (ADS)

Hatzipanayioti, Despina; Kontotheodorou, Konstantinos

2011-03-01

The effect of 2,3-dihydroxybenzoic acid (2,3DHBA, pyrocatechuic acid) on the chloro-alkoxo-species [TaCl 5- x(OMe) x], formed by dissolving TaCl 5 in MeOH, has been studied. The coordination of 2,3DHBA-H 2- on Ta (V) replacing MeO-terminal groups was monitored via NMR spectroscopy. The yellow solid 1 was isolated from the mixture of TaCl 5, with neutral 2,3-DHBA, in MeOH. From this solid the elemental (C, H and Ta), the thermogravimetric analyses, the IR, NMR, ESR and electronic spectra support the formula Ta 2(2,3DHBA) 2(O) 2Cl 4(MeO) 4. The ESR spectrum of solid 1, at 4.2 K, shows a half-field signal apart from a multiline signal around g = 2, supporting evidence for semiquinone and Ta (IV) presence. The occurrence of superoxide radical, in the low temperature of ESR spectrum recording, cannot be ruled out. By heating the solid 1 at 500 °C, an oxide phase showing porous character (SEM) and retaining CO 2 (IR), is evident. Solid 1 heated at 900 °C, leads to the formation of β-Ta 2O 5 orthorhombic phase, as the XRD pattern indicates. The hydrolytic process of solid 1, in aqueous solutions, has been studied; the presence of paramagnetic species generated in situ upon addition of base and the consequent degradative process of 2,3-DHBA, under aerobic conditions is obvious. In order to gain information for the structure of solid 1, DFT calculations have been performed for some theoretical models, based on the empirical formula of solid 1. The calculated structural and spectroscopic parameters have been correlated to experimental results. The energy optimized structures may give an idea about the way of MeCl and MeOMe formation as well some possible intermediates of the hydrolytic mechanism.

Q-switched all-solid-state lasers and application in processing of thin-film solar cell

NASA Astrophysics Data System (ADS)

Liu, Liangqing; Wang, Feng

2009-08-01

Societal pressure to renewable clean energy is increasing which is expected to be used as part of an overall strategy to address global warming and oil crisis. Photovoltaic energy conversion devices are on a rapidly accelerating growth path driven by government, of which the costs and prices lower continuously. The next generation thin-film devices are considered to be more efficiency and greatly reduced silicon consumption, resulting in dramatically lower per unit fabrication costs. A key aspect of these devices is patterning large panels to create a monolithic array of series-interconnected cells to form a low current, high voltage module. This patterning is accomplished in three critical scribing processes called P1, P2, and P3. All-solid-state Q-switched lasers are the technology of choice for these processes, due to their advantages of compact configuration, high peak-value power, high repeat rate, excellent beam quality and stability, delivering the desired combination of high throughput and narrow, clean scribes. The end pumped all-solid-state lasers could achieve 1064nm IR resources with pulse width of nanoseconds adopting acoustic-optics Q-switch, shorter than 20ns. The repeat rate is up to 100kHz and the beam quality is close to diffraction limit. Based on this, 532nm green lasers, 355nm UV lasers and 266nm DUV lasers could be carried out through nonlinear frequency conversion. Different wave length lasers are chose to process selective materials. For example, 8-15 W IR lasers are used to scribe the TCO film (P1); 1-5 W green lasers are suitable for scribing the active semiconductor layers (P2) and the back contact layers (P3). Our company, Wuhan Lingyun Photo-electronic System Co. Ltd, has developed 20W IR and 5W green end-pumped Q-switched all-solid-state lasers for thin-film solar industry. Operating in high repeat rates, the speed of processing is up to 2.0 m/s.

Trends in insect repellent formulations: A review.

PubMed

Tavares, Melanie; da Silva, Márcio Robert Mattos; de Oliveira de Siqueira, Luciana Betzler; Rodrigues, Raphaela Aparecida Schuenck; Bodjolle-d'Almeida, Lolita; Dos Santos, Elisabete Pereira; Ricci-Júnior, Eduardo

2018-03-25

The use of natural and synthetic repellents, marketed in different pharmaceutical forms, is growing in the world due to the emerging vector-borne viral diseases as Dengue, Zika, Chikungunya, Yellow Fever and Malaria. The choice of the ideal formulation will depend on a series of factors to be analyzed: type of repellent active (natural or synthetic), pharmaceutical forms (spray, lotion, cream, gel), action time duration (short or long), environment of exposure and the user (adult, pregnant women, children, newborn). The most used repellents are DEET, IR3535 (Ethyl Butylacetylaminopropionate) (EB), Icaridin (Picaridin) and essential oils, each of them presenting advantages and disadvantages. DEET is the oldest and the most powerful repellent available in the market, thus being the reference standard. For this reason, there are many classic formulations available in the market containing the chemical component DEET in spray forms and lotions. However, due to its toxicity, DEET is not recommended for children up to 6 months and pregnant women. DEET has been an option along with other market-shared products as IR3535 and Icaridin (Picaridin), which present less toxicity in their composition. IR3535 is the less toxic and may be prescribed for children over 6 months of age and pregnant women so that they have been the best option because of the lower toxicity levels presented. IR3535 is the one that has the lowest toxicity level among the three options and may be prescribed for children above 6 months of age and pregnant women. Icaridin is as potent as DEET, but less toxic, and has the advantage of having the long-lasting action among the aforementioned repellents. The new formulations have been based on controlled release systems (CRS). The CRSs for repellents comprise polymer micro/nanocapsules, micro/solid lipid nanoparticles, nanoemulsions/microemulsions, liposomes/niosomes, nanostructured hydrogels and cyclodextrins. There are many formulations based on micro and nanocapsules containing DEET and essential oils to increase repellent action time duration and decrease permeation and consequently, systemic toxicity. The development of new formulations for the IR3535 and Icaridin is a research field yet to be explored. The current trend is the use of natural repellent actives such as essential oils, which present low toxicity, do not harm the environment, but present reduced repellent action time due to rapid evaporation after skin application. CRSs have been used as vehicle of natural repellents to improve long-lasting repellent action, reduce skin permeation and systemic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

PubMed

Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

2015-11-01

To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative pain and was well tolerated in a Taiwanese population. ClinicalTrials.gov identifier: NCT01813890.

Isolation and characterization of formacell Lignins from oil empty fruits bunches

NASA Astrophysics Data System (ADS)

Hidayati, S.; Zuidar, A. S.; Satyajaya, W.; Murhadi; Retnowati, D.

2018-04-01

Lignin is the largest component in black liquor, it is about 46% of solids total and can be isolated by precipitation using acid and base method. The purpose of this study was to get the best NaOH concentration to produce lignin with yield, solids total content, metoxyle lignins content, weights equivalent of lignin in the black liquor by pulping formacell process from oil empty fruits bunches. This study was done with isolation lignin process in black liquor used by NaOH concentration were 5%, 10%, 15%, 20%, 25%, and 30% from volume black liquor and then precipitationed for 10 hours. The result of this research showed the isolation of lignin with NaOH concentration 30% get the pH 5,42%, yield of lignin was 5,67%, solids black liquor total was 65,11%, levels of metoxyle lignin 14,61%, and equivalent weights of lignin was 1787,23. The result of FT-IR identifications of isolates lignin in NaOH concentration 25 and 30% showed a pattern infiltration spektro IR that almost a part that have the same infiltration at the wave numbers that showed lignin had one of the rings lignin was guaiasil, it was building blocks of non wood lignin.

The Effects of Experimental Conditions on the Refractive Index and Density of Low-Temperature Ices: Solid Carbon Dioxide

NASA Technical Reports Server (NTRS)

Loeffler, M. J.; Moore, M. H.; Gerakines, P. A.

2016-01-01

We present the first study on the effects of the deposition technique on the measurements of the visible refractive index and the density of a low-temperature ice using solid carbon dioxide (CO2) at 14-70 K as an example. While our measurements generally agree with previous studies that show a dependence of index and density on temperature below 50 K, we also find that the measured values depend on the method used to create each sample. Below 50 K, we find that the refractive index varied by as much as 4% and the density by as much as 16% at a single temperature depending on the deposition method. We also show that the Lorentz-Lorenz approximation is valid for solid CO2 across the full 14-70 K temperature range, regardless of the deposition method used. Since the refractive index and density are important in calculations of optical constants and infrared (IR) band strengths of materials, our results suggest that the deposition method must be considered in cases where nvis and ? are not measured in the same experimental setup where the IR spectral measurements are made.

Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

PubMed

Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

2018-05-03

Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

N-acetyltransferase (nat) is a critical conjunct of photoperiodism between the circadian system and endocrine axis in Antheraea pernyi.

PubMed

Mohamed, Ahmed A M; Wang, Qiushi; Bembenek, Jadwiga; Ichihara, Naoyuki; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

2014-01-01

Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16:8 (LD) and LD12:12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4 °C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNA(NAT) caused dysfunction of photoperiodism. dsRNA(PER) upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT) decreased melatonin while dsRNA(PER) increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNA(NAT), to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.

N-acetyltransferase (nat) Is a Critical Conjunct of Photoperiodism between the Circadian System and Endocrine Axis in Antheraea pernyi

PubMed Central

Bembenek, Jadwiga; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

2014-01-01

Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16∶8 (LD) and LD12∶12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4°C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNANAT caused dysfunction of photoperiodism. dsRNAPER upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNANAT decreased melatonin while dsRNAPER increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNANAT, to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism. PMID:24667367

Research on the Characteristics and Mechanism of the Cumulative Release of Antimony from an Antimony Smelting Slag Stacking Area under Rainfall Leaching

PubMed Central

Zhou, Yingying; Deng, Renjian

2017-01-01

We aimed to study the characteristics and the mechanism of the cumulative release of antimony at an antimony smelting slag stacking area in southern China. A series of dynamic and static leaching experiments to simulate the effects of rainfall were carried out. The results showed that the release of antimony from smelting slag increased with a decrease in the solid-liquid ratio, and the maximum accumulated release was found to be 42.13 mg Sb/kg waste and 34.26 mg Sb/kg waste with a solid/liquid ratio of 1 : 20; the maximum amount of antimony was released within 149–420 μm size fraction with 7.09 mg/L of the cumulative leaching. Also, the antimony release was the greatest and most rapid at pH 7.0 with the minimum release found at pH 4.0. With an increase in rainfall duration, the antimony release increased. The influence of variation in rainfall intensity on the release of antimony from smelting slag was small. PMID:28804669

Solid Layer Thermal-conductivity Measurement Techniques

DTIC Science & Technology

1994-03-01

deposited on the sample, and the absorption of laser radiation. Temperature-measurement tools include thermocouples, infrared (IR) pyrometers , and...A, Nishimura H, and Sawada T (1990), Laser-Induc~d Surface Acoustic Waves and Photothc:rmal Surfitce Gratings Generated by Crossing Two Pulsed

Synthesis, characterization, and controlled release anticorrosion behavior of benzoate intercalated Zn-Al layered double hydroxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yi; Zhang, Dun, E-mail: zhangdun@qdio.ac.cn

2011-11-15

Graphical abstract: The benzoate anion released from Zn-Al LDHs provides a more effective long-term protection against corrosion of Q235 carbon steel in 3.5% NaCl solution. Highlights: {yields} A benzoate anion corrosion inhibitor intercalated Zn-Al layered double hydroxides (LDHs) has been assembled by coprecipitation method. {yields} The kinetic simulation indicates that the ion-exchange one is responsible for the release process and the diffusion through particle is the rate limiting step. {yields} A significant reduction of the corrosion rate is observed when the LDH nanohybrid is present in the corrosive media. -- Abstract: Corrosion inhibitor-inorganic clay composite including benzoate anion intercalated Zn-Almore » layered double hydroxides (LDHs) are assembled by coprecipitation. Powder X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectrum analyses indicate that the benzoate anion is successfully intercalated into the LDH interlayer and the benzene planes are vertically bilayer-positioned as a quasi-guest ion-pair form in the gallery space. Kinetic simulation for the release data, XRD and FT-IR analyses of samples recovered from the release medium indicate that ion-exchange is responsible for the release process and diffusion through the particle is also indicated to be the rate-limiting step. The anticorrosion capabilities of LDHs loaded with corrosion inhibitor toward Q235 carbon steel are analyzed by polarization curve and electrochemical impedance spectroscopy methods. Significant reduction of corrosion rate is observed when the LDH nanohybrid is present in the corrosive medium. This hybrid material may potentially be applied as a nanocontainer in self-healing coatings.« less

Risperidone mucoadhesive buccal tablets: formulation design, optimization and evaluation

PubMed Central

Çelik, Burak

2017-01-01

The aim of this study was to design and optimize risperidone (RIS) mucoadhesive buccal tablets for systemic delivery as an alternative route. Direct compression method was used for the preparation of buccal tablets, and screening studies were conducted with different polymers to determine their effects on tablet characteristics. Carbopol® (CP) and sodium alginate (SA) were selected as two polymer types for further optimization studies by applying response surface methodology. Tablet hardness (TH), ex vivo residence time (RT), and peak detachment force (DF) from buccal mucosa were selected as three important responses. Physicochemical compatibility of formulation excipients and RIS was evaluated by using Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analysis. In vitro drug release profiles and release kinetics were investigated; swelling index and matrix erosion studies were conducted. Optimum formulation consisted of 16.4% CP and 20.3% SA, which provided 7.67±0.29 hour ex vivo RT, 45.52±4.85 N TH, and 2.12±0.17 N DF. FT-IR spectroscopy and DSC analysis revealed that there was no chemical interaction present between tablet ingredients. Cumulative RIS release of >90% was achieved after 8 hours of in vitro dissolution studies, which was supported by swelling and matrix erosion analysis. Mechanism of RIS release was fitted best to zero-order model, while release exponent (n) value of 0.77 demonstrated an anomalous (non-Fickian) release, indicating combined erosion and swelling mechanism. The results suggested that optimized buccal tablets of RIS would be a promising and alternative delivery system for the treatment of schizophrenia. PMID:29225461

Formulation and evaluation of floating tablet of H2-receptor antagonist.

PubMed

Kesarla, Rajesh S; Vora, Pratik Ashwinbhai; Sridhar, B K; Patel, Gunvant; Omri, Abdelwahab

2015-01-01

Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT. Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem. Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3(2) factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32" flat-faced beveled edges punches followed by sublimation. FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60 K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12 h was found to be 420 mg of POLYOX and 40 mg of l-menthol. Stability studies indicated the formulation as stable. Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12 h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation.

Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury

PubMed Central

Uchiyama, Akihiko; Yamada, Kazuya; Perera, Buddhini; Ogino, Sachiko; Yokoyama, Yoko; Takeuchi, Yuko; Ishikawa, Osamu; Motegi, Sei-ichiro

2015-01-01

Botulinum toxin A (BTX-A) blocks the release of acetylcholine vesicles into the synaptic space, and has been clinically used for aesthetic indications, neuromuscular disorders and hyperhidrosis. Several studies have demonstrated that BTX-A enhanced the blood flow and improved ischemia in animal models. Our objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R areas significantly inhibited the formation of decubitus-like ulcer in cutaneous I/R injury mouse model. The number of CD31+ vessels and αSMA+ pericytes or myofibroblasts in wounds were significantly increased in the I/R mice treated with BTX-A. The hypoxic area and the number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A administration. In an in vitro assay, BTX-A significantly prevented the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in vascular endothelial cells. Furthermore, the administration of BTX-A completely suppressed the ulcer formation in an intermittent short-time cutaneous I/R injury model. These results suggest that BTX-A might have protective effects against ulcer formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting hypoxia-induced cellular damage. Exogenous application of BTX-A might have therapeutic potential for cutaneous I/R injuries. PMID:25766279

Intact and Top-Down Characterization of Biomolecules and Direct Analysis Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Coupled to FT-ICR Mass Spectrometry

PubMed Central

Sampson, Jason S.; Murray, Kermit K.; Muddiman, David C.

2013-01-01

We report the implementation of an infrared laser onto our previously reported matrix-assisted laser desorption electrospray ionization (MALDESI) source with ESI post-ionization yielding multiply charged peptides and proteins. Infrared (IR)-MALDESI is demonstrated for atmospheric pressure desorption and ionization of biological molecules ranging in molecular weight from 1.2 to 17 kDa. High resolving power, high mass accuracy single-acquisition Fourier transform ion cyclotron resonance (FT-ICR) mass spectra were generated from liquid-and solid-state peptide and protein samples by desorption with an infrared laser (2.94 µm) followed by ESI post-ionization. Intact and top-down analysis of equine myoglobin (17 kDa) desorbed from the solid state with ESI post-ionization demonstrates the sequencing capabilities using IR-MALDESI coupled to FT-ICR mass spectrometry. Carbohydrates and lipids were detected through direct analysis of milk and egg yolk using both UV- and IR-MALDESI with minimal sample preparation. Three of the four classes of biological macromolecules (proteins, carbohydrates, and lipids) have been ionized and detected using MALDESI with minimal sample preparation. Sequencing of O-linked glycans, cleaved from mucin using reductive β-elimination chemistry, is also demonstrated. PMID:19185512

Anisotropic kinetic energy release and gyroscopic behavior of CO2 super rotors from an optical centrifuge.

PubMed

Murray, Matthew J; Ogden, Hannah M; Mullin, Amy S

2017-10-21

An optical centrifuge is used to generate an ensemble of CO 2 super rotors with oriented angular momentum. The collision dynamics and energy transfer behavior of the super rotor molecules are investigated using high-resolution transient IR absorption spectroscopy. New multipass IR detection provides improved sensitivity to perform polarization-dependent transient studies for rotational states with 76 ≤ J ≤ 100. Polarization-dependent measurements show that the collision-induced kinetic energy release is spatially anisotropic and results from both near-resonant energy transfer between super rotor molecules and non-resonant energy transfer between super rotors and thermal molecules. J-dependent studies show that the extent and duration of the orientational anisotropy increase with rotational angular momentum. The super rotors exhibit behavior akin to molecular gyroscopes, wherein molecules with larger amounts of angular momentum are less likely to change their angular momentum orientation through collisions.

Anisotropic kinetic energy release and gyroscopic behavior of CO2 super rotors from an optical centrifuge

NASA Astrophysics Data System (ADS)

Murray, Matthew J.; Ogden, Hannah M.; Mullin, Amy S.

2017-10-01

An optical centrifuge is used to generate an ensemble of CO2 super rotors with oriented angular momentum. The collision dynamics and energy transfer behavior of the super rotor molecules are investigated using high-resolution transient IR absorption spectroscopy. New multipass IR detection provides improved sensitivity to perform polarization-dependent transient studies for rotational states with 76 ≤ J ≤ 100. Polarization-dependent measurements show that the collision-induced kinetic energy release is spatially anisotropic and results from both near-resonant energy transfer between super rotor molecules and non-resonant energy transfer between super rotors and thermal molecules. J-dependent studies show that the extent and duration of the orientational anisotropy increase with rotational angular momentum. The super rotors exhibit behavior akin to molecular gyroscopes, wherein molecules with larger amounts of angular momentum are less likely to change their angular momentum orientation through collisions.

VB12-coated Gel-Core-SLN containing insulin: Another way to improve oral absorption.

PubMed

He, Haibing; Wang, Puxiu; Cai, Cuifang; Yang, Rui; Tang, Xing

2015-09-30

To improve the oral absorption of insulin, a novel carrier of Vitamin B12 (VB12) gel core solid lipid nanopaticles (Gel-Core-SLN, GCSLN) was designed with a gel core, lipid matrix and VB12-coated surface. VB12-stearate was synthesized and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). Sol-gel conversion following ultrasonic heating and double emulsion technology were combined to implant the insulin-containing gel into solid lipid nanoparticles (SLN). The influence of the mode of administration, food, the amount of VB12-stearate and the particle size on the oral absorption of insulin incorporated in the VB12-GCSLN was investigated. The determined partition coefficient (LogP) of VB12-stearate in a dichloromethane (DCM)-water system was 3.4. This new structure of VB12-GCSLN had higher insulin encapsulation efficiency (EE) of 55.9%, a lower burst release of less than 10% in the first 2h. In vivo studies demonstrated that stronger absorption of insulin with a relative pharmacological availability (PA) of 9.31% compared with the normal insulin-loaded SLN and GCSLN and fairly stable blood glucose levels up to 12h were maintained without any sharp fluctuations. This study suggests that VB12-GCSLN containing insulin appears to be a promising nano carrier for oral delivery of biomacromolecules with relatively high pharmacological availability. Copyright © 2015 Elsevier B.V. All rights reserved.

40 CFR 258.12 - Wetlands.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Location Restrictions § 258.12 Wetlands. (a) New MSWLF units and lateral...) Impacts on fish, wildlife, and other aquatic resources and their habitat from release of the solid waste...

40 CFR 258.12 - Wetlands.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Location Restrictions § 258.12 Wetlands. (a) New MSWLF units and lateral...) Impacts on fish, wildlife, and other aquatic resources and their habitat from release of the solid waste...

40 CFR 267.101 - What must I do to address corrective action for solid waste management units?

Code of Federal Regulations, 2012 CFR

2012-07-01

... action for solid waste management units? 267.101 Section 267.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE FACILITIES OPERATING UNDER A STANDARDIZED PERMIT Releases from Solid Waste Management Units § 267.101 What...

40 CFR 267.101 - What must I do to address corrective action for solid waste management units?

Code of Federal Regulations, 2014 CFR

2014-07-01

... action for solid waste management units? 267.101 Section 267.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE FACILITIES OPERATING UNDER A STANDARDIZED PERMIT Releases from Solid Waste Management Units § 267.101 What...

40 CFR 267.101 - What must I do to address corrective action for solid waste management units?

Code of Federal Regulations, 2013 CFR

2013-07-01

... action for solid waste management units? 267.101 Section 267.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE FACILITIES OPERATING UNDER A STANDARDIZED PERMIT Releases from Solid Waste Management Units § 267.101 What...

40 CFR 267.101 - What must I do to address corrective action for solid waste management units?

Code of Federal Regulations, 2011 CFR

2011-07-01

... action for solid waste management units? 267.101 Section 267.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE FACILITIES OPERATING UNDER A STANDARDIZED PERMIT Releases from Solid Waste Management Units § 267.101 What...

40 CFR 267.101 - What must I do to address corrective action for solid waste management units?

Code of Federal Regulations, 2010 CFR

2010-07-01

... action for solid waste management units? 267.101 Section 267.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE FACILITIES OPERATING UNDER A STANDARDIZED PERMIT Releases from Solid Waste Management Units § 267.101 What...

Probing Gas Adsorption in Zeolites by Variable-Temperature IR Spectroscopy: An Overview of Current Research.

PubMed

Garrone, Edoardo; Delgado, Montserrat R; Bonelli, Barbara; Arean, Carlos O

2017-09-15

The current state of the art in the application of variable-temperature IR (VTIR) spectroscopy to the study of (i) adsorption sites in zeolites, including dual cation sites; (ii) the structure of adsorption complexes and (iii) gas-solid interaction energy is reviewed. The main focus is placed on the potential use of zeolites for gas separation, purification and transport, but possible extension to the field of heterogeneous catalysis is also envisaged. A critical comparison with classical IR spectroscopy and adsorption calorimetry shows that the main merits of VTIR spectroscopy are (i) its ability to provide simultaneously the spectroscopic signature of the adsorption complex and the standard enthalpy change involved in the adsorption process; and (ii) the enhanced potential of VTIR to be site specific in favorable cases.

Controlled release systems containing solid dispersions: strategies and mechanisms.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation.

PubMed

Kajimoto, Masaki; Ledee, Dolena R; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G; Portman, Michael A

2014-01-01

Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. METHODS AND RESULTS: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon ((13)C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by(13)C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults

PubMed Central

Yang, Xiaoxia; Duan, John; Fisher, Jeffrey

2016-01-01

A previously presented physiologically-based pharmacokinetic model for immediate release (IR) methylphenidate (MPH) was extended to characterize the pharmacokinetic behaviors of oral extended release (ER) MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI) tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations. PMID:27723791

Sustained release effects of berberine-loaded chitosan microspheres on in vitro chondrocyte culture.

PubMed

Zhou, Yan; Liu, Shiqing; Ming, Jianghua; Li, Yaming; Deng, Ming; He, Bin

2017-10-01

The low bioavailability and short biological half-life of berberine chloride (BBR) negatively affect the protective role of this compound against osteoarthritis (OA). The present study was performed to evaluate the effectiveness of sustained BBR release system. Novel BBR-loaded chitosan microspheres (BBR-loaded CMs) were successfully synthesized using an ionic cross-linking method for sustained release. The basic characteristics of the prepared microspheres were subsequently evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) techniques, encapsulation efficiency (EE), and in vitro release experiments. BBR-loaded CMs displayed spherical forms to encapsulate a considerable quantity of BBR (100.8 ± 2.7 mg/g); these microspheres also exhibited an ideal releasing profile. The FT-IR spectra and XRD results revealed that BBR-loaded CMs were successfully synthesized via electrostatic interaction. In vitro experiments further showed that BBR-loaded CMs significantly inhibited sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, and led to increasing mitochondrial membrane potential and maintaining the nuclear morphology. BBR-loaded CMs exerted markedly higher anti-apoptotic activity in the treatment of OA, and markedly inhibited the protein expression levels of caspase-3, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)-5 and matrix metalloproteinase (MMP)-13 induced by SNP in rat articular chondrocytes, compared with free BBR at equivalent concentration. Therefore, novel BBR-loaded CMs may offer potential for application in the treatment of OA.

Alpha-particle radiotherapy: For large solid tumors diffusion trumps targeting.

PubMed

Zhu, Charles; Sempkowski, Michelle; Holleran, Timothy; Linz, Thomas; Bertalan, Thomas; Josefsson, Anders; Bruchertseifer, Frank; Morgenstern, Alfred; Sofou, Stavroula

2017-06-01

Diffusion limitations on the penetration of nanocarriers in solid tumors hamper their therapeutic use when labeled with α-particle emitters. This is mostly due to the α-particles' relatively short range (≤100 μm) resulting in partial tumor irradiation and limited killing. To utilize the high therapeutic potential of α-particles against solid tumors, we designed non-targeted, non-internalizing nanometer-sized tunable carriers (pH-tunable liposomes) that are triggered to release, within the slightly acidic tumor interstitium, highly-diffusive forms of the encapsulated α-particle generator Actinium-225 ( 225 Ac) resulting in more homogeneous distributions of the α-particle emitters, improving uniformity in tumor irradiation and increasing killing efficacies. On large multicellular spheroids (400 μm-in-diameter), used as surrogates of the avascular areas of solid tumors, interstitially-releasing liposomes resulted in best growth control independent of HER2 expression followed in performance by (a) the HER2-targeting radiolabeled antibody or (b) the non-responsive liposomes. In an orthotopic human HER2-negative mouse model, interstitially-releasing 225 Ac-loaded liposomes resulted in the longest overall and median survival. This study demonstrates the therapeutic potential of a general strategy to bypass the diffusion-limited transport of radionuclide carriers in solid tumors enabling interstitial release from non-internalizing nanocarriers of highly-diffusing and deeper tumor-penetrating molecular forms of α-particle emitters, independent of cell-targeting. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

PubMed

Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

2016-04-01

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation and evaluation of metoclopramide solid lipid nanoparticles for rectal suppository.

PubMed

Mohamed, Radwa A; Abass, Haidy A; Attia, Mohamed A; Heikal, Ola A

2013-11-01

The purpose of this study was to formulate and characterize metoclopramide solid lipid nanoparticles (MCP-SLNs) and incorporating it into suppository bases for treatment of nausea and vomiting, produced with chemotherapeutic agents, using one dose per day. MCP-SLNs was prepared using high shear homogenization (hot homogenization) technique using different surfactants (tween 80, poloxamer 407, poloxamer 188 and cremophore) in two different concentrations (2.5% and 5%) then solid lipid nanoparticle (SLN), whose release percentage above 50%, was incorporated into suppository for treatment of nausea and vomiting. The prepared SLN and suppositories were then evaluated and characterized. Formulation of poloxamer 407 with compritol and drug (F9) produced highest in-vitro % release (80%). Transmission electron microscopy showed that SLN had round and spherical shape in form of solid dispersion or drug-enriched core. Particle size analysis of SLN showed a size range of 24.99-396.8 nm. Negative zeta potential proves complete drug entrapment. In-vivo study of MCP-SLN suppositories produced the same %GE as the market metoclopramide (MCP) suppository (Primperan) with sustained release effect. MCP-SLN suppositories (formula F) can reverse decrease in %GE because of emesis with sustained release effect. So it succeeded to be an alternative to MCP suppositories with no multiple dosing. © 2013 Royal Pharmaceutical Society.

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ying; Wang, Jianwei, E-mail: wangjianwei1968@gmail.com; Gu, Tieguang

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) indexmore » in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in fructose-fed rats. • OA attenuated fructose-induced increase in Adipo-IR index and NEFA concentrations. • OA modulated adipose IRS-1/phosphatidylinositol 3-kinase/Akt signaling. • OA ameliorates Adipo-IR via the IRS-1/PI3K/Akt signaling pathway in rats.« less

Characterization of Iridium Coated Rhenium Used in High-Temperature, Radiation-Cooled Rocket Thrusters

NASA Technical Reports Server (NTRS)

Stulen, R. H.; Boehme, D. R.; Clift, W. M.; McCarty, K. F.

1990-01-01

Materials used for radiation-cooled rocket thrusters must be capable of surviving under extreme conditions of high-temperatures and oxidizing environments. While combustion efficiency is optimized at high temperatures, many refractory metals are unsuitable for thruster applications due to rapid material loss from the formation of volatile oxides. This process occurs during thruster operation by reaction of the combustion products with the material surface. Aerojet Technical Systems has developed a thruster cone chamber constructed of Re coated with Ir on the inside surface where exposure to the rocket exhaust occurs. Re maintains its structural integrity at high temperature and the Ir coating is applied as an oxidation barrier. Ir also forms volatile oxide species (IrO2 and IrO3) but at a considerably slower rate than Re. In order to understand the performance limits of Ir-coated Re thrusters, we are investigating the interdiffusion and oxidation kinetics of Ir/Re. The formation of iridium and rhenium oxides has been monitored in situ by Raman spectroscopy during high temperature exposure to oxygen. For pure Ir, the growth of oxide films as thin as approximately 200 A could be easily detected and the formation of IrO2 was observed at temperatures as low as 600 C. Ir/Re diffusion test specimens were prepared by magnetron sputtering of Ir on Re substrates. Concentration profiles were determined by sputter Auger depth profiles of the heat treated specimens. Significant interdiffusion was observed at temperatures as low as 1000 C. Measurements of the activation energy suggest that below 1350 C, the dominant diffusion path is along defects, most likely grain boundaries, rather than bulk diffusion through the grains. The phases that form during interdiffusion have been examined by x ray diffraction. Analysis of heated test specimens indicates that the Ir-Re reaction produces a solid solution phase of Ir dissolved in the HCP structure of Re.

Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate.

PubMed

Gonzalez Novoa, Gelsys Ananay; Heinämäki, Jyrki; Mirza, Sabir; Antikainen, Osmo; Colarte, Antonio Iraizoz; Paz, Alberto Suzarte; Yliruusi, Jouko

2005-02-01

Solid-state compatibility and in vitro dissolution of direct-compressed sustained-release matrices of polyvinylacetate (PVAc) and polyvinylpyrrolidone (PVP) containing ibuprofen as a model drug were studied. Polyvinylalcohol (PVA) was used as an alternative water-soluble polymer to PVP. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) were used for characterizing solid-state polymer-polymer and drug-polymer interactions. The mechanical treatment for preparing physical mixtures of polyvinyl polymers and the drug (i.e. simple blending or stressed cogrinding) was shown not to affect the physical state of the drug and the polymers. With the drug-polymer mixtures the endothermic effect due to drug melting was always evident, but a considerable modification of the melting point of the drug in physical binary mixtures (drug:PVP) was observed, suggesting some interaction between the two. On the other hand, the lack of a significant shift of the melting endothermic peak of the drug in physical tertiary drug-polymer mixtures revealed no evidence of solid-state interaction between the drug and the present polymers. Sustained-release dissolution profiles were achieved from the direct-compressed matrices made from powder mixtures of the drug and PVAc combined with PVP, and the proportion of PVAc in the mixture clearly altered the drug release profiles in vitro. The drug release from the present matrix systems is controlled by both diffusion of the drug through the hydrate matrix and the erosion of the matrix itself.

Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and Hepatoprotective and Toxicity Evaluation.

PubMed

El-Nahas, Amira E; Allam, Ahmed N; Abdelmonsif, Doaa A; El-Kamel, Amal H

2017-11-01

The objectives of this study were to formulate, characterize silymarin-loaded Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic effects after oral administration. SNPs were prepared by nanoprecipitation technique and were evaluated for particle size, entrapment efficiency, TEM, solid-state characterization, and in vitro drug release. The hepatoprotective activity was evaluated after oral administration of selected SNPs in carbon tetrachloride-intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed. The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after 12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state and absence of chemical interaction. The hepatoprotective evaluation of the selected SNPs in CCl 4 -intoxicated rats revealed significant improvement in the activities of different biochemical parameters (P ≤ 0.01) compared to the marketed product. The histopathological studies suggested that the selected SNPs produced better hepatoprotective effect in CCl 4 -intoxicated rats compared with the commercially marketed product. Toxicity study revealed no evident toxic effect for blank or silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The obtained results suggested that the selected SNPs were safe and potentially offered enhancement in the pharmacological hepatoprotective properties of silymarin.

Impact of vibration and agitation speed on dissolution of USP prednisone tablets RS and various IR tablet formulations.

PubMed

Seeger, Nicole; Lange, Sigrid; Klein, Sandra

2015-08-01

Dissolution testing is an in vitro procedure which is widely used in quality control (QC) of solid oral dosage forms and, given that real biorelevant test conditions are applied, can also be used as a predictive tool for the in vivo performance of such formulations. However, if a dissolution method is intended to be used for such purposes, it has to deliver results that are only determined by the quality of the test product, but not by other variables. In the recent past, more and more questions were arising on how to address the effects of vibration on dissolution test results. The present study was performed to screen for the correlation of prednisone dissolution of USP Prednisone Tablets RS with vibration caused by a commercially available vibration source as well as to investigate how drug release from a range of immediate release formulations containing class 1-4 drugs of the biopharmaceutical classification scheme is affected by vibration when performing dissolution experiments at different agitation rates. Results of the present study show that the dissolution process of oral drug formulations can be affected by vibration. However, it also becomes clear that the degree of which a certain level of vibration impacts dissolution is strongly dependent on several factors such as drug properties, formulation parameters, and the design of the dissolution method. To ensure the establishment of robust and predictive dissolution test methods, the impact of variation should thus be considered in method design and validation.

Memantine extended release (28 mg once daily): a review of its use in Alzheimer's disease.

PubMed

Plosker, Greg L

2015-05-01

Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that is a well-established treatment option for moderate to severe dementia of the Alzheimer's type, either alone or in combination with cholinesterase inhibitors. The immediate-release (IR) formulations of memantine (tablets and oral solution) have been available in numerous countries, including the USA, for more than a decade and are administered orally twice daily at a maximum recommended total daily dosage of 20 mg/day. The memantine extended-release (ER) (Namenda XR(®)) 28 mg once-daily capsule formulation was approved in the USA in 2010 and became available more recently. The potential advantages of memantine ER over the IR formulation include a more convenient dosage regimen and lower pill burden that may improve adherence to therapy; also, memantine ER capsules may be opened and the contents sprinkled on applesauce for patients who have difficulty swallowing. Memantine ER provides a higher total daily dosage than the recommended memantine IR regimen and pharmacokinetic data indicate greater exposure with the ER formulation, but the clinical implications of this are unclear, as the two formulations have not been assessed in a comparative clinical trial. The efficacy of memantine ER 28 mg once daily was demonstrated in a large, multinational, phase III trial, which showed that the addition of memantine ER to ongoing oral cholinesterase inhibitors improved key outcomes compared with cholinesterase inhibitor monotherapy, including measures of cognition and global status, which were the co-primary endpoints of the study. The most common adverse events were headache, diarrhoea and dizziness.

Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

PubMed

Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

2017-09-01

An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.

Low-dose ionizing radiation increases the mortality risk of solid cancers in nuclear industry workers: A meta-analysis.

PubMed

Qu, Shu-Gen; Gao, Jin; Tang, Bo; Yu, Bo; Shen, Yue-Ping; Tu, Yu

2018-05-01

Low-dose ionizing radiation (LDIR) may increase the mortality of solid cancers in nuclear industry workers, but only few individual cohort studies exist, and the available reports have low statistical power. The aim of the present study was to focus on solid cancer mortality risk from LDIR in the nuclear industry using standard mortality ratios (SMRs) and 95% confidence intervals. A systematic literature search through the PubMed and Embase databases identified 27 studies relevant to this meta-analysis. There was statistical significance for total, solid and lung cancers, with meta-SMR values of 0.88, 0.80, and 0.89, respectively. There was evidence of stochastic effects by IR, but more definitive conclusions require additional analyses using standardized protocols to determine whether LDIR increases the risk of solid cancer-related mortality.

EVALUATION OF CHEMICAL RELEASES AND WORKER EXPOSURES FROM FILTER PRESS OPERATIONS

EPA Science Inventory

The exposures (inhalation and dermal) and releases (air, water, solids, and process streams) associated with the filtration of industrial wastewater sludge from an electronics manufacturing plant were characterized. Chemical releases and worker exposures for a target chemical (t...

Bioavailability, pharmacokinetics, and safety of riociguat given as an oral suspension or crushed tablet with and without food

PubMed Central

Frey, Reiner; Becker, Corina; Unger, Sigrun; Wensing, Georg; Mück, Wolfgang

2016-01-01

Abstract Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (Cmax) to dose were within bioequivalence criteria. After food, dose-normalized AUC and Cmax decreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The Cmax increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased Cmax of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable. PMID:27162630

Bioavailability, pharmacokinetics, and safety of riociguat given as an oral suspension or crushed tablet with and without food.

PubMed

Saleh, Soundos; Frey, Reiner; Becker, Corina; Unger, Sigrun; Wensing, Georg; Mück, Wolfgang

2016-03-01

Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (C max) to dose were within bioequivalence criteria. After food, dose-normalized AUC and C max decreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The C max increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased C max of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable.

Relationships Between Molecular Structure and Chemical Reactivity in Hypergolic Ionic Liquids: Progress Toward Designing Green Fuels for Bipropellant Applications

DTIC Science & Technology

2012-05-01

molten salts can be employed over a wide range of applications, which include solvents, 7 electrolytes , 8 pharmaceuticals and therapeutics,9 and...waxy, hygroscopic solid at room temperature, where the additional products in the HP series exist as liquids at room 9 temperature. In general...compressed aluminum pans. Melting and decomposition points for solids were measured by DSC from 40 to 400 oC at a scan rate of 5 ºC/min. IR spectra

Post-transcriptional regulation of breast cancer resistance protein after intestinal ischemia-reperfusion.

PubMed

Ogura, Jiro; Kobayashi, Masaki; Itagaki, Shirou; Hirano, Takeshi; Iseki, Ken

2008-05-01

Breast cancer resistance protein (BCRP), the product of the ABCG2 gene, is a recently identified ATP binding cassette half-transporter. BCRP is expressed in a variety of tumor cells and many normal human tissues. In the small intestine, BCRP can limit the influx and facilitate the efflux to prevent intracellular accumulation of BCRP substrates. Ischemia-reperfusion (I/R) induces the release of reactive oxygen species, and organs are severely damaged by I/R. It has been shown that the expression of transporters was altered in the organ after I/R. The present study was undertaken to clarify the expression of BCRP after intestinal I/R. We showed that the expression level of Bcrp was significantly decreased at 1 h after I/R. Bcrp mRNA level was not altered at 1 h after I/R. These results suggest that Bcrp expression was regulated by a post-transcriptional regulation mechanism after intestinal I/R. Bcrp mRNA level was increased at 24 h after I/R, and the expression level of Bcrp protein was of the same level or slightly increased compared with sham operated-rats. Bcrp was slightly located at the intestinal membrane at 24 h after intestinal I/R. These results suggested that Bcrp was not translocated to the intestinal membrane after intestinal I/R. There is little information on post-transcriptional regulation compared with information on transcriptional regulation. In this study, it was shown that Bcrp expression is regulated by post-transcriptional regulation after intestinal I/R. These results of this study may provide important information for further studies aimed at revealing the biological function of Bcrp.

Silk protein aggregation kinetics revealed by Rheo-IR.

PubMed

Boulet-Audet, Maxime; Terry, Ann E; Vollrath, Fritz; Holland, Chris

2014-02-01

The remarkable mechanical properties of silk fibres stem from a multi-scale hierarchical structure created when an aqueous protein "melt" is converted to an insoluble solid via flow. To directly relate a silk protein's structure and function in response to flow, we present the first application of a Rheo-IR platform, which couples cone and plate rheology with attenuated total reflectance infrared spectroscopy. This technique provides a new window into silk processing by linking shear thinning to an increase in molecular alignment, with shear thickening affecting changes in the silk protein's secondary structure. Additionally, compared to other static characterization methods for silk, Rheo-IR proved particularly useful at revealing the intrinsic difference between natural (native) and reconstituted silk feedstocks. Hence Rheo-IR offers important novel insights into natural silk processing. This has intrinsic academic merit, but it might also be useful when designing reconstituted silk analogues alongside other polymeric systems, whether natural or synthetic. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Preparation and Thermoelectric Properties of IR(sub x)Co(sub 1-x)Sb(sub 2) Alloys

NASA Technical Reports Server (NTRS)

Caillat, Thierry

1995-01-01

The preparation and characterization of the binary arsenopyrite compounds CoSb2 and IrSb2 and IrxCo1-xSb2 alloys is reported. Single crystals of CoSb2 were grown by the vertical gradient freeze technique from solution rich in antimony. Polycrystalline samples of IrSb2 and IrxCo1-xSb2 alloys were prepared by hot-pressing of prereacted elemental powders. Samples were investigated by X-ray diffractometry, microprobe analysis and density measurements. It was found that a range of solid solution exist in the system IrxCo1-xSb2 for 0.1

Preparation and drug release behavior of temperature-responsive mesoporous carbons

NASA Astrophysics Data System (ADS)

Wang, Xiufang; Liu, Ping; Tian, Yong

2011-06-01

A temperature-responsive composite based on poly (N-isopropylacrylamide) (PNIPAAm) and ordered mesoporous carbons (OMCs) has been successfully prepared by a simple wetness impregnation technique. The structures and properties of the composite were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), N 2 sorption, thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The results showed that the inclusion of PNIPAAm had not greatly changed the basic ordered pore structure of the OMCs. Ibuprofen (IBU) was selected as model drug, and in vitro test of IBU release exhibited a temperature-responsive controlled release delivery.

Dissolution enhancement of atorvastatin calcium by co-grinding technique.

PubMed

Prabhu, Priyanka; Patravale, Vandana

2016-08-01

Atorvastatin calcium (AC) is a BCS class II drug which shows poor bioavailability due to inadequate dissolution. Solid dispersions present a promising option to enhance the solubility of poorly soluble drugs. Co-grinding with hydrophilic excipients is an easy and economical technique to improve the solubility of poorly soluble drugs and is free from usage of organic solvents. The aim of the present study was to explore novel carrier VBP-1 (organosulphur compound) for formulating a solid dispersion by using a simple, commercially viable co-grinding technique to enhance the dissolution of AC and to develop an oral formulation of the same. Composition of the solid dispersion was optimized based on the release profile in pH 1.2 buffer. The optimized solid dispersion was further characterized for flow properties, DSC, FTIR spectroscopy, XRD, contact angle, SEM studies and release profile in phosphate buffer pH 6.8. The developed solid dispersion gave similar release profile as the innovator formulation (Lipitor® tablets) in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed solid dispersion was formulated into hard gelatin capsules (size 3). The developed capsules were found to give similar release as the innovator formulation in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed capsules were found to be stable for a period of 6 months. Anti-hyperlipidemic efficacy studies in rats showed higher reduction in cholesterol and triglyceride levels by the developed capsules in comparison to pure AC. In conclusion, novel carrier VBP-1 was successfully employed to enhance the dissolution of AC using co-grinding technique.

Hydrothermal carbonization of food waste for nutrient recovery and reuse.

PubMed

Idowu, Ifeolu; Li, Liang; Flora, Joseph R V; Pellechia, Perry J; Darko, Samuel A; Ro, Kyoung S; Berge, Nicole D

2017-11-01

Food waste represents a rather large and currently underutilized source of potentially available and reusable nutrients. Laboratory-scale experiments evaluating the hydrothermal carbonization of food wastes collected from restaurants were conducted to understand how changes in feedstock composition and carbonization process conditions influence primary and secondary nutrient fate. Results from this work indicate that at all evaluated reaction times and temperatures, the majority of nitrogen, calcium, and magnesium remain integrated within the solid-phase, while the majority of potassium and sodium reside in the liquid-phase. The fate of phosphorus is dependent on reaction times and temperatures, with solid-phase integration increasing with higher reaction temperature and longer time. A series of leaching experiments to determine potential solid-phase nutrient availability were also conducted and indicate that, at least in the short term, nitrogen release from the solids is small, while almost all of the phosphorus present in the solids produced from carbonizing at 225 and 250°C is released. At a reaction temperature of 275°C, smaller fractions of the solid-phase total phosphorus are released as reaction times increase, likely due to increased solids incorporation. Using these data, it is estimated that up to 0.96% and 2.30% of nitrogen and phosphorus-based fertilizers, respectively, in the US can be replaced by the nutrients integrated within hydrochar and liquid-phases generated from the carbonization of currently landfilled food wastes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of Detailed and Reduced Kinetics Mechanisms for Surrogates of Petroleum-Derived and Synthetic Jet Fuels

DTIC Science & Technology

2011-02-28

Meeting of Combustion, Atlanta, Georgia, paper 2A18, March 20-23, 2011. 9.2 Web Releases Sirjean, B., Dames, A., Sheen, D.A., You, X.-Q., Sung, C...was no significant interfering absorption or emission. IR diode laser absorption of CO2 and H2O: The recent commercial availability of DFB...distributed feedback) IR diode lasers in the wavelength vicinity of 2.5-2.7 microns has allowed the development of a new CO2 and H2O absorption diagnostics

Redistribution of Lunar Polar Water to Mid-latitudes and Its Role in Forming an OH Veneer

NASA Technical Reports Server (NTRS)

Farrell, William M.; Hurley, D. M.; Hodges, R. R.; Killen, R. M.; Halekas, J. S.; Zimmerman, M. I.; Delory, G. T.

2013-01-01

We suggest that energization processes like ion sputtering and impact vaporization can eject/release polar water molecules residing within cold trapped regions with sufficient velocity to allow their redistribution to mid-latitudes. We consider the possibility that these polar-ejected molecules can contribution to the water/OH veneer observed as a 3 micrometer IR absorption feature at mid-latitudes by Chandrayaan-1, Cassini, and EPOXI. We find this source cannot fully account for the observed IR feature, but could be a low intensity additional source.

Theranostic reduction-sensitive gemcitabine prodrug micelles for near-infrared imaging and pancreatic cancer therapy

NASA Astrophysics Data System (ADS)

Han, Haijie; Wang, Haibo; Chen, Yangjun; Li, Zuhong; Wang, Yin; Jin, Qiao; Ji, Jian

2015-12-01

A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06734k

Structure and magnetic properties of SiO{sub 2}/PCL novel sol–gel organic–inorganic hybrid materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catauro, Michelina, E-mail: michelina.catauro@unina2.it; Bollino, Flavia; Cristina Mozzati, Maria

2013-07-15

Organic–inorganic nanocomposite materials have been synthesized via sol–gel. They consist of an inorganic SiO{sub 2} matrix, in which different percentages of poly(ε-caprolactone) (PCL) have been incorporated. The formation of H-bonds among the carbonyl groups of the polymer chains and Si–OH group of the inorganic matrix has been proved by means of Fourier transform infrared spectroscopy (FT-IR) analysis and has been confirmed by solid-state nuclear magnetic resonance (NMR). X-Ray diffraction (XRD) analysis highlighted the amorphous nature of the synthesized materials. Scanning electron microscope (SEM) micrograph and atomic force microscope (AFM) topography showed their homogeneous morphology and nanostructure nature. Considering the opportunitymore » to synthesize these hybrid materials under microgravity conditions by means of magnetic levitation, superconducting quantum interference device (SQUID) magnetometry has been used to quantify their magnetic susceptibility. This measure has shown that the SiO{sub 2}/PCL hybrid materials are diamagnetic and that their diamagnetic susceptibility is independent of temperature and increases with the PCL amount. - Graphical abstract: Characterization and magnetic properties of SiO{sub 2}/PCL organic–inorganic hybrid materials synthesized via sol–gel. FT-IR, Fourier transform infrared spectroscopy; solid-state NMR: solid-state nuclear magnetic resonance; SQUID: superconducting quantum interference device. - Highlights: • Sol–gel synthesis of SiO{sub 2}/PCL amorphous class I organic–inorganic hybrid materials. • FT-IR and NMR analyses show the hydrogen bonds formation between SiO{sub 2} and PCL. • AFM and SEM analyses confirm that the SiO{sub 2}/PCL are homogenous hybrid materials. • The SQUID measures show that the simples are diamagnetic. • Diamagnetic susceptibility of SiO{sub 2}/PCL materials increases with the PCL amount.« less

Behavior of TiO₂ nanoparticles during incineration of solid paint waste: a lab-scale test.

PubMed

Massari, Andrea; Beggio, Marta; Hreglich, Sandro; Marin, Riccardo; Zuin, Stefano

2014-10-01

In order to assess the potential impacts posed by products containing engineered nanoparticles, it is essential to generate more data about the release of these particles from products' life cycle. Although first studies were performed to investigate the release of nanoparticles from use phase, very few data are available on the potential release from recycling or disposal of nano-enhanced products. In this work, we investigated the behavior of TiO2 nanoparticles from incineration of solid paint waste containing these particles. Solid paint debris with and without TiO2 nanoparticles were treated in a lab scale incineration plant at 950°C (combustion temperature) and in oxidizing atmosphere. The obtained ashes were also vitrified with additives and the release of Ti was finally evaluated by leaching test. From our incineration lab-scale experiment, we did not observe a release of TiO2 nanoparticles into the atmosphere, and Ti was attached to the surface of obtained solid residues (i.e. ashes). The characterization of ashes showed that TiO2 nanoparticles reacted during the incineration to give calcium titanate. Finally, a very low release of Ti was measured, less 1 mg/kg, during the leaching test of ashes vitrified with glass cullet and feldspathic inert. Our work suggests that TiO2 nanoparticles added in paints may undergo to physicochemical transformation during the incineration, and that Ti found in ashes may be strongly immobilized in glass matrix. Since this conclusion is based on lab-scale experiment, further research is required to identify which nanoparticles will be emitted to the environment from a real-word-incineration system of household hazardous waste. Copyright © 2014 Elsevier Ltd. All rights reserved.

HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

PubMed

Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

2010-02-01

Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

77 FR 16679 - Emergency Planning and Notification; Emergency Planning and List of Extremely Hazardous...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-22

...The U.S. Environmental Protection Agency (EPA or the Agency) is taking final action to revise the manner for applying the threshold planning quantities (TPQs) for those extremely hazardous substances (EHSs) that are non-reactive solid chemicals in solution. This revision allows facilities subject to the Emergency Planning requirements that have a non-reactive solid EHS in solution, to first multiply the amount of the solid chemical in solution on-site by 0.2 before determining if this quantity equals or exceeds the lower published TPQ. This change is based on data that shows less potential for non-reactive solid chemicals in solution to remain airborne and dispersed beyond a facility's fence line in the event of an accidental release. Previously, EPA assumed that 100% of non-reactive solid chemicals in solution could become airborne and dispersed beyond the fenceline in the event of an accidental release.

A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine.

PubMed

Mahmah, Osama; Tabbakh, Rami; Kelly, Adrian; Paradkar, Anant

2014-02-01

To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying. Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40°C/75% RH) over 8 weeks. Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations. Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations. © 2013 Royal Pharmaceutical Society.

Modeling the impact of solid noise barriers on near road air quality

EPA Science Inventory

Studies based on field measurements, wind tunnel experiments, and controlled tracer gas releases indicate that solid, roadside noise barriers can lead to reductions in downwind near-road air pollutant concentrations. A tracer gas study showed that a solid barrier reduced pollutan...

40 CFR 240.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pollutants released to the atmosphere. (g) Facility means all thermal processing equipment, buildings, and... hazards by spreading the solid wastes in thin layers, compacting the solid wastes to the smallest...

40 CFR 240.101 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... pollutants released to the atmosphere. (g) Facility means all thermal processing equipment, buildings, and... hazards by spreading the solid wastes in thin layers, compacting the solid wastes to the smallest...

40 CFR 240.101 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... pollutants released to the atmosphere. (g) Facility means all thermal processing equipment, buildings, and... hazards by spreading the solid wastes in thin layers, compacting the solid wastes to the smallest...

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom.

PubMed

Nazir, Jameel; Maman, Khaled; Neine, Mohamed-Elmoctar; Briquet, Benjamin; Odeyemi, Isaac A O; Hakimi, Zalmai; Garnham, Andy; Aballéa, Samuel

2015-09-01

Mirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB). To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective. A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed. Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity. Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective. Copyright © 2015. Published by Elsevier Inc.

Anaerobic stabilization of waste activated sludge at different temperatures and solid retention times: Evaluation by sludge reduction, soluble chemical oxygen demand release and dehydration capability.

PubMed

Li, Xiyao; Peng, Yongzhen; He, Yuelan; Wang, Shuying; Guo, Siyu; Li, Lukai

2017-03-01

Anaerobic treatment is the most widely used method of waste activated sludge (WAS) stabilization. Using a semi-continuous stirring tank with condensed WAS, we investigated effects of decreasing the solid retention time (SRT) from 32days to 6.4days on sludge reduction, soluble chemical oxygen demand (SCOD) release and dehydration capability, along with anaerobic digestion operated at medium temperature (MT-AD) or anaerobic digestion operated at room temperature (RT-AD). Results showed that effects of temperature on SCOD release were greater at SRT of 32d and 6.4d. When SRT was less than 8d, total solids (TS), volatile solids (VS) and capillary suction time (CST) did not change significantly. CST was lowest at SRT of 10.7days, indicating best condition for sludge dehydration. Principal component analysis (PCA) showed that the most optimum SRT was higher than 10.7d both in MT-AD or RT-AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Copper-based alloys, crystallographic and crystallochemical parameters of alloys in binary systems Cu-Me (Me=Co, Rh, Ir, Cu, Ag, Au, Ni, Pd, Pt)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Porobova, Svetlana, E-mail: porobova.sveta@yandex.ru; Loskutov, Oleg, E-mail: lom58@mail.ru; Markova, Tat’jana, E-mail: patriot-rf@mail.ru

2016-01-15

The article presents the results of the analysis of phase equilibrium of ordered phases in binary systems based on copper Cu- Me (where Me - Co, Rh, Ir, Ag, Au, Ni, Pd, Pt) to find correlations of crystallochemical and crystallographic factors. It is established that the packing index in disordered solid solutions in binary systems based on copper is close to the value of 0.74 against the background of an insignificant deviation of atomic volumes from the Zen’s law.

High Energy, Single-Mode, All-Solid-State and Tunable UV Laser Transmitter

NASA Technical Reports Server (NTRS)

Prasad, Narasimha S.; Singh, Upendra N.; Hovis, FLoyd

2007-01-01

A high energy, single mode, all solid-state Nd:YAG laser primarily for pumping an UV converter is developed. Greater than 1 J/pulse at 50 HZ PRF and pulse widths around 22 ns have been demonstrated. Higher energy, greater efficiency may be possible. Refinements are known and practical to implement. Technology Demonstration of a highly efficient, high-pulse-energy, single mode UV wavelength generation using flash lamp pumped laser has been achieved. Greater than 90% pump depletion is observed. 190 mJ extra-cavity SFG; IR to UV efficiency > 21% (> 27% for 1 mJ seed). 160 mJ intra-cavity SFG; IR to UV efficiency up to 24% Fluence < 1 J/sq cm for most beams. The pump beam quality of the Nd:YAG pump laser is being refined to match or exceed the above UV converter results. Currently the Nd:YAG pump laser development is a technology demonstration. System can be engineered for compact packaging.

C sbnd H…F hydrogen bonds as the organising force in F-substituted α-phenyl cinnamic acid aggregates studied by the combination of FTIR spectroscopy and computations

NASA Astrophysics Data System (ADS)

Tolnai, B.; Kiss, J. T.; Felföldi, K.; Pálinkó, I.

2009-04-01

Various F-substituted E-2,3-diphenyl propenoic acid molecules were synthesised and their aggregation behaviour was studied by experimental (FT-IR spectroscopy) and computational (semiempirical and DFT) methods. Experimental approach embraced the identification of potential hydrogen bonding sites through finding the relevant IR bands and monitoring their shifts upon increasing the acid concentration and on going to the solid state. It was found that fluorine engaged in C sbnd H…F hydrogen bonding easily, where the carbon atom could be of any kind available in the molecule (aromatic, aliphatic or olefinic). Shifts were found even in moderately concentrated solutions and in the solid state too. Hydrogen bonding sites could be assigned and relevant aggregate models could be built. Molecular modelling allowed obtaining good estimates for hydrogen bond lengths and angles and visualisation of the geometric arrangements even of extended networks also became feasible.

Photoluminescence studies on holmium (III) and praseodymium (III) doped calcium borophosphate (CBP) phosphors

NASA Astrophysics Data System (ADS)

Reddy Prasad, V.; Damodaraiah, S.; Devara, S. N.; Ratnakaram, Y. C.

2018-05-01

Using solid state reaction method, Ho3+ and Pr3+ doped calcium borophosphate (CBP) phosphors were prepared. These phosphors were characterized using XRD, SEM, FT-IR, 31P solid state NMR, photoluminescence (PL) and decay profiles. Structural details were discussed from XRD and FT-IR spectra. From 31P NMR spectra of these phosphors, mono-phosphate complexes Q0-(PO43-) were observed. Photoluminescence spectra were measured for both Ho3+ and Pr3+ doped calcium borophosphate phosphors and the spectra were studied for different concentrations. Decay curves were obtained for the excited level, 5F4+5S2 of Ho3+ and 1D2 level of Pr3+ in these calcium borophosphate phosphors and lifetimes were measured. CIE color chromaticity diagrams are drawn for these two rare earth ions in calcium borophosphate phosphors. Results show that Ho3+ and Pr3+ doped CBP phosphors might be served as green and red luminescence materials.

Methylphenidate Efficacy: Immediate versus Extended Release at Short Term in Mexican Children with ADHD Assessed by Conners Scale and EEG

PubMed Central

Alatorre-Miguel, Efren; Zambrano-Sánchez, Elizabeth; Reyes-Legorreta, Celia

2015-01-01

Attention deficit hyperactivity disorder (ADHD) affects 5-6% of school aged children worldwide. Pharmacological therapy is considered the first-line treatment and methylphenidate (MPH) is considered the first-choice medication. There are two formulations: immediate release (IR) MPH and long-acting (or extended release) formulation (MPH-ER). In this work, we measure the efficacy of treatment for both presentations in one month with Conners' scales and electroencephalography (EEG). Results. for IR group, in parents and teachers Conners test, all items showed significant differences, towards improvement, except for teachers in perfectionism and emotional instability. For ER group in parent's Conners test, the items in which there were no significant differences are psychosomatic and emotional instability. For teachers, there were no significant differences in: hyperactivity and perfectionism. Comparing the Conners questionnaires (parents versus teachers) we find significant differences before and after treatment in hyperactivity, perfectionism, psychosomatics, DSM-IV hyperactive-impulsive, and DSM-IV total. In the EEG the Wilcoxon test showed a significant difference (P < 0.0001). As we can see, both presentations are suitable for managing the ADHD and have the same effect on the symptomatology and in the EEG. PMID:25838946

Methylphenidate Efficacy: Immediate versus Extended Release at Short Term in Mexican Children with ADHD Assessed by Conners Scale and EEG.

PubMed

Durand-Rivera, Alfredo; Alatorre-Miguel, Efren; Zambrano-Sánchez, Elizabeth; Reyes-Legorreta, Celia

2015-01-01

Attention deficit hyperactivity disorder (ADHD) affects 5-6% of school aged children worldwide. Pharmacological therapy is considered the first-line treatment and methylphenidate (MPH) is considered the first-choice medication. There are two formulations: immediate release (IR) MPH and long-acting (or extended release) formulation (MPH-ER). In this work, we measure the efficacy of treatment for both presentations in one month with Conners' scales and electroencephalography (EEG). Results. for IR group, in parents and teachers Conners test, all items showed significant differences, towards improvement, except for teachers in perfectionism and emotional instability. For ER group in parent's Conners test, the items in which there were no significant differences are psychosomatic and emotional instability. For teachers, there were no significant differences in: hyperactivity and perfectionism. Comparing the Conners questionnaires (parents versus teachers) we find significant differences before and after treatment in hyperactivity, perfectionism, psychosomatics, DSM-IV hyperactive-impulsive, and DSM-IV total. In the EEG the Wilcoxon test showed a significant difference (P < 0.0001). As we can see, both presentations are suitable for managing the ADHD and have the same effect on the symptomatology and in the EEG.

Development and evaluation of novel flavour microcapsules containing vanilla oil using complex coacervation approach.

PubMed

Yang, Ziming; Peng, Zheng; Li, Jihua; Li, Sidong; Kong, Lingxue; Li, Puwang; Wang, Qinghuang

2014-02-15

A novel flavour microcapsule containing vanilla oil (VO) was developed using complex coacervation approach, aimed to control release of VO and enhance its thermostability for spice application in food industry. Viscosity of chitosan (CS) and VO/CS ratio were optimised for fabrication of microcapsules. The flavour microcapsules were evaluated by scanning electron micrograph (SEM), laser confocal microscopy (LSCM), particle size analyser, infrared spectrometer (FT-IR), thermal analysis and controlled-release analysis. The microcapsules were in spherical with good dispersibility when moderate viscosity CS was used. 94.2% of encapsulation efficiency was achieved in VO/CS ratio of 2:1. The FT-IR study proved chemical cross-linking reaction occurred between genipin and chitosan, but a physical interaction between CS and VO. A core-shell structure of microcapsule was confirmed by LSCM, which was beneficial to improve the thermostability of VO in microcapsule. Moreover, VO could be remained about 60% in the microcapsules after release for 30 days, which demonstrated the flavour microcapsules had good potential to serve as a high quality food spice with long residual action and high thermostability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis, structures, and phase transitions of barium bismuth iridium oxide perovskites Ba{sub 2}BiIrO{sub 6} and Ba{sub 3}BiIr{sub 2}O{sub 9}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ling, Chris D., E-mail: c.ling@chem.usyd.edu.a; Bragg Institute, ANSTO, PMB 1, Menai 2234; Kennedy, Brendan J.

The Ba-Bi-Ir-O system is found to contain two distinct perovskite-type phases: a rock-salt ordered double perovskite Ba{sub 2}BiIrO{sub 6}; and a 6H-type hexagonal perovskite Ba{sub 3}BiIr{sub 2}O{sub 9}. Ba{sub 2}BiIrO{sub 6} undergoes a series of symmetry-lowering phase transitions on cooling Fm3-barm->R3-barc->12/m(C2/m)->I1-bar(P1-bar), all of which are second order except the rhombohedral->monoclinic one, which is first order. The monoclinic phase is only observed in a 2-phase rhombohedral+monoclinic regime. The transition and 2-phase region lie very close to 300 K, making the room-temperature X-ray diffraction patterns extremely complex and potentially explaining why Ba{sub 2}BiIrO{sub 6} had not previously been identified and reported. Amore » solid solution Ba{sub 2}Bi{sub 1+x}Ir{sub 1-x}O{sub 6}, analogous to Ba{sub 2}Bi{sub 1+x}Ru{sub 1-x}O{sub 6}, 0<=x<=2/3, was not observed. The 6H-type phase Ba{sub 3}BiIr{sub 2}O{sub 9} undergoes a clean second-order phase transition P6{sub 3}/mmc->C2/c at 750 K, unlike 6H-type Ba{sub 3}LaIr{sub 2}O{sub 9}, the P6{sub 3}/mmc structure of which is highly strained below {approx}750 K but fails to distort coherently to the monoclinic phase. - Graphical abstract: Structure of Ba{sub 3}BiIr{sub 2}O{sub 9} at 300 K. BiO{sub 6} octahedra are purple, IrO{sub 6} octahedra are gold, and Ba atoms are green. Thermal ellipsoids at 90% probability.« less

Transfer of Materials from Water to Solid Surfaces Using Liquid Marbles.

PubMed

Kawashima, Hisato; Paven, Maxime; Mayama, Hiroyuki; Butt, Hans-Jürgen; Nakamura, Yoshinobu; Fujii, Syuji

2017-09-27

Remotely controlling the movement of small objects is desirable, especially for the transportation and selection of materials. Transfer of objects between liquid and solid surfaces and triggering their release would allow for development of novel material transportation technology. Here, we describe the remote transport of a material from a water film surface to a solid surface using quasispherical liquid marbles (LMs). A light-induced Marangoni flow or an air stream is used to propel the LMs on water. As the LMs approach the rim of the water film, gravity forces them to slide down the water rim and roll onto the solid surface. Through this method, LMs can be efficiently moved on water and placed on a solid surface. The materials encapsulated within LMs can be released at a specific time by an external stimulus. We analyzed the velocity, acceleration, and force of the LMs on the liquid and solid surfaces. On water, the sliding friction due to the drag force resists the movement of the LMs. On a solid surface, the rolling distance is affected by the surface roughness of the LMs.

Clotrimazole-cyclodextrin based approach for the management and treatment of Candidiasis - A formulation and chemistry-based evaluation.

PubMed

Mohammed, Noorullah Naqvi; Pandey, Pankaj; Khan, Nayaab S; Elokely, Khaled M; Liu, Haining; Doerksen, Robert J; Repka, Michael A

2016-08-01

Clotrimazole (CT) is a poorly soluble antifungal drug that is most commonly employed as a topical treatment in the management of vaginal candidiasis. The present work focuses on a formulation approach to enhance the solubility of CT using cyclodextrin (CD) complexation. A CT-CD complex was prepared by a co-precipitation method. Various characterization techniques such as differential scanning calorimetry, infrared (IR) and X-ray spectroscopy, scanning electron microscopy and nuclear magnetic resonance (NMR) spectroscopy were performed to evaluate the complex formation and to understand the interactions between CT and CD. Computational molecular modeling was performed using the Schrödinger suite and Gaussian 09 program to understand structural conformations of the complex. The phase solubility curve followed an AL-type curve, indicating formation of a 1:1 complex. Molecular docking studies supported the data obtained through NMR and IR studies. Enthalpy changes confirmed that complexation was an exothermic and enthalpically favorable phenomenon. The CT-CD complexes were formulated in a gel and evaluated for release and antifungal activity. The in vitro release studies performed using gels demonstrated a sustained release of CT from the CT-CD complex with the complex exhibiting improved release relative to the un-complexed CT. Complexed CT-CD exhibited better fungistatic activity toward different Candida species than un-complexed CT.

MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors

PubMed Central

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.

2015-01-01

MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. PMID:25936514

Coprates Chasma Landslides in IR

NASA Technical Reports Server (NTRS)

2005-01-01

[figure removed for brevity, see original site]

Today's daytime IR image is of a portion of Coprates Chasma, part of Valles Marineris. As with yesterday's image, this image shows multiple large landslides.

Image information: IR instrument. Latitude -8.2, Longitude 300.2 East (59.8 West). 100 meter/pixel resolution.

Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

Application of an NLME-Stochastic Deconvolution Approach to Level A IVIVC Modeling.

PubMed

Kakhi, Maziar; Suarez-Sharp, Sandra; Shepard, Terry; Chittenden, Jason

2017-07-01

Stochastic deconvolution is a parameter estimation method that calculates drug absorption using a nonlinear mixed-effects model in which the random effects associated with absorption represent a Wiener process. The present work compares (1) stochastic deconvolution and (2) numerical deconvolution, using clinical pharmacokinetic (PK) data generated for an in vitro-in vivo correlation (IVIVC) study of extended release (ER) formulations of a Biopharmaceutics Classification System class III drug substance. The preliminary analysis found that numerical and stochastic deconvolution yielded superimposable fraction absorbed (F abs ) versus time profiles when supplied with exactly the same externally determined unit impulse response parameters. In a separate analysis, a full population-PK/stochastic deconvolution was applied to the clinical PK data. Scenarios were considered in which immediate release (IR) data were either retained or excluded to inform parameter estimation. The resulting F abs profiles were then used to model level A IVIVCs. All the considered stochastic deconvolution scenarios, and numerical deconvolution, yielded on average similar results with respect to the IVIVC validation. These results could be achieved with stochastic deconvolution without recourse to IR data. Unlike numerical deconvolution, this also implies that in crossover studies where certain individuals do not receive an IR treatment, their ER data alone can still be included as part of the IVIVC analysis. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun

Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. We previously showed that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study was focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 hours) and wean: normal circulation (Group-C);transient coronary occlusion (10 minutes) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon labeled lactate, medium-chain and long-chain FAs were infused as oxidative substrates. Substrate fractional contribution to the citricmore » acid cycle (FC) was analyzed by 13-Carbon nuclear magnetic resonance. Results: ECMO depressed circulating T3 levels to 40% baseline at 4 hours and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [ATP]/[ADP] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions: T3 releases inhibition of lactate oxidation following ischemia-reperfusion injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.« less

Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration.

PubMed

Wissing, S A; Müller, R H

2002-06-17

The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.

G-protein-coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation.

PubMed

Meneses, David; Mateos, Verónica; Islas, Gustavo; Barral, Jaime

2015-09-01

Presynaptic modulation has been associated mainly with calcium channels but recent data suggests that inward rectifier potassium channels (K(IR)) also play a role. In this work we set to characterize the role of presynaptic K(IR) channels in corticostriatal synaptic transmission. We elicited synaptic potentials in striatum by stimulating cortical areas and then determined the synaptic responses of corticostriatal synapsis by using paired pulse ratio (PPR) in the presence and absence of several potassium channel blockers. Unspecific potassium channels blockers Ba(2+) and Cs(+) reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin-Q, a specific K(IR)3 channel family blocker, also induced a reduction of PPR, suggesting that K(IR)3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific K(IR)1.1 inward rectifier potassium channel, did not induce any change in PPR suggesting the absence of these channels in the presynaptic corticostriatal terminals. Our results indicate that K(IR)3 channels are functionally expressed at the corticostriatal synapses, since blockage of these channels result in PPR decrease. Our results also help to explain how synaptic activity may become sensitive to extracellular signals mediated by G-protein coupled receptors. A vast repertoire of receptors may influence neurotransmitter release in an indirect manner through regulation of K(IR)3 channels. © 2015 Wiley Periodicals, Inc.

Infrared observations and laboratory simulations of interstellar CH_4_ and SO_2_.

NASA Astrophysics Data System (ADS)

Boogert, A. C. A.; Schutte, W. A.; Helmich, F. P.; Tielens, A. G. G. M.; Wooden, D. H.

1997-02-01

Interstellar CH_4_ may consume a fair amount of the carbon budget in dense molecular clouds, but probably less than CO, CH_3_OH, and CO_2_. However, it can only be observed at wavelength regions in the infrared that are heavily affected by the earth atmosphere. With new space and airborne missions (e.g. ISO, SOFIA) in mind we have studied the near infrared absorption spectra of solid and gaseous CH_4_. We obtained laboratory spectra of the ν_4_ deformation mode (1302cm^-1^, 7.68μm) of solid CH_4_ in astrophysically relevant mixtures. We found that the peak position and width of this absorption band vary strongly as a function of molecular environment, compared to temperature and particle shape effects. Hence, observations of this feature will provide a powerful probe of the molecular composition of interstellar ices. Also the gas phase CH_4_ ro-vibrational spectrum of the same band has been calculated. Using observed physical conditions around the protostar W 33A, we show that unresolved gaseous CH_4_ lines are detectable (at the 2-5% level) at a resolution R>1000, when the column density N>=10^16^ cm^-2^. An astrophysically relevant molecule with a very strong transition in the same wavelength regime, is SO_2_. We studied the ν _3_ asymmetric stretching mode (1319 cm^-1^, 7.58 μm) of solid SO_2_ in several mixtures, revealing that the peak position, width and detailed profile of this band are very sensitive to the molecular environment. Besides probing the composition of ice mantles, observations of solid SO_2_ will provide important information on the sulfur budget locked up in grain mantles, which is currently poorly known. We compare the laboratory and calculated spectra of CH_4_ and SO_2_ with previously published ground based spectra and new airborne observations of young stellar objects in the 7-8μm region. W 33A, NGC 7538 : IRS1 and IRS9 show a feature near 7.68μm that is consistent with absorption by solid CH_4_ or the Q-branch of gaseous CH_4_. The column density of solid CH_4_ would be 0.3-4% of solid H_2_O, indicating that solid CH_4_ consumes 0.5+/-0.3% of the cosmic carbon abundance. A gaseous origin would imply a column density of at least this amount, being highly dependent on the assumed temperature of the absorbing gas. A second absorption feature is detected toward W 33A and NGC 7538 : IRS1 at 7.58 μm. The peak position and width of this feature are consistent with the ν_3_ mode of solid SO_2_ in a matrix of solid CH_3_OH or pure SO_2_. The derived column density is 0.1-1% of solid H_2_O, indicating that solid SO_2_ locks up 0.6-6% of the cosmic sulfur abundance. This study shows that 7-8μm spectroscopy of dense molecular clouds, using new airborne and space-based platforms, will provide valuable information on the composition of icy grain mantles and molecular cloud chemistry.

Synthesis and antibacterial studies of rhodium and iridium complexes comprising of dipyridyl hydrazones

NASA Astrophysics Data System (ADS)

Aradhyula, Basava Punna Rao; Joshi, Nidhi; Poluri, Krishna Mohan; Kollipara, Mohan Rao

2018-07-01

Reactions of Cp*Rh and Cp*Ir dimers with the dipyridyl hydrazones such as picolinic (L1), nicotinic (L2) and isonicotinic (L3) have been reported here with the formulations [Cp*MClL3](PF6) {where M = Rh (5) and Ir (6)}, [(Cp*MCl)2L1](PF6) {where M = Rh (7) and Ir (8)}, [(Cp*MCl)2L2Cl](PF6) {where M = Rh(9) and Ir(10)}, and [(Cp*MCl)2L3Cl](PF6) {where M = Rh (11) and Ir (12)} which resulted in a series of mono- and di-nuclear cationic complexes. The complexes have been characterized by various spectroscopic techniques. The solid-state structures of three complexes (5, 6 and 8) have been determined by single-crystal X-ray diffraction studies. These cationic complexes have been evaluated for the preliminary antibacterial activity towards four bacterial strains viz., Staphylococcus aureus; Bacillus thuringiensis; Escherichia coli and Pseudomonas aeruginosa by agar well diffusion method. Complexes have exhibited zone of inhibition over Bacillus thuringiensis; Escherichia coli and Pseudomonas aeruginosa strains while Staphylococcus aureus strain is resistant to the complexes 9-12. Surprisingly, these complexes are di-nuclear and trichloride complexes.

Structural and vibrational studies on 1-(5-methyl-[1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol

NASA Astrophysics Data System (ADS)

Ramesh Babu, N.; Saleem, H.; Subashchandrabose, S.; Padusha, M. Syed Ali; Bharanidharan, S.

2016-01-01

FT-Raman and FT-IR spectra were recorded for1-(5-methyl-[1,3,4]thiadiazol-2-yl)-pyrolidin-2-ol (MTPN) sample in solid state. The equilibrium geometries, harmonic vibrational frequencies, IR and the Raman scattering intensities were computed using DFT/6-311++G (d,p) level. Results obtained at this level of theory were used for a detailed interpretation of the IR and Raman spectra, based on the TED of the normal modes. Molecular parameters such as bond lengths, bond angles and dihedral angles were calculated. The intra-molecular charge transfer was calculated by means of NBO. Hyperconjugative interaction energy was more during the π-π∗ transition. Energy gap of the molecule has been found using HOMO and LUMO calculation, hence the less band gap, which seems to be more stable.

Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

PubMed

Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

2017-07-01

This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k d . Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI 95% ) revealed significant differences between k d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f 2 ) test. The final relationship between k d and k perm was found to be hyperbolic, signifying the initial effect of k perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k d and k perm . The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

Olympus Mons at Night

NASA Technical Reports Server (NTRS)

2004-01-01

[figure removed for brevity, see original site]

This nighttime IR image is of a portion of the flank of Olympus Mons. In last week's Arsia Mons flow images, it was easy to delineate lava flows. While this image is also of a region of extensive flows, it is nearly impossible to identify any flows. This illustrates one of the problems imaging high altitudes in nighttime IR, the surface is almost as cold as the atmosphere and is emitting very little signal back to the IR camera.

Image information: IR instrument. Latitude 16.4, Longitude 230.6 East (129.4 West). 100 meter/pixel resolution.

Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet.

PubMed

Cheng, Ching-Ling; Yu, Lawrence X; Lee, Hwei-Ling; Yang, Chyun-Yu; Lue, Chang-Sha; Chou, Chen-Hsi

2004-07-01

The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-infinity) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

Protective effect of N-acetylcysteine activated carbon release microcapsule on myocardial ischemia-reperfusion injury in rats

PubMed Central

Cai, Zhaobin; Shi, Tingting; Zhuang, Rangxiao; Fang, Hongying; Jiang, Xiaojie; Shao, Yidan; Zhou, Hongping

2018-01-01

With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats. PMID:29434769

Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.

PubMed

Attama, A A; Reichl, S; Müller-Goymann, C C

2009-08-01

The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct. Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography. Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water. Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.

Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation

PubMed Central

Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G.; Portman, Michael A.

2017-01-01

Background Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods and Results Nineteen immature piglets (9.1–15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon (13C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by 13C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning. PMID:25421230

Iridium emissions from Hawaiian volcanoes

NASA Technical Reports Server (NTRS)

Finnegan, D. L.; Zoller, W. H.; Miller, T. M.

1988-01-01

Particle and gas samples were collected at Mauna Loa volcano during and after its eruption in March and April, 1984 and at Kilauea volcano in 1983, 1984, and 1985 during various phases of its ongoing activity. In the last two Kilauea sampling missions, samples were collected during eruptive activity. The samples were collected using a filterpack system consisting of a Teflon particle filter followed by a series of 4 base-treated Whatman filters. The samples were analyzed by INAA for over 40 elements. As previously reported in the literature, Ir was first detected on particle filters at the Mauna Loa Observatory and later from non-erupting high temperature vents at Kilauea. Since that time Ir was found in samples collected at Kilauea and Mauna Loa during fountaining activity as well as after eruptive activity. Enrichment factors for Ir in the volcanic fumes range from 10,000 to 100,000 relative to BHVO. Charcoal impregnated filters following a particle filter were collected to see if a significant amount of the Ir was in the gas phase during sample collection. Iridium was found on charcoal filters collected close to the vent, no Ir was found on the charcoal filters. This indicates that all of the Ir is in particulate form very soon after its release. Ratios of Ir to F and Cl were calculated for the samples from Mauna Loa and Kilauea collected during fountaining activity. The implications for the KT Ir anomaly are still unclear though as Ir was not found at volcanoes other than those at Hawaii. Further investigations are needed at other volcanoes to ascertain if basaltic volcanoes other than hot spots have Ir enrichments in their fumes.

Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling

PubMed Central

Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi

2014-01-01

Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca2+ imaging. Both types of neurons responded consistently with robust intracellular Ca2+ ([Ca2+]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25–1 pps). Radiant exposures of ∼637 mJ/cm2 resulted in continual neuronal activation. Temperature or [Ca2+] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca2+ involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na+, K+, and Ca2+ plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca2+ cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca2+]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca2+ release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses. PMID:24920028

Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.

PubMed

Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi; Rajguru, Suhrud M

2014-09-15

Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses. Copyright © 2014 the American Physiological Society.

Analysis of the contaminants released from municipal solid waste landfill site: A case study.

PubMed

Samadder, S R; Prabhakar, R; Khan, D; Kishan, D; Chauhan, M S

2017-02-15

Release and transport of leachate from municipal solid waste landfills pose a potential hazard to both surrounding ecosystems and human populations. In the present study, soil, groundwater, and surface water samples were collected from the periphery of a municipal solid waste landfill (located at Ranital of Jabalpur, Madhya Pradesh, India) for laboratory analysis to understand the release of contaminants. The landfill does not receive any solid wastes for dumping now as the same is under a landfill closure plan. Groundwater and soil samples were collected from the bore holes of 15m deep drilled along the periphery of the landfill and the surface water samples were collected from the existing surface water courses near the landfill. The landfill had neither any bottom liner nor any leachate collection and treatment system. Thus the leachate generated from the landfills finds paths into the groundwater and surrounding surface water courses. Concentrations of various physico-chemical parameters including some toxic metals (in collected groundwater, soil, and surface water samples) and microbiological parameters (in surface water samples) were determined. The analyzed data were integrated into ArcGIS environment and the spatial distribution of the metals and other physic- chemical parameter across the landfill was extrapolated to observe the distribution. The statistical analysis and spatial variations indicated the leaching of metals from the landfill to the groundwater aquifer system. The study will help the readers and the municipal engineers to understand the release of contaminants from landfills for better management of municipal solid wastes. Copyright © 2016 Elsevier B.V. All rights reserved.

Cryogenic solid Schmidt camera as a base for future wide-field IR systems

NASA Astrophysics Data System (ADS)

Yudin, Alexey N.

2011-11-01

Work is focused on study of capability of solid Schmidt camera to serve as a wide-field infrared lens for aircraft system with whole sphere coverage, working in 8-14 um spectral range, coupled with spherical focal array of megapixel class. Designs of 16 mm f/0.2 lens with 60 and 90 degrees sensor diagonal are presented, their image quality is compared with conventional solid design. Achromatic design with significantly improved performance, containing enclosed soft correcting lens behind protective front lens is proposed. One of the main goals of the work is to estimate benefits from curved detector arrays in 8-14 um spectral range wide-field systems. Coupling of photodetector with solid Schmidt camera by means of frustrated total internal reflection is considered, with corresponding tolerance analysis. The whole lens, except front element, is considered to be cryogenic, with solid Schmidt unit to be flown by hydrogen for improvement of bulk transmission.

Low-dose ionizing radiation increases the mortality risk of solid cancers in nuclear industry workers: A meta-analysis

PubMed Central

Qu, Shu-Gen; Gao, Jin; Tang, Bo; Yu, Bo; Shen, Yue-Ping; Tu, Yu

2018-01-01

Low-dose ionizing radiation (LDIR) may increase the mortality of solid cancers in nuclear industry workers, but only few individual cohort studies exist, and the available reports have low statistical power. The aim of the present study was to focus on solid cancer mortality risk from LDIR in the nuclear industry using standard mortality ratios (SMRs) and 95% confidence intervals. A systematic literature search through the PubMed and Embase databases identified 27 studies relevant to this meta-analysis. There was statistical significance for total, solid and lung cancers, with meta-SMR values of 0.88, 0.80, and 0.89, respectively. There was evidence of stochastic effects by IR, but more definitive conclusions require additional analyses using standardized protocols to determine whether LDIR increases the risk of solid cancer-related mortality. PMID:29725540

Preparation and Some Properties of N-Type IrxCo1-xSB3 Solid Solutions

NASA Technical Reports Server (NTRS)

Caillat, Thierry

1995-01-01

A number of studies have been recently devoted to the preparation and characterization of binary skutterudite materials to investigate their potential as advanced thermoelectric materials. These studies show that the potential of these binary skutterudite compounds is limited because of their relatively large thermal conductivity. In order to achieve high thermoelectric figure of merits for these materials, efforts should focus on thermal conductivity reduction. Recent results obtained on n-type CoSb3 and IrSb3 compounds have shown that n-type skutterudite materials might have a better potential for thermoelectric applications than p-type materials. The thermoelectric properties of p-type IrxCo1-xSb3 solid solutions have been recently investigated and it was shown that a substantial reduction in thermal conductivity was achieved. We prepared and measured some properties of n-type IrxCo1-xSb3 solid solutions. The samples are characterized by large Seebeck coefficient values and significantly lower thermal conductivity values than those measured on the binary compounds CoSb3 and IrSb3. A maximum ZT value of about 0.4 was obtained at a temperature of about 300(deg)C. Improvements in the figure of merit are possible in this system by optimization of the doping level.

USSR and Eastern Europe Scientific Abstracts, Engineering and Equipment, Number 34

DTIC Science & Technology

1977-09-07

indices of refraction and absorption and the optical homogeneity. Values of the indices of refraction and ab- sorption of IR glasses are presented...was found that cold plastic 20 deformation accelerates processes of breakdown of the gamma solid solution. The resistance to microplastic

Isolation of Flaws by Use of Thermal Differentials on a Tire Under Mild Loading Conditions

DOT National Transportation Integrated Search

1972-02-01

Twenty-six used and rebuilt solid rubber road wheels were examined by an infrared temperature profiling technique during drum test exercise. The IR method was evaluated as a nondestructive means of predicting road wheel integrity by analysis of the c...

Desorption of Arsenic from Drinking Water Distribution System Solids

EPA Science Inventory

Given the limited knowledge regarding the soluble release of arsenic from DWDS solids, the objectives of this research were to: 1) investigate the effect of pH on the dissolution/desorption of arsenic from DWDS solids, and 2) examine the effect of orthophosphate on the soluble re...

Quantitative evaluation of malignant gliomas damage induced by photoactivation of IR700 dye

NASA Astrophysics Data System (ADS)

Sakuma, Morito; Kita, Sayaka; Higuchi, Hideo

2016-01-01

The processes involved in malignant gliomas damage were quantitatively evaluated by microscopy. The near-infrared fluorescent dye IR700 that is conjugated to an anti-CD133 antibody (IR700-CD133) specifically targets malignant gliomas (U87MG) and stem cells (BT142) and is endocytosed into the cells. The gliomas are then photodamaged by the release of reactive oxygen species (ROS) and the heat induced by illumination of IR700 by a red laser, and the motility of the vesicles within these cells is altered as a result of cellular damage. To investigate these changes in motility, we developed a new method that measures fluctuations in the intensity of phase-contrast images obtained from small areas within cells. The intensity fluctuation in U87MG cells gradually decreased as cell damage progressed, whereas the fluctuation in BT142 cells increased. The endocytosed IR700 dye was co-localized in acidic organelles such as endosomes and lysosomes. The pH in U87MG cells, as monitored by a pH indicator, was decreased and then gradually increased by the illumination of IR700, while the pH in BT142 cells increased monotonically. In these experiments, the processes of cell damage were quantitatively evaluated according to the motility of vesicles and changes in pH.

Equilibrium and kinetic models for colloid release under transient solution chemistry conditions

USDA-ARS?s Scientific Manuscript database

We present continuum models to describe colloid release in the subsurface during transient physicochemical conditions. Our modeling approach relates the amount of colloid release to changes in the fraction of the solid surface area that contributes to retention. Equilibrium, kinetic, equilibrium and...

Lasers and Optics

DTIC Science & Technology

2013-03-05

AFRL:! ... J ,, 4 DISTRIBUTION A: Approved for public release; distribution is unlimited. • High Average Power Solid-State Lasers • Ceramic Solid...Stanford Romain Gaume – U.C.F. DISTRIBUTION A: Approved for public release; distribution is unlimited. 11 DISTRIBUTION A: Approved for public...Ceramics Robert Byer - Stanford Romain Gaume – U.C.F. 12 0 5 10 15 900 1000 1100 1200 1300 1400 1500 1600 1700 A b s o rp ti o n C o e ff ic e in

Atmospheric pressure laser desorption/ionization using a 6-7 µm-band mid-infrared tunable laser and liquid water matrix.

PubMed

Hiraguchi, Ryuji; Hazama, Hisanao; Masuda, Katsuyoshi; Awazu, Kunio

2015-01-01

Due to the characteristic absorption peaks in the IR region, various molecules can be used as a matrix for infrared matrix-assisted laser desorption/ionization (IR-MALDI). Especially in the 6-7 µm-band IR region, solvents used as the mobile phase for liquid chromatography have absorption peaks that correspond to their functional groups, such as O-H, C=O, and CH3. Additionally, atmospheric pressure (AP) IR-MALDI, which is applicable to liquid-state samples, is a promising technique to directly analyze untreated samples. Herein we perform AP-IR-MALDI mass spectrometry of a peptide, angiotensin II, using a mid-IR tunable laser with a tunable wavelength range of 5.50-10.00 µm and several different matrices. The wavelength dependences of the ion signal intensity of [M + H](+) of the peptide are measured using a conventional solid matrix, α-cyano-4-hydroxycinnamic acid (CHCA) and a liquid matrix composed of CHCA and 3-aminoquinoline. Other than the O-H stretching and bending vibration modes, the characteristic absorption peaks are useful for AP-IR-MALDI. Peptide ions are also observed from an aqueous solution of the peptide without an additional matrix, and the highest peak intensity of [M + H](+) is at 6.00 µm, which is somewhat shorter than the absorption peak wavelength of liquid water corresponding to the O-H bending vibration mode. Moreover, long-lasting and stable ion signals are obtained from the aqueous solution. AP-IR-MALDI using a 6-7 µm-band IR tunable laser and solvents as the matrix may provide a novel on-line interface between liquid chromatography and mass spectrometry. Copyright © 2015 John Wiley & Sons, Ltd.

Extrahepatic ischemia-reperfusion injury reduces hepatic oxidative drug metabolism as determined by serial antipyrine clearance.

PubMed

Gurley, B J; Barone, G W; Yamashita, K; Polston, S; Estes, M; Harden, A

1997-01-01

All transplanted solid organs experience some degree of ischemia-reperfusion (I-R) injury. This I-R injury can contribute to graft dysfunction which stems in part from the acute phase response and a resultant host of cytokines. Recent evidence suggests that organs remote to the site of I-R injury can be affected by circulating cytokines originating from these I-R injuries. Since many of these acute phase cytokines inhibit hepatic cytochrome P-450 (CYP) enzymes, we chose to investigate whether extrahepatic I-R injuries could influence hepatic oxidative drug metabolism. Fifteen dogs were divided into three surgical groups: (I) sham I-R; (II) bilateral normothermic renal I-R; and (III) normothermic intestinal I-R. Antipyrine (AP) was selected as a model substrate and administered intravenously at a dose of 10 mg/kg. AP serum concentrations were determined by HPLC and cytokine activity (IL-1, IL-6, and TNFalpha) was measured via bioassay. Serial AP clearance and serum cytokine concentrations were determined 3 days prior to and at 4 hr, 24 hr, 3 days and 7 days after surgery. Hematology and blood chemistries were monitored throughout the study period. AP clearance was significantly reduced in groups II and III at 4 and 24 hrs post-l-R injury, while AP binding and apparent volume of distribution were unaffected. Peak levels of TNF and IL-6 activity occurred at 1 and 4 hours, respectively. IL-I activity was not detected in any group. AP clearance correlated strongly to circulating levels of IL-6 (r = -0.789, p = 0.0002). Our findings indicate that extrahepatic I-R injury can affect hepatic oxidative drug metabolism and this effect is mediated in part by circulating cytokines.

Near-IR-induced dissociation of thermally-sensitive star polymers.

PubMed

Dai, Yuqiong; Sun, Hao; Pal, Sunirmal; Zhang, Yunlu; Park, Sangwoo; Kabb, Christopher P; Wei, Wei David; Sumerlin, Brent S

2017-03-01

Responsive systems sensitive to near-infrared (NIR) light are promising for triggered release due to efficient deep tissue penetration of NIR irradiation relative to higher energy sources ( e.g. , UV), allowing for spatiotemporal control over triggering events with minimal potential for tissue damage. Herein, we report star polymers containing thermally-labile azo linkages that dissociate during conventional heating or during localized heating via the photothermal effect upon NIR irradiation. Controlled release during conventional heating was investigated for the star polymers loaded with a model dye, with negligible release being observed at 25 °C and >80% release at 90 °C. Star polymers co-loaded with NIR-responsive indocyanine green showed rapid dye release upon NIR irradiation ( λ ≥ 715 nm) due to the photothermally-induced degradation of azo linkages within the cores of the star polymers. This approach provides access to a new class of delivery and release systems that can be triggered by noninvasive external stimulation.

Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint.

PubMed

Yamamori, Tohru; Yasui, Hironobu; Yamazumi, Masayuki; Wada, Yusuke; Nakamura, Yoshinari; Nakamura, Hideo; Inanami, Osamu

2012-07-15

Whereas ionizing radiation (Ir) instantaneously causes the formation of water radiolysis products that contain some reactive oxygen species (ROS), ROS are also suggested to be released from biological sources in irradiated cells. It is now becoming clear that these ROS generated secondarily after Ir have a variety of biological roles. Although mitochondria are assumed to be responsible for this Ir-induced ROS production, it remains to be elucidated how Ir triggers it. Therefore, we conducted this study to decipher the mechanism of Ir-induced mitochondrial ROS production. In human lung carcinoma A549 cells, Ir (10 Gy of X-rays) induced a time-dependent increase in the mitochondrial ROS level. Ir also increased mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production, suggesting upregulation of the mitochondrial electron transport chain (ETC) function after Ir. Although we found that Ir slightly enhanced mitochondrial ETC complex II activity, the complex II inhibitor 3-nitropropionic acid failed to reduce Ir-induced mitochondrial ROS production. Meanwhile, we observed that the mitochondrial mass and mitochondrial DNA level were upregulated after Ir, indicating that Ir increased the mitochondrial content of the cell. Because irradiated cells are known to undergo cell cycle arrest under control of the checkpoint mechanisms, we examined the relationships between cell cycle and mitochondrial content and cellular oxidative stress level. We found that the cells in the G2/M phase had a higher mitochondrial content and cellular oxidative stress level than cells in the G1 or S phase, regardless of whether the cells were irradiated. We also found that Ir-induced accumulation of the cells in the G2/M phase led to an increase in cells with a high mitochondrial content and cellular oxidative stress level. This suggested that Ir upregulated mitochondrial ETC function and mitochondrial content, resulting in mitochondrial ROS production, and that Ir-induced G2/M arrest contributed to the increase in the mitochondrial ROS level by accumulating cells in the G2/M phase. Copyright © 2012 Elsevier Inc. All rights reserved.

Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

PubMed

Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

2014-01-01

Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

Evaluation of photostability of solid-state nicardipine hydrochloride polymorphs by using Fourier-transformed reflection-absorption infrared spectroscopy - effect of grinding on the photostability of crystal form.

PubMed

Teraoka, Reiko; Otsuka, Makoto; Matsuda, Yoshihisa

2004-11-22

Photostability and physicochemical properties of nicardipine hydrochloride polymorphs (alpha- and beta-form) were studied by using Fourier-transformed reflection-absorption infrared spectroscopy (FT-IR-RAS) of the tablets, X-ray powder diffraction analysis, differential scanning calorimetry (DSC), and color difference measurement. It was clear from the results of FT-IR-RAS spectra after irradiation that nicardipine hydrochloride in the solid state decomposed to its pyridine derivative when exposed to light. The photostability of the ground samples of two forms was also measured in the same manner. The two crystalline forms of the drug changed to nearly amorphous form after 150 min grinding in a mixer mill. X-ray powder diffraction patterns of those ground samples showed almost halo patterns. The nicardipine hydrochloride content on the surface of the tablet was determined based on the absorbance at 1700 cm(-1) attributable to the C=O stretch vibration in FT-IR-RAS spectra before and after irradiation by fluorescent lamp (3500 lx). The photodegradation followed apparently the first-order kinetics for any sample. The apparent photodegradation rate constant of beta-form was greater than that of alpha-form. The ground samples decomposed rapidly under the same light irradiation as compared with the intact crystalline forms. The photodegradation rate constant decreased with increase of the heat of fusion. copyright 2004 Elsevier B.V.

Evaluating the Analgesic Effect of the GLS Inhibitor 6-Diazo-5-Oxo-L-Norleucine in Vivo

PubMed Central

Crosby, Heith A; Miller, Kenneth E

2018-01-01

Glutamate is an excitatory neurotransmitter, produced by its synthetic enzyme, glutaminase (GLS), and packaged by vesicular transporters (VGluT2) into synaptic vesicles. Primary sensory peripheral nerve and spinal synaptic terminals release glutamate during nociceptive (pain) signaling. In post-incisional and inflammation models in rats, GLS and VGluT2 production is elevated in dorsal root ganglion neuronal cell bodies and transported to peripheral and spinal terminals for increased glutamate synthesis and release. 6-Diazo-5-oxo-l-norleucine (DON) is a GLS inhibitor that produces long lasting pain relief when applied to the inflamed paw of arthritic rats, but its effect in a post-incisional model has not been evaluated. In this study, we examined the analgesic efficacy of DON in a surgical incision model by measuring thermal latency and mechanical allodynia. Following behavioral evaluation, we examined the skin for VGluT2, GLS and glutamate immunoreactivity (ir). Our findings revealed that VGluT2-ir is elevated in the stratum lucidum by approximately 19%, 64 hours post-surgical incision and attenuated by approximately 5.4% after the administration of DON. During that same period GLS-ir was elevated in dermal nerve fibers by 52% and was attenuated by approximately 27.9% after the application of DON. Additionally, glutamate-ir was elevated in epidermal nerve fibers by 35% after incision and attenuated by approximately 23% after the administration of DON. Behavioral testing 24 and 48 hours after a single local administration of DON showed five out of six animals having an analgesic response to mechanical allodynia, but not to thermal hyperalgesia. Following a surgical incision, the area of injury shows increased VGluT2-, GLS-, glutamate-ir, mechanical allodynia and no change in thermal latency. After the application of the GLS inhibitor, DON, nerve fiber of the skin showed decreased VGluT2, GLS, and glutamate-ir. Furthermore, post-incision DON treated animals exhibited decreased mechanical allodynia with no change in thermal latency when compared to control animals. PMID:29888760

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats

PubMed Central

Torres-González, Liliana; Cienfuegos-Pecina, Eduardo; Perales-Quintana, Marlene M.; Muñoz-Espinosa, Linda E.; Pérez-Rodríguez, Edelmiro

2018-01-01

Introduction Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. Objective To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. Materials and Methods Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. Results None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. Conclusions S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R. PMID:29643981

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats.

PubMed

Torres-González, Liliana; Cienfuegos-Pecina, Eduardo; Perales-Quintana, Marlene M; Alarcon-Galvan, Gabriela; Muñoz-Espinosa, Linda E; Pérez-Rodríguez, Edelmiro; Cordero-Pérez, Paula

2018-01-01

Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. Animal groups ( n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.

Quasar probabilities and redshifts from WISE mid-IR through GALEX UV photometry

NASA Astrophysics Data System (ADS)

DiPompeo, M. A.; Bovy, J.; Myers, A. D.; Lang, D.

2015-09-01

Extreme deconvolution (XD) of broad-band photometric data can both separate stars from quasars and generate probability density functions for quasar redshifts, while incorporating flux uncertainties and missing data. Mid-infrared photometric colours are now widely used to identify hot dust intrinsic to quasars, and the release of all-sky WISE data has led to a dramatic increase in the number of IR-selected quasars. Using forced photometry on public WISE data at the locations of Sloan Digital Sky Survey (SDSS) point sources, we incorporate this all-sky data into the training of the XDQSOz models originally developed to select quasars from optical photometry. The combination of WISE and SDSS information is far more powerful than SDSS alone, particularly at z > 2. The use of SDSS+WISE photometry is comparable to the use of SDSS+ultraviolet+near-IR data. We release a new public catalogue of 5537 436 (total; 3874 639 weighted by probability) potential quasars with probability PQSO > 0.2. The catalogue includes redshift probabilities for all objects. We also release an updated version of the publicly available set of codes to calculate quasar and redshift probabilities for various combinations of data. Finally, we demonstrate that this method of selecting quasars using WISE data is both more complete and efficient than simple WISE colour-cuts, especially at high redshift. Our fits verify that above z ˜ 3 WISE colours become bluer than the standard cuts applied to select quasars. Currently, the analysis is limited to quasars with optical counterparts, and thus cannot be used to find highly obscured quasars that WISE colour-cuts identify in significant numbers.

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

PubMed Central

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-01-01

Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R2=0.751, P<0.001). Conclusions: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance. PMID:26563815

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

PubMed

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-04-01

Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Modelling of Ionospheric Irregularities and Total Electron Content.

DTIC Science & Technology

1983-12-01

jApproved for public release; distribution unlimited DTIC SELECTEd MAY2 11 84 AIR FORCE GEOPHYSICS LABORATORY B C3 AIR FORCE SYSTEMS COMMAND .. UNITED...DOWNGRADING 16. OISTRIBUTION STATEMENT (of this Rerport) Approved for Public Release; Distribution Unlimited 1?. DISTRIBUTION STATEMENT (o1 .he obrfoct...Space Division, Project 2029, and the Air Force Office of Scientific Research, Task 2311G2. 19. KEY WORDS (CO1ir oU ngooe I ,-- . 1d -d0n~ Id-nWI A

Melt-processed polymeric cellular dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2015-12-28

The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

Simulating the Fate and Transport of an Acid Mine Drainage Release

EPA Science Inventory

On August 5, 2015, approximately 3 million gallons of acid mine drainage were released from the Gold King Mine into Cement Creek in the San Juan River watershed (CO, NM, UT). The release further mobilized additional metals, which resulted in a large mass of solids and dissolved m...

40 CFR 60.441 - Definitions and symbols.

Code of Federal Regulations, 2010 CFR

2010-07-01

... web. Coating line means any number or combination of adhesive, release, or precoat coating applicators... solids content of the coated adhesive, release, or precoat as measured by Method 24. Flashoff area means... than an adhesive or release is applied to a surface during the production of a pressure sensitive tape...

Graphene/activated carbon supercapacitors with sulfonated-polyetheretherketone as solid-state electrolyte and multifunctional binder

NASA Astrophysics Data System (ADS)

Chen, Y.-R.; Chiu, K.-F.; Lin, H. C.; Chen, C.-L.; Hsieh, C. Y.; Tsai, C. B.; Chu, B. T. T.

2014-11-01

Sulfonated polyetheretherketone (SPEEK) has been synthesised by sulphonation process and used as the solid-state electrolyte, binder and surfactant for supercapacitors. Reduced graphene dispersed by SPEEK is used as a high-efficiency conducting additive in solid-state supercapacitors. It is found that SPEEK can improve the stability of the reduced graphene dispersion significantly, and therefore, the solid-state supercapacitors show a large decrease in IR drop and charge-transfer resistance (Rct), resulting in a higher rate capability. The solid-state supercapacitors with the activated carbon/reduced graphene/SPEEK/electrode can be operated from 1 to 8 A/g and exhibit capacity retention of 93%. The noteworthy is more than twice higher value for capacity retention by comparison with the solid-state supercapacitors using activated carbon/reduced graphene/PVDF electrode (capacity retention is 36%). The cell of reduced graphene with SPEEK can be cycled over 5000 times at 5 A/g with no capacitance fading.

IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

PubMed

Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

2016-01-01

In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Besides that, gliclazide was also compatible with the excipients used. Chickpea starch acted as a disintegrant in gliclazide IR tablets, instead of a binder. Therefore, chickpea starch can be a promising disintegrant in gliclazide IR tablets.

Applications of infrared photo-acoustic spectroscopy for wood samples

Treesearch

Mon-Lin Kuo; John F. McClelland; Siquan Luo; Po-Liang Chien; R.D. Walker; Chung-Yun Hse

1988-01-01

Various infrared (IR) spectroscopic techniques for the analysis of wood samples are briefly discussed. Theories and instrumentation of the newly developed photoacoustic spectroscopic (PAS) technique for measuring absorbance spectra of solids are presented. Some important applications of the PAS technique in wood science research are discussed. The application of the...

A statistical evaluation of spectral fingerprinting methods using analysis of variance and principal component analysis

USDA-ARS?s Scientific Manuscript database

Six methods were compared with respect to spectral fingerprinting of a well-characterized series of broccoli samples. Spectral fingerprints were acquired for finely-powdered solid samples using Fourier transform-infrared (IR) and Fourier transform-near infrared (NIR) spectrometry and for aqueous met...

Solid state linear dichroic infrared spectral analysis of benzimidazoles and their N 1-protonated salts

NASA Astrophysics Data System (ADS)

Ivanova, B. B.

2005-11-01

A stereo structural characterization of 2,5,6-thrimethylbenzimidazole (MBIZ) and 2-amino-benzimidaziole (2-NH 2-BI) and their N 1 protonation salts was carried out using a polarized solid state linear dichroic infrared spectral (IR-LD) analysis in nematic liquid crystal suspension. All experimental predicted structures were compared with the theoretical ones, obtained by ab initio calculations. The Cs to C2v* symmetry transformation as a result of protonation processes, with a view of its reflection on the infrared spectral characteristics was described.

High Energy Materials. New Preparative Approaches to Nitro and Nitroso Derivatives

DTIC Science & Technology

1982-08-01

peroxide (2.8 ml,100 amoles). The mixture was stirred until the disappear- ance (about 3 h) of the diazepine Ia (tic) left a clear yellow solution. The re...of the per- oxide ?a as a light yellow solid which was filtered and dried at room temperature, 7.2g(75%), mp 125-6’C(dec) (ethyl acetate and hexane...concentration and addition of hexane gave the bisimine S as a light yellow solid, 1.7 g(85 %), mp 161-3*C (ethyl acetate and hexane), dec around 170*C; ir

Bridging the gap between homogeneous and heterogeneous catalysis: ortho/para H(2) conversion, hydrogen isotope scrambling, and hydrogenation of olefins by Ir(CO)Cl(PPh(3))(2).

PubMed

Matthes, Jochen; Pery, Tal; Gründemann, Stephan; Buntkowsky, Gerd; Sabo-Etienne, Sylviane; Chaudret, Bruno; Limbach, Hans-Heinrich

2004-07-14

Some transition metal complexes are known to catalyze ortho/para hydrogen conversion, hydrogen isotope scrambling, and hydrogenation reactions in liquid solution. Using the example of Vaska's complex, we present here evidence by NMR that the solvent is not necessary for these reactions to occur. Thus, solid frozen solutions or polycrystalline powdered samples of homogeneous catalysts may become heterogeneous catalysts. Comparative liquid- and solid-state studies provide novel insight into the reaction mechanisms.

A cost-effective nanoporous ultrathin film electrode based on nanoporous gold/IrO2 composite for proton exchange membrane water electrolysis

NASA Astrophysics Data System (ADS)

Zeng, Yachao; Guo, Xiaoqian; Shao, Zhigang; Yu, Hongmei; Song, Wei; Wang, Zhiqiang; Zhang, Hongjie; Yi, Baolian

2017-02-01

A cost-effective nanoporous ultrathin film (NPUF) electrode based on nanoporous gold (NPG)/IrO2 composite has been constructed for proton exchange membrane (PEM) water electrolysis. The electrode was fabricated by integrating IrO2 nanoparticles into NPG through a facile dealloying and thermal decomposition method. The NPUF electrode is featured in its 3D interconnected nanoporosity and ultrathin thickness. The nanoporous ultrathin architecture is binder-free and beneficial for improving electrochemical active surface area, enhancing mass transport and facilitating releasing of oxygen produced during water electrolysis. Serving as anode, a single cell performance of 1.728 V (@ 2 A cm-2) has been achieved by NPUF electrode with a loading of IrO2 and Au at 86.43 and 100.0 μg cm-2 respectively, the electrolysis voltage is 58 mV lower than that of conventional electrode with an Ir loading an order of magnitude higher. The electrolysis voltage kept relatively constant up to 300 h (@250 mA cm-2) during the course of durability test, manifesting that NPUF electrode is promising for gas evolution.

Overexpression of IGF-I receptor in HeLa cells enhances in vivo radioresponse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaneko, Haruna; Yu, Dong; Miura, Masahiko

2007-11-30

Insulin-like growth factor I receptor (IGF-IR) is a transmembrane receptor tyrosine kinase whose activation strongly promotes cell growth and survival. We previously reported that IGF-IR activity confers intrinsic radioresistance in mouse embryo fibroblasts in vitro. However, it is still unclear whether tumor cells overexpressing IGF-IR exhibit radioresistance in vivo. For this purpose, we established HeLa cells that overexpress IGF-IR (HeLa-R), subcutaneously transplanted these cells into nude mice, and examined radioresponse in the resulting solid tumors. HeLa-R cells exhibited typical in vitro phenotypes generally observed in IGF-IR-overexpressing cells, as well as significant intrinsic radioresistance in vitro compared with parent cells. Asmore » expected, the transplanted HeLa-R tumors grew at a remarkably higher rate than parent tumors. Histological analysis revealed that HeLa-R tumors expressed more VEGF and had a higher density of tumor vessels. Unexpectedly, a marked growth delay was observed in HeLa-R tumors following 10 Gy of X-irradiation. Immunostaining of HeLa-R tumors for the hypoxia marker pimonidazole revealed a significantly lower level of hypoxic cells. Moreover, clamp hypoxia significantly increased radioresistance in HeLa-R tumors. Tumor microenvironments in vivo generated by the IGF-IR expression thus could be a major factor in determining the tumor radioresponse in vivo.« less