Alternative Injection Research Articles

The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee

Although intraarticular injections are important to the management of rheumatoid arthritis, there are few studies regarding the cost-effectiveness of alternative injection techniques. This randomized controlled study addressed the cost-effectiveness of two different low-cost, anatomic landmark palpation-directed intraarticular injection techniques. Ninety-six symptomatic rheumatoid knees were randomized to two different low-cost, palpation-guided intraarticular injection techniques utilizing (1) a conventional syringe or (2) a mechanical syringe, the RPD (the reciprocating procedure device). Three milliliters of 1% lidocaine were used to anesthetize the synovial membrane, followed by arthrocentesis and hydrodissection, and injection of 80mg of triamcinolone acetonide utilizing the one-needle two-syringe technique. Baseline pain, procedural pain, aspirated fluid volume, pain at outcome (2weeks and 6months), responders, reinjection rates, cost/patient/year, and cost/responder/year were determined. Pain was measured with the 10cm Visual Analogue Pain Scale (VAS). Both techniques significantly reduced pain scores at outcome from baseline (P<0.001). The mechanical syringe technique resulted in a greater volume of aspirated fluid (P<0.01), a 38% reduction in procedural pain (P<0.001), a 24% reduction in pain scores at outcome (P<0.03), an increase in the responder rate (P<0.025), 33% increase in the time to next injection (P<0.001), 23% ($35 US) reduction in cost/patient/year for a patient treated in a physician office (P<0.001), 24% reduction ($26 US) in cost/patient/year for a hospital outpatient (P<0.001), and 51% ($151 US) reduction in cost/responder/year (P<0.001). The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee can be improved significantly with low-cost alternations in technique.

The effects of penehyclidine hydrochloride on the withdrawal syndrome and conditioned place preference of morphine dependent rats

Objective To explore the effects of penehyclidine hydrochloride (PHC) on the withdrawal syndrome and conditioned place preference(CPP) of morphine dependent rats. Methods ( 1 ) Forty-eight male SD rats were randomly assigned to 6 groups with one of 8 rats:morphine dependent group (MOR group) ,naloxone precipitated withdrawal group ( NAL group) ,PHC treatment groups ( PHC1,2,3 ) ,normal saline control group ( NS group). Subcutaneous injection of morphine in gradually increasing doses for 5 days (from 10 to 50 mg/kg ,two times daily) to establish the model of morphine physical dependent rats. The withdrawal syndrome was precipitated by naloxone (5 mg/kg,sc) and treated with PHC in various doses (0.5,1.0,1.5 mg/kg ,ip ) 30 min before haloxone-precipitated withdrawal. The body weight loss and withdrawal syndrome were observed respectively in 20 minutes. (2) 40 male SD rats were randomly assigned to 5 groups with one of 8 rats: morphine dependent group (MOR group) ,PHC treatment groups (PHC1 ,2,3 ) ,normal saline control group (NS group). The morphine conditioned place preference was induced by alternate subcutaneous injection of morphine for 7 days in rats ( 10mg/kg,once daily,8:00 AM) and saline( 16:00 PM). At d8,the rats were received the CPP test. The rats of PHC groups were treated with PHC (0.5,1.0,1.5 mg/kg , ip) prior to the CPP test, whereas the rats were treated with saline in MOR and NS group. Results (1) Theweight loss((8.53 ±l.20)g,(7.36±l.06)g,(5.40±1.79 ) g vs ( 12.63 ± 2.22 ) g, F = 83.16, P ＜ 0.01 ) and score precipitated withdrawal symptoms ( 25.36 ± 3.11,21.38±3.50,17.06±1.78 vs 31.69 ±2.76, F=256.56, P＜0.01)of morphine withdrawal rats was obviously alleviated by ip PHC in dose-related manner before naloxone-precipitated withdrawal. (2) There were significant differences in the times spent in the drug-paired side (gray area) between MOR and PHC groups( (529 ± 83 )s,(460 ± 107 ) s, (418 ± 97 ) s vs ( 643 ± 111 ) s, F = 13.22, P ＜ 0.01 ), and also in dose-related manner. Conclusion PHC could significantly inhibit the withdrawal syndrome and the expression of CPP on morphine dependent rats in a dose-dependent manner. Key words: Penehyclidine hydrochloride; Morphine dependent; Withdrawal syndrome

Experimental Study of Pore-Scale Mechanisms of Carbonated Water Injection

Carbon dioxide (CO2) injection is a well-established method for increasing recovery from oil reservoirs. However, poor sweep efficiency has been reported in many CO2 injection projects due to the high mobility contrast between CO2 and oil and water. Various injection strategies including gravity stable, WAG and SWAG have been suggested and, to some extent, applied in the field to alleviate this problem. An alternative injection strategy is carbonated water injection (CWI). In CWI, CO2 is delivered to a much larger part of the reservoir compared to direct CO2 injection due to a much improved sweep efficiency. In CWI, CO2 is used efficiently and much less CO2 is required compared to conventional CO2 flooding, and hence the process is particularly attractive for reservoirs with limited access to large quantities of CO2 (offshore reservoirs or reservoirs far away from inexpensive natural CO2 resources). This article describes the results of a pore-scale study of the process of CWI by performing high-pressure visualisation flow experiments. The experimental results show that CWI, compared to unadulterated (conventional) water injection, improves oil recovery as both a secondary (before water flooding) and a tertiary (after water flooding) recovery method. The mechanisms of oil recovery by CWI include oil swelling, coalescence of the isolated oil ganglia and flow diversion due to flow restriction in some of the pores as a result of oil swelling and the resultant fluid redistribution. In this article the potential benefit of a subsequent depressurisation period on oil recovery after the CWI period is also investigated.

Class I and II anabolic steroids produce opposite hedonic and rewarding effects in pubertal and adult mice

Anabolic androgenic steroids (AAS) are synthetic derivates of testosterone. There are approximately 60 different AAS compounds that can be classified in three classes based upon their chemical structure and metabolites. Even short exposure to AAS can produce mood and behavioral symptoms. In previous experiments, we found that class I and II AAS induce hedonic and rewarding effects in adult mice. Recently, NIDA reported that 1.4 – 2.2% of adolescents ever tried steroids. In this study, we aimed to determine if AAS have hedonic properties in adolescent male mice. Animals received alternate androgen injections in a conditioned place preference (CPP) for 10 days. In addition, anxiety behaviors were measured. Androgens tested were testosterone propionate (TP) and 17α‐methyltestosterone (17α‐meT), class I and class III AAS, respectively. Three doses were tested (0.075, 0.75 and 7.5 mg/kg) for each drug. We have found a shift in place preference in animals treated with 17α‐meT in all doses tested, while TP showed no effect. In exploratory‐based anxiety, using light‐dark transitions, we found an increase in this parameter only with 17α‐meT (7.5 mg/kg). Body and gonadal weight were not affected in any of the AAS treatments. Our results suggest that developmental age, hormonal environment and AAS metabolism are important modulators of hedonia and reward.

Cortisol promotes and integrates the osmotic competence of the organs in North African catfish ( Clarias gariepinus Burchell): Evidence from in vivo and in situ approaches

The short-term in situ and long-term in vivo effects of cortisol were examined in North African catfish ( Clarias gariepinus) to identify how this major corticosteroid integrates the osmotic competence of fish organs. In the in situ approach, the hydromineral effects of cortisol perfusion (75–300 ng ml −1) for 20 min were tested and the indices of hydromineral and metabolic regulations were measured in our in vivo experimental fish after three alternate intraperitoneal cortisol injections (40 and 200 ng g −1 body mass) for 5 days. Na +, K +-ATPase activity, a measure of cellular osmotic competence, responded to in situ and in vivo cortisol treatments. In situ cortisol delivery increased the Na +, K +-ATPase activity in the gill ( P < 0.001) and kidney ( P < 0.001) but decreased ( P < 0.01) in the liver and showed no effect on intestine. In vivo cortisol treatment, on the contrary, increased Na +, K +-ATPase activity in the gills ( P < 0.01), intestine ( P < 0.05) and liver ( P < 0.01) but decreased ( P < 0.05) in the kidney. As expected, plasma cortisol increased ( P < 0.001) with increasing doses of cortisol injections which produced direct effects on the metabolites and the mineral contents including the elevations of glucose ( P < 0.05), lactate ( P < 0.05) and Mg 2+ ( P < 0.05) and reductions of urea ( P < 0.05), Na + ( P < 0.05) and K + ( P < 0.05) in the plasma. A decline of triiodothyronine ( P < 0.01) occurred in the catfish after in vivo cortisol treatment and that implies a direct cortisol action on the homeostatic integration in this fish. Evidence is thus presented that in catfish cortisol regulates the whole body hydromineral and metabolite homeostasis by promoting and integrating the osmotic and metabolic functions of the multiple organ systems including liver.

A 13CO isotopic study on the CO promotion effect in methane dehydroaromatization reaction over a Mo/HMCM-49 catalyst

The promotion effect of CO in methane dehydroaromatization was investigated using 13CO probe molecules. By alternative injection of 13CO to the methane feed, the distribution of 13C x C 6- x H 6 ( x = 0-3) products changed significantly, confirming the participation of 13CO in the reaction network. The addition of 13CO did not change the conversion of CH 4 but improved slightly the durability of the methane dehydroaromatization (MDA) reaction, which might be caused by the interaction of the dissociated oxygen species and the deposited carbon species. The ratio of 13C x C 6- x H 6 ( x = 0-3) varied with the time on stream, which was determined by the competitive reactions of methane decomposition and 13CO dissociation.

Improving Injectivity To Fight Gravity Segregation in Gas Enhanced Oil Recovery

Summary Models for gravity segregation in gas enhanced oil recovery (EOR) indicate that the distance injected gas and water travel together before complete segregation scales with the injection rate Q. Therefore, in cases where injection pressure is limiting, increasing injectivity can improve sweep efficiency. We examine several strategies. Reducing skin resulting from damage at the wellbore face directly increases volumetric sweep of gas. Even in the absence of damage at the wellbore face, most of the injection pressure is dissipated near the injection well, but most of segregation of gas and water occurs much further from the well. Therefore, if injection pressure is limited, increasing mobility near the injection well has a large impact on Q, with a direct benefit in delaying gravity segregation. There is also a relatively small increase in gravity segregation in the near-well region. An analytical model for gravity segregation in homogeneous reservoirs can be extended to a case where permeability is stimulated within a cylindrical region inside a larger cylindrical reservoir. The effect of this stimulation in increasing Q at fixed injection pressure can be estimated as well. One can increase the volume swept by gas before segregation by as much as 170%, though a large volume must be stimulated to reach this optimum. The model represents schematically a number of ways proposed in gas EOR for delaying segregation beyond the possibilities with uniform, steady coinjection of Newtonian fluids: alternate injection of gas and liquid [water alternating gas (WAG) or surfactant alternating gas (SAG) with foam]; injection of gas above water; and injection of shear-thinning foam. In all these cases, the process gives higher mobility near the well, allowing an increase in injection rate, and thereby increases the distance to the point of segregation. The model can be extended directly to the case of shear-thinning (power-law) foam. One obtains a differential equation for the segregation process, in place of the algebraic equation that results for Newtonian fluids. In the limit of extremely shear-thinning behavior, it is possible to double the distance to the point of segregation with no increase in injection pressure. The model can also be applied to foams that are shear-thinning only at high superficial velocity (i.e., near the well). Simulations fit the theoretical prediction well.

Design and Synthesis of High-Quality CdS/ZnSe Type-II Core/Shell Nanocrystals

High-quality (narrow size distribution, high crystallinity, high luminescent efficiency) type-II core/shell nanocrystals have been designed and prepared based on ZnSe epitaxial growth around CdS core template. The CdS/ZnSe type-II core/shell nanocrystals were prepared by the alternate injection of Se/Zn precursors into a diluted pre-prepared CdS core nanocrystals reaction solution via the successive ion layer adsorption and reaction (SILAR) technique. The claimed core/shell structure was confirmed by the optical spectra, TEM analysis and XRD measurement. The emission colors of the obtained CdS/ZnSe nanostructures can be tuned from 510 nm to 590 nm by the variation of both the size of the CdS core and the thickness of the ZnSe shell. The photoluminescence properties of the obtained CdS/ZnSe core/shell nanocrystals (emission efficiency up to 50%) are comparable to the best result reported for the extensively studied CdSe based nanocrystals.

Functional Variation in Lymph Node Arrangements within the Axilla

The aim of the project was to identify how lymphatic pathways are functionally arranged within the axilla (i.e., single linear chains, branching chains, and networks). We used ex vivo dual isotope radioassay of individual nodes resected at axillary lymphatic clearance surgery in breast cancer patients given simultaneous intradermal breast and intradermal hand injections (n = 15) or simultaneous intradermal breast and parenchymal breast injections (n = 15) of differentially labelled human immunoglobulin (Tc-99m-HIG and In-111-HIG). Nodes were ranked according to isotope content and activity-rank profiles constructed for each of the two injection sites. The majority of profiles following intradermal breast injection (17/30) were mono-exponential, consistent with a simple linear chain of nodes, with each node extracting a constant fraction of incoming HIG. In 15/17 of these, the accompanying profile from the alternative injection site was also mono-exponential and, in 11/15, essentially parallel. The profile appeared biphasic in 12/30 intradermal breast injections and of these 9/12 were accompanied by a biphasic profile (7/9 parallel) from the alternative injection site. In one patient, both profiles were polyphasic and parallel. Considering the respective shapes of paired profiles and whether the two injection sites shared the same first echelon nodes, functional lymph node arrangements are proposed. The commonest is a single linear chain, then a chain branching into two linear chains, and, least common, a network.

Successful unsaturated zone treatment of PCE with sodium permanganate

AbstractIn situ chemical oxidation (ISCO) with permanganate has been widely used for soil and groundwater treatment in the saturated zone. Due to the challenges associated with achieving effective distribution and retention in the unsaturated zone, there is a great interest in developing alternative injection technologies that increase the success of vadose‐zone treatment.The subject site is an active dry cleaner located in Topeka, Kansas. A relatively small area of residual contamination adjacent to the active facility building has been identified as the source of a large sitewide groundwater contamination plume with off‐site receptors. The Kansas Department of Health and Environment (KDHE) currently manages site remedial efforts and chose to pilot‐test ISCO with permanganate for the reduction of perchloroethene (PCE) soil concentrations within the source area. KDHE subsequently contracted Burns &amp; McDonnell to design and implement an ISCO pilot test.A treatability study was performed by Carus Corporation to determine permanganate‐soil‐oxidant‐demand (PSOD) and the required oxidant dosing for the site. The pilot‐test design included an ISCO injection approach that consisted of injecting aqueous sodium permanganate using direct‐push technology with a sealed borehole.During the pilot test, approximately 12,500 pounds of sodium permanganate were injected at a concentration of approximately 3 percent (by weight) using the methods described above. Confirmation soil sampling conducted after the injection event indicated PCE reductions ranging from approximately 79 to more than 99 percent. A follow‐up treatment, consisting of the injection of an additional 6,200 pounds of sodium permanganate, was implemented to address residual soil impacts remaining in the soil source zone. Confirmation soil sampling conducted after the treatment indicated a PCE reduction of greater than 90 percent at the most heavily impacted sample location and additional reductions in four of the six samples collected. © 2009 Wiley Periodicals, Inc.

Interferon-alpha reinstates morphine-conditioned place preference through opioid receptors in rats

Cytokine interferon-alpha (IFN-alpha) is an immunomodulator and neuromodulator, which modulates central nervous system function partially by activating opioid receptors. However, the role that IFN-alpha plays in relapse to drug abuse is still largely unknown. Thus, we studied whether human recombinant INF-alpha (rIFN-alpha) would reinstate morphine-conditioned place preference (CPP) in rats. In Experiment 1, rats were trained for morphine-CPP with 8-day alternate subcutaneous (s.c.) injections of morphine and saline, and the effect of human rIFN-alpha (20 000 IU/5 microl, intracerebroventricularly) on CPP reinstatement was examined after extinction. In Experiment 2, rats underwent morphine (5 mg/kg, s.c.) unconditioned training with 8 daily alternate injections of morphine (5 mg/kg, s.c.) and saline. Then, the effect of human rIFN-alpha (20 000 IU/5 microl, intracerebroventricularly) on reinstatement of CPP was examined after extinction. In Experiment 3, the effect of opioid receptor antagonist naloxone (1 mg/kg, intraperitoneally) on human rIFN-alpha-induced reinstatement of morphine-CPP was investigated. We found that human rIFN-alpha reinstated morphine-CPP in rats trained under morphine conditioning after extinction, but did not affect CPP in rats that underwent unconditioned training. Naloxone significantly inhibited human rIFN-alpha-induced reinstatement of morphine-CPP. These results indicate that IFN-alpha is a stimulus for reinstatement of morphine-CPP by activation of opioid receptors, which extends our understanding on the high comorbidity of heroin relapse and viral infection.

Hand recontouring with calcium hydroxylapatite (Radiesse)®

The aging hand is a common area of concern for many patients. Until recently, adequate treatment options have been hampered by pain of injecting into the dorsum and, post-injection, by the absence of longevity of treatment. In this article, we describe the off-label use of the soft tissue filler calcium hydroxylapatite (CaHA; Radiesse) for hand rejuvenation. The product is inherently biocompatible and, when placed in soft tissue, induces neocollagenesis. An alternative injection mixture of CaHA combined with lidocaine is described, as well as the novel "bolus" injection technique. The CaHA-lidocaine emulsion reduces the pain of injection to nearly none at all, improves the rheology of the procedure, and allows for deposition of the product into the correct plane of tissue. The volume of CaHA injected as well as the amount of lidocaine used for the mixture vary according to physician preference. In our practice, 1.3 mL of CaHA combined with 0.5 mL lidocaine per hand usually appears to be sufficient to improve the appearance of the atrophic dorsum of the hand. Side-effects of CaHA (Radiesse), particularly in this off-label application, are minimal and of short duration. The aesthetic result is immediate and generally persists for longer than 6 months. As a treatment option, hand rejuvenation with CaHA (Radiesse) is a very gratifying procedure both to the patient and to the physician.

CO2 storage in saline aquifers: In the Southern North Sea and Northern Germany

CO2 storage in depleted gas fields is attractive but gas fields are unequally distributed geographically and can be utilized only within a restricted window of opportunity. Therefore, CO2 storage in saline aquifers can be expected to become an important element of CO2 capture and storage (CCS) systems. CO2 storage in saline aquifers is studied in the European DYNAMIS project, where special attention was paid to the relation between the geological structure, geological properties and achievable injection rates. This paper presents the results from simulations of CO2 storage in two aquifer structures. One aquifer structure is located in the English sector of the Southern North Sea and one aquifer structure located in Northern Germany. The geological model of the Southern North Sea structure was built using existing knowledge of facies geometry and distribution from literature and well logs and the overall geometry from interpreted horizons. The distributions of properties like lithology, net-to-gross ratios, porosity and permeability were stochastically modelled to represent the braided and meandering river and fan systems within the Bunter Sandstone Formation. High-porosity and high-permeability zones model fluvial channels running through the reservoir. A different approach was chosen for the North German structure. Because there is no information on the facies or petrophysical parameter distribution of the aquifer, three different model scenarios were generated. One model was created with homogeneous properties throughout the aquifer. Two other model scenarios were generated allowing the porosity and permeability to vary within certain ranges. This was done using a sequential Gaussian simulation with the known mean, minimum and maximum values of porosity and permeability, respectively. Due to the size of the aquifer structures and computing limits, up-scaling of the geological model of the Southern North Sea was required. The up-scaling was aimed to retain as much as possible of the modelled geological features such as braided river and fan systems. Several reservoir simulations were carried out in collaboration between TNO and IFP to assess CO2 injection. Given the injection rate constraints, the aim of the injection simulations was to: •assess the achievable rate of injection;•study the migration and behavior of the CO2 in the reservoir;•assess the most appropriate location(s) for the CO2 injection wells using alternate injection strategies. The injection strategy is relevant especially for the Southern North Sea structure, where river and fan systems may results in high-permeability zones through the reservoir. Accessing such systems may significantly improve a reservoir's value for CO2 storage. The effect of such systems on the injection rates is demonstrated. The reservoir simulations also demonstrate the injection rates that can be achieved in tight reservoirs as in the North Germany case, and the effect of spatial variability of geological parameters. This will show whether it is reasonable to assume spatial geological homogeneity, when data on the reservoir formation are scarce. © 2009 Elsevier Ltd. All rights reserved.

Aripiprazole blocks reinstatement but not expression of morphine conditioned place preference in rats

Aripiprazole is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D 2 receptors and serotonin-1A (5-hydroxytryptamine, 5-HT 1A) receptors and minimal side effects. Based on its pharmacological profile, including stabilization of mesocorticolimbic DA activity (a pathway implicated in drug addiction), we investigated the effects of aripiprazole on relapse to morphine seeking in rats. In experiment 1, rats underwent morphine-induced conditioned place preference (CPP) training with alternate injections of morphine (5 mg/kg, s.c.) and saline (1 ml/kg, s.c.) for 8 consecutive days. To examine the effect of aripiprazole on the expression of morphine-induced CPP, rats received aripiprazole (0, 0.03, 0.1, and 0.3 mg/kg, i.p.) 30 min before testing for the expression of CPP. In experiment 2, rats underwent the same CPP training as in experiment 1 and subsequent extinction training. To examine the effect of aripiprazole on reinstatement of morphine-induced CPP, rats received aripiprazole 30 min before testing for reinstatement of CPP. In experiment 3, to assess the effects of aripiprazole on locomotor activity, aripiprazole was administered 30 min before testing for locomotor activity. Aripiprazole significantly decreased the reinstatement of CPP induced by a priming injection of morphine but had no effect on the expression of morphine-induced CPP or locomotor activity. The D 2 and 5-HT 1A partial agonist and 5-HT 2A antagonist properties of aripiprazole likely account for the blockade of relapse to drug seeking. These findings suggest that aripiprazole may have therapeutic value for reducing craving and preventing relapse to drug seeking.

Augmentation of Morphine-Induced Sensitization but Reduction in Morphine Tolerance and Reward in Delta-Opioid Receptor Knockout Mice

Studies in experimental animals have shown that individuals exhibiting enhanced sensitivity to the locomotor-activating and rewarding properties of drugs of abuse are at increased risk for the development of compulsive drug-seeking behavior. The purpose of the present study was to assess the effect of constitutive deletion of delta-opioid receptors (DOPr) on the rewarding properties of morphine as well as on the development of sensitization and tolerance to the locomotor-activating effects of morphine. Locomotor activity testing revealed that mice lacking DOPr exhibit an augmentation of context-dependent sensitization following repeated, alternate injections of morphine (20 mg/kg; s.c.; 5 days). In contrast, the development of tolerance to the locomotor-activating effects of morphine following chronic morphine administration (morphine pellet: 25 mg: 3 days) is reduced relative to WT mice. The conditioned rewarding effects of morphine were reduced significantly in DOPrKO mice as compared to WT controls. Similar findings were obtained in response to pharmacological inactivation of DOPr in WT mice, indicating that observed effects are not due to developmental adaptations that occur as a consequence of constitutive deletion of DOPr. Together, these findings indicate that the endogenous DOPr system is recruited in response to both repeated and chronic morphine administration and that this recruitment serves an essential function in the development of tolerance, behavioral sensitization, and the conditioning of opiate reward. Importantly, they demonstrate that DOPr has a distinct role in the development of each of these drug-induced adaptations. The anti-rewarding and tolerance-reducing properties of DOPr antagonists may offer new opportunities for the treatment and prevention of opioid dependence as well as for the development of effective analgesics with reduced abuse liability.

Uptake kinetics and biodistribution of 14C-d-luciferin—a radiolabeled substrate for the firefly luciferase catalyzed bioluminescence reaction: impact on bioluminescence based reporter gene imaging

Firefly luciferase catalyzes the oxidative decarboxylation of D: -luciferin to oxyluciferin in the presence of cofactors, producing bioluminescence. This reaction is used in optical bioluminescence-based molecular imaging approaches to detect the expression of the firefly luciferase reporter gene. Biokinetics and distribution of the substrate most likely have a significant impact on levels of light signal and therefore need to be investigated. Benzene ring (14)C(U)-labeled D-luciferin was utilized. Cell uptake and efflux assays, murine biodistribution, autoradiography and CCD-camera based optical bioluminescence imaging were carried out to examine the in vitro and in vivo characteristics of the tracer in cell culture and in living mice respectively. Radiolabeled and unlabeled D-luciferin revealed comparable levels of light emission when incubated with equivalent amounts of the firefly luciferase enzyme. Cell uptake assays in pCMV-luciferase-transfected cells showed slow trapping of the tracer and relatively low uptake values (up to 22.9-fold higher in firefly luciferase gene-transfected vs. nontransfected cells, p = 0.0002). Biodistribution studies in living mice after tail-vein injection of (14)C-D-luciferin demonstrated inhomogeneous tracer distribution with early predominant high radioactivity levels in kidneys (10.6% injected dose [ID]/g) and liver (11.9% ID/g), followed at later time points by the bladder (up to 81.3% ID/g) and small intestine (6.5% ID/g), reflecting the elimination routes of the tracer. Kinetics and uptake levels profoundly differed when using alternate injection routes (intravenous versus intraperitoneal). No clear trapping of (14)C-D-luciferin in firefly luciferase-expressing tissues could be observed in vivo. The data obtained with (14)C-D-luciferin provide insights into the dynamics of D: -luciferin cell uptake, intracellular accumulation, and efflux. Results of the biodistribution and autoradiographic studies should be useful for optimizing and adapting optical imaging protocols to specific experimental settings when utilizing the firefly luciferase and D: -luciferin system.

Nutritional Deficit And Volume Overload In Renal Transplant Patients.

The antitumour activity of the dendritic cell (DC)-based cellular vaccines is greatly reduced in hostile tumour microenvironment. Therefore, there are many attempts to eliminate or neutralize both suppressor cells and cytokines. The aim of the investigation was to verify if temporary elimination of IL-10 just before injection of bone marrow-derived DCs (BMDCs) enhance the antitumour activity of applied vaccines and help to overcome the immunosuppressive tumour barrier.Mice bearing colon carcinoma MC38 were given single dose of cyclophosphamide (CY) followed by alternate injections of anti-IL-10 antibodies and BMDC-based vaccines consisted of BMDCs stimulated with MC38 tumour antigen (BMDC/TAg) or the combination of BMDC/TAg with BMDCs transduced with IL-12 genes (BMDC/IL-12).The high tumour growth inhibition was observed in mice treated with CY + anti-IL-10 + BMDC/TAg as well as CY ± anti-IL-10 + BMDC/TAg + BMDC/IL-12. However, the mechanisms of action of particular treatment schemes were diversified. Generally, it was observed that application of anti-IL-10 Abs reduced suppressor activity of myeloid-derived suppressor cells (MDSCs). However, anti-IL-10 Abs in combination with diversely composed BMDC-based vaccines induced different components of an antitumour response. The high cytotoxic activity of spleen-derived NK cells and increased influx of these cells into tumours of mice treated with CY + anti-IL-10 + BMDC/TAg indicate that mice from the group developed strong NK-dependent response. Whereas, application of anti-IL-10 Abs just before injection of BMDC/TAg + BMDC/IL-12 did not enhanced NK cell activity. Furthermore, it significantly impaired effectiveness of therapy composed of CY + BMDC/TAg + BMDC/IL-12 vaccine in induction of Th1 type immune response.Taken together, our results indicate that temporary elimination of IL-10 is an important and effective way to decrease the immune suppression associated with MDSCs activity and represents a useful strategy for successful enhancement of the antitumour activity of BMDC/TAg-based vaccines.

Kidney Donors' Demographics And Motivation For Donation (a Tertiary Care Experience)

The antitumour activity of the dendritic cell (DC)-based cellular vaccines is greatly reduced in hostile tumour microenvironment. Therefore, there are many attempts to eliminate or neutralize both suppressor cells and cytokines. The aim of the investigation was to verify if temporary elimination of IL-10 just before injection of bone marrow-derived DCs (BMDCs) enhance the antitumour activity of applied vaccines and help to overcome the immunosuppressive tumour barrier.Mice bearing colon carcinoma MC38 were given single dose of cyclophosphamide (CY) followed by alternate injections of anti-IL-10 antibodies and BMDC-based vaccines consisted of BMDCs stimulated with MC38 tumour antigen (BMDC/TAg) or the combination of BMDC/TAg with BMDCs transduced with IL-12 genes (BMDC/IL-12).The high tumour growth inhibition was observed in mice treated with CY + anti-IL-10 + BMDC/TAg as well as CY ± anti-IL-10 + BMDC/TAg + BMDC/IL-12. However, the mechanisms of action of particular treatment schemes were diversified. Generally, it was observed that application of anti-IL-10 Abs reduced suppressor activity of myeloid-derived suppressor cells (MDSCs). However, anti-IL-10 Abs in combination with diversely composed BMDC-based vaccines induced different components of an antitumour response. The high cytotoxic activity of spleen-derived NK cells and increased influx of these cells into tumours of mice treated with CY + anti-IL-10 + BMDC/TAg indicate that mice from the group developed strong NK-dependent response. Whereas, application of anti-IL-10 Abs just before injection of BMDC/TAg + BMDC/IL-12 did not enhanced NK cell activity. Furthermore, it significantly impaired effectiveness of therapy composed of CY + BMDC/TAg + BMDC/IL-12 vaccine in induction of Th1 type immune response.Taken together, our results indicate that temporary elimination of IL-10 is an important and effective way to decrease the immune suppression associated with MDSCs activity and represents a useful strategy for successful enhancement of the antitumour activity of BMDC/TAg-based vaccines.

Late summer changes in burning conditions in the boreal regions and their implications for NOxand CO emissions from boreal fires

Building emission inventories for the fires in boreal regions remains a challenging task with significant uncertainties in the methods used. In this work, we assess the impact of seasonal trends in fuel consumption and flaming/smoldering ratios on emissions of species dominated by flaming combustion (e.g., NOx) and species dominated by smoldering combustion (e.g., CO). This is accomplished using measurements of CO and NOyat the free tropospheric Pico Mountain observatory in the central North Atlantic during the active boreal fire seasons of 2004 and 2005. ΔNOy/ΔCO enhancement ratios in aged fire plumes had higher values in June‐July (7.3 × 10−3mol mol−1) relative to the values in August‐September (2.8 × 10−3mol mol−1), indicating that NOx/CO emission ratios declined significantly as the fire season progressed. This is consistent with our understanding that an increased amount of fuel is consumed via smoldering combustion during late summer, as deeper burning of the drying organic soil layer occurs. A major growth in fuel consumption per unit area is also expected, due to deeper burning. Emissions of CO and NOxfrom North American boreal fires were estimated using the Boreal Wildland Fire Emissions Model, and their long‐range transport to the sampling site was modeled using FLEXPART. These simulations were generally consistent with the observations, but the modeled seasonal decline in the ΔNOy/ΔCO enhancement ratio was less than observed. Comparisons using alternative fire emission injection height scenarios suggest that plumes with the highest CO levels at the observatory were lofted well above the boundary layer, likely as a result of intense crown fires.

An Open-Label Safety Study of Enfuvirtide Injection with a Needle-Free Injection Device or Needle/Syringe: The Biojector 2000 Open-Label Safety Study (BOSS)

Enfuvirtide (ENF) administration by needle/syringe is commonly associated with injection site reactions (ISRs). This study assessed ISRs and participant preference between a needle-free injection device (NFID) and a 27-gauge 1/2-inch needle/syringe (NS). A total of 349 participants with human immunodeficiency virus infection, who had difficulty tolerating long-term administration of ENF by NS, underwent randomization (2:1) to ENF administered twice daily by NFID for 8 weeks, or by NS for 4 weeks followed by NFID for 4 weeks. The objectives of the study were to compare ISRs associated with ENF injection using NFID or NS based on a composite endpoint, ISR incidence/severity, overall ISR scores, and discontinuations. In the NFID group, ISRs improved as the percentage of participants meeting the composite endpoint decreased from baseline (40.1%) to week 4 (25.4%) and remained stable at week 8 (21.2%). In the NS --> NFID group, the percentage meeting the composite endpoint worsened from baseline (36.5%) to week 4 (45.1%), but improved at week 8 (26.1%) after switching. Between-participant comparison showed a statistically significant greater improvement from baseline to week 4 in overall ISR score in the NFID group compared to the NS group. Within-participant comparison of the NS --> NFID group showed a significantly greater decrease in overall ISR score from baseline to week 8. In responses to a questionnaire, 87.2% of the participants surveyed preferred the NFID delivery system over NS. NFID is an alternative injection method that may reduce the incidence and severity of treatment-limiting ISRs associated with ENF administration.