scholarly journals Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

Drug Research ◽  
2020 ◽  
Vol 70 (04) ◽  
pp. 145-150 ◽  
Author(s):  
Viviana Noriega ◽  
Hugo F. Miranda ◽  
Juan Carlos Prieto ◽  
Ramón Sotomayor-Zárate ◽  
Fernando Sierralta

AbstractThere are different animal models to evaluate pain among them the formalin hind paw assay which is widely used since some of its events appear to be similar to the clinical pain of humans. The assay in which a dilute solution of formalin is injected into the dorsal hindpaw of a murine produces two ‘phases’ of pain behavior separated by a inactive period. The early phase (Phase I) is probably due to direct activation of nociceptors and the second phase (Phase II) is due to ongoing inflammatory input and central sensitization. Mice were used to determine the potency antinociceptive of piroxicam (1,3,10,and 30 mg/kg), parecoxib (0.3, 1,3,10 and 30 mg/kg), dexketoprofen (3,10,30 and 100 mg/kg) and ketoprofen (3,10,30 and 100 mg/kg). Dose-response for each NSAIDs were created before and after 5 mg/kg of L-NAME i.p. or 5 mg/kg i.p. of 7-nitroindazole. A least-squares linear regression analysis of the log dose–response curves allowed the calculation of the dose that produced 50% of antinociception (ED50) for each drug. The ED50 demonstrated the following rank order of potency, in the phase I: piroxicam > dexketoprofen > ketoprofen > parecoxib and in the phase II: piroxicam > ketoprofen > parecoxib > dexketoprofen. Pretreatment of the mice with L-NAME or 7-nitroindazol induced a significant increase of the analgesic power of the NSAIDs, with a significant reduction of the ED50. It is suggested that NO may be involved in both phases of the trial, which means that nitric oxide regulates the bioactivity of NSAIDs.

2015 ◽  
Vol 45 (3) ◽  
pp. 326-332 ◽  
Author(s):  
Renato Coradello Lourenço ◽  
Saul Jorge Pinto de Carvalho

ABSTRACTIn sugarcane crop areas, the application of preemergence herbicides with long residual effect in the soil has been frequently necessary. The herbicide persistence in the soil must be high especially because of applications during the dry season of the year, after sugarcane harvest. This study aimed at estimating the sulfentrazone persistence and dissipation in dry soil using bioindicator. Five experiments were carried out, divided into two phases. In the first phase, three dose-response curves were adjusted to select the best bioindicator to be adopted in the second phase. Niger was adopted due to its lower sensibility to sulfentrazone. In the second phase, a new dose-response curve was carried out, with six doses of sulfentrazone, in order to standardize the bioindicator sensibility to sulfentrazone. At the end, another experiment with six periods of sulfentrazone persistence in dry clay soil was developed. Persistence periods were: 182, 154, 125, 98 and 30 days. The bioindicator was seeded at the application day in treated plots and control. In this experiment, the sulfentrazone dose applied was 800 g ha-1. Niger was considered a good species to estimate the sulfentrazone persistence in dry soil. The sulfentrazone phytotoxic activity was identified up to 182 days after application, and its average dissipation rate was 2.15 g ha-1 day-1, with half-life higher than 182 days.


2018 ◽  
Vol 33 (09) ◽  
pp. 1843004 ◽  
Author(s):  
◽  
M. Agostini ◽  
A. M. Bakalyarov ◽  
M. Balata ◽  
I. Barabanov ◽  
...  

The GERmanium Detector Array (GERDA) is a low background experiment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN designed to search for the rare neutrinoless double beta decay ([Formula: see text]) of [Formula: see text]Ge. In the first phase (Phase I) of the experiment, high purity germanium diodes were operated in a “bare” mode and immersed in liquid argon. The overall background level of [Formula: see text] was a factor of ten better than those of its predecessors. No signal was found and a lower limit was set on the half-life for the [Formula: see text] decay of [Formula: see text]Ge [Formula: see text] yr (90% CL), while the corresponding median sensitivity was [Formula: see text] yr (90% CL). A second phase (Phase II) started at the end of 2015 after a major upgrade. Thanks to the increased detector mass and performance of the enriched germanium diodes and due to the introduction of liquid argon instrumentation techniques, it was possible to reduce the background down to [Formula: see text]. After analyzing 23.2 kg[Formula: see text]⋅[Formula: see text]yr of these new data no signal was seen. Combining these with the data from Phase I a stronger half-life limit of the [Formula: see text]Ge [Formula: see text] decay was obtained: [Formula: see text] yr (90% CL), reaching a sensitivity of [Formula: see text] yr (90% CL). Phase II will continue for the collection of an exposure of 100 kg[Formula: see text]yr. If no signal is found by then the GERDA sensitivity will have reached [Formula: see text] yr for setting a 90% CL. limit. After the end of GERDA Phase II, the flagship experiment for the search of [Formula: see text] decay of [Formula: see text]Ge will be LEGEND. LEGEND experiment is foreseen to deploy up to 1-ton of [Formula: see text]Ge. After ten years of data taking, it will reach a sensitivity beyond 10[Formula: see text] yr, and hence fully cover the inverted hierarchy region.


2018 ◽  
Vol 29 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Eric Boakye-Gyasi ◽  
Ella Anle Kasanga ◽  
Elvis Ofori Ameyaw ◽  
Wonder Kofi Mensah Abotsi ◽  
Robert Peter Biney ◽  
...  

AbstractBackground:Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts ofPhyllanthus muellerianus(Kuntze) Exell. (Euphorbiaceae). SeveralPhyllanthusspecies are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts ofP. muellerianusand of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects.Methods:The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and diclofenac (10–100 mg/kg) to obtain the ED50values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50values for the formalin test.Results:Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test.Conclusions:The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.


2021 ◽  
Vol 288 (1945) ◽  
pp. 20203207
Author(s):  
Maiki K. Wakai ◽  
Mitsuru J. Nakamura ◽  
Satoshi Sawai ◽  
Kohji Hotta ◽  
Kotaro Oka

Marine invertebrate larvae are known to begin metamorphosis in response to environmentally derived cues. However, little is known about the relationships between the perception of such cues and internal signalling for metamorphosis. To elucidate the mechanism underlying the initiation of metamorphosis in the ascidian, Ciona intestinalis type A ( Ciona robusta ), we artificially induced ascidian metamorphosis and investigated Ca 2+ dynamics from pre- to post-metamorphosis. Ca 2+ transients were observed and consisted of two temporally distinct phases with different durations before tail regression which is the early event of metamorphosis. In the first phase, Phase I, the Ca 2+ transient in the papillae (adhesive organ of the anterior trunk) was coupled with the Ca 2+ transient in dorsally localized cells and endoderm cells just after mechanical stimulation. The Ca 2+ transients in Phase I were also observed when applying only short stimulation. In the second phase, Phase II, the Ca 2+ transient in papillae was observed again and lasted for approximately 5–11 min just after the Ca 2+ transient in Phase I continued for a few minutes. The impaired papillae by Foxg -knockdown failed to induce the second Ca 2+ transient in Phase II and tail regression. In Phase II, a wave-like Ca 2+ propagation was also observed across the entire epidermis. Our results indicate that the papillae sense a mechanical cue and two-round Ca 2+ transients in papillae transmits the internal metamorphic signals to different tissues, which subsequently induces tail regression. Our study will help elucidate the internal mechanism of metamorphosis in marine invertebrate larvae in response to environmental cues.


2019 ◽  
Vol 75 (6) ◽  
pp. 740-749
Author(s):  
Nataliya E. Novikova ◽  
Timofei A. Sorokin ◽  
Alexander M. Antipin ◽  
Nadezhda B. Bolotina ◽  
Olga A. Alekseeva ◽  
...  

Crystals with the La18W10O57-type structure (6H and 5H polytypes) were obtained by a self-flux method from high-temperature solutions. Some of the crystal samples were studied by single-crystal X-ray structure analysis. The diffraction patterns indicated that two phases co-exist in each sample. The hexagonal lattices have a common period of a ≈ 9.0 Å and are non-equal in length but have equally oriented superstructure periods 6c (phase I) and 5c (phase II), c ≈ 5.4 Å. The structures of phases I and II were solved in the symmetry groups P\overline{6}2c and P321, respectively, based on the X-ray data for crystals I and II, with predominant content of the first and second phase. The motif of isolated WO6 prisms with W atoms on the cell edges is common to both phases. WO6 octahedra, both isolated and joined by faces, are distributed along the c axis within the unit cells. Phase I contains extra layers of isolated WO6 octahedra compared to phase II. Tungsten sites in joined octahedra are disordered and partially occupied. Disordering is more expressed in phase II, which in return contains rather more W and O per atom of La. The refined chemical compositions are La18W10O57 for I and La15W8.5O48 for II.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nhat Thanh Hoang Le ◽  
Nhan Thi Ho ◽  
Bryan Grenfell ◽  
Stephen Baker ◽  
Ronald B. Geskus

Abstract Background Infection with measles virus (MeV) causes immunosuppression and increased susceptibility to other infectious diseases. Only few studies reported a duration of immunosuppression, with varying results. We investigated the effect of immunosuppression on the incidence of hospital admissions for infectious diseases in Vietnamese children. Methods We used retrospective data (2005 to 2015; N = 4419) from the two pediatric hospitals in Ho Chi Minh City, Vietnam. We compared the age-specific incidence of hospital admission for infectious diseases before and after hospitalization for measles. We fitted a Poisson regression model that included gender, current age, and time since measles to obtain a multiplicative effect measure. Estimates were transformed to the additive scale. Results We observed two phases in the incidence of hospital admission after measles. The first phase started with a fourfold increased rate of admissions during the first month after measles, dropping to a level quite comparable to children of the same age before measles. In the second phase, lasting until at least 6 years after measles, the admission rate decreased further, with values up to 20 times lower than in children of the same age before measles. However, on the additive scale the effect size in the second phase was much smaller than in the first phase. Conclusion The first phase highlights the public health benefits of measles vaccination by preventing measles and immune amnesia. The beneficial second phase is interesting, but its strength strongly depends on the scale. It suggests a complicated interaction between MeV infection and the host immunity.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Luciana Caravatta ◽  
Consuelo Rosa ◽  
Maria Bernadette Di Sciascio ◽  
Andrea Tavella Scaringi ◽  
Angelo Di Pilla ◽  
...  

Abstract Background COVID-19 in Italy has led to the need to reorganize hospital protocols with a significant risk of interruption to cancer treatment programs. In this report, we will focus on a management model covering the two phases of the COVID-19 emergency, namely lockdown-phase I and post-lockdown-phase II. Methods The following steps were taken in the two phases: workload during visits and radiotherapy planning, use of dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, hospital environments and intra-institutional meetings and tumor board management. Due to the guidelines set out by the Ministry of Health, oncological follow-up visits were interrupted during the lockdown-phase I; consequently, we set about contacting patients by telephone, with laboratory and instrumental exams being viewed via telematics. During the post-lockdown-phase II, the oncological follow-up clinic reopened, with two shifts operating daily. Results By comparing our radiotherapy activity from March 9 to May 4 2019 with the same period in 2020 during full phase I of the COVID-19 emergency, similar results were achieved. First radiotherapy visits, Simulation Computed Tomography and Linear Accelerator treatments amounted to 123, 137 and 151 in 2019 compared with 121, 135 and 170 in 2020 respectively. There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals, who were all negative to the swab tests performed. Conclusion During both phases of the COVID-19 emergency, the planned model used in our own experience guaranteed both continuity in radiotherapy treatments whilst neither reducing workload nor interrupting treatment and, as such, it ensured the safety of cancer patients, hospital environments and staff.


Author(s):  
Juanjuan Luo ◽  
Huadong Ma ◽  
Dongqing Zhou

Abstract Similarity matrix has a significant effect on the performance of the spectral clustering, and how to determine the neighborhood in the similarity matrix effectively is one of its main difficulties. In this paper, a “divide and conquer” strategy is proposed to model the similarity matrix construction task by adopting Multiobjective evolutionary algorithm (MOEA). The whole procedure is divided into two phases, phase I aims to determine the nonzero entries of the similarity matrix, and Phase II aims to determine the value of the nonzero entries of the similarity matrix. In phase I, the main contribution is that we model the task as a biobjective dynamic optimization problem, which optimizes the diversity and the similarity at the same time. It makes each individual determine one nonzero entry for each sample, and the encoding length decreases to O(N) in contrast with the non-ensemble multiobjective spectral clustering. In addition, a specific initialization operator and diversity preservation strategy are proposed during this phase. In phase II, three ensemble strategies are designed to determine the value of the nonzero value of the similarity matrix. Furthermore, this Pareto ensemble framework is extended to semi-supervised clustering by transforming the semi-supervised information to constraints. In contrast with the previous multiobjective evolutionary-based spectral clustering algorithms, the proposed Pareto ensemble-based framework makes a balance between time cost and the clustering accuracy, which is demonstrated in the experiments section.


Author(s):  
Sreejith S. S. ◽  
Muthu Mathirajan

Reward and Recognition (R&R) should be given to employees in a timely manner, based on continuous evaluation of their performance. Success of an R&R process lies in clear and well defined criteria for continuous evaluation of employee performance. Often such criteria are decided by the organization with no input from the employees. The purpose of this paper is to use qualitative research methods to explore and identify the criteria to be used for continuous employee performance evaluation for R&R in Information Technology organizations, from the perspectives of software engineers (SEs) and project managers (PMs). Exploratory research was conducted in two phases. In Phase I, unstructured interviews are used to elicit information from 7 SEs. Caselets are prepared based on these interviews and 19 criteria are identified. In Phase II, the criteria identified in Phase I are confirmed using content analysis of semi-structured interviews, conducted on relatively larger group of SEs (in stage 1) and PMs (in stage 2). Additionally, 12 criteria are also identified in Phase II. Collectively 31 criteria are identified. The proposed criteria set is expected to comprehensively cover the SE performance on a continuous basis in various dimensions to award R&R.


2016 ◽  
Vol 32 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Claudia Der-Martirosian ◽  
Tiffany A. Radcliff ◽  
Alicia R. Gable ◽  
Deborah Riopelle ◽  
Farhad A. Hagigi ◽  
...  

AbstractIntroductionThere have been numerous initiatives by government and private organizations to help hospitals become better prepared for major disasters and public health emergencies. This study reports on efforts by the US Department of Veterans Affairs (VA), Veterans Health Administration, Office of Emergency Management’s (OEM) Comprehensive Emergency Management Program (CEMP) to assess the readiness of VA Medical Centers (VAMCs) across the nation.Hypothesis/ProblemThis study conducts descriptive analyses of preparedness assessments of VAMCs and examines change in hospital readiness over time.MethodsTo assess change, quantitative analyses of data from two phases of preparedness assessments (Phase I: 2008-2010; Phase II: 2011-2013) at 137 VAMCs were conducted using 61 unique capabilities assessed during the two phases. The initial five-point Likert-like scale used to rate each capability was collapsed into a dichotomous variable: “not-developed=0” versus “developed=1.” To describe changes in preparedness over time, four new categories were created from the Phase I and Phase II dichotomous variables: (1) rated developed in both phases; (2) rated not-developed in Phase I but rated developed in Phase II; (3) rated not-developed in both phases; and (4) rated developed in Phase I but rated not- developed in Phase II.ResultsFrom a total of 61 unique emergency preparedness capabilities, 33 items achieved the desired outcome – they were rated either “developed in both phases” or “became developed” in Phase II for at least 80% of VAMCs. For 14 items, 70%-80% of VAMCs achieved the desired outcome. The remaining 14 items were identified as “low-performing” capabilities, defined as less than 70% of VAMCs achieved the desired outcome.Conclusion:Measuring emergency management capabilities is a necessary first step to improving those capabilities. Furthermore, assessing hospital readiness over time and creating robust hospital readiness assessment tools can help hospitals make informed decisions regarding allocation of resources to ensure patient safety, provide timely access to high-quality patient care, and identify best practices in emergency management during and after disasters. Moreover, with some minor modifications, this comprehensive, all-hazards-based, hospital preparedness assessment tool could be adapted for use beyond the VA.Der-MartirosianC, RadcliffTA, GableAR, RiopelleD, HagigiFA, BrewsterP, DobalianA. Assessing hospital disaster readiness over time at the US Department of Veterans Affairs. Prehsop Disaster Med. 2017;32(1):46–57.


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