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1.
Medicine (Baltimore) ; 101(2): e28463, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029189

RESUMO

BACKGROUND: The administration of Janus kinase inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved the clinical outcomes of patients with rheumatoid arthritis (RA). Previous trials have shown that upadacitinib, a Janus kinase inhibitor, can effectively improve disease activity and prevent progression of joint destruction in RA patients with inadequate responses to methotrexate (MTX). It remains unclear whether reduced disease activity can be maintained after discontinuation of MTX in patients treated with upadacitinib plus MTX. Thus, the aim of this study is to evaluate changes in disease activity after administration of upadacitinib plus MTX in RA patients who failed to achieve an adequate response to MTX and to determine whether clinical relapse can be avoided after discontinuation of MTX in those who achieved clinical remission. METHODS/DESIGN: The proposed study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. The cohort will include 155 RA patients with at least moderate disease activity during treatment with MTX. Patients will receive upadacitinib and MTX will be discontinued for those who achieve clinical remission. Disease activity will be evaluated longitudinally by measuring clinical disease activity indices and with musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who sustain a disease activity score-28- C reactive protein score of ≤3.2 from week 24 to 48 after a disease activity score-28- C reactive protein score of <2.6 at week 24. Important secondary endpoints are changes from baseline MSUS scores. Serum levels of multiple biomarkers, including cytokines and chemokines, will be comprehensively analyzed. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of MTX after achieving clinical remission by treatment with upadacitinib plus MTX combination therapy. The strength of this study is the prospective evaluation of therapeutic efficacy using clinical disease activity indices and standardized MSUS, which can accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers. Furthermore, parameters to predict clinical remission after administration of upadacitinib plus MTX combination therapy and nonclinical relapse after discontinuation of MTX will be screened by integrated multilateral assessments (i.e., clinical disease activity indices, MSUS findings, and serum biomarkers).

2.
Am Surg ; : 31348211060438, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34974742

RESUMO

Although there are many reports on surgical repair for umbilical hernia, there is no standard procedure at present. Since 2012, we have performed surgery with transumbilical repair using an original procedure. With this procedure, a longitudinal incision is made in the umbilicus, and the fascial defect is closed. Excess skin is excised at a fixed length. The fascia and dermis are sutured vertically over a length of 15 mm. A total of 424 patients with pediatric umbilical hernia who underwent this procedure between September 2012 and December 2020 were reviewed. The mean operative duration was 52 minutes. All patients were followed up to 6 months after surgery. Postoperative complications included infection in 15 patients and wound granulation in 5 patients. The morphology of the umbilicus is natural and satisfying. We conclude that this procedure is safe and simple and the results are satisfactory.

3.
Environ Toxicol Chem ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040199

RESUMO

Use of the moribund state as an endpoint for acute toxicity testing in fish is complicated by the lack of consensus about the sublethal signs that define the state or that can predict imminent death. Defining the moribund state in fish requires determination of the association between each observable sublethal sign and transition to imminent death. Here, to establish a criterion for defining the moribund state in Japanese medaka (Oryzias latipes), we determined death/clinical-sign ratios, defined as the proportion of fish with each clinical sign that transitioned to imminent death, for 13 clinical signs observed in individually housed fish exposed to one of two typical toxicants, three pharmaceuticals, two pesticides and one metal. Also, the time from onset of each clinical sign to transition to imminent death (referred to as the survival time) was determined by continuous monitoring. Three of the observed clinical signs-immobility, lethargy, and immobility at the surface-were found to be indicators of the moribund state, with each of these signs having a death/clinical-sign ratio of 1.0. Evaluation of the survival time after onset of the other 10 signs enabled determination of whether timely euthanasia would be appropriate, thereby providing a means of reducing the suffering of laboratory fish in the period before death. This article is protected by copyright. All rights reserved.© 2022 SETAC.

4.
Vasc Endovascular Surg ; 56(1): 121-125, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34237235

RESUMO

INTRODUCTION: The family of Amplatzer Vascular Plugs (AVPs) is characterized by their precise deployment and high resistance to migration. However, a risk of recanalization of the embolized vessels has been reported. To augment the effectiveness of embolization, the coil-in-plug (CIP) technique was developed, exclusively using AVP I or IV. However, these plugs cannot be used for large vessels like portovenous shunt because of the size limitation. AVP II has a larger-sized model up to 22 mm. This article reports two cases of embolizing high-flow and large-caliber portosystemic shunts where the CIP technique with multilayer AVP II was effectively employed. MATERIALS AND METHODS: The CIP technique using AVP II was utilized for one case with a portocaval shunt and another with a splenorenal shunt. CIP was established with wire penetration through the multilayer meshes, followed by a microcatheter insertion. After the microcatheter was positioned in the central lobe, the internal space was embolized tightly using pushable or detachable coils. RESULTS: A use of guidewire with a high tip load enabled an establishment of CIP and complete occlusion of the target vessels immediately without migration of the embolic devices in both cases. The symptom of encephalopathy improved after the procedure in both the case of the portocaval and the splenorenal shunt. CONCLUSION: The CIP technique with the AVP II was safe and effective to achieve complete occlusion of the large-caliber portosystemic shunts.


Assuntos
Embolização Terapêutica , Derivação Portossistêmica Transjugular Intra-Hepática , Embolização Terapêutica/efeitos adversos , Humanos , Resultado do Tratamento
5.
Environ Toxicol Chem ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34913527

RESUMO

Equilibrium partitioning (EqP) theory and spiked-sediment toxicity tests are useful methods to develop sediment quality benchmarks. However, neither approach has been directly compared based on species sensitivity distributions (SSDs) to date. In the present study, we compared SSDs for 10 nonionic hydrophobic chemicals (e.g., pyrethroid insecticides, other insecticides, and polycyclic aromatic hydrocarbons) based on 10-14-day spiked-sediment toxicity test data with those based on EqP theory using acute water-only tests. Because the exposure periods were different between the two tests, effective concentrations (i.e., median effective/lethal concentration) were corrected to compare SSDs. Accordingly, we found that hazardous concentrations for 50% and 5% of species (HC50 and HC5, respectively) differed by up to a factor of 100 and 129 between the two approaches, respectively. However, when five or more species were used for SSD estimation, their differences were reduced to a factor of 1.7 and 5.1 for HC50 and HC5, respectively, and the 95% confidence intervals of HC50 values overlapped considerably between the two approaches. These results suggest that when the number of test species is adequate, SSDs based on EqP theory and spiked-sediment tests are comparable in sediment risk assessments. Environ Toxicol Chem 2022;00:1-12. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

6.
Aquat Toxicol ; 243: 106058, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34965494

RESUMO

Juvenile hormone (JH) are a family of multifunctional hormones regulating larval development, molting, metamorphosis, reproduction, and phenotypic plasticity in arthropods. Based on its importance in arthropod life histories, many insect growth regulators (IGRs) mimicking JH have been designed to control harmful insects in agriculture and aquaculture. These JH analogs (JHAs) may also pose hazards to nontarget species by causing unexpected endocrine-disrupting (ED) effects such as molting and metamorphosis defects, larval lethality, and disruption of the sexual identity. This critical review summarizes the current knowledge of the JH-mediated effects in the freshwater cladoceran crustaceans such as Daphnia species on JHA-triggered endocrine disruptive outputs to establish a systematic understanding of JHA effects. Based on the current knowledge, adverse outcome pathways (AOPs) addressing the JHA-mediated ED effects in cladoceran leading to male offspring production and subsequent population decline were developed. The weight of evidence (WoE) of AOPs was assessed according to established guidelines. The review and AOP development aim to present the current scientific understanding of the JH pathway and provide a robust reference for the development of tiered testing strategies and new risk assessment approaches for JHAs in future ecotoxicological research and regulatory processes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34907425

RESUMO

A 74-year-old woman with Takayasu's arteritis previously underwent aortic valve replacement at 59 years old. She was initially diagnosed with aortic valve stenosis and valve detachment. Moreover, preoperative computed tomography revealed ∼40 mm distance between the coronary artery ostium and the prosthetic valve (PV) and an aneurysm at the sinus of Valsalva. A Bentall procedure was subsequently performed. Intraoperative findings revealed no detachment of the PV. Following PV removal, the subvalvular tissue was noted to protrude into the left ventricular outflow tract. Subsequently, it was revealed that the tissue could have interfered with the PV; however, the PV appeared to have been detached considering the imaging findings.

8.
Case Rep Oncol ; 14(3): 1561-1566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34949996

RESUMO

Pembrolizumab-induced adrenal insufficiency (AI) is recognized as a rare immune-related adverse event (irAE) that can be fatal if diagnosis is delayed. Clinical features of AI in patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab as the first-line treatment were observed. Five out of 49 patients with untreated advanced NSCLC developed AI between April 2017 and February 2021. Of the 5 patients, 4 developed AI with a grade >3 and were hospitalized. The median time of the onset of AI from the start of first-line treatment was 4.63 months. All the patients improved after corticosteroid replacement therapy. The efficacy of treatment was complete response in 1 patient and partial response in 4 patients. Median progression-free survival was 37.7 months, and overall survival had not been reached. This case series revealed the efficacy of immunotherapy in AI as an irAE.

9.
Ann Thorac Surg ; 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34921816

RESUMO

Reverse Lutembacher syndrome is a rare cause of hypoxia characterized by the triad of tricuspid valve stenosis (TS), elevated right atrial pressure, and an interatrial right-to-left shunt. We report a case of pacemaker lead-induced reverse Lutembacher syndrome in a 45-year-old woman who presented with dyspnea. The patient also developed pacemaker lead-induced superior vena cava obstruction accompanied by a right-to-left shunt through systemic-to-pulmonary venous collaterals, which exacerbated the hypoxia. Tricuspid valve replacement using a bioprosthetic valve and patent foramen ovale closure improved her hypoxia. Reverse Lutembacher syndrome is a rare cause of hypoxia characterized by the triad of tricuspid valve stenosis (TS), elevated right atrial pressure, and an interatrial right-to-left shunt. Rheumatic valvular disease and bioprosthetic degeneration of the tricuspid valve (TV) have been identified as underlying illnesses.1,2 In this report, we describe the clinical features of reverse Lutembacher syndrome due to pacemaker-induced TS and its surgical management.

10.
J Endovasc Ther ; : 15266028211067730, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969293

RESUMO

PURPOSE: To describe a technique of vascular plug penetration by a guidewire with a heavy tip load for additional embolization of a type 2 endoleak after endovascular aortic aneurysm repair (EVAR). TECHNIQUE: The technique of vascular plug penetration is effective for additional embolization of a type 2 endoleak, when large arteries such as left subclavian artery (LSA) or hypogastric artery remain patent even after the embolization of the vessel has been performed using a vascular plug and are responsible for the endoleak. A tapered guidewire with a heavy tip load enables the penetration of the disk of the plug, followed by introduction of a microcatheter into the endoleak nidus. In the presented case, the technique successfully eliminated a type 2 endoleak in a thoracic aortic aneurysm for which a patent LSA despite the embolization by a vascular plug was responsible. CONCLUSION: The technique of vascular plug penetration allows an access to an endoleak cavity via a vascular plug placed in an aortic side branch for additional embolization of a type 2 endoleak after EVAR.

11.
Int J Mol Sci ; 22(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34769147

RESUMO

Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC. The activation of cultured mouse PSCs was evaluated by qPCR. The induction of epithelial mesenchymal transition (EMT) in PDAC cell lines was assessed under stimulation with culture supernatant from activated PSCs. A total of 155 surgically resected PDAC subjects (83 nondiabetic, 18 with ≦3-years and 54 with >3-years history of diabetes) were clinicopathologically evaluated. A high-fat diet increased the expression of activated markers in cultured PSCs, which was abrogated by RAGE deletion. Culture supernatant from activated PSCs facilitated EMT of PDAC cells with elevation of TGF-ß and IL-6, but not from RAGE-deleted PSCs. Diabetic subjects complicated with metabolic syndrome, divided by cluster analysis, showed higher PSC activation and RAGE expression. In such groups, PDAC cells exhibited an EMT nature. The complication of metabolic syndrome with diabetes significantly worsened disease-free survival of PDAC subjects. Thus, RAGE in PSCs can be viewed as a new promoter and a future therapeutic target of PDAC in diabetic subjects with metabolic syndrome.

12.
J Gastrointest Oncol ; 12(5): 2334-2344, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790396

RESUMO

Background: Stereotactic body radiation therapy (SBRT) has high efficacy for early-stage hepatocellular carcinoma (HCC) and is an accepted alternative to radiofrequency ablation (RFA). However, SBRT for HCC may cause subacute liver injury leading to negative clinical outcomes. In this study, we compared changes of liver function and prognosis after SBRT or RFA in patients with single, small HCC by using a propensity-score matching analysis. Methods: We reviewed medical records of 140 patients with single ≤3 cm HCC treated with SBRT or RFA at Kurashiki Central Hospital between January 2014 and February 2019. Changes of albumin-bilirubin (ALBI) score, local recurrence, and overall survival were compared between the propensity-score matched groups (31 patients treated with SBRT and 62 treated with RFA). Results: The ALBI score increased modestly but significantly after SBRT, while it was unchanged in the RFA group; the intergroup difference was statistically significant (P=0.004). No local recurrence was identified in the SBRT group, whereas the cumulative recurrence incidence was 9.7% in the RFA group (P=0.023). Overall survival was not significantly different between the two groups (hazard ratio: 1.32, 95% confidence interval: 0.60-2.89, P=0.401). Conclusions: SBRT had modestly negative impact on liver function but with appraisable local control of HCC. Our findings should contribute to the selection of this modality for treatment of single, small HCC.

13.
Plant Physiol ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792607

RESUMO

Plastid terminal oxidase (PTOX) accepts electrons from plastoquinol to reduce molecular oxygen to water. We introduced the gene encoding Chlamydomonas reinhardtii (Cr)PTOX2 into the Arabidopsis (Arabidopsis thaliana) wild type (WT) and proton gradient regulation5 (pgr5) mutant defective in cyclic electron transport around photosystem I (PSI). Accumulation of CrPTOX2 only mildly affected photosynthetic electron transport in the WT background during steady-state photosynthesis but partly complemented the induction of nonphotochemical quenching (NPQ) in the pgr5 background. During the induction of photosynthesis by actinic light (AL) of 130 µmol photons m-2 s-1, the high level of PSII yield (Y(II)) was induced immediately after the onset of AL in WT plants accumulating CrPTOX2. NPQ was more rapidly induced in the transgenic plants than in WT plants. P700 was also oxidized immediately after the onset of AL. Although CrPTOX2 does not directly induce a proton concentration gradient (ΔpH) across the thylakoid membrane, the coupled reaction of PSII generated ΔpH to induce NPQ and the downregulation of the cytochrome b6f complex. Rapid induction of Y(II) and NPQ was also observed in the pgr5 plants accumulating CrPTOX2. In contrast to the WT background, P700 was not oxidized in the pgr5 background. Although the thylakoid lumen was acidified by CrPTOX2, PGR5 was essential for oxidizing P700. In addition to acidification of the thylakoid lumen to downregulate the cytochrome b6f complex (donor-side regulation), PGR5 may be required for draining electrons from PSI by transferring them to the plastoquinone pool. We propose a reevaluation of the contribution of this acceptor-side regulation by PGR5 in the photoprotection of PSI.

14.
J Clin Med ; 10(22)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34830517

RESUMO

The published literature on the association of circulatory branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) with reduced kidney function is inconsistent or conflicting. Clarification of it might help to better understand the underlying pathophysiology and to determine potential biomarkers for early detection and evaluation of kidney function decline. Our main purpose was to explore and clarify the potential relationships of individual BCAAs and AAAs with estimated glomerular filtration rate (eGFR) decline. We included the data from 2804 healthy subjects and categorized them into three groups based on eGFR tertiles. The associations between individual amino acids and eGFR were explored by covariate-adjusted logistic regression models. There was a progressive increase in the concentrations of BCAAs and AAAs from the upper to the lower tertiles. We revealed significant positive associations of isoleucine, leucine, and phenylalanine with lower tertiles of eGFR in the adjusted models (p < 0.01-0.001). The findings hold a promising potential of using plasma isoleucine, leucine, and phenylalanine levels for evaluation of kidney function decline. Future longitudinal studies should investigate the causal association between altered levels of these amino acids and impaired kidney function and also the utility of the former as potential biomarkers for evaluating the risk and early detection of the latter.

15.
J Oncol Pharm Pract ; : 10781552211042525, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709082

RESUMO

PURPOSE: Occupational exposure to antineoplastic drugs in hospital settings is recognized to be hazardous, and as such environmental decontamination including degradation and inactivation of such drugs is recommended. To data, although various agents such as oxidants have been reported to be useful for decontamination, simpler, safer, and more convenient methods are required. In this study, the degradation and inactivation efficacy of ozone water, which has newly been introduced for decontamination of antineoplastic drugs in spills, was investigated for formulations of gemcitabine, irinotecan, and paclitaxel. METHODS: Antineoplastic formulations (medicinal ingredient: ∼1.5 µmol) were mixed with 50 mL of ozone water (>4 mg/L). The reactions were monitored by high-performance liquid chromatography, and the degradation mixtures were analyzed by 1H nuclear magnetic resonance spectroscopy in order to obtain the structural information of the degradation products. The formulations of gemcitabine and irinotecan and those degradation mixtures were evaluated for their mutagenicity using the Ames test and cytotoxicity against human cancer cells. RESULTS: gemcitabine and irinotecan were found to be readily degraded by the ozone treatment, and their active sites were suggested to be degraded. In contrast, paclitaxel was hard to be decomposed, possibly owing to the consumption of ozone by the polyoxyethylene castor oil added as a pharmaceutical additive of the formulation. No significant mutagenic changes of Salmonella typhimurium strains used for the Ames test were observed for the samples within the concentration ranges examined. The ozone treatment showed obvious increases in cell viability for gemcitabine formulation, and mild increases for irinotecan formulation. CONCLUSIONS: Ozone water was shown to be effective as a decomposition agent for the antineoplastic drug formulations examined, although the efficacy depends on the chemical structures of the drugs and the pharmaceutical additives. It was also suggested that ozone treatment has a tendency to decrease the toxicity of the antineoplastic drug formulations. As such, further studies are required in order to clarify the effects and application limitations of ozone water.

16.
Phys Rev Lett ; 127(12): 126602, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34597079

RESUMO

A spin-polarized state is examined under charge current at room temperature without magnetic fields in chiral disilicide crystals NbSi_{2} and TaSi_{2}. We found that a long-range spin transport occurs over ten micrometers in these inorganic crystals. A distribution of crystalline grains of different handedness is obtained via location-sensitive electrical transport measurements. The sum rule holds in the conversion coefficient in the current-voltage characteristics. A diamagnetic nature of the crystals supports that the spin polarization is not due to localized electron spins but due to itinerant electron spins. A large difference in the strength of antisymmetric spin-orbit interaction associated with 4d electrons in Nb and 5d ones in Ta is oppositely correlated with that of the spin polarization. A robust protection of the spin polarization occurs over long distances in chiral crystals.

17.
Mitochondrial DNA B Resour ; 6(10): 2995-2996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568559

RESUMO

A non-biting midge Chironomus yoshimatsui has been widely used in ecotoxicology and chemical risk assessments. In this study, the complete mitochondrial genome (mitogenome) sequence of C. yoshimatsui was determined using short-read next-generation sequencing technologies. The mitogenome was 15,734 bp in length and consisted of 13 protein coding genes, 2 ribosomal RNAs, and 22 transfer RNAs. The A + T content was 77.8%. The gene order was identical to the pattern conserved across Diptera. The mitocgenome sequence obtained in this study provides a useful resource for further evolutionary and ecological studies.

18.
J Phys Chem Lett ; 12(38): 9283-9292, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34542299

RESUMO

Heterohelicenes are potential materials in molecular electronics and optics because of their inherent chirality and various electronic properties originating from the introduced heteroatoms. In this work, we comprehensively investigated two kinds of double NO-hetero[5]helicenes composed of 12H-benzo[b]phenoxazine (BPO) and 13H-dibenzo[b,i]phenoxazine (DBPO). These helicenes exhibit good electron-donor properties reflecting the electron-rich character of their monomers and were demonstrated to work as p-type semiconductors. The enantiomers of these helicenes show the largest class of dissymmetry factors for circularly polarized luminescence (CPL) (|gCPL| > 10-2) among helicenes reported to date. Interestingly, the signs of CPL are opposite for BPO and DBPO double helicenes of the same helicity. The origin of the large gCPL values and the inversion of the CPL sign was addressed by analysis of the transition electronic dipole moments and transition magnetic dipole moments based on TD-DFT calculations.

19.
ERJ Open Res ; 7(3)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34476246

RESUMO

This study suggests that IgG4 + IP with abundant IgG4 + cells and elevated serum IgG4 levels could be treated differently from IgG4-related respiratory disease due to potential differences in disease behaviour and response to corticosteroid therapy https://bit.ly/3dUo2cu.

20.
Ecotoxicol Environ Saf ; 223: 112585, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365212

RESUMO

The fish acute toxicity test (TG203; OECD, 2019) is frequently used and highly embedded in hazard and risk assessment globally. The test estimates the concentration of a chemical that kills 50% of the fish (LC50) over a 96 h exposure and is considered one of the most severe scientific procedures undertaken. Over the years, discussions at the Organisation for Economic Co-operation and Development (OECD) have resulted in changes to the test which reduce the number of fish used, as well as the development of a (potential) replacement test (TG236, OECD, 2013). However, refinement of the mortality endpoint with an earlier (moribundity) endpoint was not considered feasible during the Test Guideline's (TG) last update in 2019. Several stakeholders met at a UK-based workshop to discuss how TG203 can be refined, and identified two key opportunities to reduce fish suffering: (1) application of clinical signs that predict mortality and (2) shortening the test duration. However, several aspects need to be addressed before these refinements can be adopted. TG203 has required recording of major categories of sublethal clinical signs since its conception, with the option to record more detailed signs introduced in the 2019 update. However, in the absence of guidance, differences in identification, recording and reporting of clinical signs between technicians and laboratories is likely to have generated piecemeal data of varying quality. Harmonisation of reporting templates, and training in clinical sign recognition and recording are needed to standardise clinical sign data. This is critical to enable robust data-driven detection of clinical signs that predict mortality. Discussions suggested that the 96 h duration of TG203 cannot stand up to scientific scrutiny. Feedback and data from UK contract research organisations (CROs) conducting the test were that a substantial proportion of mortalities occur in the first 24 h. Refinement of TG203 by shortening the test duration would reduce suffering (and test failure rate) but requires a mechanism to correct new results to previous 96 h LC50 data. The actions needed to implement both refinement opportunities are summarised here within a roadmap. A shift in regulatory assessment, where the 96 h LC50 is a familiar base for decisions, will also be critical.


Assuntos
Peixes , Organização para a Cooperação e Desenvolvimento Econômico , Animais , Humanos , Dose Letal Mediana , Medição de Risco , Testes de Toxicidade Aguda
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