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Biobased Products for Viral Diseases
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Gleice Ribeiro Orasmo, Giovanna Morghanna Barbosa do Nascimento, Maria Gabrielly de Alcântara Oliveira, Jéssica Missilany da Costa
HCV infection is considered one of the main causes of human hepatitis. HCV belongs to the Flaviviridae family, as does the Bovine Viral Diarrhea Virus (BVDV). The discovery of diphenylmethane analogues as viral anti-bovine diarrhea agents is important because HCV does not replicate efficiently in cell cultures or animals. Based on the antiviral screening of our diphenylmethane derivatives prepared as steroid substitutes, one 1,1-diphenylcyclobutane analogue and two diethyldiphenylsilane analogues were identified as lead compounds with potent activity against bovine viral diarrhea virus (BVDV), having 50% of effectiveness (Hosoda et al. 2009). Thus, BVDV is considered a good model for human HCV.
Be Clear, an intensive treatment for non-progressive dysarthria
Published in Margaret Walshe, Nick Miller, Clinical Cases in Dysarthria, 2021
Stacie Park, Deborah Theodoros, Emma Finch, Elizabeth Cardell
Acoustic analysis was included in the Be Clear assessment protocol to provide an objective means of quantifying changes to the speech signal. MP’s monologue and Grandfather Passage samples were used to examine changes in articulation rate (syllables/second), percent pause time, fundamental frequency and frequency range. To promote efficient batch processing of the speech samples, acoustic analysis was conducted using an automated PRAAT script (Vogel, Fletcher, & Maruff 2014). The bVd tokens produced by MP were used to investigate changes in VSA and vowel duration. This analysis was conducted manually using standard acoustic criteria.
Environmental Factors Impacting Bioactive Metabolite Accumulation in Brazilian Medicinal Plants
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Camila Fernanda de Oliveira Junkes, Franciele Antonia Neis, Fernanda de Costa, Anna Carolina Alves Yendo, Arthur Germano Fett-Neto
Q. brasiliensis leaf saponins show structural and functional similarities to those of Q. saponaria barks, which are currently used as adjuvants in vaccine formulations (Fleck et al., 2006, 2012; Kauffmann et al., 2004). Previous studies with saponins of Q. brasiliensis showed a pronounced immunoadjuvant activity in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus, rabies and bovine viral diarrhea virus in mice (Cibulski et al., 2016; Fleck et al., 2006; Yendo et al., 2016). The accumulation patterns of the immunoadjuvant fraction of leaf triterpene saponins QB-90 in response to stress factors were examined. Higher yields of bioactive saponins were observed upon exposure to SA, JA and by mechanical damage, as well as by applying ultrasound to leaves (de Costa et al., 2013). A significant increase in QB-90 content was observed when leaf disks were submitted to 1 mM SA or 40 μM JA, supporting a general defense role for these metabolites in plants.
Development of ERK1/2 inhibitors as a therapeutic strategy for tumour with MAPK upstream target mutations
Published in Journal of Drug Targeting, 2020
Ulixertinib (BVD-523, VRT752271) was the first small-molecule ERK1/2 kinase inhibitor to progress to the clinical stage. This compound demonstrated potent and selective inhibition of ERK1/2 kinases in a reversible, ATP-competitive manner [36]. BVD-523 inhibits BRAF-mutant melanoma and colorectal xenografts, as well as displays efficacy in KRAS-mutant colorectal and pancreatic models in vivo [37]. Excitingly, BVD-523 demonstrated antitumour activity in both in vitro and in vivo models of acquired resistance to BRAF/MEK targeted therapy. In addition, BVD-523 also produces synergistic anti-proliferative effects when used in combination with BRAF inhibitors [38–41]. Based on its safety and favourable pharmacokinetics, BVD-523 is expected to become a treatment for ERK-dependent cancers, especially for cancers that are resistant to inhibitors of the upstream node of the MAPK pathway. The clinical evaluations of BVD-523 have demonstrated preliminary antitumour activity in patients with NRAS, BRAF mutant cancers. Current common adverse side effects include diarrhoea, nausea, fatigue, and dermatitis acneiform. Clinical trials evaluating the safety, tolerability, and initial clinical efficacy of BVD-523 administered alone or in combination with other drugs are currently underway (NCT01781429, NCT02296242, NCT 02608229, NCT03698994, NCT03155620, NCT03454035) [42,43].
Prehospital Manual Ventilation: An NAEMSP Position Statement and Resource Document
Published in Prehospital Emergency Care, 2022
John W. Lyng, Francis X. Guyette, Michael Levy, Nichole Bosson
Manual ventilation, especially using a BVM technique, is a challenging but basic skill that all EMS clinicians must master. Strategies to imporove success when using a BVM approach include using a two-person technique, two-handed mask seal, and airway patency adjuncts. For both BVM and BVD approaches, use of volume-restricted bags for adult patients and use of PEEP both adult and pediatric patients are recommended, and use of timing devices may also have utility. Continued research is needed to identify strategies to objectively confirm quality of manual ventilation and to identify the optimal manual ventilation strategies and technology for both adult and pediatric patients.
A look at treatment strategies for relapsed multiple myeloma
Published in Expert Review of Anticancer Therapy, 2018
Giusy Cetani, Mario Boccadoro, Stefania Oliva
Among the alkylating medications, bendamustine has activity both as a single-agent and in combination with prednisone (ORR 30–55% and PFS 8–9.3 months) [71]. Small-sized phase I/II studies tested bendamustine in combination with lenalidomide and dexamethasone, yielding good results in RRMM patients and increasing ORR up to 76% [72]. The triplet regimen bortezomib plus bendamustine at the dose of 70 mg/m2 on day 1 and 8 of 28 days cycles and dexamethasone (BVD) was evaluated in phase II trials. Similar response rates were observed (with 70% ORR) but different survival rates were reported among studies (median PFS ranging from 10 to 15 months) [73–75]. Hematologic toxicities were frequent with BVD regimen and required adequate supportive care. Retrospective studies showed that a primary prophylaxis with pegfilgrastim (a single dose, subcutaneous, once per cycle) is more effective than prophylaxis with filgrastim, allowing patients to receive the planned schedule of treatment [76]. Histone deacetylase inhibitors play an essential role in the wide-ranging set of novel agents for the treatment of RRMM. The oral-pandeacetylase inhibitor Panobinostat has been recently approved for the treatment of both bortezomib- and lenalidomide-refractory patients. Preclinical studies suggested a synergistic action of panobinostat with bortezomib and dexamethasone [77]. Thereafter, in the large-scale randomized Phase III trial Panorama 1, the triplet combination was compared with placebo plus bortezomib and dexamethasone. Panobinostat was administered orally at the dose of 20 mg, on days 1, 3, 5, 8, 10, and 12. While the ORR did not differ between the two groups, PFS was longer in the panobinostat group (12 months vs 8 months) and CR was also more easily achieved (27.6% vs 15.7%) [78].