METHOD: Endolysin and VAPGH genes were cloned and expressed in L. lactis NZ9000 after fusion with the SPK1 signal peptide for secretion. The recombinant proteins were expressed and purified, then analyzed for antimicrobial activity using plate assay and turbidity reduction assay. In addition, the spent media of the recombinant lactococcal culture was analyzed for its ability to inhibit the growth of the S. aureus PS 88.
RESULTS: Extracellular recombinant endolysin (Endo88) and VAPGH (VAH88) was successfully expressed and secreted from L. lactis which was able to inhibit S. aureus PS 88, as shown by halozone formation on plate assays as well as inhibition of growth in the turbidity reduction assay. Moreover, it was observed that the spent media from L. lactis NZ9000 expressing Endo88 and VAH88 reduced the viability of PS 88 by up to 3.5-log reduction with Endo88 being more efficacious than VAH88. In addition, Endo88 was able to lyse all MRSA strains tested and Staphylococcus epidermidis but not the other bacteria while VAH88 could only lyse S. aureus PS 88.
CONCLUSION: Recombinant L. lactisNZ9000 expressing phage 88 endolysin may be potentially developed into a new antimicrobial agent for the treatment of MDRSA infection.
Methods: The control group was administered with phosphate buffer solution (PBS) while the other two groups received PCM alone (1000 mg/kg) and PCM + 25 mg/kg ZER, respectively, at 0 h and 4 h after PCM injection. After 24 h, the blood and liver were collected for differential white blood cell count, liver histological observation and biochemical analysis including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein concentration in serum and liver.
Results: Treatment with ZER was found to significantly reduce ALT (P = 0.041), AST (P = 0.044) and total hepatic protein (P = 0.045) in comparison to PCM-induced rats. Rats treated with ZER exhibited the normal structure of hepatocytes with no vacuolisation or necrosis and showed significantly reduced neutrophil count (P = 0.037). This finding suggests its ability to suppress the inflammatory processes caused by PCM overdosage and decrease the hepatocytes tendency to go through necrotic processes.
Conclusion: ZER possessed protective activity against PCM-induced acute hepatotoxicity in a rat model.
DESIGN: A systematic review and meta-analysis was performed. The following databases were searched using the keywords ("rebamipide" OR "gastroprotective agent*" OR "mucosta") AND ("dyspepsia" OR "indigestion" OR "gastrointestinal symptoms"): PubMed, Wed of Science, Embase, CINAHL, Cochrane Clinical Trials Register. The primary outcome was dyspepsia or upper GI symptom score improvement. Pooled analysis of the main outcome data were presented as risk ratio (RR) for dichotomous data and standardized mean difference (SMD) for continuous data.
RESULTS: From an initial 248 records, 17 randomised controlled trial (RCT) publications involving 2170 subjects (1224 rebamipide, 946 placebo/control) were included in the final analysis. Twelve RCTs were conducted in subjects with organic dyspepsia (peptic ulcer disease, reflux esophagitis or NSAID-induced gastropathy) and five RCTs were conducted in patients with functional dyspepsia (FD). Overall, dyspepsia symptom improvement was significantly better with rebamipide compared to placebo/control drug (RR 0.77, 95% CI = 0.64-0.93; SMD -0.46, 95% CI = -0.83 to -0.09). Significant symptom improvement was observed both in pooled RR and SMD in subjects with organic dyspepsia (RR 0.72, 95% CI = 0.61-0.86; SMD -0.23, 95% CI = -0.4 to -0.07), while symptom improvement in FD was observed in pooled SMD but not RR (SMD -0.62, 95% CI = -1.16 to -0.08; RR 1.01, 95% CI = 0.71-1.45).
CONCLUSION: Rebamipide is effective in organic dyspepsia and may improve symptoms in functional dyspepsia.
METHODS: A systematic search of articles was conducted in scientific databases, with the latest update in May 2021. This paper systematically reviewed the clinical evidence available (randomized controlled trials, compassionate use studies, and case reports) on the use of remdesivir for patients with moderate or severe COVID-19.
RESULTS: A total of eleven studies were included: four studies based on compassionate use of remdesivir, three randomized, double-blind, placebo-controlled, multicentre trials, three randomized, open-label, phase III trials, and one case report. Clinical improvement and mortality rates in patients who used remdesivir varied across studies.
CONCLUSION: Given the current evidence, there is insufficient data to confidently recommend the use of remdesivir alone for the treatment of adult hospitalized patients with moderate-to-severe COVID-19. However, remdesivir may be considered along with an anti-inflammatory agent in patients with pneumonia, on oxygen support, provided there is close monitoring of clinical and laboratory parameters and adverse events.
METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.
FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.
INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).
FUNDING: WHO.