METHODS: Pressurized hot water extraction P. tenellus was carried out and standardized to 7.9% hydrosable tannins. In vitro toxicity of the extract was tested on NIH 3 T3 cell by MTT assay. The cellular antioxidant level was quantified by measuring cellular level of glutathione. Oral sub-chronic toxicity (200, 1000 and 3000 mg/kg body weight) of P. tenellus extract were evaluated on healthy mice. Liver and kidney antioxidant level was quantified by measuring levels of Ferric Reducing Antioxidant Potential (FRAP), superoxide dismutase, glutathione.
RESULTS: The P. tenellus extract did not induce cytotoxicity on murine NIH 3 T3 cells up to 200 μg/mL for 48 h. Besides, level of glutathione was higher in the extract treated NIH 3 T3 cells. P. tenellus extract did not cause mortality at all tested concentration. When treated with 1000 mg/kg of the extract, serum liver enzymes (ALP and ALT) and LDH were lower than normal control and mice treated with 200 mg/kg of extract. Moreover, SOD, FRAP and glutathione levels of liver of the mice treated with 200 and 1000 mg/kg of extract were higher than the normal control mice. On the other hand, when treated with 3000 mg/kg of extract, serum liver enzymes (ALP and ALT) and LDH were higher than normal mice without changing the liver SOD and glutathione level, which may contribute to the histological sign of ballooning hepatocyte.
CONCLUSION: P. tenellus extract standardized with 7.9% hydrosable tannins and their catabolites increased the antioxidant levels while reducing the nitric oxide levels in both liver and kidney without causing any acute and sub-chronic toxicity in the mice.
METHOD: A randomized controlled open-label study was performed at the cardiothoracic intensive care unit of Penang Hospital, Malaysia. A total of 28 patients who underwent cardiac surgeries were randomly assigned to receive either dexmedetomidine or morphine. Both groups were similar in terms of preoperative baseline characteristics. Efficacy measures included sedation scores and pain intensity and requirements for additional sedative/analgesic. Mean heart rate and arterial blood pressure were used as safety measures. Other measures were additional inotropes, extubation time and other concurrent medications.
RESULTS: The mean dose of dexmedetomidine infused was 0.12 [SD 0.03] μg kg⁻¹ h⁻¹, while that of morphine was 13.2 [SD 5.84] μg kg⁻¹ h⁻¹. Dexmedetomidine group showed more benefits in sedation and pain levels, additional sedative/analgesic requirements, and extubation time. No significant differences between the two groups for the outcome measures, except heart rate, which was significantly lower in the dexmedetomidine group.
CONCLUSION: This preliminary study suggests that dexmedetomidine was at least comparable to morphine in terms of efficacy and safety among cardiac surgery patients. Further studies with larger samples are recommended in order to determine the significant effects of the outcome measures.
DESIGN: A systematic review of the literature followed by a consensus-based voting process.
SETTING: A web-based international consensus conference.
PARTICIPANTS: Two hundred fifty-one physicians from 46 countries.
INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines.
MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed.
CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.
METHODS AND RESULTS: In this study, recombinant TYMVcHis6 expressed in Escherichia coli self-assembled into VLPs of approximately 30-32 nm. SDS-PAGE and Western blot analysis of protein fractions from the immobilized metal affinity chromatography (IMAC) showed that TYMVcHis6 VLPs interacted strongly with nickel ligands in IMAC column, suggesting that the fusion peptide is protruding out from the surface of VLPs. These VLPs are highly stable over a wide pH range from 3·0 to 11·0 at different temperatures. At pH 11·0, specifically, the VLPs remained intact up to 75°C. Additionally, the disassembly and reassembly of TYMVcHis6 VLPs were studied in vitro. Dynamic light scattering and transmission electron microscopy analysis revealed that TYMVcHis6 VLPs were dissociated by 7 mol l-1 urea and 2 mol l-1 guanidine hydrochloride (GdnHCl) without impairing their reassembly property.
CONCLUSIONS: A 10-residue peptide was successfully displayed on the surface of TYMVcHis6 VLPs. This chimera demonstrated high stability under extreme thermal conditions with varying pH and was able to dissociate and reassociate into VLPs by chemical denaturants.
SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first C-terminally modified TYMVc produced in E. coli. The C-terminal tail which is exposed on the surface can be exploited as a useful site to display multiple copies of functional ligands. The ability of the chimeric VLPs to self-assemble after undergo chemical denaturation indicates its potential role to serve as a nanocarrier for use in targeted drug delivery.
DESIGN: A post hoc analysis of a randomized trial.
SETTING: Cardiac surgical operating rooms.
PARTICIPANTS: Patients undergoing elective, isolated CABG.
INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes.
MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03).
CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.
METHODS: We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤-3.
RESULTS: The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7%) and 110/237 (46.4%). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93%) versus 72 (28%) patients (P < 0.0001) for 966 (39.6%) versus 183 (7.5%) study days respectively. Deep sedation occurred in (182/257) 71% patients at first assessment and in 159 (61%) patients and 1,658 (59%) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.97, P = 0.003], hospital death (HR 1.11, 95% CI 1.05-1.18, P < 0.001) and 180-day mortality (HR 1.09, 95% CI 1.04-1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44%) of patients.
CONCLUSION: Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.