METHODS: The medical records of ICU patients receiving colistin therapy in Hospital Serdang and Hospital Sungai Buloh from 2010 to 2012 were retrospectively reviewed. Demographics data, treatment characteristic as well as culture result and creatinine level were documented. Nephrotoxicity was determined based on RIFLE criteria.
RESULTS: A total of 100 patients were included. Median daily dose, cumulative dose and duration of colistin therapy were 3.0 MIU (IQR: 4, range 1-12), 17.8 MIU (IQR: 31.5, range 2-180) and seven days (IQR: 4, range 1-30). Nephrotoxicity was found in 23% of the study population. All cases were reversible but marginally associated with higher mortality. No statistical association exist between age, gender and race as well as administration routes with nephrotoxicity by univariable analysis. The association of dose and duration with nephrotoxicity was also not significant by univariable analysis. After adjustment for confounders, statistical association between the independent variables and dependent variable remains not significant.
CONCLUSION: Lower dose and shorter duration in local settings contribute to lack of association between colistin therapy and nephrotoxicity in this study. Higher dosing regimen with loading dose application has been introduced in the latest National Antibiotic Guideline. Further evaluation of colistin-induced nephrotoxicity and potential risk factors is therefore warranted.
OBJECTIVE: To provide an overview and identify the present landscape of hemp research topics, trends, and gaps.
METHODS: A systematic search and analysis strategy according to the preferred reporting items for systematic review and meta-analysis-ScR (PRISMA-ScR) checklist on electronic databases including MEDLINE, OVID (OVFT, APC Journal Club, EBM Reviews), Cochrane Library Central and Clinicaltrials.gov was conducted to include and analyse hemp research articles from 2009 to 2019.
RESULTS: 65 primary articles (18 clinical, 47 pre-clinical) were reviewed. Several randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) improving spontaneous bowel movement in functional constipation. There was also evidence suggesting benefits in cannabis dependence, epilepsy, and anxiety disorders. Pre-clinically, hemp derivatives showed potential anti-oxidative, anti-hypertensive, anti-inflammatory, anti-diabetic, anti-neuroinflammatory, anti-arthritic, anti-acne, and anti-microbial activities. Renal protective effects and estrogenic properties were also exhibited in vitro.
CONCLUSION: Current evidence on hemp-specific interventions are still preliminary, with limited high quality clinical evidence for any specific therapeutic indication. This is mainly due to the wide variation in test item formulation, as the multiple variants of this plant differ in their phytochemical and bioactive compounds. Future empirical research should focus on standardising the hemp plant for pharmaceutical use, and uniformity in experimental designs to strengthen the premise of using hemp in medicine.
RESULTS: The dengue fever mouse model was established by intraperitoneal inoculation of dengue virus, New Guinea C strain at 2 × 106 PFU. Daily oral administration of 1000 mg/kg freeze-dried C. papaya leaf juice (FCPLJ) was done starting from day 1 to day 3 post infection. The RNA was extracted from liver tissues harvested on day 4 post infection. The expression levels of 84 genes related to mouse endothelial cell biology were determined by qRT-PCR technique. Dengue virus infection upregulated 15 genes and downregulated two genes in the liver of AG129 mice. The FCPLJ treatment upregulated monocyte chemoattractant protein 1 and downregulated intercellular adhesion molecule 1, integrin beta 3 and fibronectin 1 genes during dengue virus infection. The data showed the potential effect of FCPLJ treatment on the expression profile of endothelial cell biology related genes in the liver of dengue virus infected-AG129 mice. Further proteomic studies are needed to determine the functional roles of the genes affected by FCPLJ treatment.
METHODS: Anti-SARS-CoV-2 potential of the SKF7® was evaluated in SARS-CoV-2-infected Vero E6 cells and SARS-CoV-2-infected A549 cells by cytopathic effect-based assay and RT-qPCR, respectively. Target based assays were performed on the SKF7® against the S1-ACE2 interaction and 3CL protease activities. Anti-inflammatory activity of the SKF7® was evaluated by nitric oxide inhibitory and TLR2/TLR4 receptor blocker assays.
RESULTS: The SKF7® inhibited wild-type Wuhan (EC50 of 21.99 µg/mL) and omicron (EC50 of 16.29 µg/mL) SARS-CoV-2 infections in Vero-E6 cells. The SKF7® also inhibited the wild-type SARS-CoV-2 infection in A549 cells (EC50 value of 6.31 µg/mL). The SKF7® prominently inhibited 3CL protease activity. The SKF7® inhibited the LPS induced-TLR4 response with the EC50 of 16.19 µg/mL.
CONCLUSIONS: In conclusion, our in vitro study highlighted anti-SARS-CoV-2 and anti-inflammatory potentials of the SKF7®. Future pre-clinical in vivo studies focusing on antiviral and immunomodulatory potentials of the SKF7® in affecting the COVID-19 pathogenesis are warranted.
METHODS: The dengue infection in mouse model was established by inoculation of non-mouse adapted New Guinea C strain dengue virus (DEN-2) in AG129 mice. The freeze-dried CPLJ compounds were identified by Ultra-High Performance Liquid Chromatography High Resolution Accurate Mass Spectrometry analysis. The infected AG129 mice were orally treated with 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ, starting on day 1 post infection for 3 consecutive days. The blood samples were collected from submandibular vein for plasma NS1 assay and quantitation of viral RNA level by quantitative reverse transcription PCR.
RESULTS: The AG129 mice infected with dengue virus showed marked increase in the production of plasma NS1, which was detectable on day 1 post infection, peaked on day 3 post-infection and started to decline from day 5 post infection. The infection also caused splenomegaly. Twenty-four compounds were identified in the freeze-dried CPLJ. Oral treatment with 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ did not affect the plasma NS1 and dengue viral RNA levels. However, the morbidity level of infected AG129 mice were slightly decreased when treated with freeze-dried CPLJ.
CONCLUSION: Oral treatment of 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ at the onset of viremia did not affect the plasma NS1 and viral RNA levels in AG129 mice infected with non-mouse adapted New Guinea C strain dengue virus.
METHODS: The AG129 mice were fed orally with FCPLJ for 3 consecutive days after 24 h of dengue virus inoculation. Plasma cytokines were screened by using ProcartaPlex immunoassay. The gene expression in the liver was analyzed by using RT2 Profiler PCR Array.
RESULTS: The results showed that FCPLJ treatment has increased the plasma CCL2/MCP-1 level during peak of viremia. Gene expression study has identified 8 inflammatory cytokine genes which were downregulated in the liver of infected AG129 mice treated with FCPLJ. The downregulated inflammatory cytokine genes were CCL6/MRP-1, CCL8/MCP-2, CCL12/MCP-5, CCL17/TARC, IL1R1, IL1RN/IL1Ra, NAMPT/PBEF1 and PF4/CXCL4.
CONCLUSION: The findings indicated the possible immunomodulatory role of FCPLJ during dengue virus infection in AG129 mice.