OBJECTIVES: The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats.
METHODS: Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes.
RESULTS: HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac.
CONCLUSION: This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract.
AIM OF THE STUDY: This study was aimed to reveal three different PBs' aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent's profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index.
MATERIALS AND METHODS: PBs' extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model.
RESULTS: The GC-MS analysis revealed 10 similar compounds in all PBs' extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs' extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts.
CONCLUSIONS: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose.
METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates.
RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.
CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.
METHODS: A systematic electronic literature search of PubMed, Embase, the Cochrane Library and Science Direct was conducted for the period 1995-2019. In these databases, search terms describing hypokalaemia and cardiotoxicity were combined with the term laxative use.
RESULTS AND DISCUSSION: Over the 23 years, 27 incidents were identified in 12 countries. There were 19 female and eight male patients, with ages ranging from 1 month to 93 years. The frequency of reported cases according to severity was the following: severe hypokalaemia 48%, moderate hypokalaemia 44.4% and mild hypokalaemia 7.4%. In 70% of patients, the effect of laxative on the heart was typical hypokalaemic electrographic changes, 7.4% showed abnormal changes in cardiac rhythm, whereas in 18.5%, the cardiotoxicity observed was a very serious kind. Two patients died due to severe cardiac effects.
WHAT IS NEW AND CONCLUSION: The laxatives-along with the involvement of some other contributing factors-caused mild-to-severe hypokalaemic cardiotoxicity. These factors were non-adherence of the patient to the recommended dosage, laxative abuse, drug-drug and drug-disease interactions, non-potassium electrolyte imbalances and the use of herbal laxatives. We recommend that laxatives and aggravating factors should be taken into account in the assessment of patients with suspected hypokalaemic cardiotoxicity.
Objective: To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.
Design, Setting, and Participants: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.
Interventions: Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.
Main Outcomes and Measures: Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.
Results: Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P
METHODS: The PubMed, Scopus, and MEDLINE databases were systematically searched up to December 2019 to identify relevant studies. Random-effects model was used to calculate summary ORs and 95%CI for I 2 >50%. If the heterogeneity is not significant, the fixed-effects model was used. Overall analysis of the studies, inverse variance weighting after transforming the estimates of each study into log OR and its standard error were used.
RESULTS: 21 studies were included in this meta-analysis. Results showed that aspirin significantly reduced the GC risk (OR=0.64, 95%CI=0.54-0.76) with substantial heterogeneity (I 2 =96%). Effect of GC risk reduction in low dose (OR=0.80, 95%CI=0.59-1.09) is slightly greater than high dose aspirin (OR=1.08, 95%CI=0.77-1.52). Protective effect of aspirin uses >5 years (OR=0.67, 95%CI=0.34-1.31) was greater than <5 years (OR=1.01, 95%CI=0.72-1.43) Conclusion: In conclusion, this meta-analysis showed that low dose aspirin with longer duration of more than 5 years were associated with a statistically significant reduction in GC risk. However, due to possible confounding variables and bias, these results should be cautiously treated.
METHODS: This paper presents two hybrid methodologies that combines optimal control theory with multi-objective swarm and evolutionary algorithms and compares the performance of these methodologies with multi-objective swarm intelligence algorithms such as MOEAD, MODE, MOPSO and M-MOPSO. The hybrid and conventional methodologies are compared by addressing CMOOP.
RESULTS: The minimized tumor and drug concentration results obtained by the hybrid methodologies demonstrate that they are not only superior to pure swarm intelligence or evolutionary algorithm methodologies but also consumes far less computational time. Further, Second Order Sufficient Condition (SSC) is also used to verify and validate the optimality condition of the constrained multi-objective problem.
CONCLUSION: The proposed methodologies reduce chemo-medicine administration while maintaining effective tumor killing. This will be helpful for oncologist to discover and find the optimum dose schedule of the chemotherapy that reduces the tumor cells while maintaining the patients' health at a safe level.