Hepatotoxicity and Mutagenicity assessment during chronic in vivo exposure to aqueous extracts from Peperomia pellucida.

Studies on herbal medicine have exposed some toxic effects on humans. Peperomia pellucida (L.) HBK (P. pellucida) is one of the herbal medicines recommended as an alternative to synthetic medicine for diseases. Studies exist on the pharmacological activities of P. pellucida extracts, but studies on the potential hepatotoxic and mutagenic effects of subchronic administration of P. pellucida aqueous extracts, which is very important knowledge when we venture into alternative medicine, are lacking. In this study, two concentrations (60 mg/kg and 30 mg/kg) of P. pellucida aqueous extracts - decoction and freeze-dried extracts -were administered in vivo to BALB/c mice for nine (9) weeks. Significant differences were observed between the 60 mg/kg freeze-dried extract and the control in terms of mice weight and micronucleus frequency at 7-8 weeks of treatment. Also, no significant differences were found between groups in serum transaminases levels. Generally, there is no sufficient evidence to show that subchronic exposure to P. pellucida aqueous extracts is hepatotoxic though 60 mg/kg concentration may be mutagenic. This study suggests that although the herbal medicine is safe for prolonged consumption, users are advised to take precautions and moderations of its use due to the possibility of potential mutagenic effects.

Enhanced recovery principles applied to revision hip and knee arthroplasty leads to better patient outcomes.

AIMS: There is very little published literature on Enhanced Recovery Principles (ERP) used in primary joint replacements applied to revision hip and knee arthroplasty (rTHA, rTKA). METHODS: Retrospective series of 268 rTHA and rTKA surgeries from 2010 -2018, treated with ERP, focusing on multimodal pain management, blood management and early functional recovery. RESULTS: No patients from the latest cohort required readmission within 6 weeks. Only 20 patients (7.5%) required a blood transfusion. Surgical site local anaesthetic infiltration was associated with lower PCA use in aseptic rTHA and rTKA (p<0.001; p<0.001). Revisions for infection had a longer length of stay (LOS) and increased PCA usage in both rTHA (6.5 vs. 5.2 days) and rTKA (10.1 vs. 5.3 days), similar to our previous study.1 Use of an intra-articular catheter for analgesia in rTKA showed reduced PCA use. Tourniquets were not beneficial for blood loss in rTKA and had greater PCA use post-operatively (p<0.001). CONCLUSION: The application of ERP to revision THA and TKA surgery is safe and effective.

Moving Towards Optimized Noncommunicable Disease Management in the ASEAN Region: Recommendations from a Review and Multidisciplinary Expert Panel.

INTRODUCTION: Noncommunicable diseases (NCDs) are the leading cause of morbidity and mortality in the Association of Southeast Asian Nations (ASEAN) member states. Progress has been slow despite the World Health Organization action plan for the prevention and control of NCDs in the region. This paper presents recommendations focused on practical strategies for optimizing NCD management in the ASEAN region. METHODS: A multidisciplinary group of experts from six ASEAN member states convened for two face-to-face meetings to discuss barriers and possible recommendations for optimizing NCD management, focused on cardiovascular diseases and mental disorders, in the region. Multiple approaches, ie, analysis of insights from the meetings and a review of existing literature on NCD programs in the ASEAN region were followed. The proposed recommendations were also based on selected successful interventions in ASEAN member states, thus providing actionable strategies. RESULTS: The gaps identified in NCD management for cardiovascular diseases and mental disorders in the ASEAN region were classified into gaps relating to policies and to clinical and public health practice. The proposed solutions addressing policy gaps include fostering multisectoral public-private partnerships, employing "whole-of-government" and "whole-of-society" approaches and promoting "health-in-all policies approach" to manage issues with financing, accessibility, efficiency and quality of health services. Whereas proposed solutions to bridge clinical and public health practice gaps entail strengthening primary care services, building the capacity of trained healthcare workers and employing collaborative care for holistic management of patients. CONCLUSION: The scale of premature and preventable deaths from NCDs in the ASEAN region remains a serious public health concern and requires a "whole-of-system approach". The interventions proposed in this paper build on regional collaborations and knowledge sharing to help develop a concerted and targeted response to NCDs.

Conus striatus venom exhibits non-hepatotoxic and non-nephrotoxic potent analgesic activity in mice.

Constant research into the pharmaceutical properties of marine natural products has led to the discovery of many potentially active agents considered worthy of medical applications. Genus Conus, which approximately comprises 700 species, is currently under every researcher's interest because of the conopeptides in their crude venom. Conopeptides have a wide range of pharmacological classes and properties. This research focused on the crude venom of Conus striatus to assess its analgesic activity, mutagenicity, nephrotoxicity, and hepatotoxicity in mice. The crude venom was extracted from the conus snails and the protein concentration was determined using Bradford's method. The analgesic activity of the venom was determined using the hot-plate method and standard IFCC method was used to determine the alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Evaluation of mutagenicity was done using micronucleus assay and the nephrotoxicity of the venom was determined using Kidney Coefficient and serum creatinine concentration. The maximum tolerable dose (MTD) of the crude venom was found to be 75 ppm. The venom exhibited potent analgesic activity even higher than the positive control (Ibuprofen). Most of the analgesic drugs can usually impact damage in the liver and kidneys. However, AST and ALT results revealed that the venom has no adverse effects on the liver. Although the venom increased the incidence of micronucleated polychromatic erythrocytes, making it mutagenic, with MTD concentration's mutagenicity comparable to the positive control methyl methanesulfonate (MMS). The kidney coefficients, on the other hand, showed no significant difference between the treated groups and that of the untreated group. The serum creatinine also showed a concentration-dependent increase; with MTD treated mice got the highest creatinine concentration. However, MTD/2 and MTD/4 showed no significant difference in creatinine levels with respect to the untreated groups. Hence, the nephrotoxicity of the venom was only evident when used at higher concentration. The venom exhibited potent analgesic activity indicated that the C. striatus crude venom extract could have a potential therapeutic component as analgesic drugs that displayed no hepatic damage. This study also suggests that for this venom to be utilized for future medical applications, their usage must be regulated and properly monitored to avoid nephrotoxic effect.

Glycosylated and non-glycosylated quantum dot-displayed peptides trafficked indiscriminately inside lung cancer cells but discriminately sorted in normal lung cells: An indispensable part in nanoparticle-based intracellular drug delivery.

Difference in sub-cellular trafficking of glycosylated and naked peptides, between normal and lung cancer cells, was established. Normal lung tissue discriminately sorted glycosylated from non-glycosylated peptides by allowing golgi localization of the glycosylated peptides while restricting golgi entry of the naked peptides. This mechanism was surprisingly not observed in its cancer cell counterpart. Lung cancer cells tend to allow unrestricted localization of both glycosylated and naked peptides in the golgi apparatus. This newly discovered difference in sub-cellular trafficking between normal and lung cancer cells could potentially be used as an effective strategy in targeted intracellular delivery, especially targeting golgi-resident enzymes for possible treatment of diseases associated with glycans and glycoproteins, such as, congenital disease of glycosylation (CDG). This very important detail in intracellular trafficking inside normal and cancer cells is an indispensable part in nanoparticle-based intracellular drug delivery.

Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides.

A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems.