RECENT FINDINGS: Recent studies have been focused on the interactions of mitragynine, the most abundant alkaloid, and opioid-like effects. This has been driven by the harm that kratom products have produced in the Western world, in stark contrast to the lack of harm in Southeast Asian traditional use over centuries. Many users in the Western world ingest kratom for mood enhancement and/or to ween themselves from prescription or illicit opioids. Highly concentrated products and recreational use and misuse have resulted in individuals pushing doses to levels that have not been imagined or ever studied in animal, let alone humans.
SUMMARY: Kratom, as a preparation and how it is utilized is different around the world.
OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD.
METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019).
RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT.
CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
METHODS: Stigmasterol (1) and β-caryophyllene oxide (2) were isolated from the n-hexane fraction of the leaves of M. ferrae using a bioassay-guided fractionation approach.
RESULTS: The isolated compounds displayed anti-Staphylococcus and anti-MRSA activities. It is worth to note that both compounds demonstrated synergism with β-lactam antibiotics against S. aureus and MRSA. Gas chromatography-mass spectrometry (GC-MS) analysis indicated the n-hexane fraction was dominated by triterpenes and sesquiterpenes, suggesting the total antibacterial activity exhibited by the fraction.
CONCLUSION: Based on the findings, it could conclude that M. ferrae is a promising natural source for the discovery of new anti-MRSA lead compounds.
AIM OF THE STUDY: However, there are no scientific reports documented on the wound healing activities of this plant against Staphylococcus aureus infections in the Sprague Dawley male rat model. Thus, the present study was conducted to evaluate the wound healing potential of E. guineensis extract leaves.
MATERIALS AND METHODS: The crude extract was prepared in 10% (w/w) ointment and evaluated for wound healing activity using excision and infected wound models in Sprague Dawley rats. The wound healing activity was evaluated from wound closure rate, CFU reduction, histological analysis of granulation tissue and matrix metalloprotease expression.
RESULTS: The results show that the E. guineensis extract has potent wound healing ability, as manifest from improved wound closure and tissue regeneration supported by histopathological parameters. Assessment of granulation tissue every fourth day showed a significant reduction in the microbial count. The expression of matrix metalloproteinases was well correlated with the other results, hence confirming E. guineensis wound healing activity's effectiveness.
CONCLUSIONS: E. guineensis enhanced infected wound healing in rats, thus supporting its traditional use.
AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.
MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.
RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.
CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.