ABSTRACT
BACKGROUND: Natural products play a key role as potential sources of biologically active substances for the discovery of new drugs. This study aimed to identify secondary metabolites from actinomycete library extracts that are potent against the asexual stages of Plasmodium falciparum (P. falciparum). METHODS: Secondary metabolites from actinomycete library extracts were isolated from culture supernatants by ethyl acetate extraction. Comprehensive screening was performed to identify novel antimalarial compounds from the actinomycete library extracts (n = 28). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) lines of P. falciparum. The cytotoxicity was then evaluated in primary adult mouse brain (AMB) cells. RESULTS: Out of the 28 actinomycete extracts, 17 showed parasite growth inhibition > 50% at a concentration of 50 µg/mL, nine were identified with an IC50 value < 10 µg/mL, and seven suppressed the parasite significantly with an IC50 value < 5 µg/mL. The extracts from Streptomyces aureus strains HUT6003 (Extract ID number: 2), S. antibioticus HUT6035 (8), and Streptomyces sp. strains GK3 (26) and GK7 (27), were found to have the most potent antimalarial activity with IC50 values of 0.39, 0.09, 0.97, and 0.36 µg/mL (against 3D7), and 0.26, 0.22, 0.72, and 0.21 µg/mL (against Dd2), respectively. Among them, Streptomyces antibioticus strain HUT6035 (8) showed the highest antimalarial activity with an IC50 value of 0.09 µg/mL against 3D7 and 0.22 µg/mL against Dd2, and a selective index (SI) of 188 and 73.7, respectively. CONCLUSION: Secondary metabolites obtained from the actinomycete extracts showed promising antimalarial activity in vitro against 3D7 and Dd2 cell lines of P. falciparum with minimal toxicity. Therefore, secondary metabolites obtained from actinomycete extracts represent an excellent starting point for the development of antimalarial drug leads.
ABSTRACT
During follow-up of a 60-year-old patient with dilated cardiomyopathy, a Holter electrocardiogram revealed monomorphic premature ventricular complexes (PVCs) accounting for 21-30% of total beats. Oral beta-blockers led to no improvement in PVC burden. The first radiofrequency catheter ablation attempt identified the PVC arising from the left ventricle summit communicating vein (CV) but failed to eliminate the PVC's origin. The second ablation attempt with selective infusions of 100% ethanol into the summit CV resulted in immediate termination of PVCs. The post-ablation course was uneventful. Echocardiography showed an improved ejection fraction, and a repeated Holter electrocardiogram showed no recurrence of PVCs during follow-up. Ethics The RCVEA procedures were approved by the Takagi Hospital Ethical Committee and were performed under an institutional review board-approved protocol. (Kouhou-kai Ethical Committee, ID: KR168) Fundings This work was supported by the Takagi Hospital Cardiology Research Grant. The authors declare no competing interests. Acknowledgements: We thank the patient, the patient's family, and the medical staff of Takagi Hospital for their valuable cooperation and kind support. Consent Written informed consent was obtained from the patient for the publication of this case report and accompanying images.
ABSTRACT
Segmental gastrectomy, mini-distal gastrectomy and local resection of the stomach are function-preserving curative gastrectomies (FPGs), which are used to treat gastric cancer in specialized centers. These surgical options are less invasive and can alleviate postgastrectomy symptoms more than standard gastrectomy; however, their association with prognosis remains to be fully elucidated. The present study aimed to compare the survival prognosis of patients diagnosed as node-negative by sentinel node biopsy (SNB) treated via FPG with reduced lymph node dissection with that of patients who underwent guideline gastrectomy (GL). This retrospective study was conducted between April 1999 and March 2016. The inclusion criteria were a diagnosis of gastric cancer type 0, of ≤5 cm, located in L or M areas, and pT1N0. Patients who underwent distal gastrectomy and pylorus-preserving gastrectomy were included as controls in the GL group. Among the 146 and 300 patients in the FPG and GL groups, respectively, only 1 patient in the GL group experienced recurrence. The overall survival (OS) of the FPG group was 96.6% at 5 years and 92.5% at 10 years, which was significantly higher than that of the GL group (P<0.05). In addition, the cumulative incidence of non-cancer-related deaths, especially pulmonary diseases, was lower in the FPG group than that in the GL group (P<0.05). Notably, the OS and non-cancer death rate in the FPG group remained significantly better after propensity score-matching analysis. In conclusion, for early gastric cancer located in M or L areas, patients treated via FPG guided by SNB have a better prognosis and fewer deaths caused by respiratory disease than those treated via GL. The present clinical trial was registered under the following trial registration numbers: UMIN000010154 (2013/3/4), UMIN000023828 (2016/8/29), jRCTs041180006 (2018/10/9).