An In Vitro Examination of Whether Kratom Extracts Enhance the Cytotoxicity of Low-Dose Doxorubicin against A549 Human Lung Cancer Cells.

Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10-60 ppm of crude and alkaloid extracts derived from the leaves of Kratom (Mitragyna speciosa (Korth.) Havil. Rubiaceae). A549 cancer cell lines were insensitive to the crude extract containing low mitragynine (MG) (4-5%), while these cells were moderately inhibited by the alkaloid extract containing 40-45% MG (IC50 of 48-55 ppm). The alkaloid extract was found to inhibit A549 cancer cells via apoptosis as suggested by the higher relative fluorescence intensity with Annexin compared to that in propidium iodide (PI), i.e., a positive Annexin and a negative PI. The combination of crude extract and doxorubicin sensitized A549 cancer cells to doxorubicin by 1.3 to 2.4 times, while the combination with the alkaloid induced a 2.6- to 3.4-fold increase in sensitivity. The calculated combination index (CI) for doxorubicin with the crude and alkaloid extracts was 0.6 and 0.3, respectively, showing potential synergistic combinations to reduce the level of dosage of doxorubicin used in chemotherapy. In addition, the synergistic enhancement effect of crude extract on the cytotoxic activity of doxorubicin provides insights into the plausibility of non-alkaloids to influence the biological activities of Kratom.

Spectrum dependency to rate and spike timing in neuronal spike trains.

BACKGROUND: Spike trains are series of interspike intervals in a specific order that can be characterized by their probability distributions and order in time which refer to the concepts of rate and spike timing features. Periodic structure in the spike train can be reflected in oscillatory activities. Thus, there is a direct link between oscillator activities and the spike train. The proposed methods are to investigate the dependency of emerging oscillatory activities to the rate and the spike timing features. METHOD: First, the circular statistics methods were compared to Fast Fourier Transform for best estimation of spectra. Second, two statistical tests were introduced to help make decisions regarding the dependency of spectrum, or individual frequencies, onto rate and spike timing. Third, the methodology is applied to in-vivo recordings of basal ganglia neurons in mouse, primate, and human. Finally, this novel framework is shown to allow the investigation of subsets of spikes contributing to individual oscillators. RESULTS: Use of circular statistical methods, in comparison to FFT, minimizes spectral leakage. Using virtual spike trains, the Rate versus Timing Dependency Spectrum Test (or RTDs-Test) permits identifying spectral spike trains solely dependent on the rate feature from those that are also dependent on the spike timing feature. Similarly, the Rate versus Timing Dependency Frequency Test (or RTDf-Test), allows to identify individual oscillators with partial dependency on spike timing. Dependency on spike timing was found for all in-vivo recordings but only in few frequencies. The mapping in frequency and time of dependencies showed a dynamical process that may be organizing the basal ganglia function. CONCLUSIONS: The methodology may improve our understanding of the emergence of oscillatory activities and, possibly, the relation between oscillatory activities and circuitry functions.

A retrospective cross-sectional study of urinary tract infections and prevalence of antibiotic resistant pathogens in patients with diabetes mellitus from a public hospital in Surabaya, Indonesia.

INTRODUCTION: Diabetes mellitus (DM) is a metabolic disease that can cause many complications. The occurrence of urinary tract infection is also considered to be the cause of complications in patients with DM. This study aimed to evaluate the prevalence of urinary tract infection (UTI) and antibiotic-resistant bacteria found in urine culture from patients with DM in Surabaya, Indonesia. METHODS: This study was conducted with a retrospective cross-sectional study design, using a database of 1551 patients with DM admitted to Haji Hospital, Surabaya, Indonesia, from January 2017 to December 2018. Data regarding the bacteria isolated from urine and antimicrobial sensitivity were analyzed. RESULTS: The prevalence of UTI was 3.93% - 61 patients were confirmed with urine culture for UTI diagnosis. The predominant isolates found were Escherichia coli (24.5%) and Enterococcus faecalis (8%). This study also showed multidrug-resistant organisms (MDRO) found in UTI such as Escherichia coli MDRO (3.3 %), Klebsiella pneumoniae MDRO (3.3%), Acinetobacter baumannii MDRO (1.6%), extended-spectrum beta-lactamase (ESBL) Escherichia coli (3.3%). The E. coli were sensitive to fosfomycin (93%), meropenem (93%) and nitrofurantoin (67%). No significant difference in the prevalence of UTI was found among ages, sex, and duration of disease in all patients with DM. CONCLUSIONS: The cases of UTI seen in patients with DM show the importance of monitoring UTI occurrence in this patient category to ensure better treatment for these patients.