Development and Validation of TLC-Densitometric Method for Analysis of Paracetamol, Mefenamic Acid and Ibuprofen Simultaneously in “Pegel Linu” Traditional Medicines

Jamu is a traditional or herbal medicine that is widely used by Indonesian people for prevention, maintenance and treatment of diseases. Traditional medicines contain plants or extracted plant material, or combinations thereof. The adulteration practice violates the laws. However, the presence of undeclare synthetic chemical drugs in the herbal products are still often found, among others, analgesic and anti-inflammatory drugs. The purpose of this study is to obtain a validated, simpler and lower operational cost of TLC-densitometric method to analyze paracetamol, mefenamic acid and ibuprofen in herbal medicines in “pegel linu” herbal medicines. The samples were extracted with ethanol, then separated over silica gel GF254 TLC plate with mixture of chloroform-ethanol (8:1) as mobile phase and analyzed using TLC-densitometry. The method has a satisfactorily specificity and linearity, and met the precision and accuracy criteria at the concentration of 1500 ng/spot for paracetamol, 1250 ng/spot for mefenamic acid, and 2000 ng/spot for ibuprofen. The results of the determination of eight samples showed that four of them were positive containing paracetamol with the concentration of 337.12 - 505.55 mg/single dosage

QUANTIFICATION OF HYALURONIC ACID AND METHYLSULFONYLMETHANE IN DIETARY SUPPLEMENTS

Objective: Osteoarthritis can be treated by taking oral supplements containing compounds that can nourish bones and joints such as hyaluronic acid,methylsulfonylmethane (MSM), chondroitin, glucosamine, and collagen. This study aimed to develop and validate tests for analyzing two compounds,namely, hyaluronic acid and MSM, simultaneously and to determine both their levels in a mixed sample.Methods: Hyaluronic acid derivatization was carried out using fluorenylmethyloxycarbonyl chloride and then analyzed by liquid chromatographywith fluorescence detection, while MSM was analyzed using gas chromatography. After the development of optimal conditions for each separation,system suitability tests were developed and calibration curves used for tests of accuracy and precision as well as for level determination. Hyaluronicwas detected at an excitation wavelength of 255 nm and emission wavelength of 330 nm. The mobile phase used was acetonitrile-acetate pH 4.2 (1: 4)with a flow rate of 1.0 mL/min.Results: The developed method was linear (r=0.9983) in the range of 5–50 ppm and the limits of detection (LOD) and quantitation (LOQ) were 3.55and 11.84 ppm, respectively. The initial column temperature for MSM analysis was 110°C and the mobile phase used was nitrogen gas at a flow rate of0.8 mL/min. The method was linear (r=0.9998) in the range of 4000–15,000 ppm and the LOD and LOQ were 332.90 and 1109.67 ppm, respectively.Conclusion: A simulated sample containing both compounds was assessed to contained 98.63% hyaluronic acid and 99.35% MSM

Diversity-based Attribute Weighting for K-modes Clustering

Categorical data is a kind of data that is used for computational in computer science. To obtain the information from categorical data input, it needs a clustering algorithm. There are so many clustering algorithms that are given by the researchers. One of the clustering algorithms for categorical data is k-modes. K-modes uses a simple matching approach. This simple matching approach uses similarity values. In K-modes, the two similar objects have similarity value 1, and 0 if it is otherwise. Actually, in each attribute, there are some kinds of different attribute value and each kind of attribute value has different number. The similarity value 0 and 1 is not enough to represent the real semantic distance between a data object and a cluster. Thus in this paper, we generalize a k-modes algorithm for categorical data by adding the weight and diversity value of each attribute value to optimize categorical data clustering

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Extramedullary myeloma in an HIV-seropositive subject. Literature review and report of an unusual case

Myeloma is characterized by monoclonal bone marrow plasmacytosis, the presence of M-protein in serum and/or in urine and osteolytic bone lesions. HIV-seropositive subjects with myeloma are younger at the time of diagnosis of the tumour and usually the myeloma has a more aggressive clinical course than it does in HIV-seronegative subjects

A Test of Highly Optimized Tolerance Reveals Fragile Cell-Cycle Mechanisms Are Molecular Targets in Clinical Cancer Trials

Robustness, a long-recognized property of living systems, allows function in the face of uncertainty while fragility, i.e., extreme sensitivity, can potentially lead to catastrophic failure following seemingly innocuous perturbations. Carlson and Doyle hypothesized that highly-evolved networks, e.g., those involved in cell-cycle regulation, can be resistant to some perturbations while highly sensitive to others. The “robust yet fragile” duality of networks has been termed Highly Optimized Tolerance (HOT) and has been the basis of new lines of inquiry in computational and experimental biology. In this study, we tested the working hypothesis that cell-cycle control architectures obey the HOT paradigm. Three cell-cycle models were analyzed using monte-carlo sensitivity analysis. Overall state sensitivity coefficients, which quantify the robustness or fragility of a given mechanism, were calculated using a monte-carlo strategy with three different numerical techniques along with multiple parameter perturbation strategies to control for possible numerical and sampling artifacts. Approximately 65% of the mechanisms in the G1/S restriction point were responsible for 95% of the sensitivity, conversely, the G2-DNA damage checkpoint showed a much stronger dependence on a few mechanisms; ∼32% or 13 of 40 mechanisms accounted for 95% of the sensitivity. Our analysis predicted that CDC25 and cyclin E mechanisms were strongly implicated in G1/S malfunctions, while fragility in the G2/M checkpoint was predicted to be associated with the regulation of the cyclin B-CDK1 complex. Analysis of a third model containing both G1/S and G2/M checkpoint logic, predicted in addition to mechanisms already mentioned, that translation and programmed proteolysis were also key fragile subsystems. Comparison of the predicted fragile mechanisms with literature and current preclinical and clinical trials suggested a strong correlation between efficacy and fragility. Thus, when taken together, these results support the working hypothesis that cell-cycle control architectures are HOT networks and establish the mathematical estimation and subsequent therapeutic exploitation of fragile mechanisms as a novel strategy for anti-cancer lead generation

Mechanical and microstructural response of the Al0.5CoCrFeNi high entropy alloy to Si and Ni ion irradiation

© 2020 The Authors The nearly infinite compositional design space of high entropy alloys (HEAs) presents many opportunities to improve performance in extreme environments, particularly for nuclear reactors. The ability of some HEAs to resist high amounts of radiation damage, while well documented, has not yet been fully exploited. We studied the irradiation effect of different ions (Si and Ni) on the microstructure and mechanical properties of the Al0.5CoCrFeNi alloy at its equilibrium state, and of the individual response of each phase to irradiation. The results show a stronger effect of Si ions and differences in response of the ductile FCC (A1) and brittle ordered BCC (B2) phases towards irradiation. This finding highlights the need to further probe unexplored compositional spaces in HEAs, as further optimization is likely to yield further compositional and microstructural stability with practical applications