In-vivo Kinetics of Silymarin (Milk Thistle) on Healthy Male Volunteers

Purpose: The study was aimed at evaluating the in vivo kinetics of silymarin tablets, a product with antihepatotoxic and free radical scavenging activities.Methods: Silimarin® (Amson Vaccines & Pharma Pvt Ltd) was used as the test product while another silymarin tablet brand, Silliver® (Abbott Laboratories Pak Ltd) was the reference product. The tablets were administered to healthy male volunteers orally at a dose of 200 mg following an overnight fast according to a randomized cross-over design. Scheduled blood samples were collected, centrifuged and the plasma assayed using a sensitive and validated reversed phase high performance liquid chromatographic (RP-HPLC) method. Various pharmacokinetic parameters were calculated based on the non-compartmental model.Results: Non-significant difference (p < 0.05) was observed in the area under the curve (AUC) of the two brands with values of 10.8 ± 0.4 μg h/ml and 11.2 ± 0.7 μg h/ml, respectively. There was, however, a significant difference (p < 0.05) in the Cmax of the two brands. Other pharmacokinetic parameters evaluated did not show any statistical difference (p < 0.05) between the two products except for meanresidence time Conclusion: The test product can be used as an alternative to the brand, Silliver®-Abbot (reference), only in conditions where maximum plasma concentration (Cmax) is not an important consideration

In-vivo Kinetics of Silymarin (Milk Thistle) on Healthy Male Volunteers

Purpose: The study was aimed at evaluating the in vivo kinetics of silymarin tablets, a product with anti-hepatotoxic and free radical scavenging activities. Methods: Silimarin® (Amson Vaccines & Pharma Pvt Ltd) was used as the test product while another silymarin tablet brand, Silliver® (Abbott Laboratories Pak Ltd) was the reference product. The tablets were administered to healthy male volunteers orally at a dose of 200 mg following an overnight fast according to a randomized cross-over design. Scheduled blood samples were collected, centrifuged and the plasma assayed using a sensitive and validated reversed phase high performance liquid chromatographic (RP-HPLC) method. Various pharmacokinetic parameters were calculated based on the non-compartmental model. Results: Non-significant difference (p < 0.05) was observed in the area under the curve (AUC) of the two brands with values of 10.8 ± 0.4 µg h/ml and 11.2 ± 0.7 µg h/ml, respectively. There was, however, a significant difference (p < 0.05) in the Cmax of the two brands. Other pharmacokinetic parameters evaluated did not show any statistical difference (p < 0.05) between the two products except for mean residence time Conclusion: The test product can be used as an alternative to the brand, Silliver®-Abbot (reference), only in conditions where maximum plasma concentration (Cmax) is not an important consideration

Feasibility of preoperative tattooing of percutaneously biopsied axillary lymph node: An experimental pilot study

Background: In the last three decades, axillary lymph node dissection (ALND) has been replaced by sentinel lymph node biopsy (SLNB) in all clinically node-negative patients. However, when SLNB alone is performed in clinically node-positive patients who are rendered node-negative by neoadjuvant chemotherapy, the procedure has a high false-negative rate and other complementary procedures have been described to improve its reliability. Preoperative tattooing of the suspicious lymph node with India ink at the time of biopsy, in addition to sentinel lymph node biopsy, is a reasonable alternative. The objective of our study is to determine, in clinically node-positive patients, the feasibility of tattooing suspicious axillary lymph node at the time of percutaneous needle biopsy and its retrieval at the time of surgery.Methods: A prospective experimental study will be conducted divided into two phases-phases I and II. In phase I, 10 patients committed to undergo upfront surgery (without neoadjuvant chemotherapy) will have a suspicious lymph node tattooed by injecting India ink at the time of core needle biopsy. All patients will undergo a SLNB, during which the axilla will be inspected to determine if the tattooed lymph node can be visualized. Routine microscopic examination will follow, and concordance between the sentinel and tattooed node will also be established. In phase II, the process will be repeated for 30 patients who undergo surgery after neoadjuvant chemotherapy. The analysis will be performed in Stata version 12.Discussion: There is a need to identify and test the techniques for the down-staged axilla in post-neoadjuvant chemotherapy patients, which are not only practical and limit the number of invasive procedures necessary but are representative of the new axillary status and help limit the extent of axillary surgery without negatively impacting outcomes. We propose that, for the patient undergoing neoadjuvant chemotherapy with a biopsy-proven disease in the axilla, this could be achieved by India ink which allows marking, identification, and retrieval of the biopsied lymph node. Retrieval of this previously biopsied lymph node along with sentinel nodes, if found to be representative of the status of the remainder of the axilla, could potentially eliminate the need for routine axillary lymph node dissection and thus limit morbidity

Optimization of Wire Electric Discharge Machining (WEDM) Process Parameters for AISI 1045 Medium Carbon Steel Using Taguchi Design of Experiments

With the growth of the manufacturing industry, the demand for alloy materials with high hardness, toughness, and impact strength has increased. Since products from such alloy materials are extremely difficult to manufacture with high accuracy and reduced surface roughness using traditional machining techniques, wire electric discharge machining can be used to machine such complex parts with more precision. In this case-study-based research, machining factors such as current, pulse-on time, and voltage are studied to determine their effects on the material removal rate for AISI 1045 medium carbon steel. The Taguchi L9 orthogonal array is used in the design of experiments for optimization. Statistical techniques such as analysis of variance and signal-to-noise ratio are used to identify the control parameters that matter most in bringing about optimal results. Based on the results, the current is the most crucial control variable in this investigation. Moreover, the maximum material removal rate obtained was 0.7112 mm3/min with the obtained optimized values of current (I) = 16 A, voltage (V) = 50 V, and pulse-on time (Ton) = 100 &micro;s

Process Parameter Optimization of Additively Manufactured Parts Using Intelligent Manufacturing

Additive manufacturing is the technique of combining materials layer by layer and process parameter optimization is a method used popularly for achieving the desired quality of a part. In this paper, four input parameters (layer height, infill density, infill pattern, and number of perimeter walls) along with their settings were chosen to maximize the tensile strength for a given part. Taguchi DOE was used to generate an L27 orthogonal array which helped to fabricate 27 parts on the Ender 3 V2 fused deposition modeling (FDM) printer. The ultimate testing machine was used to test all 27 samples to generate the respective tensile strength values. Next, the Microsoft Azure ML database was used to predict the values of the tensile strength for various input parameters by using the data obtained from Taguchi DOE as the input. Linear regression was applied to the dataset and a web service was deployed through which an API key was generated to find the optimal values for both the input and output parameters. The optimum value of tensile strength was 22.69 MPa at a layer height of 0.28 mm, infill density of 100%, infill pattern of honeycomb, and the number of perimeter walls as 4. The paper ends with the conclusions drawn and future research directions

Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers

Purpose: Disease state may contribute to alteration in drug pharmacokinetics. The purpose of this study was to determine the effect of non-insulin dependent diabetes mellitus (NIDDM) on the pharmacokinetics of glipizide. Methods: An open, single-dose, parallel design was applied to the study. Glipizide tablet (5 mg) was administered to healthy and diabetic human volunteers after over-night fast. Blood samples were collected, centrifuged and the plasma assayed using a sensitive and validated reverse phase high performance liquid chromatography (RP-HPLC) method. Various pharmacokinetic parameters were computed from the data obtained. Results: The AUC0-∞ values for healthy and diabetic volunteers was 1878 ± 195 and 1723 ± 138 ng.h/ml, respectively; these values were not significantly different (p > 0.05). The t1/2 for healthy volunteers was 3.04± 0.27 h while that for diabetic subjects was 2.98 ± 0.16 h. Clearance for healthy and diabetic volunteers was 0.59±0.06 and 0.64±0.05 ml/min/kg, respectively. These and other pharmacokinetic parameters assessed were not significantly different between healthy and diabetic volunteers (p > 0.05). Conclusion: Although glipizide showed slightly more rapid clearance from the body of diabetic volunteers than from healthy volunteers, this difference, like those for other pharmacokinetic parameters, was not significant (p > 0.05)

Chemical profiling and evaluation of toxicological, antioxidant, anti-inflammatory, anti-nociceptive and tyrosinase inhibitory potential of Portulacaria afra using in-vitro, in-vivo and in-silico studies

Portulacaria afra Jacq (Portulacaceae) is a medicinal plant used traditionally in the treatment of pain and inflammation. This study aimed to evaluate the phytochemical composition, toxicity, antinociceptive, and enzyme inhibition potential of P. afra. The methanol extract (PAME) was prepared through maceration and fractionated with ethanol to ethanol fraction of P. afra (ETPA). Both PAME and ETPA were found to be rich in total phenolic (TPC) and total flavonoid contents (TFC). Similarly, PAME showed the highest antioxidant potential through ABTS 93.16 ± 0.05 mg TE /g of dry extract (D.E.) while ETPA showed maximum results (462 ± 1.44 mg TE/g) in the CUPRAC method. The RP-UHPLC-MS analysis of PAME showed tentative identification of 101 compounds in the positive mode and 14 compounds in the negative mode of ionization while GC–MS profiling gave a total of 15 compounds. The acute oral toxicity study of PAME revealed the safety and biocompatibility of the extract up to a dose of 5000 mg/kg orally in rats. In-vitro data revealed that varying concentrations of P. afra significantly (p < 0.05) inhibited heat-induced BSA denaturation compared to indomethacin in a concentration-dependent manner. PAME suppressed carrageenan-induced paw edema at the 4th hr with maximum inhibition. The analgesic efficacy of PAME was determined by the hotplate, writhing method, and tail-flicking rat models. In the hot plate method, PAME treated groups showed a significant effect (p < 0.0001). While in the writhing model, the PAME treated groups showed a significant (p < 0.0001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg compared to the control group. Similarly, PAME treated groups in the tail flicking model showed a significant (p < 0.001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg. A dose-dependent increase in latency time (8.78 ± 0.090 at (30 min), 11.39 ± 0.005 at (60 min), 12.14 ± 0.01 at (90 min) 15.19 ± 0.03 at (120 min), p < 0.0001 was observed, compared to the control group. Similarly, the extract and fraction showed significant inhibitory potential against tyrosinase in in vitro and in-silico studies. Conclusively the current study unveiled P. afra as a novel non-toxic source with good total antioxidant-mediated anti-inflammatory and analgesic potential