The clinical application of new antineoplastic drugs has been limited because of low therapeutic index and lack of efficacy in humans. Improvement in efficacy of new anticancer drugs has been attempted by manipulating their pharmacokinetic properties. Four inter-related factors, which determine the pharmacokinetic behavior of a drug include absorption, distribution, metabolism and excretion. The drug-metabolizing enzymes have been classified in two major groups: phase I and phase II enzymes. Phase I enzymes comprise the oxidases, dehydrogenases, deaminases, hydrolases. Phase II enzymes include primarily UDP-glucuronosyltransferases (UGTs), glutathionetransferases (GSTs), sulfotransferases (SULTs), N-acetyl transferases (NATs), methyltransferases and aminoacid transferases that conjugate products of phase I reactions and parent compounds with appropriate functional groups to generate more water soluble compounds which are more readily eliminated. The importance of these enzymes in the metabolism of specific drugs varies according to the chemical nature of the drug. Drug metabolism is modulated by factors that change among species and even among individuals in a population. Such factors can be environmental or genetic in origin and influence how a drug is metabolized and to what extent. An awareness of these variables is invaluable when the safety and efficacy of new anticancer drugs are evaluated.

The clinical application of new antineoplastic drugs has been limited because of low therapeutic index and lack of efficacy in humans. Thus, improvement in efficacy of old and new anticancer drugs has been attempted by manipulating their pharmacokinetic properties. Four inter-related factors, which determine the pharmacokinetic behavior of a drug include absorption, distribution, metabolism and excretion. The drug-metabolizing enzymes have been classified in two major groups: phase I and phase II enzymes. Phase I enzymes comprise the oxidases, dehydrogenases, deaminases, hydrolases. Phase II enzymes include primarily UDPglucuronosyltransferases (UGTs), glutathionetransferases (GSTs), sulfotransferases (SULTs), N-acetyl transferases (NATs), methyltransferases and aminoacid transferases that conjugate products of phase I reactions and parent compounds with appropriate functional groups to generate more water soluble compounds which are more readily eliminated. The importance of these enzymes in the metabolism of specific drugs varies according to the chemical nature of the drug. Drug metabolism is modulated by factors that change among species and even among individuals in a population. Such factors can be environmental or genetic in origin, and influence how a drug is metabolized and to what extent. An awareness of these variables is invaluable when the safety and efficacy of new anticancer drugs are evaluated.
enzymology ; seconds ; metabolic aspects ; cancer therapy ; Metabolic

Chemical preservatives have been used in the food industry for many years. However, with increased health concerns, consumers prefer additive-free products or food preservatives based on natural products. This study evaluated antimicrobial activities of extracts from Emilia sonchifolia L. (Common name: lilac tassel flower), Tridax procumbens L. (Common name: tridax daisy) and Vernonia cinerea L. (Common name: Sahadevi), belonging to the Asteracea family, to explore their potential for use against general food spoilage and human pathogens so that new food preservatives may be developed. Three methanol extracts of these plants were tested in vitro against 20 bacterial species, 3 yeast species, and 12 filamentous fungi by the agar diffusion and broth dilution methods. The V. cinerea extract was found to be most effective against all of the tested organisms and the methanol fraction showed the most significant (p < 0.05) antimicrobial activity among all the soluble fractions tested. The minimum inhibitory concentrations (MICs) of extracts determined by the broth dilution method ranged from 1.56 to 100.00mg/mL. The MIC of methanol fraction was the lowest in comparison to the other four extracts. The study findings indicate that bioactive natural products from these plants may be isolated for further testing as leads in the development of new pharmaceuticals in food preservation as well as natural plant-based medicine.

Ascorbic Acid ; administration & dosage ; Child ; Child Nutrition Disorders ; complications ; diet therapy ; Diagnosis, Differential ; Femoral Neoplasms ; diagnosis ; Femur ; diagnostic imaging ; Humans ; Male ; Protein-Energy Malnutrition ; complications ; diet therapy ; Radiography ; Scurvy ; diagnosis ; diet therapy ; etiology ; physiopathology ; Treatment Outcome

STUDY DESIGN: Retrospective analysis. PURPOSE: We evaluated the functional, neurological, and radiological outcome in patients with thoracic and thoracolumbar tuberculosis operated through the transpedicular approach. OVERVIEW OF LITERATURE: For surgical treatment of thoracic and thoracolumbar tuberculosis, the anterior approach has been the most popular because it allows direct access to the infected tissue, thereby providing good decompression. However, anterior fixation is not strong, and graft failure and loss of correction are frequent complications. The transpedicular approach allows circumferential decompression of neural elements along with three-column fixation attained via pedicle screws by the same approach. METHODS: A total of 47 patients were diagnosed with tuberculosis of the thoracic or thoracolumbar region from August 2012 to August 2013. Of these, 28 patients had progressive neurological deterioration or increasing back pain despite conservative measures and underwent transpedicular decompression and pedicle screw fixation with posterior fusion. Antituberculosis therapy was given till signs of radiological healing were evident (9–16 months). Functional outcome (visual analog scale [VAS] score for back pain), neurological recovery (Frankel grading), and radiological improvement were evaluated preoperatively, immediate postoperatively, and at 3 months, 6 months, and 1 year. RESULTS: Mean VAS score for back pain improved from 8.7 preoperatively to 1.1 at 1 year follow-up. Frankel grading preoperatively was grade B in 7, grade C in 11, and Grade D in 10 patients, which improved to grade D in 6 and grade E in 22 patients at the last follow-up. Radiological healing was evident in the form of reappearance of trabeculae formation, resolution of pus, fatty marrow replacement, and bony fusion in all patients. Mean correction of segmental kyphosis postoperatively was 10.5°. Mean loss of correction at final follow-up was 4.1°. CONCLUSIONS: Transpedicular decompression with instrumented fusion is a safe and effective approach for management of patients with thoracic and thoracolumbar tuberculosis.
Back Pain ; Bone Marrow ; Decompression* ; Follow-Up Studies ; Humans ; Kyphosis ; Pedicle Screws ; Retrospective Studies ; Suppuration ; Transplants ; Tuberculosis* ; Tuberculosis, Spinal

BACKGROUND: In times of continuous change and volatile markets, organizations are increasingly characterized by downsizing, work intensification, and resource rationalization. This has resulted in diversification, and the emergence of new risks within the field of occupational health and safety, with an important impact. This paper focuses on one such type of risk in the modern workplace-psychosocial risks. The current study aimed to explore stakeholder perspectives, regarding the extent to which psychosocial risks are incorporated into strategic risk management practices, at both the business and policy level. METHODS: Semi-structured interviews were conducted with 14 professionals, representing employer, expert, policy maker, and trade union stakeholder perspectives. RESULTS: It was found that the majority of organizations do not sufficiently, if at all, understand and incorporate psychosocial risks into strategic decision making, whereby the key barrier related to practical difficulties of not knowing how to manage psychosocial risks adequately. CONCLUSION: The study found that there is a need to close the gap between policy and practice on a number of levels. Future recommendations comprise a policy framework and infrastructure underpinned by educational initiatives, partnerships, and networks to drive a shift in attitudes toward recognizing the duality of the concept of risk (including both potential negative and positive outcomes) and moving beyond simple regulatory compliance.
Administrative Personnel ; Commerce* ; Compliance ; Decision Making ; Humans ; Labor Unions ; Occupational Health ; Policy Making* ; Rationalization ; Risk Management*

Self-expanding metal stents play a crucial role in the management of patients with biliary obstruction. Endoscopic extraction of uncovered metal stents (UCMSs) and partially covered metal stents (PCMSs) could be challenging because of tissue ingrowth. No standardized technique can guarantee universal success. We present our technique and experience of endoscopic extraction of biliary stents in two patients with a UCMS and three patients with a PCMS. Three of the five patients had a previous failed attempt of stent extraction at an outside hospital. Overall, our composite success rate was 80% (4/5). The individual success rate was 100% (3/3) for PCMSs and 50% (1/2) for UCMSs. The stent-in-stent technique, in which a fully covered metal stent is placed through an existing UCMS/PCMS, was used in 60% (3/5) of the cases, with a success rate of 66.7% (2/3). We share our algorithmic approach to each case, with detailed emphasis on the technical aspects of the procedure.

Self-expanding metal stents play a crucial role in the management of patients with biliary obstruction. Endoscopic extraction of uncovered metal stents (UCMSs) and partially covered metal stents (PCMSs) could be challenging because of tissue ingrowth. No standardized technique can guarantee universal success. We present our technique and experience of endoscopic extraction of biliary stents in two patients with a UCMS and three patients with a PCMS. Three of the five patients had a previous failed attempt of stent extraction at an outside hospital. Overall, our composite success rate was 80% (4/5). The individual success rate was 100% (3/3) for PCMSs and 50% (1/2) for UCMSs. The stent-in-stent technique, in which a fully covered metal stent is placed through an existing UCMS/PCMS, was used in 60% (3/5) of the cases, with a success rate of 66.7% (2/3). We share our algorithmic approach to each case, with detailed emphasis on the technical aspects of the procedure.

Background/Aims: Diagnostic abdominal paracentesis has been described in literature to have variable sensitivity of 50%–75% for the detection of peritoneal carcinomatosis (PC). We believe that random needle aspirates from the omentum, even in the absence of obvious deposits by endoscopic ultrasound (EUS), could prove malignancy in patients with PC. Methods: Consecutive patients who underwent EUS for diagnosis and staging of cancer and found to have ascites were included after obtaining informed consent. EUS-guided fine needle aspiration (EUS-FNA) from random sites in the omentum was performed through the transgastric route using a linear echoendoscope. Results: Fifty-four patients underwent EUS during October 2015 to April 2017 for detection, staging, or FNA of a suspected malignant lesion. Ascites was seen in 17 patients and 15 patients who fulfilled the criteria were included. The procedure was successful in all patients. Cytology was suggestive of malignancy in 12 (80%) but not suggestive of malignancy in 3 (20%) patients. Three patients who tested negative had hyperbilirubinemia with biliary obstruction. Their ascitic fluid analysis result was also negative. Conclusions Random FNA of the omentum in patients with malignancy-related ascites is highly effective in the diagnosis of PC and could be employed during EUS evaluation of malignancies.

Elbow dislocation with concomitant diaphyseal fractures of radius and ulna has been reported rarely. This injury could be included in Monteggia equivalent lesions based on the mechanism of injury, radiographic pattern and method of treatment as described by Bado. We report a rare case of Monteggia equivalent lesion in an adult with unclear mechanism of injury. The possible mechanism of injury, its management and the follow-up results were described. An attempt to solve the controversy regarding whether labeling it as type 1 or type 2 was made.
Adult ; Elbow ; Humans ; Joint Dislocations ; Monteggia's Fracture ; Radius ; injuries ; Radius Fractures ; therapy ; Ulna