1.
Recent advances in nanotechnology for the treatment of metabolic syndrome.
Bahadori, E, Farjami, Z, Rezayi, M, Lngari, H, Darroudi, M, Avan, A, Ghayour-Mobarhan, M
Diabetes & metabolic syndrome. 2019;(2):1561-1568
Abstract
Metabolic syndrome is a main clinical challenge of global health which is growing universally. It would be resulted from over-consumption of energy, increased obesity, and lack of movement during life. The metabolic syndrome causes a five-fold increase in the risk of type 2 diabetes mellitus and a double increase in the risk of rising cardiovascular disease over the next 5-10 years. Based on this, more attention has been drawn to the diagnosis and treatment options of this disease. Nanotechnology is one of the preferred methods for improving this disease. This way is a natural development in many health domains, including synthetic and nanostructures. The use of nanoparticles with the purpose of increase the effectiveness of treatment, decrease the side effects and the amount of drug usage, through their small size, permeability and maintenance strength lead to their absorption by target organs. Meanwhile, different nanoparticles with consumption values and particle size have been investigated.
2.
In silico identification of potential drug compound against Peroxisome proliferator-activated receptor-gamma by virtual screening and toxicity studies for the treatment of Diabetic Nephropathy.
Singh, S, Mohanty, A
Journal of biomolecular structure & dynamics. 2018;(7):1776-1787
Abstract
Diabetic Nephropathy is a serious complication of diabetes mellitus. Current therapeutic strategies of Diabetic Nephropathy are based on control of modifiable risks like hypertension, glucose levels, and dyslipidemia. Peroxisome proliferator activated receptor-gamma (PPAR-γ) is implicated in several metabolic syndromes including Diabetic Nephropathy, besides obesity, insulin insensitivity, dislipidemia, inflammation, and hypertension. In the present study, virtual screening of 617 compounds from two different public databases was done against PPAR-γ with an objective to find a possible lead compound. Two softwares, PyRx and iGEMDOCK, were used to achieve the docking accuracy in order to avoid loss of candidate compounds. Rosiglitazone (used to treat Diabetic Nephropathy) was taken as the standard compound. A total of 30 compounds with good binding affinity with PPAR-γ were selected for further filtering, on the basis of absorption, distribution, metabolism, excretion, and toxicity (ADMET). The interaction profiling of these 30 compounds, showed a minimum of one and maximum of three interactions with reference to rosiglitazone (SER-289, HIS-449, HIS-323, TYR-473). The fulfilling of ADMET analysis criteria of 30 compounds led to the selection of four compounds (ZINC ID 00181552, 00276456, 00298314, 00448009). Molecular dynamics simulation of these lead compounds in complex with PPAR-γ revealed that three of the four compounds formed a stable complex in the ligand-binding pocket of PPAR-γ during 20-ns simulation. Hence, these three (ZINC ID 00181552, 00276456, 00298314) of the four compounds are potential candidates for experimental validation of biological activity against PPAR-γ in future drug discovery studies.
3.
The development of drug metabolising enzymes and their influence on the susceptibility to adverse drug reactions in children.
Johnson, TN
Toxicology. 2003;(1):37-48
Abstract
Altered drug disposition in the developing child occurs as a result of both biochemical and physiological changes. The clearance of many drugs is dependent on their biotransformation in the liver and small bowel and consequently is developmentally determined by a number of factors including both the activity and abundance of enzymes involved in Phase 1 and 2 drug metabolism. Altered drug metabolism can lead to the development of adverse effects in neonates and small infants that are not generally seen in the adult population. For instance, the altered metabolism of sodium valproate in children under 3 years of age is thought to be responsible for a higher incidence of hepatotoxicity, the impaired metabolism of chloramphenicol in neonates has resulted in the grey baby syndrome (cyanosis and respiratory failure) and metabolic acidosis following the use of propofol in the critically ill child may be due to altered drug metabolism. This paper reviews the potential contribution of the ontogeny of a number of drug metabolising enzymes including cytochrome P450 and glucuronoslytransferases to the development of adverse drug reactions in children.