Biomarkers are the most significant diagnosis tools tending towards unique approaches and solutions for the prevention and cure of Alzheimer's Disease (AD). The current report provides a clear perception of the concept of various biomarkers and their prominent features through analysis to provide a possible solution for the inhibition of events in AD. Scientists around the world truly believe that crucial hallmarks can serve as critical tools in the early diagnosis, cure, and prevention, as well as the future of medicine. The awareness and understanding of such biomarkers would provide solutions to the puzzled mechanism of this neuronal disorder. Some of the argued biomarkers in the present article are still in an experimental phase as they need to undergo specific clinical trials before they can be considered for treatment.
- MeSH
- Alzheimerova nemoc * farmakoterapie diagnóza metabolismus MeSH
- amyloidní beta-protein metabolismus antagonisté a inhibitory MeSH
- biologické markery * analýza metabolismus MeSH
- lidé MeSH
- proteiny tau metabolismus antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
In this randomized, open-label, 2-part, 2 × 2 crossover, phase 1 study, the effect of a low-fat low-calorie (LFLC) meal on the relative bioavailability of a trametinib 2-mg tablet or dabrafenib 150-mg capsule was evaluated in healthy participants. Trametinib adjusted geometric mean ratios (90%CI) of fed : fasted for area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration and AUC from time 0 extrapolated to infinity were 0.76 (0.71-0.82) and 0.82 (0.77-0.88), respectively. For dabrafenib, the adjusted geometric mean ratios of AUC from time 0 to the last quantifiable concentration and AUC from time 0 extrapolated to infinity (90%CI) for fed:fasted were 0.85 (0.79-0.91) and 0.86 (0.80-0.92), respectively. Consumption of an LFLC meal delayed trametinib and dabrafenib absorption, with an increase in time to maximum concentration of ≈15 and ≈30 minutes, respectively, compared to the fasted state. These findings indicate that consumption of an LFLC meal reduced the bioavailability and delayed the absorption of trametinib and dabrafenib, supporting current recommendations to administer both drugs in the fasting state; however, an occasional LFLC meal is unlikely to affect the pharmacokinetics of the drugs once steady state is reached and, by consequence, not likely to alter the overall intended efficacy.
Selective, sensitive and affordable techniques to detect disease and underlying health issues have been developed recently. Biosensors as nanoanalytical tools have taken a front seat in this context. Nanotechnology-enabled progress in the health sector has aided in disease and pandemic management at a very early stage efficiently. This report reflects the state-of-the-art of nanobiosensor-based virus detection technology in terms of their detection methods, targets, limits of detection, range, sensitivity, assay time, etc. The article effectively summarizes the challenges with traditional technologies and newly emerging biosensors, including the nanotechnology-based detection kit for COVID-19; optically enhanced technology; and electrochemical, smart and wearable enabled nanobiosensors. The less explored but crucial piezoelectric nanobiosensor and the reverse transcription-loop mediated isothermal amplification (RT-LAMP)-based biosensor are also discussed here. The article could be of significance to researchers and doctors dedicated to developing potent, versatile biosensors for the rapid identification of COVID-19. This kind of report is needed for selecting suitable treatments and to avert epidemics.
Alzheimer's disease (AD) is considered as one of widespread dementia with no approved diagnosis, cure or prevention. Currently, only symptomatic relief can be provided upon administration of anti-AD drugs generally belonging to a category of anticholinesterases and antagonists of N-methyl-D-aspartate (NMDA) receptors. In present investigation, a sensing platform has been designed for studying recently developed anti-AD drugs viz., PC-25 (N-(2-{4-[(4-bromophenyl)methyl]piperazin-1-yl}ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride), PC-37 (7-methoxy-N-(2-{4-[(3-methylphenyl)methyl]piperazin-1-yl}ethyl)-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride) and PC-48 (N-(2-{4-[(3-bromophenyl) methyl]piperazin-1-yl}ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride) and two known standard tacrine (THA) and donepezil drugs for their estimation of in vitro potency towards AD using spectroscopic method. Anti-AD drugs have been accounted for individually with highly fluorescent nitrogen-doped graphene quantum dots (NGQDs). The designed anti-AD drugs exerted the efficacy related to cholinergic hypothesis of AD. While the enzyme action is sensed by interacted species of NGQDs and acetylcholine, the fluorescence of NGQDs is quenched by the hydrolyzing action of acetylcholinesterase (AChE) enzyme but the lost fluorescence is recovered upon addition of anti-AD drugs. These alterations in fluorescence of NGQDs are expected to have biological relevance akin to sensing. Moreover, these results advocate that out of all the drugs tested PC-37 displayed maximum inhibition efficiency. Our investigations suggest that synthesized drugs have the AD treating potential and can be entrusted in the near future for AD treatment. The validation parameters such as LOD, LOQ and recovery (%) were calculated in the range of 2.87 mM, 9.58 mM and 85-96%, respectively.Communicated by Ramaswamy H. Sarma.
- MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- cholinesterasové inhibitory farmakologie MeSH
- dusík MeSH
- grafit * MeSH
- kvantové tečky * MeSH
- léčivé přípravky * MeSH
- lidé MeSH
- takrin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria. Complex I activity was decreased by galantamine, donepezil, and memantine; complex II + III activity was increased by galantamine. None of the tested drugs caused significant changes in the rate of mitochondrial oxygen consumption, even at high concentrations. Except galantamine, all tested drugs were selective MAO-A inhibitors. Latrepirdine, donepezil, and 7-MEOTA were found to be the most potent MAO-A inhibitors. Succinate-induced mitochondrial hydrogen peroxide production was not significantly affected by the drugs tested. The direct effect of cognitives and nootropics used in the treatment of AD on mitochondrial respiration is relatively small. The safest drugs in terms of disturbing mitochondrial function appear to be piracetam and rivastigmine. The MAO-A inhibition by cognitives and nootropics may also participate in mitochondrial neuroprotection. The results support the future research aimed at measuring the effects of currently used drugs or newly synthesized drugs on mitochondrial functioning in order to understand their mechanism of action.
- MeSH
- Alzheimerova nemoc metabolismus MeSH
- cholinesterasové inhibitory farmakologie MeSH
- galantamin metabolismus MeSH
- indany farmakologie MeSH
- kognice účinky léků MeSH
- memantin farmakologie MeSH
- mitochondrie účinky léků metabolismus MeSH
- monoaminoxidasa účinky léků metabolismus MeSH
- mozek účinky léků metabolismus MeSH
- nootropní látky farmakologie MeSH
- piperidiny farmakologie MeSH
- prasata MeSH
- rivastigmin farmakologie MeSH
- spotřeba kyslíku účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In the early stage of drug development the solubility of drug candidate is the most crucial physicochemical parameter to be defined for the selection of lead compound. Conventional shake flask method of solubility determination has now been replaced with more precise measurements like ultraviolet absorption, nephelometry, nuclear magnetic resonance and potentiometry. The development of a simple, rapid, sensitive and precise spectrophotometric method for the routine quantitative determination of samples will definitely reduce unnecessary tedious sample preparations and the cost of materials and labour. This article accounts for the measurement of solubility limit of few selected drugs by spectrophotometry using dilution technique. This has been done to optimize the method for rapid and convenient determination of drug solubility limit. Concentration of saturated solution of drug was determined from the absorbance versus concentration plots of various diluted solutions of drug as per Beer-Lambert law and was reported as drug solubility limit.
- MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- cholinesterasové inhibitory terapeutické užití MeSH
- inhibitory MAO terapeutické užití MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. However, statins can have serious adverse effects, which may be related to development of mitochondrial dysfunctions. The aim of study was to demonstrate the in vivo effect of high and therapeutic doses of statins on mitochondrial respiration in blood platelets. Model approach was used in the study. Simvastatin was administered to rats at a high dose for 4 weeks. Humans were treated with therapeutic doses of rosuvastatin or atorvastatin for 6 weeks. Platelet mitochondrial respiration was measured using high-resolution respirometry. In rats, a significantly lower physiological respiratory rate was found in intact platelets of simvastatin-treated rats compared to controls. In humans, no significant changes in mitochondrial respiration were detected in intact platelets; however, decreased complex I-linked respiration was observed after statin treatment in permeabilized platelets. We propose that the small in vivo effect of statins on platelet energy metabolism can be attributed to drug effects on complex I of the electron transport system. Both intact and permeabilized platelets can be used as a readily available biological model to study changes in cellular energy metabolism in patients treated with statins.
Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity.
- MeSH
- Alzheimerova nemoc farmakoterapie metabolismus patologie MeSH
- energetický metabolismus účinky léků MeSH
- inhibitory MAO chemie metabolismus farmakologie terapeutické užití MeSH
- lidé MeSH
- mitochondrie účinky léků metabolismus MeSH
- objevování léků metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
