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Topic Review
Magnesium and Morphine in Chronic Neuropathic Pain
The effectiveness of opioids in the treatment of neuropathic pain is limited. It was demonstrated that magnesium ions (Mg2+), physiological antagonists of N-methyl-D-aspartate receptor (NMDAR), increase opioid analgesia in chronic pain. Early data indicate the cross-regulation of mu-opioid receptor (MOR) and NMDAR in pain control. Morphine acting on MOR stimulates protein kinase C (PKC), while induction of NMDAR (for example in a state of neuropathic pain) recruits protein kinase A (PKA) leading to disruption of the MOR-NMDAR complex and promoting functional changes in receptors. The level of phosphorylated NMDAR NR1 subunit (pNR1) and phosphorylated MOR (pMOR) in the periaqueductal gray matter was determined with the Western blot method. The activity of PKA and PKC was examined by standard enzyme immunoassays. Mg2+ administered alone significantly decreased the level of pNR1 and pMOR, and activity of both tested kinases. The results suggest that blocking NMDAR signaling by Mg2+ restores the MOR-NMDAR complex and thus enables morphine analgesia in neuropathic rats.
  • 529
  • 03 Mar 2022
Topic Review
Plant-Based Antidiabetic Agents
Diabetes mellitus is a prevalent metabolic syndrome that is associated with high blood glucose levels. The number of diabetic patients is increasing every year and the total number of cases is expected to reach more than 600 million worldwide by 2045. Modern antidiabetic drugs alleviate hyperglycaemia and complications that are caused by high blood glucose levels. Due to the side effects of these drugs, plant extracts and bioactive compounds with antidiabetic properties have been gaining attention as alternative treatments for diabetes. Natural products are biocompatible, cheaper and expected to cause fewer side effects than the current antidiabetic drugs. Various nanocarrier systems are discussed, such as liposomes, niosomes, polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles and metallic nanoparticles. These systems have been applied to overcome the limitations of the current drugs and simultaneously improve the efficacy of plant-based antidiabetic drugs. The main challenges in the formulation of plant-based nanocarriers are the loading capacity of the plant extracts and the stability of the carriers. Lipid nanocarriers and the amphipathic properties of phospholipids and liposomes that encapsulate hydrophilic, hydrophobic and amphiphilic drugs is also described. A special emphasis is placed on metallic nanoparticles, with their advantages and associated complications being reported to highlight their effectiveness for treating hyperglycaemia.
  • 529
  • 02 Aug 2022
Topic Review
Factors Affecting Vitamin C Pharmacokinetics
The pharmacokinetics of vitamin C (vitC) is highly complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), both the absorption and elimination phases display high dose-dependency. Also, tissue specific expression of SVCT subtypes result in a diverse distribution pattern with organ concentrations of vitC at homeostasis ranging from about 0.2 mM up to 10 mM. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of human intervention studies, giving rise to misinterpretations and erroneous conclusions.
  • 529
  • 23 Sep 2022
Topic Review
Critically Ill Patients Antimicrobial Dosing
In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. 
  • 528
  • 13 Jul 2021
Topic Review
Fenretinide in Cancer and Neurological Disease
Cancer and neurodegeneration share leadership as causes of morbidity and death worldwide. They can be thought as disease mechanisms at opposite ends: while in neurodegeneration, induction of inflammatory genes and suppression of cell-cycle genes are the prominent signals; the opposite happens in cancer. Fenretinide (all-trans-N-(4-hydroxyphenyl) retinamide, 4-HPR) is a synthetic derivative of all-trans-retinoic acid initially proposed in anticancer therapy for its antitumor effects combined with limited toxicity. It is also studied in many other diseases for its ability to influence several biological pathways and provide a broad spectrum of pharmacological effects.
  • 527
  • 18 Jul 2022
Topic Review
Traditional Cancer Healing with Herbs and Mushrooms
Traditional herbal medicine (THM) is a “core” from which modern medicine has evolved over time. Besides this, one third of people worldwide have no access to modern medicine and rely only on traditional medicine. To date, drugs of plant origin, or their derivates (paclitaxel, vinblastine, vincristine, vinorelbine, etoposide, camptothecin, topotecan, irinotecan, and omacetaxine), are very important in the therapy of malignancies and they are included in most chemotherapeutic regimes. 
  • 527
  • 28 Jul 2022
Topic Review
Oxycodone Efficacy in Pain Management
Oxycodone is a widely used opioid for the management of chronic pain. Analgesic effects observed following the administration of oxycodone are mediated mostly by agonistic effects on the μ-opioid receptor. Wide inter-subject variability observed in oxycodone efficacy could be explained by polymorphisms in the gene coding for the μ-opioid receptor (OPRM1).
  • 525
  • 18 Oct 2021
Topic Review
Intranasal Insulin in Ischemia, Brain Injuries and Diabetes
A decrease in the activity of the insulin signaling system of the brain leads to neurodegeneration and impaired regulation of appetite, metabolism, and endocrine functions. This is due to the neuroprotective properties of brain insulin, its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine and other systems. One of the approaches to restore the brain insulin system is the use of intranasally administered insulin (INI). INI is being considered as a promising drug to treat Alzheimer's disease and mild cognitive impairment. Clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. It has been shown that INI can be used for the treatment of cerebral ischemia, traumatic brain injuries, postoperative delirium, as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes.
  • 525
  • 20 Apr 2023
Topic Review
Non-Steroidal Anti-Inflammatory Drugs
The non-steroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in knee OA (osteoarthritis) treatment. Despite their efficiency in pain and inflammation alleviation, NSAIDs accumulate in the environment as chemical pollutants and have numerous genetic, morphologic, and functional negative effects on plants and animals. Ultrasound (US) therapy can improve pain, inflammation, and function in knee OA, without impact on environment, and with supplementary metabolic beneficial effects on cartilage compared to NSAIDs. These features recommend US therapy as alternative for NSAIDs use in knee OA treatment. 
  • 524
  • 01 Jun 2021
Topic Review
Histone Deacetylases
Histone acetylation status is considered a potential diagnostic biomarker for depression, while inhibitors of histone deacetylases (HDACs) have garnered interest as novel therapeutics.
  • 524
  • 08 Jun 2021
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