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Topic Review
Voltage Gated Ion Channels
Safety Pharmacology is one of the most dynamically developing disciplines, whose objective is to assess the potential risks of improperly conducted pharmacotherapy. Evaluation of a potential risks in the use of a given substance is vital for placing a new medicine on the market. The Organisation for Economic Co-operation and Development (OECD) has issued a number of guidelines for drug safety testing [1, 2]. However, the continuous development of medicine demands the extension and refinement of the test panel that a new molecule must undergo before it can be released for use by patients. Toxic effects of compounds on the most important organs are among the most frequent reasons of elimination of substances from further tests. Additionally, safety tests are also performed for medicines already approved for use. Such trials are required, e.g., to register new indications for "old" drugs.  The above mentioned activities require a suitable identifications of the antitargets which are commonly defined as undesirable molecular targets that play an essential role in the proper functioning of cells. Down modulation of an antitarget results in clinically unacceptable side effects, initiation of disease, or deleterious alterations in disease progression. This results in shorter onset time of the disease, increased disease burden, poorer patient outcome, or decreased survival time.
  • 711
  • 27 Jan 2021
Topic Review
Neurotoxicity in Acute Lymphoblastic Leukemia Treatment
Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. 
  • 711
  • 17 May 2022
Topic Review
Oxidative Stress in Pregnancy
Human pregnancy can be affected by numerous pathologies, from those which are mild and reversible to others which are life-threatening.  Oxidative stress is caused by an imbalance between production and accumulation of reactive oxygen species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. In pregnancy, ROS are generated mainly in the placenta, but xanthine oxidase (XO) are present in the vascular endothelium, and nitric oxide synthase (NOS) are also sources of ROS.
  • 710
  • 25 May 2022
Topic Review
Myasthenia Gravis
Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness and fatigue. The cause is a postsynaptic defect of neuromuscular transmission, which brings, in the majority of patients, to develop autoantibodies directed against the postsynaptic nicotinic acetylcholine receptor (AChR).
  • 710
  • 17 Oct 2020
Topic Review
Tetrodotoxin for Neuropathic&Cancer Pain Relief
Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain.
  • 710
  • 21 Jul 2021
Topic Review
Neuroprotective Role of Lactoferrin during Early Brain Development
Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many “constitutive” elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophins production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). Lactoferrin has also been considered a potential biomarker of neurodegeneration and its mechanisms of action make it a good candidate to be tested in the prevention of neurodegenerative diseases.
  • 710
  • 08 Aug 2022
Topic Review
Cyclosporine CsA
The bioavailability of CsA was matched and enhanced with nanoparticles in the context of the physicochemical properties and the character of its interactions with lipid membranes. This study can suggest the suitability of liposome/microemulsion as promising vehicles for CsA oral or injection delivery. As the most hopeful proved to be formulation with the smaller particle size because can facilitating absorption, but none of the formulations is flawless. However, when safety of the product is assessed, relying on just the particle size cannot be the only criteria.
  • 710
  • 18 Nov 2020
Topic Review
MiR-615
miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It, therefore, serves as a biomarker for several types of cancer and recently has also been found to be involved in reparative processes and neural repair.
  • 710
  • 27 Oct 2020
Topic Review
Cancer Treatment-Induced Accelerated Aging
There is a growing concern about accelerated aging among the rapidly increasing number of cancer survivors. Clinically, “accelerated aging” phenotypes in cancer survivors include premature mortality and comorbidities – secondary cancers, frailty, chronic organ dysfunction, and cognitive impairment which can impact long-term health and quality of life in cancer survivors.
  • 709
  • 28 Sep 2021
Topic Review
Melatonin in Disease and Health
Melatonin is a derivative of tryptophan, synthesized mainly in the pineal gland. Its synthesis is characterized by a regular circadian rhythm, with a peak concentration in plasma reached in the night hours. The intensity of melatonin production is related to exposure to light, with an increase of its synthesis in the dark part of the day.
  • 709
  • 25 Aug 2021
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