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1.
Cent Nerv Syst Agents Med Chem ; 19(3): 215-222, 2019.
Article in English | MEDLINE | ID: mdl-31267880

ABSTRACT

BACKGROUND: Retinopathy of Prematurity (ROP) is a potentially blinding disorder that commonly afflicts premature infants who are born prior to 31weeks of gestation or with a body weight less than 1250 grams (about 2.75 pounds). Another risk factor is excessive oxygen in incubators, which can lead to blindness. A compounding factor is that survival rates for premature infants are rising with concomitantly more cases of ROP. We have reported an unsuspected intrinsic property of melanin to dissociate water. This capability can be considered an alternative treatment option for adult and neonatal diseases. It is known that exogenous surfactant administration suppresses bronchopulmonary dysplasia and consequent death, randomized, controlled trials with various respiratory interventions did not show any significant reductions in morbidity and mortality rates. During a descriptive study about the three leading causes of blindness in the world, the ability of melanin to transform light energy into chemical energy through the dissociation of water molecule was unraveled. Initially, during 2 or 3 years; we tried to link together our findings with the widely accepted metabolic pathways already described in molecular pathway databases, which have been developed to collect and organize the current knowledge on metabolism scattered across a multitude of scientific evidence. OBSERVATIONS: The current report demonstrates the main problems that afflict premature babies with an emphasis on the growth of abnormal vessels in the retina, the explanation for which is unknown until date. We also reported a case of a baby who suffered digestive and respiratory problems with a brain haemorrhage that was successfully treated by laser photocoagulation. We hypothesise that most likely this effect was due to the melanin level and melanin itself produces oxygen via dissociating with water molecules. CONCLUSION: We postulate that the intrinsic effect of melanin may easily convert visible and invisible light into chemical energy via a water dissociation reaction similar to the one in plant's chlorophyll, and markedly elevated with diagnosis and treatment of the complications related to premature babies.


Subject(s)
Infant, Extremely Premature/metabolism , Melanins/metabolism , Oxygen/metabolism , Retinopathy of Prematurity/drug therapy , Retinopathy of Prematurity/metabolism , Water/metabolism , Child, Preschool , Humans , Infant, Newborn , Male , Melanins/therapeutic use , Oxygen/chemistry , Treatment Outcome , Water/chemistry
2.
CNS Neurol Disord Drug Targets ; 17(10): 743-756, 2018.
Article in English | MEDLINE | ID: mdl-30179148

ABSTRACT

BACKGROUND & OBJECTIVE: Regulation of composition, volume and turnover of fluids surrounding the brain and damp cells is vital. These fluids transport all substances required for cells and remove the unwanted materials. This regulation tends to act as barrier to prevent free exchange of materials between the brain and blood. There are specific mechanisms concerned with fluid secretion of the controlled composition of the brain, and others responsible for reabsorption eventually to blood and the extracellular fluid whatever their composition is. The current view assumes that choroidal plexuses secrete the major part of Cerebrospinal Fluid (CSF), while the Blood-Brain Barrier (BBB) has a much less contribution to fluid production, generating Interstitial Fluid (ISF) that drains to CSF. The skull is a rigid box; thereby the sum of volumes occupied by the parenchyma with its ISF, related connective tissue, the vasculature, the meninges and the CSF must be relatively constant according to the Monroe-Kellie dogma. This constitutes a formidable challenge that normal organisms surpass daily. The ISF and CSF provide water and solutes influx and efflux from cells to these targeted fluids in a quite precise way. Microvessels within the parenchyma are sufficiently close to every cell where diffusion areas for solutes are tiny. Despite this, CSF and ISF exhibit very similar compositions, but differ significantly from blood plasma. Many hydrophilic substances are effectively prevented from the entry into the brain via blood, while others like neurotransmitters are extremely hindered from getting out of the brain. Anatomical principle of the barrier and routes of fluid transfer cannot explain the extraordinary accuracy of fluids and substances needed to enter or leave the brain firmly. There is one aspect that has not been deeply analyzed, despite being prevalent in all the above processes, it is considered a part of the CSF and ISF dynamics. This aspect is the energy necessary to propel them properly in time, form, space, quantity and temporality. CONCLUSION: The recent hypothesis based on glucose and ATP as sources of energy presents numerous contradictions and controversies. The discovery of the unsuspected intrinsic ability of melanin to dissociate and reform water molecules, similar to the role of chlorophyll in plants, was confirmed in the study of ISF and CSF biology.


Subject(s)
Biological Transport/physiology , Blood-Brain Barrier/physiology , Brain/physiology , Cerebrospinal Fluid/metabolism , Melanins/metabolism , Water-Electrolyte Balance/physiology , Animals , Brain Edema/cerebrospinal fluid , Brain Edema/metabolism , Choroid Plexus/metabolism , Choroid Plexus/ultrastructure , Homeostasis , Humans , Melanins/chemistry
3.
Mol Neurobiol ; 55(8): 6712, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29700774

ABSTRACT

The original version of this article unfortunately contained mistake in its Funding inforation. That is, the Grant Number has an error currently read as "This work was supported by the Fondo de Ciencia y Tecnología (FONDECYT) de Chile, Grant #1150149".

4.
Mol Neurobiol ; 55(8): 6700-6711, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29335846

ABSTRACT

Post-traumatic stress disorder (PTSD) is a mental disorder that may develop after exposure to exceptionally threatening or unescapable horrifying events. Actual therapies fail to alleviate the emotional suffering and cognitive impairment associated with this disorder, mostly because they are ineffective in treating the failure to extinguish trauma memories in a great percentage of those affected. In this review, current behavioral, cellular, and molecular evidence supporting the use of cotinine for treating PTSD are reviewed. The role of the positive modulation by cotinine of the nicotinic acetylcholine receptors (nAChRs) and their downstream effectors, the protection of astroglia, and the inhibition of microglia in the PTSD brain are also discussed.


Subject(s)
Cotinine/pharmacology , Extinction, Psychological/drug effects , Memory/drug effects , Stress Disorders, Post-Traumatic/psychology , Stress Disorders, Post-Traumatic/therapy , Animals , Humans , Neuronal Plasticity/drug effects , Receptors, Nicotinic/metabolism
5.
Mol Neurobiol ; 55(3): 2285-2300, 2018 03.
Article in English | MEDLINE | ID: mdl-28332151

ABSTRACT

Previous studies have indicated that paracrine factors (conditioned medium) increase wound closure and reduce reactive oxygen species in a traumatic brain injury in vitro model. Although the beneficial effects of conditioned medium from human adipose tissue-derived mesenchymal stem cells (hMSCA-CM) have been previously suggested for various neurological diseases, their actions on astrocytic cells are not well understood. In this study, we have explored the effect of hMSCA-CM on human astrocyte model (T98G cells) subjected to scratch assay. Our results indicated that hMSCA-CM improved cell viability, reduced nuclear fragmentation, attenuated the production of reactive oxygen species, and preserved mitochondrial membrane potential and ultrastructural parameters. In addition, hMSCA-CM upregulated neuroglobin in T98G cells and the genetic silencing of this protein prevented the protective action of hMSCA-CM on damaged cells, suggesting that neuroglobin is mediating, at least in part, the protective effect of hMSCA-CM. Overall, this evidence suggests that the use of hMSCA-CM is a promising therapeutic strategy for the protection of astrocytic cells in central nervous system (CNS) pathologies.


Subject(s)
Astrocytes/physiology , Culture Media, Conditioned/pharmacology , Mesenchymal Stem Cells/physiology , Neuroglobin/antagonists & inhibitors , Neuroglobin/physiology , Adult , Astrocytes/drug effects , Cell Line , Cells, Cultured , Humans , Neuroprotective Agents/administration & dosage , Oxidative Stress/drug effects , Oxidative Stress/physiology , Physical Stimulation/adverse effects , Young Adult
6.
Curr Alzheimer Res ; 14(11): 1155-1163, 2017.
Article in English | MEDLINE | ID: mdl-28356047

ABSTRACT

BACKGROUND: The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions. CONCLUSION: In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.


Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Cotinine/therapeutic use , Neuroprotective Agents/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Animals , Cotinine/pharmacology , Humans , Neuroprotective Agents/pharmacology
7.
Curr Top Med Chem ; 17(12): 1438-1447, 2017.
Article in English | MEDLINE | ID: mdl-28049399

ABSTRACT

Gliomas are central nervous system tumors originated from glial cells, whose incidence and mortality is expected to rise in coming years, especially in developing countries. Diagnosis and classification of gliomas have largely relied on tumor histopathologic features that provide limited information regarding response to therapy or prognosis. Current treatment of gliomas is surgery combined with chemotherapy and/or radiotherapy. However, many tumors show a high resistance to these interventions, and recurrences are frequent since conventional therapies do not take into account the unique molecular features of different subtypes of glioma. Molecular genetics provide new insights in classifying gliomas and predicting response to therapy that can range from conventional treatments to new revolutionary therapeutic approaches. This article offers a review of the intracellular signaling pathways involved in carcinogenesis of gliomas, as well as a description of new tools for their diagnosis, prognosis, and treatment with a target-oriented approach.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms , Glioma , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/therapy , Glioma/diagnosis , Glioma/genetics , Glioma/therapy , Humans , Signal Transduction/drug effects , Signal Transduction/genetics
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