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1.
Curr Pharm Des ; 27(27): 3074-3081, 2021.
Article in English | MEDLINE | ID: mdl-33292115

ABSTRACT

BACKGROUND: In patients admitted to the Intensive Care Unit (ICU), mortality is high due to multiple organ damage. Mitochondrial dysfunction and impaired oxygen consumption, as causative mechanisms, play a significant role in reducing the activity of immune cells in sepsis, resulting in the progression of the multiple organ dysfunction syndromes (MODS). The evaluation of mitochondrial function in critical care patients in the immune cells, especially in lymphocytes, could reveal the target point that determines mitochondrial failure. OBJECTIVE: To find the relationship between mitochondrial reactive oxygen species production (mROS), mitochondrial membrane potential (ΔΨm), and mitochondrial oxygen consumption (mVO2) in peripheral plasma lymphocytes collected from ICU patients. We also compared these three characteristic mitochondrial functions with C-reactive protein (CRP), serum lactate, and central venous saturation (SvO2) that would enable the prediction of the ultimate outcome. METHODS: Isolated lymphocytes from 54 critical care patients with SIRS by sepsis and non-sepsis etiologies were analyzed with flow cytometry by staining with dihydroethidium and JC-1, measuring mROS, ΔΨm, and mVO2. Clinical variables, such as serum lactate (mmol/L) and C-reactive protein (mg/L) from peripheral blood, were measured in the first 24 hours of admission. A confounding analysis was performed using logistic regression, and a p-value of <0.05 was considered statistically significant. RESULTS: It has been confirmed that there is a drastic increase in reactive oxygen species (ROS) and mVO2 in critically ill patients immediately after exposure to the insult pathogen-associated molecular pattern /damageassociated molecular pattern (PAMPS/DAMPS) and continued for the first 24 hours thereafter. The results showed no significant alterations in the mitochondrial membrane potential (ΔΨm) compared with the lymphocytes in controls. A significant correlation between CRP and SvO2 and a strong positive relationship between CRP, values above 3 mg/l, and white blood cells were observed. CONCLUSION: Lymphocytes from patients with SIRS displayed higher mitochondrial respiratory capacities and reactive oxygen species production compared with controls. Clinical markers of inflammation indirectly evaluate the mitochondrial function, most of which have been validated in a clinical setting.


Subject(s)
Sepsis , Critical Care , Critical Illness , Humans , Intensive Care Units , Mitochondria , Prognosis
2.
Cent Nerv Syst Agents Med Chem ; 20(3): 218-225, 2020.
Article in English | MEDLINE | ID: mdl-33167844

ABSTRACT

BACKGROUND: AMD is becoming one of the leading causes of blindness in older adults. The prevalence rate of the wet form of AMD has been increasing due to the lack of selective therapeutic modalities. Current therapeutic interventions such as drugs targeting VEGF, and VEGF receptors, laser coagulants delivered unsuccessful clinical outcomes in AMD patients. Hence, the cost-effective anti-oxidant therapeutic interventions like molecular hydrogen to protect retinal pigment epithelium (RPE) by mitigating oxidative stress may deliver effective clinical outcomes in AMD patients. METHODS: Female patients with late-stage AMD of age above 70 years were chosen for this case report. The patients were administered QIAPI1©, a melanin precursor via sublingual route and the photographs were obtained for left and right eye to depict the efficacy of QIAPI1© against the wet form of AMD. RESULTS: The administration of QIAPI1© extensively mitigated yellow-colored drusen accumulations in the retina, retinal edema, exudates, and hemorrhages in the right eye, but the effect was minimal in the case of left eye; the overall drusen accumulation was lesser than the first consultation. CONCLUSION: Current case report has concluded the intrinsic effect of melanin in producing the molecular hydrogen and chemical energy across the retinal tissues by dissociating water molecules and dissipating the drusen accumulations, retinal edema, and hemorrhages in AMD patients. Our preliminary study reported the usage of QIAPI1© as a prospective therapeutic modality to mitigate the oxidative stress-mediated pathophysiology of the wet form of AMD.


Subject(s)
Macular Degeneration , Melanins , Aged , Female , Humans , Macular Degeneration/drug therapy , Retina , Retinal Pigment Epithelium
3.
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
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