Chemical Composition and Antibacterial Activities of Eight Plant Essential Oils from Morocco against Escherichia coli Strains Isolated from Different Turkey OrgansRead the full article
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A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections
Background. At the present time, COVID-19 vaccines are at the testing stage, and an effective treatment for COVID-19 incorporating appropriate safety measures remains the most significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently required. Aim. This study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. This study was conducted at four different clinical study sites in Indonesia. The subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RT-PCR test. The present study constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed with mild to moderate COVID-19 infection. Materials and Methods. Six treatment groups participated in this study: a Control group administered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. Results. 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%–99.2% of the subjects in Groups A–E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups ( and ) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups (). The administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 () compared with day 1. Decreases in ALT and AST levels were observed in all groups (). There was an increase in creatinine in the serum level of the Control, C, D, and E groups (), whereas the BUN level was elevated in all groups (). Conclusions. The study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.
Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
Purpose. The role of oxidative stress in Aluminum (Al)-induced apoptotic effects has been investigated and suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and phosphatidylserine externalization (PSE) at the surface of the erythrocyte cell membrane. Eryptosis is stimulated by an increase in cytosolic Ca2+ concentration and reactive oxygen species (ROS). This ex vivo study was conducted to evaluate the effect of well-known antioxidants including vitamin C (vit C) and N-acetylcysteine (NAC), against Al-induced hemolysis and eryptosis. Methods. Isolated erythrocytes from the healthy volunteers were partitioned into various groups (6 replicates/group) and treated by various concentrations of Al (3–100 µM) in the presence and absence of vit C (0.6 mM) and NAC (1 mM). After 24 hours of treatment, hemolysis was determined from hemoglobin levels in the supernatant. Flowcytometric methods were applied to measure PSE, cell shrinkage, Ca2+ content, and ROS abundance using annexin V-binding, forward scatter, Fluo3-fluorescence, and DCFDA dependent fluorescence, respectively. Reduced glutathione (GSH) was measured by the ELISA method. Results. The results showed that a 24 hours’ exposure of the erythrocytes to Al (10–100 µM) significantly increased hemolysis in a dose and Ca2+dependent manner. Al also dramatically decreased forward scatter. The percentage of PSE cells, Fluo3-fluorescence, and DCFDA fluorescence were increased by Al. Furthermore, cotreatment with NAC inhibited the effect of Al on hemolysis, eryptosis, and ROS production. Vit C decreased Al-induced ROS production. However, increased Al-induced eryptosis. There were no significant changes in glutathione after the ALCL3 treatment. Conclusions. Al-induced eryptosis and hemolysis through triggering oxidative stress, while NAC could diverse this effect. In contrast, vit C might intensify Al-induced eryptosis at particular doses through a less known mechanism.
The Role of Glutamine in the Prevention of Ultraviolet-C-Induced Platelet Activation
Background and Objectives. The primary function of platelets is to prevent bleeding. The use of UV-C light in the treatment of platelets has become a valuable method for preserving the efficacy of platelet concentrates in blood banks. However, its deleterious effect remains, such as the activation of platelets, thus causing the platelets to lose their physiological function. In this study, we intended to demonstrate the impact of UV-C on platelets and how the use of glutamine could mitigate the loss of physiological function of the platelets caused by UV-C. Materials and Methods. This study was conducted using mouse platelets. We assessed calcium signaling using Fura-2 AM incubation and dense granule secretion of the platelets using luminescence assay by measuring ATP. At the molecular level, the activation of integrin using PAC-1 antibody was analyzed. Phosphorylation of immune-precipitated cPLA2 was assessed using a specific antibody. All the experiments were carried out with or without glutamine in the presence of UV-C. Positive and negative controls were used in all experiments to validate the findings. Results. We have demonstrated that physiological and biochemical damage arises as a result of the exposure of platelet concentrate to UV-C and that the use of glutamine could alleviate this damage. Various experiments, thrombus formation, integrin activation, and phosphorylation of cPLA2 were preserved using 50 mM of glutamine in the presence of UV-C, which reduces 50% of platelet viability. Conclusions. Our study demonstrates that the storage of platelet concentrates under the UV-C activates their physiological process and renders them to the thrombus formation, hence decreasing their viability. The presence of a moderate amount of glutamine can alleviate the toxic effect of UV-C, and platelet concentrates could be kept viable for a long time.
Interaction of Agaric Acid with the Adenine Nucleotide Translocase Induces Mitochondrial Oxidative Stress
Mitochondrial permeability transition is characterized by the opening of a transmembranal pore that switches membrane permeability from specific to nonspecific. This structure allows the free traffic of ions, metabolites, and water across the mitochondrial inner membrane. The opening of the permeability transition pore is triggered by oxidative stress along with calcium overload. In this work, we explored if oxidative stress is a consequence, rather than an effector of the pore opening, by evaluating the interaction of agaric acid with the adenine nucleotide translocase, a structural component of the permeability transition pore. We found that agaric acid induces transition pore opening, increases the generation of oxygen-derived reactive species, augments the oxidation of unsaturated fatty acids in the membrane, and promotes the detachment of cytochrome c from the inner membrane. The effect of agaric acid was inhibited by the antioxidant tamoxifen in association with decreased binding of the thiol reagent eosin-3 maleimide to the adenine nucleotide translocase. We conclude that agaric acid promotes the opening of the pore, increasing ROS production that exerts oxidative modification of critical thiols in the adenine nucleotide translocase.
Characterization of the Volatile Components of Essential Oils of Selected Plants in Kenya
Essential oils are secondary metabolites that plants produce for protection from pests and predators, attraction of pollinators, and seed dispersal. The oils are made up of a mixture of compounds that give a characteristic flavour and odour. Currently, essential oils are receiving great attention in research for their phytochemical and antimicrobial activities. However, there is scanty information on the chemical composition of many plants. This study provides a detailed analysis of the chemical composition of essential oils of ginger, garlic, tick berry, and Mexican marigold in Kenya. The essential oils were extracted by steam distillation and analysed by gas chromatography–mass spectrometry. The study identified a total of 52 different chemical classes from the essential oils of the four different plants that were analysed. Their percentage composition was also found to vary between the test plants. The essential oils of Mexican marigold constituted the highest composition of the identified chemical classes at 71.2%, followed by ginger at 55.8%, while both tick berry and garlic oils constituted 53.8% of the total classes identified. Terpenes constituted the highest composition in the essential oils of all the four test plants. Other major chemical classes included esters, ketones, organosulfurs, alkanes, cycloalkanes, steroids, aromatic hydrocarbons, and alkanols. Some of these chemical compounds have been shown to have a huge utility potential in biopesticides, pharmaceutical, and food industries, and hence, their industrial extraction and purification from the essential oils of these plants are recommended.
Biochemical Constituents of Phaleria macrocarpa (Leaf) Methanolic Extract Inhibit ROS Production in SH-SY5Y Cells Model
Background. Reactive oxygen species generation in mammalian cells profoundly affects several critical cellular functions, and the lack of efficient cellular detoxification mechanisms which remove these radicals may lead to several human diseases. Several studies show that ROS is incriminated as destructive agents in the context of the nervous system especially with advance in age leading to neurodegeneration. Current treatments of this disease are not effective and result in several side effects. Thus, the search for alternative medicines is in high demand. Therefore, the aim of this study is to evaluate the reactive oxygen inhibitory effect of Phaleria macrocarpa 80% (leaf) extract. Methods. The leaf was extracted with 80% methanol. Cytotoxicity studies were carried out using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and ROS inhibitory activities were evaluated using dichlorofluorescein diacetate (DCF-DA) assay in the SH-SY5Y cells model. Results. The result revealed ROS inhibitory activities of the crude extract with highly significant differences at between the group that were treated with crude extract only, the group treated with crude extract and exposed to H2O2, and the group exposed to H2O2 only as well as the group that were maintained in complete media. Bioactive compounds show the presence of vitexin and isovitexin following the HPLC method. Conclusion. High antioxidant activities and low toxicity effect of this crude revealed its high benefit to be used as natural medicine/supplements.