scholarly journals Effect of Tilorone on the Dynamics of Viral Load and the Levels of Interferons and Interleukin-1β in the Lung Tissue and Blood Serum of Mice with Experimental Influenza

Author(s):  
O. V. Kalyuzhin ◽  
E. I. Isaeva ◽  
E. N. Vetrova ◽  
A. I. Chernysheva ◽  
L. O. Ponezheva ◽  
...  
2021 ◽  
Author(s):  
Neeltje van Doremalen ◽  
Jyothi N. Purushotham ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Trenton Bushmaker ◽  
...  

AbstractIntramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 protected rhesus macaques against pneumonia but did not reduce shedding of SARS-CoV-2. Here we investigate whether intranasally administered ChAdOx1 nCoV-19 reduces shedding, using a SARS-CoV-2 virus with the D614G mutation in the spike protein. Viral load in swabs obtained from intranasally vaccinated hamsters was significantly decreased compared to controls and no viral RNA or infectious virus was found in lung tissue, both in a direct challenge and a transmission model. Intranasal vaccination of rhesus macaques resulted in reduced shedding and a reduction in viral load in bronchoalveolar lavage and lower respiratory tract tissue. In conclusion, intranasal vaccination reduced shedding in two different SARS-CoV-2 animal models, justifying further investigation as a potential vaccination route for COVID-19 vaccines.


Author(s):  
K. N. Filin ◽  
V. N. Bykov ◽  
V. D. Gladkikh ◽  
I. A. Lugovik ◽  
A. N. Grebenyuk

The aim of the study was to clarify the toxicity of mefloquine and to evaluate the effectiveness of its use for Syrian hamsters infected with sARS-Cov-2.Material and methods. The experiments were performed on 96 Syrian hamsters. The toxicity of mefloquine was determined with a single administration, as well as with a course of administration at doses comparable to therapeutic for humans. To study the effectiveness of the drug against SARS-CoV-2 infection, a comprehensive indicator of the state of lung tissue and a comparison of the dynamics of viral load in the lungs were used.Results. The LD50 of mefloquine with a single oral administration is 817 mg/kg, the maximum tolerated dose is 600 mg/kg. When administered for 7 days at a cumulative dose of 900 mg/kg, no death was observed. Administration of mefloquine to animals infected with SARS-CoV-2 was accompanied by a decrease in the severity of lung damage and a faster decrease of viral load in the lung tissue.


2021 ◽  
Vol 6 (3) ◽  
pp. 192-198
Author(s):  
I. I. Topchii ◽  
◽  
K. O. Savicheva ◽  
P. S. Semenovykh ◽  
V. Yu. Galchinska

Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of chronic kidney disease worldwide. The majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The progression of fibrotic processes in the diabetic kidneys occurs with the participation of universal mediators of inflammation. Given the clinical and social significance of diabetic kidney damage, the determination of interleukin-1β and interleukin-6 in blood serum may expand the understanding of this problem, as well as help in the development of individualized therapeutic approaches. The purpose of the study is to investigate interleukin-1β and interleukin-6 levels in the serum of patients with type 2 diabetes mellitus, depending on kidney functional state in the dynamics of therapy and with additional prescription of dapagliflozin. Materials and methods. 72 patients with type 2 diabetes were examined. The control group consisted of 20 healthy individuals. The patients were divided into the following groups: group I – type 2 diabetic patients with normal glomerular filtration rate and without albuminuria (n = 25); group II – patients with type 2 diabetes with normal glomerular filtration rate and albuminuria (n = 23); group III – patients with type 2 diabetes with decreased glomerular filtration rate and albuminuria (n = 24). The complex pathogenetic therapy of patients of group 1 included renin-angiotensin-aldosterone system blockers, metformin and hypolipidemic agents. Patients of group 2 were additionally prescribed dapagliflozin. The control was carried out after 6 months. Results and discussion. According to the results of the study, the development of diabetic nephropathy in patients with type 2 diabetes is accompanied by a significant increase in the level of interleukin-1β and interleukin-6 in the blood plasma compared with the control and in patients with diabetes without signs of nephropathy. Nephroprotective therapy contributed to a significant decrease of interleukin-1β and interleukin-6 levels in the blood serum in all groups of patients. The highest response to treatment was observed in patients with diabetic nephropathy and albuminuria. Most significant decrease of albuminuria, normalization of blood pressure and lipid spectrum improvement were observed in patients with the initial stages of the disease. Additional using of dapagliflozin leads to a more significant decrease in the content of proinflammatory cytokines in the blood serum of patients with type 2 diabetes mellitus with diabetic nephropathy. Conclusion. The results of the study indicate the advisability of using interleukin-1β and interleukin-6 as a diagnostic marker of cardiac disorders, assessment of prognosis, and improvement of the cardionephroprotective strategy in diabetic patients. The therapeutic potential of dapagliflozin in the treatment of diabetic nephropathy and the prevention of cardiovascular events in patients with diabetes is of great scientific interest and requires further research


Author(s):  
Oleg F. Melnikov ◽  
Natalia O. Peleshenko ◽  
Мarina D. Timchenko ◽  
Oksana G. Rylska ◽  
Alexander Yu. Bredun ◽  
...  

Topicality: In recent years, ideas about the mechanisms of action of a local lysozyme containing antiseptic have been significantly expanded. Data on the availability of antiviral drugs and a positive effect on regeneration processes have been obtained. Objective: In order to further study the properties of the drug, its effect on the mechanisms of inflammation in a clinical setting and model of inflammation in an animal experiment was investigated. Material and methods: Clinical and immunological studies were conducted in 22 children aged 9-12 years, of which 10 people represented a group of healthy donors. 12 people with exacerbation of chronic catarrhal pharyngitis received the drug Lizak in the form of monotherapy according to the instructions. The oropharyngeal secretion was studied, where the pro-inflammatory cytokine interleukin-1β (Cytokine, RF), lactoferrin (Vector Best, RF), as well as the macrophage inflammatory protein MIP-1b (Hucaltbiotecknolgy, Netherlands) were determined by the ELISA method. As an analyzer, a Lab line reader (Austria) was used. The studies were carried out at two points: before the start of therapy and a day after its completion. Under the experimental conditions, a model of caraginan edema of rat paws was used, which, prior to the introduction of phlogogen, received per os drug lizak. The degree of edema was determined using a special installation with an installed micrometer for measuring the thickness of the feet in the time interval from 0 to 24 hours. In addition, the levels of proinflammatory cytokine interleukin-1β and anti-inflammatory interleukin-10 were determined in the blood serum of animals at the same time intervals. Statistics were carried out using the ‘t’ –Student criterion. Results: Under monotherapy with the drug Lysak in children with acute pharyngitis, a decrease in the content of proinflammatory factors, interleukin-1β and Mip-1b, in the oropharyngeal secretion is shown. When studying the effect of the drug on the development of aseptic inflammation (stage of exudation) in the foot of rats, it was found that the drug Lizak had an inhibitory effect on the development of edema in the range of 1-4 hours, after which its effect was not detected (24 hours). In the control group and the “pure” control group, inflammatory edema was detected compared to the initial level (p=0.02) at 4 hours and was not detected after 24 hours. The drug Lysac has the ability to inhibit the development of aseptic local inflammation in the initial stages of its development. Confirmation of the systemic nature of the action of the drug is to reduce the level of pro-inflammatory cytokine-interleukin-1 in the blood serum of animals by 4 hours from the onset of the inflammatory process. Conclusions: The drug Lizak actively reduces the levels of pro-inflammatory cytokines both systemically and with local use and has a pronounced decongestant effect.


2020 ◽  
pp. 409-418
Author(s):  
E.P. KISHKURNO ◽  
◽  
T.V. AMVROSIEVA ◽  
YU.E. MAREYKO ◽  
E.V. DIVAKOVA ◽  
...  

Objective: To evaluate the frequency of reactivation of HHV-6 infection in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT); determine viral load in serum/plasma and associated clinical manifestations; to determine the criteria for initiating anti-viral prophylaxis and etiotropic therapy in patients with this infection in the Republic of Belarus. Methods: Monitoring of polymerase chain reaction (PCR) of blood serum in 42 patients after allo-HSCT. Results: In 31% of patients, HHV-6 DNA was detected in serum/plasma on 14-28 days after allo-HSCT. The concentration of HHV-6 DNA in blood serum was up to 2.3-6.5×103 copies/ml, in 3 patients (18.8%) with the concentration of DNA≥2.3×103 copies/ml, developed clinical manifestations in the form of hepatitis. Regular monitoring of HHV-6 infection revealed reactivation of the infection and, with a viral load of≥100 copies/ml, initiate timely preventive treatment with ganciclovir. Conclusions: HHV-6 DNA is detected in one-third of patients after allo-HSCT and in the form of hepatitis. Timely prevention and therapy with ganciclovir reduce the risk of severe complications and fatal outcomes. Keywords: Children, HHV-6, hematology, stem cells transplantation, hepatitis.


2017 ◽  
Vol 53 (2) ◽  
pp. 124
Author(s):  
Laksmi Wulandari ◽  
Muhammad Amin ◽  
Soedarto Soedarto ◽  
Gatot Soegiarto

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis that are often associated with uneffectiveness of the BCG vaccine and the high worm infection. The objective of this study was to determine the differences in the activity of Limfosit T type Th1 (IFN-g) and Th2 (IL-4) in lung tissue on Heligmosomoides polygyrus nematode and Mycobacterium tuberculosis sequential co-infection. This research using 49 mice were divide into 7 groups treated with infection by Mycobacterium tuberculose inhaled and Heligmosomoides polygyrus orally within 8 and 16 weeks. The levels of IFN-g in peripheral blood serum (89.929 + 3.533 pg/mL) resembles the pattern of the percentage of lymphocytes T CD4+ Th1 in lung tissue (3.246 + 0.519%) and peripheral blood (4.950 + 0.237%), while the levels IL-4 in the peripheral blood serum (20.782 + 4.043%) resembles the pattern of the percentage of lymphocytes T CD4+ Th2 in intestinal tissue (1.048 + 0.359%) and peripheral blood (1.196 + 0.557%). In conclusion, there is difference in the activity of lymphocytes T type Th1 and Th2 but it does not affect the immune response to Mycobacterium tuberculosis infection.


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