scholarly journals Antiviral Activity of Kagocel® on the Model of Experimental Lethal Influenza Infection

2020 ◽  
Vol 65 (1-2) ◽  
pp. 15-20
Author(s):  
V. V. Zarubaev ◽  
A. V. Garshinina ◽  
A. V. Slita ◽  
S. V. Belyaevskaya ◽  
I. N. Lavrentieva
Keyword(s):  
Antiviral Activity ◽  
Influenza Infection ◽  
High Morbidity ◽  
Interferon Inducer ◽  
Reference Drug ◽  
Specific Mortality ◽  
Influenza Pneumonia ◽  
Prophylactic Use ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Despite the obvious advances in vaccination and therapy, influenza remains a poorly controlled infection with high morbidity and mortality. This study examined the antiviral activity of interferon inducer Kagocel on a mouse model of lethal influenza pneumonia. It has been shown that the therapeutic and prophylactic use of Kagocel leads to a dose-dependent decrease in specific mortality and suppression of virus reproduction in lung tissue. The effect of Kagocel was statistically identical to the effect of the reference drug — Arbidol (umifenovir).

scholarly journals PROTECTIVE ACTIVITY OF NOVEL BENZIMIDAZOLE DERIVATIVES AT EXPERIMENTAL INFLUENZA INFECTION

2018 ◽  
Vol 8 (2) ◽  
pp. 195-200
Author(s):  
V. V. Zarubaev ◽  
S. V. Vasilieva ◽  
Y. L. Esaulkova ◽  
A. V. Garshinina ◽  
V. M. Veprintseva ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Influenza Infection ◽  
Morphological Structure ◽  
Antigenic Drift ◽  
Control Group ◽  
Protective Activity ◽  
Reference Drug ◽  
Specific Mortality ◽  
Influenza Pneumonia

Influenza is an acute respiratory viral infection, which represents an important health problem. Every year, influenza causes epidemics  and pandemics, leading to increase in morbidity and mortality in all  regions of the globe. Due to the segmental organization of the  genome and low accuracy of its replication, the influenza virus is  capable of escaping the host’s immune response (antigenic drift), as  well as the selection of drug-resistant variants. This calls for  constant monitoring of the sensitivity of viral isolates to antiviral  drugs and the development of new etiotropic antiviral agents that  have alternative targets and mechanisms of activity. The purpose of  this study was to characterize the new aminobenzimidazole  derivatives as protective agents in lethal influenza infection in white  mice. The efficacy of the compounds was assessed by their ability to  reduce specific mortality of animals in the course of lethal influenza  pneumonia caused by the influenza A/Puerto Rico/8/34 (H1N1)  irus, increase the life duration of animals, and normalize the  morphological structure of lung tissue comparing to the placebo  group. For all the compounds studied, a decrease in the specific  mortality of animals (from 20 to 60%) has been shown. The  reference drug (oseltamivir phosphate) reduced the mortality of  mice by 80%. The benzimidazole derivative 2519 demonstrated the  highest indices of protective activity, its use reduced the mortality of  animals by 60% and increased their mean day of death by 1.6 days in comparison with the control group. Morphological analysis showed that the activity of derivative 2519 was manifested in the  normalization of the morphological structure of lung tissue in the  course of influenza pneumonia. On day 5 after infection, the cells of  the bronchial epithelium looked intact, in contrast to destroyed cells  with numerous viral inclusions in control animals. The foci of  inflammation themselves occupied a smaller area compared to the  control. At the same time, there was no correlation between the  previously obtained data on the virus-inhibiting effect of these  compounds in vitro and the data obtained in animals. This suggests  that despite the presence of direct antiviral activity detected  previously in in vitro experiments, the protective properties of the  studied aminobenzimidazoles on animals are caused, in addition to  the etiotropic effect, by other pathogenetic factors. In conclusion,  amino derivatives of benzimidazole should be considered as  compounds that are promising for further development and  introduction as an anti-influenza agents. 

Anti-inflammatory and antinociceptive activities of the aqueous leaf extract of Phyllanthus amarus Schum (Euphorbiaceae) in some laboratory animals

2015 ◽  
Vol 26 (1) ◽  
Author(s):  
Adeolu A. Adedapo ◽  
Sunday O. Ofuegbe
Keyword(s):  
Acetic Acid ◽  
Analgesic Effect ◽  
Leaf Extract ◽  
Herbal Remedy ◽  
Laboratory Animals ◽  
Traditional Use ◽  
Reference Drug ◽  
Anti Inflammatory ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Abstracthas a history of use in Ayurvedic medicine for over 2000 years as well as a wide variety of traditional applications and has gained popularity in many continents as a herbal remedy; hence, it is being assessed for its safety potential and anti-inflammatory and analgesic properties in some laboratory animals.Standard phytochemical methods were used to test for the presence of phytoactive compounds in the plant. Acute toxicity testing was carried out in mice to determine safe doses for the extract. The anti-inflammatory activity of the leaf extract of this plant was assessed using carrageenan-induced and histamine-induced paw edema. The analgesic effect was determined using the acetic acid writhing method as well as formalin test.The extract at 100 and 200 mg/kg body weight reduced significantly, the formation of edema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by reduction in the number of writhes when compared to the control. The extract caused dose-dependent decrease of licking time in rats injected with 2.5% formalin, signifying its analgesic effect. These results were also comparable to those of ibuprofen, the reference drug used in this study.The plant extract reduced significantly the formation of edema induced by carrageenan and histamine as well as reducing the number of writhes in acetic acid-induced writhing models and dose-dependent decrease of licking time in rats injected with 2.5% formalin. The results have validated the basis for the traditional use of

scholarly journals Broad Antiviral Activity of Ginkgolic Acid against Chikungunya, Mayaro, Una, and Zika Viruses

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 449 ◽  
Author(s):  
Dalkiria Campos ◽  
Susana Navarro ◽  
Yessica Yadira Llamas-González ◽  
Madelaine Sugasti ◽  
José González-Santamaría
Keyword(s):  
Antiviral Activity ◽  
Protein Expression ◽  
Viral Protein ◽  
Biological Activities ◽  
Virucidal Activity ◽  
Ginkgolic Acid ◽  
Viral Protein Expression ◽  
Viral Progeny ◽  
Dose Dependent Decrease ◽  
Dose Dependent

The alphaviruses Chikungunya (CHIKV), Mayaro (MAYV), Una (UNAV), and the flavivirus Zika (ZIKV) are emerging or re-emerging arboviruses which are responsible for frequent epidemic outbreaks. Despite the large impact of these arboviruses on health systems, there are no approved vaccines or treatments to fight these infections. As a consequence, there is an urgent need to discover new antiviral drugs. Natural products are a rich source of compounds with distinct biological activities, including antiviral properties. Thus, we aimed to explore the potential antiviral activity of Ginkgolic acid against the arboviruses CHIKV, MAYV, UNAV, and ZIKV. Viral progeny production in supernatants from cells treated or not treated with Ginkgolic acid was quantified by plaque-forming assay. Ginkgolic acid’s direct virucidal activity against these arboviruses was also determined. Additionally, viral protein expression was assessed using Western blot and immunofluorescence. Our results reveal that Ginkgolic acid promotes a dose-dependent decrease in viral titers in all tested viruses. Moreover, the compound demonstrated strong virucidal activity. Finally, we found that viral protein expression was affected by treatment with this drug. Collectively, these findings suggest that Ginkgolic acid could have broader antiviral activity.

Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Low Temperatures ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Exogenous Insulin ◽  
Metabolic Substrate ◽  
Endogenous Insulin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

scholarly journals A Reversible Shift of Driver Dependence from EGFR to Notch1 in Non-Small Cell Lung Cancer as a Cause of Resistance to Tyrosine Kinase Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2022
Author(s):  
Francesca Iommelli ◽  
Viviana De Rosa ◽  
Cristina Terlizzi ◽  
Rosa Fonti ◽  
Rosa Camerlingo ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Epithelial Mesenchymal Transition ◽  
Parental Cell ◽  
Egfr Inhibitors ◽  
Simultaneous Increase ◽  
Adherent Cells ◽  
Binding Assays ◽  
Mesenchymal Transition ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Notch1 plays a key role in epithelial-mesenchymal transition (EMT) and in the maintenance of cancer stem cells. In the present study we tested whether high levels of activated Notch1 in oncogene-driven NSCLC can induce a reversible shift of driver dependence from EGFR to Notch1, and thus causing resistance to EGFR inhibitors. Adherent cells (parental) and tumor spheres (TS) from NSCLC H1975 cells and patient-derived CD133-positive cells were tested for EGFR and Notch1 signaling cascade. The Notch1-dependent modulation of EGFR, NCID, Hes1, p53, and Sp1 were then analyzed in parental cells by binding assays with a Notch1 agonist, DLL4. TS were more resistant than parental cells to EGFR inhibitors. A strong upregulation of Notch1 and a concomitant downregulation of EGFR were observed in TS compared to parental cells. Parental cell exposure to DLL4 showed a dose-dependent decrease of EGFR and a simultaneous increase of NCID, Hes1, p53, and Sp1, along with the dislocation of Sp1 from the EGFR promoter. Furthermore, an enhanced interaction between p53 and Sp1 was observed in TS. In NSCLC cells, high levels of active Notch1 can promote a reversible shift of driver dependence from EGFR to Notch1, leading to resistance to EGFR inhibitors.

scholarly journals Antiviral Activity of BL-3849A, a Low-Molecular-Weight Oral Interferon Inducer

1976 ◽  
Vol 10 (4) ◽  
pp. 691-696 ◽  
Author(s):  
E. R. Kern ◽  
J. R. Hamilton ◽  
J. C. Overall ◽  
L. A. Glasgow
Keyword(s):  
Molecular Weight ◽  
Antiviral Activity ◽  
Low Molecular Weight ◽  
Interferon Inducer

Inhibitory Effects of Purple Sweet Potato Leaf Extract on the Proliferation and Lipogenesis of the 3T3-L1 Preadipocytes

2015 ◽  
Vol 43 (05) ◽  
pp. 915-925 ◽  
Author(s):  
Shou-Lun Lee ◽  
Hsien-Kuang Lee ◽  
Ting-Yu Chin ◽  
Ssu-Chieh Tu ◽  
Ming-Hsun Kuo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sweet Potato ◽  
Early Stage ◽  
Water Extract ◽  
Potato Leaf ◽  
Purple Sweet Potato ◽  
Pre Treatment ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti-oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but its efficacy has not yet been verified. The purpose of this study was to investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was used to treat the 3T3-L1 cells, and the effects on cell proliferation and adipogenesis were investigated. The results showed that PSPLE caused a dose-dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3-L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition of lipogenesis could result from the PSPLE-induced down-regulation of the expression of the C/EBPα and SREBP-1 transcription factors during 3T3-L1 adipocyte differentiation. These results suggest that PSPLE not only inhibits cell proliferation at an early stage but also inhibits adipogenesis at a later stage of the differentiation program.

scholarly journals Comparative Drug Disposition, Urinary Pharmacokinetics, and Renal Effects of Multilamellar Liposomal Nystatin and Amphotericin B Deoxycholate in Rabbits

2003 ◽  
Vol 47 (12) ◽  
pp. 3917-3925 ◽  
Author(s):  
Andreas H. Groll ◽  
Diana Mickiene ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Raul M. Alfaro ◽  
...  
Keyword(s):  
Total Dose ◽  
Amphotericin B ◽  
Drug Disposition ◽  
Fungal Infections ◽  
Standard Dose ◽  
Concentration Data ◽  
Drug Concentrations ◽  
Amphotericin B Deoxycholate ◽  
Dose Dependent Decrease ◽  
Dose Dependent

ABSTRACT The comparative drug dispositions, urinary pharmacokinetics, and effects on renal function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were determined by high-performance liquid chromatography as total concentrations of LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in escalating maximum concentrations (C max) (17 to 56μ g/ml for LNYS versus 3.36 μg/ml for DAMB; P< 0.001) and values for the area under the concentration-time curve from 0 to 24 h (AUC0-24) (17 to 77μ g · h/ml for LNYS versus 12μ g · h/ml for DAMB; P < 0.001) in plasma but a significantly faster total clearance from plasma (0.117 to 0.080 liter/h/kg for LNYS versus 0.055 liter/h/kg for DAMB; P = 0.013) and a ≤8-fold-smaller volume of distribution at steady state (P = 0.002). Urinary drug concentration data revealed a ≥10-fold-higher C max (16 to 10 μg/ml for LNYS versus 0.96μ g/ml for DAMB; P = 0.015) and a 4- to 7-fold-greater AUC0-24 (63 to 35μ g · h/ml for LNYS versus 8.9μ g · h/ml for DAMB; P = 0.015) following the administration of LNYS, with a dose-dependent decrease in the dose-normalized AUC0-24 in urine (P= 0.001) and a trend toward a dose-dependent decrease in renal clearance. Except for the kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after dosing were severalfold lower than those after administration of DAMB (P,<0.002 to <0.001). Less than 1% each of the total dose of LNYS was recovered from the kidneys, liver, spleen, and lungs; in contrast, a quarter of the total dose was recovered from the livers of DAMB-treated animals. LNYS had dose-dependent effects on glomerular filtration and distal, but not proximal, renal tubular function which did not exceed those of DAMB at the highest investigated dosage of 6 mg/kg. The results of this experimental study demonstrate fundamental differences in the dispositions of LNYS and DAMB. Based on its enhanced urinary exposure, LNYS may offer a therapeutic advantage in systemic fungal infections involving the upper and lower urinary tracts that require therapy with antifungal polyenes.

scholarly journals Systemic and portal hemodynamic effects of anandamide

2001 ◽  
Vol 280 (1) ◽  
pp. G14-G20 ◽  
Author(s):  
Nelson Garcia ◽  
Zoltán Járai ◽  
Faridoddin Mirshahi ◽  
George Kunos ◽  
Arun J. Sanyal
Keyword(s):  
Vascular Resistance ◽  
Nordihydroguaiaretic Acid ◽  
Hemodynamic Effects ◽  
Venous Flow ◽  
Portal Hemodynamics ◽  
Sr 141716A ◽  
Dose Dependent Decrease ◽  
Endogenous Cannabinoid ◽  
Dose Dependent ◽  
Mesenteric Vascular Resistance

The endogenous cannabinoid anandamide causes hypotension and mesenteric arteriolar dilation. A detailed analysis of its effects on systemic and portal venous hemodynamics had not yet been performed. We assessed the effects of anandamide (0.4–10 mg/kg) on systemic and portal hemodynamics with and without prior treatment with various antagonists. The specific antagonists used included SR-141716A, N ω-nitro-l-arginine methyl ester, indomethacin, and nordihydroguaiaretic acid. Anandamide produced a dose-dependent decrease in mean arterial pressure due to a drop in systemic vascular resistance (SVR) that was accompanied by a compensatory rise in cardiac output. Anandamide also elicited an increase in both portal venous flow and pressure, along with a decline in mesenteric vascular resistance (MVR). Pretreatment with 3 mg/kg SR-141716A, a CB1 antagonist, prevented the decline of SVR and MVR from the lower dose of anandamide. Antagonism of nitric oxide synthetase, cyclooxygenase, or 5-lipoxygenase did not prevent the systemic nor the portal hemodynamic effects of anandamide. Furthermore, the use of R-methanandamide, a stable analog of anandamide, produced similar hemodynamic effects on the mesenteric vasculature, thereby implying that the effects of anandamide are not related to its breakdown products. Anandamide produced profound, dose-dependent alterations in both the systemic and portal circulations that could be at least partially blocked by pretreatment with SR-141716A.

scholarly journals Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

1999 ◽  
Vol 340 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Russell R. HOOVER ◽  
Klaus H. THOMAS ◽  
Joanna FLOROS
Keyword(s):  
Protein Complex ◽  
Promoter Activity ◽  
Nuclear Extract ◽  
Surfactant Protein ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Cis Acting ◽  
Lung Adenocarcinoma Cell Line ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Glucocorticoids have complex effects on human surfactant protein (SP) SP-A1 and SP-A2 gene expression that occur at both transcriptional and post-transcriptional levels. In the lung adenocarcinoma cell line NCI-H441, dexamethasone causes a dose-dependent decrease in total SP-A mRNA levels and inhibits SP-A gene transcription. In this study, a deletional analysis of the SP-A1 promoter was performed in order to identify cis-acting elements that mediate dexamethasone responsiveness in NCI-H441 cells. The region -32/+63 relative to the start of SP-A1 transcription mediated both basal promoter activity and dexamethasone repression of transcription. Removal of the region +18/+63 abolished dexamethasone responsiveness, indicating that sequences within this region are necessary for the inhibitory effect. Furthermore, the region -32/+63 formed a sequence-specific DNA-protein complex with NCI-H441 nuclear extract. This DNA-protein complex was induced by dexamethasone exposure and its formation was mediated partially by sequences within the region +26/+63.

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