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Vol 14, No 2 (2016)


Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy

Vaschenko V.I., Vil’yaninov V.N., Shabanov P.D.


Defensins, the cationic antimicrobial peptides (AMPs) of phagocytes and epithelial cells, are the key effector molecules of the innate immune system providing the anti-infective host defense. Besides the antimicrobial action, AMPs exert a broad spectrum of varied effects towards host cells giving a ground for considering these peptides as possible biomodulatory molecules. The review outlines different types of the biological activity of structurally diverse AMPs. AMPs posses the potent antimicrobial, antiviruses and lipopolysaccharide-binding activity; some of them are cytotoxic for tumor and normal human cells in vitro, while others demonstrate the wound healing action. AMPs of the defensin family display the corticostatic activity: they inhibit stimulated by adrenocorticotropic hormone (ACTH) steroidogenesis in adrenal cells in vitro. We also showed that defensins and protegrin 3 abolish ACTH- or stress-induced increase of the corticosterone level in blood of experimental animals. Taken together, the described in the literature and our own data contribute to the idea that AMPs are the multifunctional molecules participating in the interaction between the innate and adaptive immune systems as well as between immune and neuroendocrine systems. It considers structure and mechanism of defensins interaction with lipid membrane and intracellular targets of pathogens. Special attention is paid to modern state and perspectives of defensins practical application and also to approaches that increase efficacy by chemical modification of their structure.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(2):3-37
pages 3-37 views

Mitochondrial nitric oxide synthase and its role in the mechanisms of cell adaptation to hypoxia

Novikov V.E., Levchenkova O.S., Pozhilova E.V.


Mitochondrial nitric oxide synthase (mtNOS) actively participates in mechanisms of regulation of cell adaptation to extreme factors. It is closely interacted with other mitochondrial regulatory factors and is involved in adaptation reactions of cells to hypoxia, ischemia and other pathogenic action. Analysis of the role of mtNOS in cell functioning in hypoxia condition and its influence on apoptosis is presented in the article. Complex mechanism of cell adaptation with participation of mitochondrial nitric oxide (NO) is considered. Mitochondrial NO is a modulator of cell respiration, synthesis of ATP, activity of mitochondrial ATP-sensitive potassium channels, mitochondrial megapore and the specific protein factor to hypoxia adaptation. The possibility of pharmacological regulation of mtNOS activity is discussed. This approach seems to be promising for searching of new drugs for the pharmacotherapy of diseases with hypoxia and ischemia in their pathogenesis. There is possible to regulate cell homeostasis, for example, resistance to hypoxia by modulating the activity of mtNOS and synthesis of mitochondrial NO.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(2):38-46
pages 38-46 views

Aromatase inhibitors of the third generation in endocrine therapy of breast cancer and endometrial cancer: the successes and failures of the combination therapy

Fadeeva E.P., Lisyanskaya A.S., Manikhas G.M., Glushakov R.I., Tapilskaya N.I.


This review provides the current evidence of clinical studies on the effectiveness of endocrine therapy for breast cancer and endometrial cancer, including endometrial stromal sarcoma, by aromatase inhibitor (AI) III generation. The review presents dates from clinical trials comparing the effectiveness of AI and tamoxifen, as well as dates on combination therapy AI with inhibitors of mTOR pathway (BOLERO-2 trial), an antiestrogen (SWOG S0226, FACT, FIRST trials), an inhibitor of CDK4 / 6 (PALOMA -1 trial) and other drugs.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(2):47-57
pages 47-57 views

Beta-adrenoblockers of third generation as medicines for drug therapy of patients with chronic kidney disease

Kuzmin O.B., Zhezha V.V., Belyanin V.V., Buchneva N.V.


The review discusses the results of preclinical and clinical trials on the identification of nephroprotective action of β-blockers 3 generation carvedilol and nebivolol on models of hypertensive and diabetic nephropathy and patients with chronic kidney disease. It was concluded that nebivolol and especially carvedilol differs from its predecessors additional antioxidant and nephroprotective properties may be the drugs of choice from β-blockers for drug therapy of hypertensive patients with chronic kidney disease.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(2):58-64
pages 58-64 views

Experimental estimation of efficiency of antihypoxants at toxic pulmonary edema caused by nitrogen oxide (IV)

Sherbasov K.A., Basharin V.A., Marysheva V.V., Konshakov Y.O., Shabanov P.D.


The The efficiency of antihypoxants for prophylactic use on the model of toxic pulmonary edema caused by the use of nitrogen oxide (IV) was studied. It was found that the antihypoxants amtizol (25 mg/kg) and cytoflavin (100 mg/kg for succinic acid), increase the daily survival of rats have a pronounced anti-edematous action. The use of cytoflavin and amtizol increased the daily survival rate to 50 and 40%, respectively. Antihypoxants amtizol and cytoflavin decreased the pulmonary coefficient and the degree of hydration of the lungs, increased the dry residue of the lungs. The coefficient of protection for cytoflavin was 1.33 and 1.28 for amtizol. The use of succinic acid at a dose of 25 and 100 mg/kg did not lead to a higher daily survival rate of the animals and significant change in gravimetric parameters in comparison with the control group.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(2):65-68
pages 65-68 views

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