acth-(4-7)--pro-gly-pro- and Chronic-Disease

The study of chronic partial denervation (CPD) and quality of life was carried out in 27 patients with definite, probable and possible diagnosis of motor neuron disease (MND) treated with semax (1% solution). The needle electromyography (EMG) was performed thrice with short-term 2 month interval (60 days before enrollment and on day 1 and day 48 of the study) in three muscles on bulbar, cervical and lumbosacral levels on the less affected side. According to Revised El-Escorial Criteria (1998) the needle EMG for diagnostic purposes was also performed in two muscles on the cervical and lumbosacral levels on the more affected side along with stimulation electroneuronmyography of motor and sensory fibers of the peripheral nerves of neck, upper and lower extremities. The open-label clinical trial of Semax (1% solution) was conducted in sequential groups of patients. The drug was administered intranasally in two 10-day-long courses with 2-weeks break in daily dose of 12 mg. Sixty days before enrollment, and on days 1, 10, 24, 34 and 48, patients were assessed by the Norris ALS, the ALS Functioning Rating Scale and the ALSAQ-40 quality of life in the ALS scale. It was shown that CPD on the early as well as on the late stages was characterized by forward-backward, but not unidirectional course, that did not allow to recommend the follow-up needle EMG with short-term interval for evaluation of drug efficacy monitoring. Early CPD stages were characterized by forward-backwards fluctuations reflecting the compensatory reinnervation process (a phenomenon of exchange of muscle fibers, more rational in view of reinnervation, between adjacent motor units) whereas on the late CPD stages these forward-backwards CPD fluctuations reflected the processes of progressive deterioration of muscle fibers and secondary demyelination of large motor axons. Semax (1% solution) does not influence either the course of CPD or the dynamics of clinical estimates, in particular the terms of ensuing marked functional deficits on bulbar, cervical and lumbosacral levels of segmental innervation. However, 1% semax significantly improves the total estimate of life quality due to the improvement of emotional state and motivation in MND patients with the maximal effect on day 10. This finding suggests that it is feasible to administer 1% semax in complex MND palliative therapy.

Topics: Administration, Intranasal; Adrenocorticotropic Hormone; Adult; Aged; Chronic Disease; Dose-Response Relationship, Drug; Electromyography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Motor Neuron Disease; Muscle, Skeletal; Neprilysin; Nerve Regeneration; Neuroprotective Agents; Peptide Fragments; Peripheral Nerves; Prognosis; Quality of Life

The effect of ACTH4-7-PGP (Semax) intraperitoneal injection at the doses of 5, 50, 150 and 450 μg/kg b. w. on lipid peroxidation and functional hepatocytes state in Wistar male rats subjected to acute and chronic electrical foot-shock stress was investigated. It was observed that peptide at the doses of 50 and 450 μg/kg normalized malondialdehyde (MDA) level elevation in the liver homogenate caused by acute foot-shock stress. On the contrary, at the doses of 5 and 150 μg/kg Semax significantly increased MDA content without essential changes of antioxidant defense activity (catalase, superoxide dismutase, common antioxidative activity). In serum peptide at the all doses decreased stress-induced asparate aminotransferase activity elevation. In chronic stress peptide provided the normalization of protein synthetic hepatocytes function and the serum alanine aminotransferase activity with less effect on lipid peroxidation.

Topics: Acute Disease; Adrenocorticotropic Hormone; Animals; Antioxidants; Chronic Disease; Dose-Response Relationship, Drug; Electroshock; Foot; Free Radicals; Hepatocytes; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Peptide Fragments; Rats, Wistar; Stress, Psychological; Transaminases

The effect of ACTH-(4-7)-PGP (semax) intraperitoneal injection at doses of 5, 50, 150 and 450 μg/kg b.w. on the free-radical oxidation and the activity of serum transaminases in Wistar male rats subjected to acute and chronic immobilization stress has been studied. It was found that the peptide administration in the entire dose range studied produced antioxidant effect in hepatocytes and significantly increased the activity of serum ALT and AST at a dose of 450 μg/kg under chronic stress conditions. On the contrary, prooxidant effects were observed at a drug dose of 150 mg/kg under acute stress conditions, and the direction of changes in the ALT and AST values activity depended on the semax dose. The ALT activity was decreased at doses of 5 and 50 μg/kg, but increased at a dose of 450 μg/kg. The AST activity was already reliably increased at a dose of 5 μg/kg.

Topics: Acute Disease; Adrenocorticotropic Hormone; Animals; Chronic Disease; Enzyme Inhibitors; Immobilization; Lipid Peroxidation; Liver; Male; Peptide Fragments; Rats; Rats, Wistar; Stress, Physiological; Transaminases