Plasma pharmacokinetics and tissue distribution of L-lysine α-oxidase from Trichoderma cf. aureoviride RIFAI VKM F- 4268D in mice.

L-lysine α-oxidase (LO) is an L-amino acid oxidase with antitumor, antimicrobial and antiviral properties. Pharmacokinetic (PK) studies were carried out by measuring LO concentration in plasma and tissue samples by enzyme immunoassay. L-lysine concentration in samples was measured spectrophotometrically using LO. After single i.v. injection of 1.0, 1.5, 3.0 mg/kg the circulating T1/2 of enzyme in mice varied from 51 to 74 min and the AUC0-inf values were 6.54 ± 0.46, 8.66 ± 0.59, 9.47 ± 1.45 µg/ml × h, respectively. LO was distributed in tissues and determined within 48 h after administration with maximal accumulation in liver and heart tissues. Mean time to reach the maximum concentration was highest for the liver-9 h, kidney-1 h and 15 min for the tissues of heart, spleen and brain. T1/2 of LO in tissues ranged from 7.75 ± 0.73 to 26.10 ± 2.60 h. In mice, plasma L-lysine decreased by 79% 15 min after LO administration in dose 1.6 mg/kg. The serum L-lysine levels remained very low from 1 to 9 h (< 25 µM, 17%), indicating an acute lack of L-lysine in animals for at least 9 h. Concentration of L-lysine in serum restored only 24 h after LO administration. The results of LO PK study show that it might be considered as a promising enzyme for further investigation as a potential anticancer agent.

Frequency of detection of some markers of endothelial dysfunction in patients with inflammatory bowel diseases.

AIM: The purpose of our study was to determine the frequency of detection of some markers of endothelial dysfunction in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: The study was conducted on the basis of the Therapy Department of of A. Aliyev Azerbaijan State Advanced Training Institute for Doctors, the Department of Inflammatory Bowel Diseases "MedEra Hospital" and "Memorial Klinika" between March 2015 and September 2017. In patients with ulcerative colitis and Crohn's disease, homocysteine (Axis-Shield, IFA method) and hs-CRP (Biomerica, IFA method) in the blood, albumin (MicralTest, Roche Diagnostics) in urine were determined. The study included 87 patients with inflammatory bowel diseases (the diagnosis was confirmed on the basis of ECCO recommendations) in whom there was no history of nephro-, cerebro- and cardiovascular pathology in the anamnesis. RESULTS: Of the 48 patients with Crohn's disease, 45 homocysteine levels were elevated and comprised 12.9-48.7 µmol/L in the 15-60 year old; and in the group of patients older than 60 years fluctuated within 16.5-34.6 µmol/L. Out of 48 patients with Crohn's disease, 47 showed both albuminuria (micro- and macroalbuminuria) and was 22.8-98.5 mg/L. Of the 48 patients with Crohn's disease, 31 had an increase in hs-CRP between 4.3-47.1 mg/L; of them in 14 patients less than 10 mg/L, in 8 patients from 10.1-20.0 mg/L, and in 9 patients it ranged more than 20.0 mg/L. Of the 39 patients with ulcerative colitis, the level of homocysteine in 33 was elevated and amounted to 13.4-48.7 µmol/L in the 17-40 year old group; in the 41-59 year old group, 14.9-31.3 µmol/L; and in the group of patients older than 60 years fluctuated within the range of 16.9-41.7 µmol/L. Out of 39 patients with ulcerative colitis, 24 had albuminuria (both micro- and macroalbuminuria) and was 21.9-146.5 mg/L. Of 39 patients with ulcerative colitis in 36, an increase in hs-CRP was observed in the range 3.5-118.7 mg/L; of them in 17 patients less than 10 mg/L, in 6 patients from 10.1-20.0 mg/L, in 13 patients it ranged more than 20.0 mg/L. CONCLUSION: The frequency of detection of some markers of endothelial dysfunction in Crohn's disease was on the average 85.3%: for homocysteine 93.7%; for hs-CRP 64.5%; for albuminuria 97.9%, and for ulcerative colitis averaged 79.4%: for homocysteine, 84.6%; for hs-CRP 92.3%; for albuminuria 61.5%. Because of the high incidence of these markers, patients with inflammatory bowel diseases need a multi-disciplinary approach.