Synthesis of N3-fumaramoyl-L-2,3-diaminopropanoic acid analogues,the irreversible inhibitors of glucosamine synthetase

Several analogues of N³-fumaramoyl-L-2,3-diaminopropanoic acid were synthesized and evaluated for inhibition of glucosamine-6-phosphate synthetase activity. The syntheses were accomplished by acylation reaction of N²-tert.-butoxycarbonyl-L-2,3-diaminopropanoic acid (Boc-A₂pr) or N²-tert.-butoxy-carbonyl-L-2,4-diaminobutanoic acid (Boc-A₂-bu) with the N-succinimidoyl esters of several derivatives of α, β-unsaturated acids 2a-d followed by deprotection of the Boc groups. The obtained compounds were tested for inhibition of glucosamine synthetase isolated from Salmonella typhimurium and Saccharomyces cerevisiae. The results indicated that among the synthesized compounds, N³-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP) was the most powerful inhibitor of glucosamine synthetase.     

ANTI-LOW-DENSITY LIPOPROTEIN ANTIBODIES IN ALCOHOLICS WITHOUT AND WITH LIVER DISEASE AND IN SOCIAL DRINKERS

Antibodies directed to native and to in-vitro acetaldehyde-modified(ethylated) low-density lipoproteins (LDL) were determined in28 alcoholic subjects divided into two groups: one with do clinicalnor laboratory evidence of liver involvement and the secondwith histologically proven alcohol-related liver disease. Thecontrol group consisted of 18 individuals who drank alcoholsocially. In the individuals with alcoholic liver disease igGreactivity against both native and ethylated LDL was significantlyhigher than in alcoholic individuals without liver injury. Highlevels of IgG reactivity in individuals with alcoholic liverdisease were also observed against malondialdehyde-modified,methylated, acetylated and carbamylated LDL. A selective highanti-ethylated LDL IgG reactivity was observed in 11% of controlsubjects.     

Drug Delivery at the Aortic Valve Tissues of Healthy Domestic Pigs with a Paclitaxel-Eluting Valvuloplasty Balloon

Background: Restenosis occurs invariably within 1 year following balloon valvulopasty in aortic valve stenosis. The mechanism of restenosis seems to involve a dynamic cellular component that could be a target for drug inhibition. We investigated the feasibility of local drug delivery at the aortic valve tissues of healthy pigs with a paclitaxel-eluting balloon.
Methods: Aortic valvuloplasty was performed in eight anesthetized domestic pigs using paclitaxel-eluting balloons (3 μg/mm² balloon surface area). They were assigned to two or four times 15-second balloon inflations and were sacrificed 30 minutes after final balloon inflation.
Results: The aortic annulus to balloon diameter ratio was 1.15 ± 0.07. The mean paclitaxel concentration in the aortic valve leaflets was 0.91 ± 1.36 μg/mL (0.34 ± 0.05 μg/mL in the two-inflation group, 1.48 ± 1.86 μg/mL in the four-inflation group, P = 0.23). The percentage of the total paclitaxel dose recovered in the aortic valve leaflets was 18 ± 11⁻⁶% (13 ± 6⁻⁶% and 25 ± 14⁻⁶% in the two- and four-inflation group, P = 0.16).
Conclusion: Local drug delivery at the aortic valve leaflets of healthy pigs with a paclitaxel-eluting balloon is feasible and concentrations within the therapeutic window are detected 30 minutes after the procedure. The antirestenotic potential of this treatment should be studied.     

BENIGN THYROID INCLUSIONS WITHIN CERVICAL LYMPH NODES: AN ALARMING INCIDENTAL FINDING

Small clusters of microscopically normal thyroid follicles within cervical lymph nodes are very occasionally encountered during histological examination. We support the view that provided the thyroid gland is not palpable and a technetium thyroid scan is normal, these should be regarded as benign thyroid inclusions and do not represent small metastatic lesions from thyroid carcinoma. We report an example of these inclusions in a cervical lymph node which was removed incidentally during the excision of a branchial cyst in a 25-year-old woman. The inclusion was too small to be noticed macroscopically and consisted of a small aggregation of histologically normal thyroid follicles situated in the subcapsular region of the lymph node.