Synthesis and biological activity of a novel adenosine analogue, 3-beta-D-ribofuranosylthieno[2,3-d]pyrimidin-4-one

The title nucleoside 5 was prepared by a condensation of the silylated heterocycle thieno[2,3-d]pyrimidin-4-one (1) with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (2a) in the presence of a Lewis acid or with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide (2b) in the presence of mercuric oxide and mercuric bromide. The site of ribosylation and anomeric configuration of this nucleoside were established by 1H NMR. The synthesis of 3-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidin-4-one (8), 1-phenyl-5-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-one (9), 5-methyl-3-beta-D-ribofuranosylthieno[2,3-d]pyrimidin-4-one (10), and 2-methyl-6-beta-D-ribofuranosyltriazolo[5,4-d]pyrimidin-7-one (11) is also described. The title compound inhibited the growth of murine L-1210 leukemic cells in vitro with an ID50 of 3 X 10(-5)M. The growth inhibition could not be prevented by uridine, cytidine, thymidine, deoxycytidine, cytosine, hypoxanthine, or uridine and hypoxanthine together. On the other hand, inhibition of adenosine kinase by 10(-7) M 5-iodotubercidin prevented the cytotoxic effect. Also a subline of L-1210 cells resistant to several cytotoxic adenosine analogues was also resistant to this nucleoside. Thus it appears that this compound 5 may act as an adenosine analogue.     

Comparison of the biological effects of selected 5,8-dideazafolate analogues with their 2-desamino counterparts

Three new 5,8-dideaza analogues of folic acid devoid of an amino group at position 2 have been prepared by using synthetic routes patterned after earlier methodologies. They were 2-desamino-5,8-dideazaisofolic acid, 2b, 2-desamino-10-thia-5,8-dideazafolic acid, 2c, and 2-desamino-10-oxa-5,8-dideazafolic acid, 2d. These compounds were found to be 4-6-fold more cytoxic toward L1210 leukemia cells than their 2-NH2 counterparts and to be poor inhibitors of mammalian thymidylate synthase. However, they were only 1.5-3-fold less inhibitory toward dihydrofolate reductase than the analogous compounds containing a 2-NH2 group. The known thymidylate synthase inhibitors 2-desamino-10-propargyl-5,8-dideazafolic acid and 10-propargyl-5,8-dideazafolic acid were included in this study for purposes of comparison.     

Histological and bacteriological studies of burn wounds treated with boiled potato peel dressings

Histological and clinical studies have been made on comparable burn wounds covered with either boiled potato peels affixed to gauze bandages or gauze dressings alone; both dressings were applied over a thin layer of 5 per cent silver sulphadiazine. Compared with treatment with plain gauze dressings, the application of the potato peel dressing reduced or eliminated dessication, permitted the survival of superficial skin cells and hastened epithelial regeneration. Bacteriological studies showed that the potato peels had no intrinsic antibacterial activity, the wounds beneath both dressings showing either no growth or, on most occasions, the same bacterial species. The easy availability of potato peels and gauze bandages on to which they can be affixed, the simplicity of the preparation of this dressing, the ease of sterilization and its low cost of production make this the dressing of choice for burn wounds in our developing country.     

Tinnitus in central vestibular disorders

A total of100 patients on whom cranio-corpo-graphy and pure tone audiometry was performed is included in the study. The incidence and nature of tinnitus in various central and peripheral dysequilibrium states is analysed. The presence of vestibulo-auditory connection at the central level is confirm ed. It is seen that tinnitus does not bear a topodiagnostic relationship to the site of lesion in central vestibular disorders. Tinnitus in diabetes as a further sub group is analysed. All results are graphically displayed.     

A simple and safe technique for the proper placement of intercostal drainage tubes

A simple and safe technique for accurate placement of intercostal drainage tubes with the help of metal urethral dilators is described.     

Target localization on standard axial images in computed tomography (CT) stereotaxis for functional neurosurgery—a technical note

Summary A simple technique for marking functional neurosurgery target on computed tomography (CT) axial image is described. This permits the use of standard axial image for computed tomography (CT) stereotaxis in functional neurosurgery.     

Duchenne muscular dystrophy in monozygotic twins: Deletion of 5′ fragments of the gene

A recombinant DNA study for deletion evaluation was performed in a 4 generation family with Duchenne muscular dystrophy (DMD) in twins. The patients were 6 years old, had a history of progressive difficulty in walking since age 4, and showed weak gluteals, iliopsoas, latissimus dorsi, rhomboids, lower trapezius, sternocleidomastoids, pseudohypertrophic calves, and tight heelcords. Both patients had high serum creatine kinase of 19,000 and 11,000 IU, respectively, and the muscle biopsy of the left vastus lateralis showed dystrophic alterations. Both twins had the same red cell types for ABO, Rh, CDE, MNSs, Kelly, Lewis, Duffy, and Kidd. HLA typing also detected the same antigens in both twins: A2, B44, DR4, and DR5. Cytogenetic studies were consistent with 46, XY male individuals with normal banding pattern. By cDNA probes the entire DMD gene was surveyed for missing or abnormal-sized restriction fragments. Both twin boys showed absence of 8.5, 8.0, 4.6, 4.2, and 3.1 kb fragments on Hind III blots and absence of 13.5, 3.7, 2.9, and 1.4 kb fragments on Bgl II blots both hybridized with cDNA l-2a corresponding to most 5′ region of the DMD gene. The mother and other relatives of the patient did not show deletion. These findings strongly suggest that the deletion in the DMD monozygotic twins represents a new mutation.