Cyclic analogues of Thr6-bradykinin,N8-Lys-bradykinin and endo-Lys8a-vespulakinin 1

Syntheses are described of the endo-Lys^8a-vespulakinin 1 and of cyclo-Thr⁶- and cyclo-N^ε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys^8a-VSK-1 and Thr⁶-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its N^α-Boc-[(Gal β)Thr³, (Gal β)Thr⁴]-analogue, were used to prepare N^α-(1–8 VSK 1)-cyclo-N^ε-kallidin and N^α-[(Gal β)Thr³, (Gal β)Thr⁴, 1–8 VSK 1]-cyclo-N^ε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995.     

The association between Coffin-Lowry syndrome and psychosis: a family study

ABSTRACT. This paper discusses a family presenting with features of Coffin-Lowry syndrome, namely abnormal facies, skeletal abnormalities and mental handicap. Two of the mildly affected females had psychotic illness with predominant depressive features, and all the severely affected males had profound sensor-ineural deafness.     

PERORAL ENDOSCOPIC DUODENAL BIOPSY IN INFANTS AND CHILDREN

ABSTRACT. Peroral endoscopic duodenal biopsy was used in the diagnosis and follow-up of forty-nine infants and children with suspected small intestine disease. Their ages ranged between one month and 12 years. Fifty-four upper gastrointestinal endoscopy procedures were performed and 139 biopsies were taken. The mean procedure time was 3.2 min with a range of 1.5–5.5 min. There were no complications. Tissue adequate for histopathologic examination was obtained in all but one of the fifty-four procedures. On the basis of this experience we think that peroral endoscopic duodenal biopsy is faster, safer and as diagnostic as conventional suction biopsy in infants and children. It is also more informative when other diseases of the upper gastrointestinal tract are suspected.     

Role of presynaptic purinoceptors and cyclic AMP on the noradrenaline release in cat cerebral arteries

Field electrical stimulation (ES), K+ (50 mM) or ionophore X-537A (0.01 mM) induced tritium release from cat cerebral arteries preincubated with [3H]noradrenaline (NA). Adenosine and AMP (0.5 mM) did not modify tritium release caused by ionophore X-537A, but these agents and ATP (0.5 mM) significantly reduced that elicited by ES and K+; this reduction was antagonized by 1-methyl-3-isobutylxanthine (MIX; 0.05 mM). Inosine (0.5 mM) and the agonist of purinergic A2-receptors, 5'N-ethyl-carboxamide adenosine (NECA; 0.5 mM) had no effect, but the agonist of purinergic A2-receptors L-N6-phenylisopropyl adenosine (L-PIA; 0.1 mM) diminished tritium efflux caused by ES and K+. The adenosine inhibition of ES-induced radioactivity release was not affected by indomethacin (0.05 mM). MIX (0.05 mM) increased tritium release evoked by ES and K+. Agents that increase intracellular cyclic (c)AMP levels, such as dibutyryl cAMP (0.5 mM), the phosphodiesterase inhibitor Ro 20-1724 (0.1 mM), and the activators of adenylate cyclase, forskolin (0.005 mM) and NaF (2 mM) reduced tritium secretion elicited by ES and K+. However, the intracellular increase of cyclic GMP (cGMP) caused by 8-Br-cGMP did not affect this secretion. Dipyridamole (0.05 mM) and the adenosine deaminase inhibitor erythro-9-2-hydroxy-3 nonyl adenosine (EHNA; 0.1 mM) also produced inhibition of tritium secretion elicited by ES and K+. Dipyridamole reduced both the uptake of [3H]NA and [3H]adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of a Precocious New Lesion Distal to a Stent Site by Atherectomy

A 58-year-old woman presented with a new rapidly progressive lesion distal to a stent. This lesion was treated with atherectomy through the stem in order to characterize it pathologically. The aggressive proliferative response discovered suggested that this unusually distal lesion was produced by the trauma of her previous angioplasty .     

PLASMA INSULIN DISAPPEARANCE CURVE AFTER INTRAVENOUS INSULIN INJECTION IN HUMAN HYPERTHYROIDISM

The disappearance curves of plasma insulin after intravenous injection of unlabelled pork insulin was studied in nine young female hyperthyroid subjects with Graves' disease and eleven young female normal subjects, who served as controls. Comparison of the curves by analysis of variance did not reveal statistical differences between them (F obtained = 2.8, F F 0.05 = 4.41), implying that there was no significant differences in the transference of injected insulin from plasma to the extra-vascular space between hyper- and euthyroid subjects. The results may suggest that the metabolism of insulin is not appreciably affected in hyperthyroidism.     

A Speculative Approach to the Myeloproliferative Syndromes

1. A survey of 66 cases of the myeloproliferative syndromes revealed twoclinical conditions not associated specifically with this group of blood dyscrasias.

2. Of particular interest were an apparent increased incidence of diabetesmellitus, and myelofibrosis associated with scleroderma.

3. These combinations may reflect a biochemical or metabolic error whichmay be present in some of these patients (such as increased 5-HIAA) andwhich may be related to the course, progression, and symptomatology of thesedisorders.

Submitted on October 17, 1961 Accepted on December 15, 1961     

An acid-labile anchoring linkage for solid-phase synthesis of C-terminal peptide amides under mild conditions*

A series of polymer-supported benzylamides substituted with one to three alkoxy groups in the ring positions were prepared and shown to give carboxamides upon treatment with acid. Based on the initial screening, the bis(o-methoxy)-p-alkoxybenzylamide anchoring linkage was selected for a detailed evaluation of its suitability for solid-phase synthesis of C-terminal peptide amides. The handle derivative 5-[(2′ or 4′)-Fmoc-aminomethyl-3′,5′-dimethoxyphenoxy]valeric acid ( 1 ) was prepared in seven facile steps [purification of intermediates unnecessary; overall yield 15% for crystalline product, which is a mixture of positional isomers], and was quantitatively coupled onto amino group-containing supports by use of N,N'-dicyclohexylcarbodiimide plus 1-hydroxybenzotriazole in N,N-dimethylformamide. Stepwise elaboration of peptide chains proceeded smoothly with both N^α-9-fluorenyl-methyloxycarbonyl (Fmoc) and N^α-dithiasuccinoyl (Dts) amino acids, and final cleavage of tert.-butyl side-chain protecting groups and of the anchoring linkage occurred readily in trifluoroacetic acid–dichloromethane (7:3) at 25°. The methodology was demonstrated by the syntheses of H-Trp-Asp-Met-Phe-NH₂ (tetragastrin) and H-Tyr-Gly-Gly-Phe-Met-NH₂ (methionine-enkephalinamide), both with high yields and purities.