Delta opioid receptor selective ligands; DPLPE-deltorphin chimeric peptide analogues†

Further efforts to correlate the topography of the bioactive structures of DPDPE and the deltorphins, two δ-opioid receptor active peptide families, are reported. A number of DPLPE-deltorphin chimeric peptides have been synthesized in which the C-terminal dipeptide δ-address of the deltorphins (-Val-GlyNH₂, -Nle-GlyNH₂) have been linked to the highly δ-opioid selective cyclic peptides DPDPE or DPLPE. These studies demonstrate that a major structural feature determining high potency of hybrid analogues is the chirality of the amino acid residue in position 5. The radioligand binding assays have revealed a decrease in potency (compared to DPDPE) at §-receptors when the C-terminal dipeptides were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these same C-terminal dipeptides retained high δ-selectivity and affinity. Similar results were obtained using the mouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions 2 and 5 for δ-selectivity is consistent with the previous finding for DPLPE and DPDPE. On the other hand, the replacement of phenylalanine-4 with p-chlorophenylalanine-4 did not increase δ-selectivity as in DPDPE. These findings suggest that the δ-receptor interacts with hybridized enkephalins and deltorphins somewhat differently than with DPDPE.     

Randomized, Evaluator-Blind, Split-Face Comparison Study of Single Cross-linked versus Double Cross-linked Hyaluronic Acid in the Treatment of Glabellar Lines

BACKGROUND At present, various hyaluronic acids are being used to rejuvenate facial skin. There is no comparative study of single cross-linked hyaluronic acid (SCHA) versus double cross-linked hyaluronic acid (DCHA). The objective of our study is to compare the effectiveness and complications of SCHA versus DCHA in the treatment of glabellar lines.
METHODS Ten female patients were enrolled in this randomized, evaluator-blind study. One side (left vs. right) of each patient's glabellar lines was treated with SCHA and the other side was treated with DCHA. Two independent blinded observers reviewed the clinical photographs at 3, 6, 9, and 12 months after the treatment and assessed for degree of improvement as well as complications.
RESULTS The two products were equally effective in producing an optimal cosmetic result, although at 6, 9, and 12 months posttreatment, a higher proportion of patients showed over 50% improvement with DCHA than with SCHA. At 12 months posttreatment, DCHA was considered superior in 70% of patients, whereas SCHA was superior in 10% of patients.
CONCLUSIONS Both SCHA and DCHA are equally effective in producing an optimal cosmetic result. DCHA provides a more durable esthetic improvement when compared to SCHA in the treatment of glabellar lines.     

The Clinical Utility of Pacemaker Follow-up Visits

Because of the increased complexity of modern pacemakers, pacemaker follow-up visits in specialized centers become more and more indispensable. In this study, the results of 15,000 outpatient visits to the cardiac pacing center between the years 1983–1985 are presented. In most cases (92.8%), verification of normal function was made; however, mandatory reprogramming was required in 1.2%, and hospitalization for various reasons was required in 6% of visits. Careful outpatient monitoring of pacemakers is therefore very important for detecting early or late pacemaker complications.     

EOSINOPHILIC POLYMYOSITIS PRESENTING AS A PSEUDOTUMOUR IN THE HYPEREOSINOPHILIC SYNDROME

This report describes an unusual case of pseudotumour of musclecaused by an eosinophilic myositis associated with peripheralblood eosinophilia, systemic illness and a pericardial effusion. The relationship of this case to other reported cases of eosinophilicmyositis and the hypereosinophilic syndrome is discussed briefly. KEY WORDS: Eosinophilic myositis, Hypereosinophilic syndrome, Pseudotumour, Pericardial effusion     

1H-n.m.r. investigation of conformational features of cyclic,penicillamine-containing enkephalin analogs

Conformational features of a series of cyclic, penicillamine-containing enkephalin analogs, all of which display selectivity for the delta opioid receptor, were studied by ¹H n.m.r. in aqueous solution. Comparison of chemical shifts, coupling constants, and temperature dependence of amide proton chemical shifts suggests different conformational features among the analogs, some of which can be related to the different primary sequences of these peptides. The observation that some of the analogs display disparate individual conformational features while exhibiting similar opioid potency and receptor selectivity suggests that such analogs may share a similar overall topography or at the least maintain the same relative orientations of key portions of the molecule.     

HEMORRHAGIC MYOCARDIAL INFARCTION COMPLICATED BY FREE WALL-RUPTURE: A CASE ASSOCIATED WITH UNUSUAL CLINICAL FEATURES FOLLOWING INTRAVENOUS THROMBOLYTIC THERAPY

A patient is described who developed a systolic murmur soon after she was administered intravenous thrombolytic therapy for acute myocardial infarction. She died and autopsy revealed extensive hemorrhagic myocardial infarction and a free-wall rupture. A review of the literature suggests that this may be an unusual complication of thrombolytic therapy.     

MITOCHONDRIAL MYOPATHIES. A CLINICO-PATHOLOGICAL STUDY OF CASES WITH AND WITHOUT EXTRA-OCULAR MUSCLE INVOLVEMENT

Abstract The clinical and pathological features of 28 patients with mitochondrial myopathy were reviewed. The cases were divided into a group with involvement of the extra-ocular muscles alone or with limb muscle involvement, and a group with a facioscapulohumeral syndrome or generalised weakness without extra-ocular muscle involvement. Cardiac and central nervous system manifestations occurred particularly in the first group which included six patients with multisystemic features and two with the complete Kearns-Sayre syndrome. Diabetes mellitus occurred in the second group only. Quantitative histology on limb muscle biopsies showed a higher proportion of fibres with abnormal mitochondrial aggregates in the second group. No one type of mitochondrial inclusion or other ultrastructural change was specific for either group of cases. The findings illustrate the clinical heterogeneity of cases of mitochondrial myopathy and the lack of specificity of any of the myopathological changes for different subgroups of patients.