[d-Met2, Pro5] enkephalin [N1.5-β-d-glucopyranosyl] amide: a glycosylpeptide with high antinociceptive activity

Different synthetic strategies have been attempted for the synthesis of a glycosylpeptide resulting from the covalent bonding of a sugar residue to the C-terminal carboxyl group of an enkephalin related pentapeptide. The final structure is: Tyr-d -Met-Gly-Phe-Pro [N¹⁵-β-d -glucopyranosyl] amide. The in vitro potency on the GPI test of this analogue was IC₅₀= 64.0 nm . However, its antinociceptive activity by tail immersion tests, after intraperitoneal administration, was 2000 and 200 times higher than morphine in rats and mice, respectively.     

Transvalvular Impedance (TVI) Recording Under Electrical and Pharmocological Cardiac Stimulation

The cardiac electric impedance was recorded between right atrium and ventricle, throughout the cardiac cycle, by means of a tripolar single pass lead for VDD pacing. The transvalvular impedance signal (TVI) is a sharp periodic wave, with high signal-to-noise ratio, that is detected exclusively in the presence of cardiac mechanical activity. The minimum TVI value is attained during the atrial systole, the maximum at the end of ventricular systole. Different parameters of TVI waveform are affected by changes in the inotropic state, and could therefore be proposed as potential signals for new rate responsive algorithms based on the correlation between inotropic and chronotropic regulation. The signal might be used, moreover, for pacing and sensing validation in autoregulating pacemakers and for fibrillation recognition in ICDs.     

Power Doppler sonography in the diagnosis of hemophilic synovitis – a promising tool

Summary. Background: Recurrent hemarthroses in hemophilia results in synovitis and joint arthropathy. Primary prophylaxis when universally instituted at current doses can prevent joint deterioration but is expensive. Alternatively, the selective implementation of prophylaxis would require a more sensitive tool for detecting synovitis than possible with clinical surveillance or plain radiographs. Magnetic resonance imaging (MRI) is such a tool and is utilized for the evaluation of hemophilic joint disease (HJD). However, it is expensive, and requires sedation in younger children precluding its utility for monitoring of synovitis. Ultrasonography (USG) with power Doppler (USG‐PDS) has been utilized to detect and quantitate synovial vascularity in other arthritides and could provide an equally effective but less costly tool for HJD, particularly in children who would not require sedation. Objectives: To determine whether USG‐PDS is comparable to MRI in the evaluation of hemophilic synovitis. Patients: A prospective cohort of 31 subjects including 33 joints (knees, elbows, ankles) underwent dynamic contrast enhanced (DCE)‐MRI and USG‐PDS. Results: USG‐PDS measurements of synovial thickness(r = 0.70, P < 0.0001) and synovial vascularity (r = 0.73, P < 0.0001) correlated strongly with those obtained with DCE‐MRI. A cutoff of PDS intensity of 1.3 decibels (dB) per mm² was found to yield a sensitivity of 100% and a specificity of 94.1% in 17 joints with/without a history of hemarthroses. Pettersson radiographic scores correlated significantly with synovial thickness in adults but not children. Conclusions: Our data suggest that USG‐PDS may be an inexpensive and easily implemented imaging tool for detecting hemophilic synovitis and could be useful in tailoring effective prophylaxis.     

Synthesis and biological activity of substance P analogues

The synthesis of the hexapeptide [Glu⁶]SP_6-11 and its glycosylated analogue at the Glu⁶γ-carboxyl position by solution procedures according to several strategies is discussed. The biological activity of SP, [GIu⁶]SP_6-11 (VI) and [Glu(β-d -Glcp)⁶]SP_6-11 (VIII) have been determined and compared to SP by the GPI and RVD assays. The introduction of a β-d -glucopyranosyl moiety at the sixth position of the [Glu⁶]SP_6-11 did not affect to a great extent the in vitro activity pattern of the parent hexapeptide.     

The transition from injecting to smoking heroin in three Spanish cities

Aims. To measure the current prevalence of different routes of heroin administration among users and to describe the most frequent patterns in the evolution of the main route from the time of first use to the present and their implications for the control of the HIV epidemic. Design. Cross-sectional study. Face-to-face interviews using a structured questionnaire. Setting and participants. Nine hundred and nine regular heroin users from Madrid, Barcelona and Seville (about 300 per city), half of them recruited in treatment centres and the other half out of treatment. Measurements. Socio-demographic characteristics, current and historical behaviours related to route of administration. Findings. Before 1980 injection was the first main route of heroin administration for most users in Barcelona and Madrid; in Seville smoking already predominated, although 40% of users began by injecting. Sniffing subsequently became predominant in Barcelona, while smoking became the predominant first route in Madrid and Seville (smoking has been the only first route in Seville since 1991). The prevalence of injection as the main route of administration during the last 30 days was 77.3% in Barcelona, 24.3% in Madrid and 23.9% in Seville; smoking predominated in the latter two cities. The factors most strongly associated with injection as the preferred route were city of recruitment and having a partner who injected. Some 73% of those who stopped injecting in their last change of route stated that the results of their HIV test or fear of becoming infected had been important in making this decision. Conclusions. The change from injecting to smoking will greatly facilitate the control of HIV infection in Spain. However, the main causal factor does not appear to be the perception of HIV risk, but rather other, ecological factors (cultural or market-related). The absence of these factors in some areas may impede the spread of smoking.