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.     

Treatment of interproximal angular defects by guided tissue regeneration: 1 year follow-up

SUMMARY The periodontal regeneration of interproximal bone defects of the posterior teeth produced by guided tissue regeneration (GTR), with expanded Polytetrafluoroethylene barrier membranes and conventional therapy, was clinically evaluated in 20 intrabony periodontal defects in 10 patients. The material included the presence of at least two proximal angular lesions for the same patient, probing pocket depth ≥ 6 mm, bone defect depth ≥ 3 mm, and 2-wall defects with crestal involvement relative to the tooth circumference ranging from 90 to 270°. Healing was clinically evaluated by surgical re-entry of GTR-treated sites (10 sites) and debridement only sites (10 sites) 1 year after initial surgery following a strict plaque control regimen. A significant correlation was observed between probing depth reduction, attachment gain and defect depth (test sites); there was increased bone fill in GTR-treated lesions of 2.95 ± 1.3 mm corresponding to a 69.4% improvement compared to control sites, and 1–3 ± 1.0 mm corresponding to a 32% improvement ( P < 0.0039). The results demonstrated that bone regeneration is highly reliable, as compared to conventional therapy, in cases of severe periodontal bone loss from posterior teeth provided that the principles of GTR are applied.     

Evaluation of Different Drugs in Two Models of Immediate Hypersensitivity

Abstract— The effect of the calcium antagonists, verapamil, nicardipine and diltiazem, the two cromones, disodium cromoglycate and SM-857 (11-oxo-11 H-pyrido[2,1-b]quinazoline-2-carboxylic acid), and the anthelmintic, diethylcarbamazine citrate, have been compared on the ovalbumin (OA)-induced contraction of the isolated trachea and longitudinal muscle-myenteric plexus (LM-MP) from sensitized guinea-pigs. The calcium antagonists prevented the OA-induced contractions in LM-MP and to a lesser degree the OA-induced contractions in trachea. Similar doses of SM-857 protected both tissues but neither cromoglycate (10^?5M) nor diethylcarbamazine (10^?5M) affected these contractions. The OA-induced contraction in trachea had a tonic phase that was not present in the LM-MP response. Only the calcium antagonists succeeded in relaxing this OA tonic component, diltiazem being the more potent. These results unmask different mechanisms of drug action on immediate hypersensitivity and specific sensibilities, depending on the kind of tissue.     

Can infant mortality be reduced by promoting breastfeeding? Evidence from Sao Paulo city

An ambitious breastfeeding promotion programme was launchedin Brazil in 1981 which included the use of mass media, healthpersonnel training and re-organization of health service routines.A comparison of two health surveys carried out in Greater SãoPaulo before (1981) and after (1987) the implementation of theprogramme showed an important increase in the median durationof breastfeeding from 84 to 146 days, respectively. The potentialimpact of the programme on infant mortality rates has been estimated,using the relative risks associated with breastfeeding obtainedin a case-control study in a similar urban population in southernBrazil. During this period the infant mortality rate in SãoPaulo fell by 49%. The observed change in feeding practicesmay have been responsible for a reduction of 12% of this 49%or, expressed another way, for one-quarter of the observed declinein infant mortality. The calculations suggest that the programmemay have led to reductions in deaths caused by diarrhoea of32%, in respiratory infections of 22% and in deaths due to otherinfections of 17%.     

Asystole with Syncope Secondary to Hyperventilation in Three Young Athletes

We describe three athletes who had syncope after (case 1) or during (cases 2, 3) hyperventilation. During the episode, ECG showed prolonged sinus arrest. Clinical data and noninvasive investigations were normal and the phenomenon was not reproducible. Electrophysiological study after autonomic blockade allowed a prolonged intrinsic heart rate in case 1, and abnormal corrected sinus node recovery time in cases 1 and 2. During follow-up, symptomatic sinus arrest provoked by deep inspiration occurred in case 3. These cases document prolonged asystole of unknown etiology, secondary to hyperventilation, and probably caused by different vagally-mediated mechanisms.     

The Effect of DDD Pacing on Ergospirometric Parameters and Neurohormonal Activity in Patients with Hypertrophic Obstructive Cardiomyopathy

This study examined the acute and long-term effects of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive Cardiomyopathy (HOCM). We studied eight patients (five males), aged 56 ± 7 years, with HOCM refractory to drugs. In all patients a DDD pacemaker was implanted and programmed with an atrioventricular (AV) delay that insured full ventricular activation. The patients underwent echocardiographic examination and exercise stress testing before and 3 days, 3 months, and 12 months after pacemaker implantation. Oxygen consumption was measured at the anaerobic threshold (VO_2AT) and peak exercise (pVO₂). Atrial natriuretic peptide (ANP) and cyclic adenosine monophosphate (c-AMP) levels were measured concomitantly. Left ventricular outflow tract (LVOT) pressure gradient decreased significantly from 70 ± 18 to 25 ± 12 mmHg (P < 0.05) 3 days after pacing and remained unchanged at 3 and 12 months. pVO₂ and VO_2AT increased significantly, from 20.1 ± 3 to 23.4 ± 3 mL/kg/min and from 16 ± 3 to 17.8 ± 2 mL/kg/min, respectively (P < 0.05). This improvement continued up to 3 months, and then remained stable until the end of the 12-month follow-up period. ANP levels decreased at 3 days from 85.4 ± 5.7 to 75.4 ± 7.3 fmol/mL (P < 0.05), and remained unchanged over the 12 months. c-AMP levels did not change significantly after the onset of pacing. DDD pacing in patients with HOCM not only reduces the LVOT pressure gradient but also causes a significant early and long-term improvement in exercise capacity and neurohormonal profile.     

Molecular analysis of HLA DR4-/β1 gene in malaria vaccinees. Typing and subtyping by PCR technique and oligonucleotides

The combination of the PCR technique and the synthetic oligonucleotides has proved to be a useful tool in the molecular analysis of HLA class II genes, allowing recognition of as little as a single nucleotide modification in the sequence of the gene. The molecules encoded by these genes have been associated with genetic control of the immune response and with susceptibility to certain diseases. Studies carried out in our laboratory have shown three patterns of humoral immune response in the human volunteers vaccinated with the synthetic protein SPf 66; high, intermediate and low responders. Approximately 73.3% of the low responders were serologically typed as HLA DR4 and 42% as DQw6. These results moved us to look for a subtype (Dw) correlation between the DR4 positive individuals and the different humoral immune response patterns. Using oligo-typing methods after previous amplification of the DR4 B1 exon, we subtyped 20 DR4 volunteers, classified as high, intermediate and low responders. We did not find any direct association between the HLA DR4 Dw special subtype in the high or low responders immunized with the SPf 66 vaccine.     

Technical and Clinical Problems in Patients with Simultaneous Implantation of a Cardiac Pacemaker and Spinal Cord Stimulator

Spinal cord stimulators are used to relieve pain associated with peripheral ischemia and angina pectoris. In patients with both a permanent pacemaker (PPM) and a spinal cord stimulator (SCS), electromagnetic signals from the SGS may inhibit the PPM. A bipolar PPM configuration is preferred to minimize myopotential or electromagnetic interference but patients have safely had unipolar devices implanted. We report ten patients (six males and four females; median age 73.3 years) with both a SCS and a PPM implanted between 1987–1991. Intermittent interference with one PPM (Ela Medical Model Opus 3001)was noted after an increase in the output voltage of the SCS for continued clinical efficacy. Inhibition was output voltage dependent, and reversion to the noise mode was frequency dependent. Sensitivity to both could he managed by changing the pacemaker sensitivity. Interference with pocemaker function occurred if the SCS output was set above a voltage and pulse duration which resulted in a product of these values above 1.9–2 mVs. Seven VVI, one VDD, and two DDD PPM had been implanted. In five potients hoth PPM and SCS were unipolar. In two patients the SCS was bipolar and the PPM unipolar, in two potients a bipolar PPM was associated with a bipolar SCS and with one patient, a unipolar SCS. Multiprogrammable and/or bipolar PPMs should be implanted in a patient with a SCS to allow reprogramming of the PPM and to minimize the risk of inter-device interference. Inhibition of the PPM may occur at different SCS stimulation frequencies. The frequency at which inhibition occurs varies with different models of implanted pacemaker