Bioorganic stereochemistry. A study of the peptide oxazolones from Z-(Aib)n-OH (n = 2–4) in the solid state*

An investigation of the preferred conformations and modes of self-association of the peptide oxazolones from Z(-Aib-)_n-OH (n = 2–4) in the solid state has been performed by infrared absorption. More detailed information on the peptide oxazolone from Z(-Aib-)₃ OH (2) has been obtained using X-ray diffraction. In this compound the conformations of the first two Aib residues differ substantially, only the N -terminal one being found in the usual 3_10- (or α-) helical region of the Ramachandran map. The C=N-bond of the oxazolone group is not conjugated with the lactone moiety. A very weak intermolecular interaction occurs between the urethane N-H and the carbonyl group of the oxazolone ring.     

Cardiac resynchronization improves heart failure in one patient with Myotonic Dystrophy type 1. A case report

We report an improvement in symptoms of heart failure, a reduced left ventricular dysfunction and induced reverse remodelling in one patient with Myotonic Dystrophy type 1, showing an early onset ventricular dysfunction secondary to a complete left bundle branch block (LBBB) who underwent cardioverter defibrillator CRT (ICD- CRT) implantation.Key words: myotonic dystrophy, cardiac resynchronization therapy, sudden death     

Side reactions in solid phase synthesis of histidine-containing peptides

The flow-polyamide synthesis of a histidine-containing sequence (Ac-YDNVLDHLTGR) produced two major impurities which were isolated through Sample Displacement Chromatography and characterized by Fast Atom Bombardment-mass analysis. The impurities correspond to the sequence Ac-YDNVLDH, and to a peptide with the Asp residue cyclized to a succinimide. The latter side-reaction took place during the acetylation procedure, and demands attention where capping procedures are planned in the synthesis of Asp-His sequences.     

Echocardiographic and Doppler Findings in Primary Sarcoma of the Pulmonary Artery

Primary sarcoma of the pulmonary artery is a rare heart tumor. In the reported case, the clinical findings were nonspecific, and were characterized by progressive dyspnea, fever, and a systolic murmur in the pulmonary area. Echocardiographic examination showed an echogenic mass partially obstructing the pulmonary artery trunk, dilation of the right cardiac chambers, and a pressure overload pattern. Doppler and color Doppler demonstrated a high-velocity systolic flow jet in the pulmonary artery due to obstruction of the vessel by the tumor, as well as severe high-velocity tricuspid regurgitation. The patient died suddenly soon thereafter. The autopsy confirmed almost total occlusion of the pulmonary artery by a neoplastic mass. Histopathological diagnosis was primary vascular leiomyosarcoma of the pulmonary artery. In addition, a large tumor embolus had occluded the right pulmonary artery. Doppler echocardiography proved useful in noninvasively recognizing the sarcoma of the pulmonary artery, and explaining the clinical picture and hemodynamic derangements produced by this tumor. This could, in other patients, allow an early diagnosis and timely surgical intervention.     

Cross-bridge kinetics studied with staircase shortening in single fibres from frog skeletal muscle

The kinetics of actin-myosin interaction has been studied in single active muscle fibres by repetitively eliciting tension transients with staircase shortening, consisting in a sequence of step releases of identical size (1--5 nm per half-sarcomere) imposed at regular time intervals (3--11 ms). Under sarcomere length-clamp conditions, the quick phase of tension recovery following each step in the staircase is the manifestation of the working stroke by synchronized cross-bridges. Different average shortening velocities are obtained by varying both the size of the step and the time interval between steps. Ti, the tension just before each step in the sequence, and T2, the tension attained at the end of the quick phase of tension recovery, decrease with the number of steps, reaching a steady state value, which is lower the larger the shortening velocity. In agreement with previous results on tension response to steady shortening, the overall shortening necessary to approach the steady state values of Ti and T2 is about 15 nm. The normalized amplitude of quick tension recovery (T2r), which is measured by the ratio of the amount of tension recovered at the end of the quick phase (T2--T1) over the tension drop simultaneous with the step (Ti--T1), has been used to measure the extent of the working stroke elicited by each step in the staircase. The steady state value of T2r decreases progressively with the increase of shortening velocity. At velocities higher than 0.5 μm s−1 per half-sarcomere the steady state value of T2r is attained after a transitory depression, which reaches a maximum for an amount of overall shortening increasing from about 8 nm up to about 13 nm with increase in shortening velocity from 0.5 to 1.4 μm s−1 per half-sarcomere. The velocity-dependent transitory depression of T2r can be explained with the mechanical-kinetic model described previously. In the model cross-bridges cycle through two pathways distinct for the kinetics of the detachment/reattachment process. Shortening promotes are distribution of cross-bridges interacting in the isometric conditions among the various states of the force-generating process. Shortening at high speed, preventing most of cross-bridges from undergoing the relatively fast (100 s−1) detachment/reattachment process, uncovers a rate limiting step in the cycle at the end of the 12 nm working stroke. Under these conditions, the finding that the fraction of the working stroke elicited by each step is transitorily depressed with respect to the steady state value reveals that in the original isometric state a large fraction of interacting cross-bridges was accumulated near the beginning of the working stroke This revised version was published online in July 2006 with corrections to the Cover Date.     

Glycated plasma proteins in experimentally induced acute toxic renal failure by dichromate injection: evidence for loss with urine and decreased plasma levels.

In the rat, a single subcutaneous injection of sodium dichromate (20 mg/kg) causes acute renal injury and significant polyuria, proteinuria, and glycosuria (peaking 2–3 days after treatment, and returning to normal by day 5) without any changes in the plasma levels of protein, glucose, and glycated haemoglobin. Surprisingly, the percentage levels of glycated plasma total proteins and albumin (assayed by boronate affinity chromatography) transiently and significantly decrease during recovery from proteinuria (days 4 and 10 after treatment) and were found in the normal range of values by day 18. These changes are concomitant with a significant increase in the percentage level of glycated albumin in urine. Constancy of total plasma protein and the temporal pattern of levels of glycation suggest that changes in the percentage values of glycated proteins are secondary to a transient selective loss of glycated plasma proteins in urine.     

Caffeine Stimulates in vivo Platelet Reactivity

ABSTRACT The effect of coffee drinking on platelet reactivity was studied in 12 healthy subjects. Plasma beta-thromboglobulin concentration was determined before and one hour after administration of 100 mg of caffeine, corresponding to one cup of coffee. Mean values were 47.0±19.3 and 179.3±85.5 ng/ml before and after caffeine administration respectively. The increase, 298±150%, is highly significant (p<0.001).     

Neurotensin-like immunoreactivity in the brain of the chicken, Gallus domesticus

The distribution of neurons containing neurotensin in the central nervous system of the chicken was studied immunohistochemically. The majority of the neurotensin-immunoreactive (-ir) cell bodies were located in the hypothalamus. Extensive groups of labelled perikarya were found in the hypothalamic periventricular nucleus and in the magnocellular periventricular nucleus. In addition, ir-perikarya were scattered throughout the lateral hypothalamic area and in the ventromedial hypothalamic nucleus. The only extrahypothalamic site of ir-perikarya was in the region immediately under the lateral forebrain bundle. Immunoreactive fibres were detected in the hippocampus, the parahippocampal area, the hypothalamus, the region of the tractus corticohabenular and corticoseptal tracts, the median eminence, the region above the posterior commissure and in the intercollicular nucleus. The distribution pattern of the neurotensin-ir neurons suggests that neurotensin-like peptides are involved in the hypophysiotropic functions.