Heterodetic bicyclic decapeptide cyclo (Glu1 -Leu2 -Pro3-Gly4-Ser5-Ile6-Pro7-Ala8) cyclo-(1γ-5β) Phe9-Gly10

Bycyclic peptides are useful model molecules that can mimic the constrained local folding of a great number of natural peptides and proteins, such as ionophoric peptides, enzyme active site, and ligand-receptor active site. The synthesis of the bicyclic title compound with the liquid phase method is described with experimental details. Of particular interest is the heterodetic closure of the second ring. The peptide showed a complexing activity with metal cations like Ba²⁺, Ca²⁺, and Mg²⁺ . The free bicyclic peptide conformation in solution has been studied by means of NMR spectroscopy and a plausible structure model worked out with model building on NMR constraints is proposed.     

Idiopathic Premature Ventricular Contraction Conducting over a Ventricle Myocardial Extension from the Pulmonary Artery

Ventricle myocardial extensions (VMEs) from the right ventricular outflow tract to the pulmonary artery (PA) serve as arrhythmogenic foci for idiopathic ventricular arrhythmias (VAs). Although an autopsy study revealed the heterogeneity of the VME, only the electrocardiographic features of PA‐VAs arising from septal VMEs have been discussed. Here, we describe a case of idiopathic PA‐VAs conducting over a VME accompanied by unique ventricle activation patterns, which contributed to the appearance of an S wave in the inferior limb leads despite an arrythmogenic focus in the outflow tract.     

1H-n.m.r. studies on the specificity of the interaction between bovine pancreatic ribonuclease A and dideoxynucleoside monophosphates

The titration curves of the C-2 histidine protons of bovine pancreatic ribonuclease A in the presence of several dideoxynucleoside monophosphates (dNpdN) were studied by means of proton nuclear magnetic resonance at 270 MHz in order to obtain information on the ligand — RNase A interaction. The changes in the chemical shift and pKs of the C-2 proton resonances of His-12, -48, -119 in the complexes RNase A — dNpdN were smaller than those previously found when the enzyme interacted with mononucleotides. The pK₂ of His-12 was not affected by the interaction of the enzyme with these ligands, whereas, the perturbation of the pK₂ of His-119 was clearly dependent on the nature of the ligand. If there is a pyrimidine nucleoside at the 3′ side of the dideoxynucleoside monophosphates, as in TpdA and TpT, an enhancement due to the well known interaction of the phosphate in p₁, the catalytic site, was found. However, when there is a purine nucleoside, as in dApT and dApdA, a decrease in the pK₂ value was observed and we propose that in such cases the phosphate group interacts in a secondary phosphate binding site, p₂. The results obtained suggest the existence of different specific interactions depending on the structure of the dideoxynucleoside monophosphate studied.     

Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature

A retrospective study on a consecutive series of 116 patients affected by acute leukaemia with documented pulmonary filamentous mycosis (FM) admitted between 1987 and 1992 to 14 tertiary-care hospitals in Italy was made in order to evaluate the characteristics of those patients who developed fatal massive haemoptysis.
In 59/116 cases of pulmonary FM the infection was the principal cause of death and in 12 of these patients a massive haemoptysis was responsible for death. The diagnosis of FM infection was made ante-mortem in only four out of these 12 patients. The autopsy was performed in 11/12 patients and documented a FM infection. The mycetes isolated were: Hyphomycetes spp. (three patients), Mucorales spp. (two patients), Aspergillus spp. (seven patients).
At the time of the massive haemoptysis the mean neutrophil count was 7.2x10⁹/1, and no patient had relevant thrombocytopenia (mean 184x10⁹/1, range 28-350) or coagulative abnormalities. The mean time which elapsed between resolution of chemotherapy-induced neutropenia (WBC <10⁹/1) and occurrence of haemoptysis was 7 d. No signs or symptoms predictive of this fatal complication were identified.
Massive haemoptysis can be the cause of death in patients with acute leukaemia and pulmonary FM which in the majority of patients was not diagnosed in vivo. This complication occurs most frequently shortly after the recovery from chemotherapy-induced aplasia. The mechanism of lesion is unknown, but it may involve the vascular tropism of FM and the release of leucocyte enzymes. Better preventive and therapeutic antifungal treatments are needed to avoid this serious, albeit rare, complication.     

ROLE OF ALCOHOLIC BEVERAGES IN ESSENTIAL HYPERTENSIVE PATIENTS

To evaluate the importance of alcohol and other environmentalfactors in essential hypertensives, we conducted a cross-sectionalstudy on 627 patients (322 women, 305 men) subdivided in foursubgroups according to sex and presence or absence of drug therapy,to evaluate differences due to drugs and changes in life style.Multiple regression analyses were run where systolic and diastolicblood pressures were considered as separate dependent variableswith the following independent variables: age, body mass index,physical activity, alcohol and coffee consumption, smoking,educational level; considered as continuous or categorical variables.Eighty-eight per cent of all patients showed a moderate-lowalcohol intake (1–50 g/day); wine was the preferred beverage.We found a negative independent relationship between mild/moderatealcohol consumption levels and systolic blood pressure in untreatedmen and untreated women, and no relationship between alcoholand diastolic blood pressure in all subgroups considered. Bodymass index and age were positively associated with both systolicand diastolic blood pressure. Our data suggest that mild tomoderate alcohol consumption does not affect blood pressurecontrol in either treated or untreated hypertensive patients.     

1 H-n.m.r. studies on the existence of substrate binding sites in bovine pancreatic ribonuclease A

The reaction of ribonuclease A with either 6-chloropurine riboside 5′-monophosphate or the corresponding nucleoside yields one derivative, with the reagent covalently bound to the α-amino group of Lys-1, called derivative II and derivative E, respectively. We studied by means of ¹H-n.m.r. at 270 MHz the interaction of these derivatives with different purine ligands. The pK values of His-12- and -119 were obtained and compared with those resulting from the interaction with ribonuclease A. The results showed that the interaction of derivative E with 3′AMP is similar to that described for RNase A as the pK₂ of His-12 is increased while that of His-119 remains unaltered. However, derivative II presents some differences as it was found an enhancement of the pK₂ values of both His-12 and His-119. Interaction of derivative II and derivative E with dApdA increases the pK₂ of His-119, whereas a decrease is found when it interacts with ribonuclease A. These results suggest that the phosphate group and the nucleoside of both derivatives are located in regions of the enzyme where natural substrate analogues have secondary interactions and they can be interpreted as additional binding sites.     

S-deoxo-Abu1, Ile3-amaninamide,an inactive amatoxin analogue

The title compound 3, an amatoxin analogue containing l -α-aminobutyric acid instead of l -asparagine in position 1, as in natural toad stool peptides, has been synthesized. It does not inhibit the eukaryotic DNA-dependent RNA polymerase form II (or B) in concentrations up to 10^-4M, whereas 50% inhibition is exerted in M solution by the corresponding Asn-analogue S-deoxo-Ile³-amaninamide 2. The striking difference seems to be due to a relatively small variation of the conformation recognized by sensitive NMR spectroscopic methods.