Conformational investigation of α,β-dehydropeptides VII*. Conformation of Ac-Pro-ΔAla-NHCH3 and Ac-Pro-(E)-ΔAbu-NHCH3: comparison with (Z)-substituted α,β-dehydropeptides†

The crystal structure and solution conformation of Ac-Pro-ΔAla-NHCH₃ and the solution conformation of Ac-Pro-(E)-ΔAbu-NHCH₃ were investigated by X-ray diffraction method and NMR, FTIR and CD spectroscopies. Ac-Pro-ΔAla-NHCH, adopts an extended-coil conformation in the crystalline state, with all-trans peptide bonds and the ΔAla residue being in a C₅ form, φ₁=– 71.4(4), ψ₁=– 16.8(4), φ₂=– 178.4(3) and ψ₂= 172.4(3)°. In inert solvents the peptide also assumes the C₅ conformation, but a γ-turn on the Pro residue cannot be ruled out. In these solvents Ac-Pro-(E)- ΔAbu-NHCH₃ accommodates a βII-turn, but a minor conformer with a nearly planar disposition of the CO—NH and C=C bonds (φ₂～0°) is also present. Previous spectroscopic studies of the (Z)-substituted dehydropeptides Ac-Pro-(Z)- ΔAbu-NHCH, and Ac-Pro-ΔVal-NHCH₃ reveal that both peptides prefer a βII-turn in solution. Comparison of conformations in the family of four Ac-Pro-ΔXaa-NHCH₃ peptides let us formulate the following order of their tendency to adopt a β-turn in solution: (Z)- ΔAbu > (E)- δAbu > ΔVal; ΔAla does not. None of the folded structures formed by the four compounds is stable in strongly solvating media. © Munksgaard 1996.     

PROLONGED EXPRESSION OF THE c-kit RECEPTOR IN GERM CELLS OF INTERSEX FETAL TESTES

Stem cell factor (SCF) and its receptor Kit encoded by the c- kit proto-oncogene are crucial for the development and migration of primordial germ cells in rodents. The expression of Kit has been examined immunohistochemically in gonads obtained from five specimens of fetal tissues with intersex conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects expressed Kit at a later developmental age than controls, in which no Kit protein was detectable beyond the 15th week of gestation. This finding may indicate a disturbance of the chronology of germ cell development, or it may suggest a change of the regulation of c- kit expression in subjects with disorders of gonadal development.     

Synthesis of derivatives of phosphonic glutathione analogs*

Five analogs of S-t-butyl glutathione containing phosphonic analogs of glycine and glutamic acid were obtained by standard procedures of MA activation in solution. Simultaneous deprotection of phosphonic, carboxylic and amino groups was achieved in the silylation reaction.     

Surprising Pharmacological Activity of Analogues Designed by Substitution of Position 3 in Arginine Vasopressin (AVP) and 8-D-Arginine Vasopressin with l-2-Naphthylalanine

In an attempt to develop more active and selective analogues of arginine vasopressin (AVP), two peptides have been designed, synthesized and tested for vasopressor (V₁-receptors) and antidiuretic (V₂-receptors) activities. We also estimated the uterotonic and anti-uterotonic activities of these compounds in-vitro. The first peptide, [(l -2-Nal)³] AVP is a highly active V₂-agonist. The second analogue, [(l -2-Nal)³, (d -Arg)⁸]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first V₁-antagonist devoid of anti-uterotonic activity. High antipressor potency of the second peptide was achieved without modification of position 1.     

PLASMA TESTOSTERONE AND ANDROSTENEDIONE LEVELS DURING MONITORED INDUCTION OF OVULATION IN INFERTILE WOMEN WITH 'SIMPLE' AMENORRHOEA AND WITH THE POLYCYSTIC OVARY SYNDROME

Twenty-seven infertile patients with ‘simple’ amenorrhoea-oligomenorrhoea and eighteen with the polycystic ovary (PCO) syndrome were treated for induction of ovulation with clomiphene, human menopausal gonadotrophin and human chorionic gonadotrophin. The treatment was monitored by plasma oestradiol, testosterone, andfostenedione and progesterone estimation. Women with PCO had significantly higher plasma androgen levels than women with ‘simple’ amenorrhoea (P < 0.01 to P < 0.001) both before treatment and during induction of ovulation. When ovulation was induced the pregnancy rate for women with the PCO syndrome with elevated androgens was 21% while for those with uncomplicated amenorrhoea it was 75%. It is concluded that high levels of circulating androgens might be a factor preventing conception in some patients in whom ovulation is apparently successfully induced.     

Atrial natriuretic factor enhances vasopressin-induced bradycardia in normotensive (WKY) but not in spontaneously hypertensive (SHR) rats

Effect of elevation of blood atrial natriuretic peptide (rat 1-28 ANF) level on pressor responses and bradycardia elicited by vasopressin (AVP) was compared in conscious normotensive (WKY) and spontaneously hypertensive (SHR) rats 14-16 weeks old, instrumented with arterial and venous catheters 1-2 days prior to the experiment. Blood pressure and heart rate were determined before and after i.v. injection of 2.5, 5.0 and 10.0 ng of AVP under control conditions (infusion of saline) and during infusion of ANF at a rate of 0.3 micrograms kg-1 min-1. Administration of ANF did not influence pressor responsiveness to AVP (determined as a maximum increase of systolic blood pressure) neither in WKY nor in SHR, however, it elongated the pressor response to the lowest dose of AVP in WKY. Atrial natriuretic factor significantly enhanced bradycardic responsiveness to AVP (determined as a maximum decrease of HR) in WKY but not in SHR. Reduction of heart rate in relation to the corresponding elevation of the systolic pressure (delta HR/delta SP) was also significantly greater in WKY but not in SHR. This effect was significant when blood pressure increases elicited by AVP did not exceed 40 mmHg. The results suggest that ANF potentiates reflex bradycardia elicited by AVP. This action may be a mechanism buffering blood pressure increases in response to AVP. Absence of this effect in SHR may be related to the impairment of the reflex control of blood pressure in this strain.     

Evaluation of Sinus and Atrioventricular Nodes Function in Patients with Vasovagal Syncope

Aim: Evaluation of sinus and atrioventricular nodes function as a potential factor responsible for prolonged bradycardia, asystole, or both in patients with cardioinhibitory and non-cardioinhibitory vasovagal syncope (VVS). The study included 258 patients (mean age = 47.7 ± 17.2 years; range 18–62; 147 females) with a history of VVS. They were divided among four groups, according to results of head-up tilt test (HUTT).
Methods: All patients underwent standard HUTT, carotid sinus massage (CSM), and rapid transesophageal atrial pacing for evaluation of total sinus node recovery time (SNRT), and corrected sinus node recovery time (CNRT), resting and intrinsic heart rate (IHR), and Wenckebach point (WP). Values of SNRT > 1,500 ms, CNRT > 525 ms, WP < 130 bpm, and CSM-induced pause >3 seconds were considered abnormal.
Results: SNRT, CNRT, and WP before and after pharmacological blockade, resting heart rate, and IHR did not differ significantly among the study groups. The prevalence of mild sinus node dysfunction (SND), decreased value of WP, and cardioinhibitory carotid sinus hypersensitivity was similar among all study groups.
Conclusions: The prevalence of mild SND, abnormal atrioventricular conduction, and carotid sinus hypersensitivity (CSH) was similar among patients with VVS regardless of the type of vasovagal reaction. SND and CSH do not seem to play an important role in the pathogenesis of cardioinhibitory vasovagal reaction.     

Adhesion of Streptococcus rattus and Streptococcus mutans to metal surfaces

Abstract – The adhesion of Streptococcus rattus BHT and Streptococcus mutans IB to metal specimens of amalgam, silver, tin and copper was studied using (6-³H)thymidine labeled cells. In the standard assay the metal specimens were suspended by a nylon thread in an adhesion solution containing a chemically defined bacterial growth medium (FMC), sucrose, and radiolabeled bacteria, Maximum amounts of adhering bacteria were obtained after about 100 min of incubation. Saturation of the metal specimens with bacteria was not observed. Both strains also adhered in the absence of sucrose, indicating that glucan formation was not necessary for adhesion. However, in the presence of glucose, adhesion was only 26–45% of that observed in the presence of equimolar sucrose. Sucrose-dependent stimulation of adhesion seemed to be due to increased cell-to-cell adhesion capacity. Isolated radiolabeled water-insoluble and watersoluble polysaccharides produced from sucrose by S. rattus BHT were not adsorbed to the metal surfaces.