Functional hypothalamic amenorrhoea ­ diagnostic challenges, monitoring, and treatment.

Functional hypothalamic amenorrhoea (FHA) is associated with functional inhibition of the hypothalamic-pituitary-ovarian axis. Causes of FHA can be classified into the three groups: 1) stress-related factors, 2) consequences of weight loss and/or underweight, and 3) consequences of physical exercise or practicing sports. Diagnosis of FHA should be based on a history of menstrual disorders. During physical examination, patients with FHA present with secondary and tertiary sex characteristics specific for the pubertal stage preceding development of the condition and with the signs of hypoestrogenism. Laboratory results determine further management of patients with amenorrhea, and thus their correct interpretation is vital for making appropriate therapeutic decisions. Treatment of chronic anovulation, menstrual disorders, and secondary amenorrhea resulting from hypothalamic disorders should be aimed at the elimination of the primary cause, i.e. a decrease in psycho-emotional strain, avoidance of chronic stressors, reduction of physical exercise level, or optimisation of BMI in patients who lose weight. If menses do not resume after a period of six months or primary causative treatment is not possible, neutralisation of hypoestrogenism consequences, especially unfavourable effects on bone metabolism, become the main issue. Previous studies have shown that oestroprogestagen therapy is useful in both the treatment of menstrual disorders and normalisation of bone mineral density. Hormonal preparations should be introduced into therapeutic protocol on an individualised basis.

New imidazoline/α(2)-adrenoceptors affecting compounds-4(5)-(2-aminoethyl)imidazoline (dihydrohistamine) derivatives. Synthesis and receptor affinity studies.

Compilation of agmatine structure and imidazoline moiety leads to a new group of imidazoline/α(2)-adrenoceptor ligands, 4(5)-(2-aminoethyl)imidazoline derivatives. In this study the exploration of previously unknown 4(5)-(2-aminoethyl)imidazolines including the analogues of reported imidazoline and α(2)-aderenoceptors ligands: clonidine, rilmenidine, idazoxan, efaroxan, antazoline, tracizoline is described. The synthesis of a variety of novel 4(5)-(2-aminoethyl)imidazolines and their I(1), I(2), α(2)-adrenoceptors affinities are reported.

Glutamine analogues containing a keto function--novel inhibitors of fungal glucosamine-6-phosphate synthase.

A series of novel inhibitors of glucosamine-6-phosphate synthase, analogues of AADP and BADP, have been synthesized and their inhibitory, lipophilic and antifungal properties have been tested. The improvement in lipophilicity has not much affected the antifungal activity of the new compounds. Dipeptides containing norvaline and selected inhibitors have shown substantial activity against S. cerevisiae and C. glabrata and only poor activity against C. albicans strain. These peptides do not seem to be toxic towards human cells.

Anticandidal properties of N-acylpeptides containing an inhibitor of glucosamine-6-phosphate synthase.

A series of N-acyl peptides 1-9, containing an inhibitor of glucosamine-6-phosphate synthase have been synthesised and tested against Candida strains. N-Acylated peptides inhibit glucosamine-6-phosphate synthase in cell free extracts from Candida albicans. Antifungal activities of the tested compounds correlated with their lipophilic properties. Peptides acylated with decanoic acid were found to be the most potent in the series. N-decanoylpeptides also showed activity against Candida albicans Gu5 resistant mutant with Cdr1 and Cdr2 drug extrusion proteins that causes MDR by an active efflux mechanism.