[Algorithm for stratification of women for differentiated therapy of menopausal syndrome in combination with perimenopausal melatonin deficiency syndrome.]

Climacteric syndrome (CS) is considered to be a frequent manifestation of pathological menopause. Menopause associated not only with deficiency of sex steroids, decrease of melatonin secretion is observed. Perimenopausal melatonin deficiency syndrome (SPDM) is the complex of symptoms, which is often formed amid decrease of melatonin synthesis and clinically characterized by the prevalence of complaints of sleep disorders (problems), bodily pain, depression, anxiety/fears and somatic symptoms. CS and SPD are co-morbidities, that impair the «women menopausal health¼. The article presents the stratification algorithm of peri- and post-menopausal women with the co-morbid pathology of CS and SPDM for selection of differentiated therapy. The algorithm involves detection of indications for monotherapy with melatonin or synthetic genistein, and for combined treatment with menopausal hormone therapy. The usage of this concept is reasonable for improvement of treatment efficiency of co-morbid pathology of CS and SPDM, for quality of life improvement and for induction of active ageing of women of senior group.

[Perimenopausal melatonin deficiency syndrome in system of personalized management of quality of life of women with climacteric syndrome.]

The aim of our study is to search diagnostic tools for early detection of prenosological melatonin deficiency in postmenopausal women and women in menopausal transition with climacteric syndrome for establishment effective personalized prevention and treatment programs. In this study 221 women were enrolled. They were divided into four groups: the 1st group - 39 women in menopausal transition with climacteric syndrome, the 2nd group - 104 menopausal women with climacteric syndrome, the 3rd group - 41 women with physiological menopause, the 4th group - 37 healthy women in reproductive-age. The study was conducted using the test for detecting melatonin deficiency, women's health questionnaire (WHQ), and morning level detection of 6-sulfatoxymelatonin in urine. A new prenosological state - perimenopausal melatonin deficiency syndrome was build on the data obtained. It is appropriate to evaluate prognosis of melatonin treatment in women with climacteric syndrome during the planning of personalized prevention and treatment programs. The assessment of prognosis is carried out with the help of the discriminant mathematical model, which is the basis of personalized management of quality of life in women with climacteric syndrome. This system is based on participatory principles.

C3a and C5a anaphylatoxins bind to heparin-based sorbent in low density lipoprotein apheresis: in vitro and in vivo investigations.

Plasmasorption on a heparin-based sorbent was performed in vitro. It demonstrated affinity of the C3a and C5a anaphylatoxins for the sorbent: C3a was removed almost completely (97%), and the C5a concentration decreased on average by 55%. The plasma level of C3a and C5a complement components was also monitored during the procedure of clinical extracorporeal low density lipoprotein (LDL) apheresis on the sorbent in patients with familial hypercholesterolemia. A two- to threefold increase in C3a (up to 1,500 ng/ml) was observed after plasma separation by the IBM 2997 cell sorter. Subsequent processing of the plasma through the column led to the low level of C3a detected (less than 50 ng/ml), demonstrating significant uptake of C3a by the sorbent column. The removed C3a was found in the eluate obtained after regeneration of the sorbent with 2 M NaCl solution. No significant increase in C5a was found during the procedure. Nevertheless, some C5a was detected in the eluate from the sorbent. The content of C3a and C5a in patients blood after the treatment was approximately the same as it was initially, 200-500 ng/ml for C3a and less than 10 ng/ml for C5a. The removal of C3a and C5a anaphylatoxins by heparin-based sorbent should be regarded as an advantage of this type of plasmasorbent.

Apheresis of low density lipoproteins using a heparin-based sorbent with low antithrombin III binding capacity.

A sorbent based on heparin fraction with low affinity for antithrombin III is proposed for low density lipoproteins apheresis in hypercholesterolemia. Heparin was fractionated on antithrombin III-Sepharose; fractions with high and low affinity for antithrombin III were immobilized on CNBr-activated Sepharose 4B. Both sorbents appeared to have an LDL-binding capacity essentially similar to that of the sorbent based on unfractionated heparin. However only plasmasorption on a low affinity heparin-containing sorbent did not reduce plasma antithrombin III. Hence the use of this sorbent may be advantageous over the currently applied sorbents with unfractionated heparin in the treatment of familial hypercholesterolemia.

[Use of avidin for speedy clearance of biotinylated immunoglobulins from the blood flow]. / Ispol'zovanie avidina dlia uskorennogo vyvedeniia biotinilirovannykh immunoglobulinov iz krovotoka.

The phenomenon of a hundredfold more rapid blood clearance of biotinylated immunoglobulins after post-injection of an equiponderate dose of avidin is described. The concentration of 125I-labeled biotinylated IgG in rat circulation slowly decreased to 20% of the initial level in 24 hours. Avidin injection at any moment of this period induced a 90-95% reduction of blood radioactivity in 15 minutes. Up to 70% of the radioactivity was recovered in the liver. The technique of enhanced blood clearance developed in rats was checked in dogs using biotinylated monoclonal anti-human fibrinogen antibodies, capable of concentrating in dog thrombus. The results obtained offer the possibility of thrombus/blood contrast increase in radioimmunoimaging.

Heparin-sorbent for low density lipoproteins removal in hypercholesterolemia.

Heparin-sorbent was developed in the USSR Cardiology Research Center for LDL-apheresis in patients with familial hypercholesterolemia. Clinical trials of the sorbent were started in 1985. Heparin-sorbent has a high capacity for LDL. One column (400ml) can remove 3 - 6g of LDL cholesterol, depending on the initial LDL content in the plasma. The sorbent demonstrates a high stability, it can withstand more then 75 sorbtion-desorbtion cycles with only a slight loss of the initial capacity. It means that one column can work for 1,5-2,0 years when used weekly. Heparin-sorbent is the sorbent of limited selectivity, apo-B content in eluate is 40-60% of the total protein content, but it is important that it does not bind HDL.

Rapid blood clearance of biotinylated IgG after infusion of avidin.

The techniques of immunotherapy and radioimmunoimaging suffer from the problem of background: intravenously injected antibodies remain in the circulation much longer than it is necessary for effective binding to the target. Various approaches, including the postinjection of second antibodies, were explored to overcome the problem with some success. The phenomenon of a 100-fold more rapid blood clearance of biotinylated immunoglobulins after postinjection of an equivalent dose of avidin is described. The concentration of 125I-labeled biotinylated IgG in the circulation of rats slowly decreased to 20% of initial in 24 hr. Avidin injection at any interval during this period induced 90-95% reduction of radioactivity in blood in 15 min. Up to 70% of the radioactivity was recovered in the liver. Avidin-induced blood clearance of biotinylated immunoglobulins may find applications in immunotherapy and radio- or nuclear magnetic resonance immunoimaging.