THE ROLE OF MYOSTATIN AND PROTEIN KINASE-B IN THE DEVELOPMENT OF PROTEIN-ENERGY DEFICIENCY IN PATIENTS WITH END-STAGE RENAL DISEASE ON HEMODIALYSIS.

In patients with chronic renal failure receiving hemodialysis, the development of protein-energy wasting (PEW) has a significant impact on the quality and duration of life. Myostatin (MSTN) and protein kinase-ß (AKT) play an important role in this process. The aim of our study was to assess the contribution of these molecular markers of muscle metabolism to the development of PEW in patients with chronic kidney disease stage 5D (CKD5D). The study included 80 patients with CKD5D. All patients underwent anthropometric research, hand dynamometry, bio-impedancemetry. MSTN and AKT levels were determined in the blood by ELISA. In the study, the prevalence of PEW was 90%. We have proposed a catabolic muscle tissue index (CMTI), which takes into account the complex effect of the relationship between MSTN and AKT on the development of PEW. An increase in this index in degrees from 0-2 characterizes the prevalence of catabolic processes in muscle tissue. There is an increase in CMTI with the progression of nutritional disorders in patients on hemodialysis (HD). An increase in CMTI is associated with a decrease in muscle strength, muscle mass (measured by the diameter of the shoulder). No correlation was found between CMTI and gender, age, or bio-impedance indicators, which requires further investigation.

[Juvenile xanthogranuloma of the eye]. / Iuvenil'naia ksantogranulema organa zreniia.

Juvenile xanthogranuloma (JX) is a benign growth of fibrohistiocytoma range that mainly affects children. The most frequent localization of the tumor is skin integument. Non-cutaneous forms of JX are found in 5-10% of cases; they are manifested as deep lesions of soft tissues, involvement of various organs (oropharynx, lungs, liver, spleen, pericardium, gastrointestinal tract, central nervous system, bone marrow) including the organ of vision. JX can develop in any part of the eye and its appendages. Taking into consideration how rare this pathology is, its diagnosis and treatment are complicated. The article reviews 2 clinical cases of JX observed by the authors.

[A man's role in recurrent miscarriage in a spouse].

In a review article based on the published literature and their own research, the authors examine the role of a man in recurrent miscarriage and reproductive losses in a spouse. Detailed description is presented of the negative impact of elevated levels of sperm DNA fragmentation on the course of pregnancy, especially during the first trimester, on the occurrence of recurrent miscarriage or missed abortion, on the effectiveness of assisted reproductive technology (ART) programs. The etiology and pathogenesis of damage to sperm DNA are described. Outlined are positive effects of correcting adverse lifestyle factors, the role of varicocelectomy and antioxidant therapy, and advances in ART. The review specifies the role of different male karyotype abnormalities (translocations) in the pathogenesis of pregnancy loss. The implications of urologic surgery, preimplantation genetic diagnosis in solving this problem are discussed. New treatment strategies using correction of male disorders for couples with recurrent miscarriage are offered.

Poly(2-hydroxyethyl methacrylate) microspheres/liquid poly(dimethylsiloxane) composition for correction of small defects in face: histological evaluation in animal experiment.

Two kinds of composition based on commercial liquid poly(dimethylsiloxane) and laboratory-made poly(2-hydroxyethyl methacrylate) (PHEMA) microspheres of different size fractions (30-40 or 125-180 microm) were prepared. Tissue reaction on injection of the compositions, optimum microsphere size and morphology were investigated in the experiments on rats. The microspheres induced foreign body reaction characterized by an increased content of fibroblasts and mild infiltration of injection field by inflammatory cells. The 125-180 microm microspheres seemed to be well covered with poly(dimethylsiloxane) and more uniformly distributed in the tissue than the 30-40 microm ones. As a result, the extent of foreign body reaction induced by the former microspheres was somewhat lower than that induced by the latter. Moreover, time-dependent degradation of 30-40 microm PHEMA microspheres was more pronounced than that of 125-180 microm ones, which can affect duration of the aesthetic effect after prospective facioplasty. Results of histological investigations demonstrate a good prospect of the proposed composition for contour and bulk facioplasty of small soft tissue defects and skin wrinkles.

The capacity of mesenchymal stem cells for neural differentiation in vitro.

It has been shown that mesenchymal stem cells (MSCs) of bone marrow from newborn rabbits can be induced for neuronal differentiation. The epidermal growth factor (EGF) introduced in the culture at the rate of 2 ng/ml is able to promote differentiation of neurons from bone marrow mesenchymal stem cells in 27 days of cultivation. Differentiated cells were marked by monoclonal antibodies to 70 kDa neurofilaments. The data obtained show a possibility of using bone marrow stem cells in therapy of neurodegenerative diseases.

Transplantation of cultured human neural stem cells in rabbits with experimental laser-induced damage to the retina.

Cultured neural stem/progenitor cells from human fetal brain were transplanted into the retrobulbar and suprachoroid space in rabbits with laser-induced damage to the retina. Transplanted cells survived, retained multipotent activity, migrated into the zone of injury, and stimulated reparation and regeneration in the traumatized retina.

Effects of a phasic oral contraceptive containing desogestrel on facial seborrhea and acne.

BACKGROUND: The combined oral contraceptive containing ethinylestradiol and the selective progestogen, desogestrel, in a phasic regimen (DSG-OC, Tri-merci) has been shown to reduce facial oiliness. OBJECTIVE: This study was designed to evaluate further the effects of this OC on the skin of women with facial seborrhea and mild or moderate acne. DESIGN AND METHODS: This was an open, noncomparative, bicenter study in 60 healthy Russian women, aged 18-30 years, with facial seborrhea and mild or moderate facial acne, who wished to use oral contraception. All women received the OC containing desogestrel (50/100/150 microg) and ethinylestradiol (35/30/30 microg) for three phases of 7 days followed by a 7-day pill-free interval, for six cycles. Seborrhea was assessed using the Sebutape technique, in which strips of adhesive microporous polymeric film pressed onto facial sites are used to assess sebaceous activity. Acne was assessed by counting facial lesions. Subjective evaluations of skin and hair condition, patients' feelings to them and satisfaction with the OC were made using a visual analogue scale (VAS). Assessments were made at baseline, and after one, three and six treatment cycles. RESULTS: Sebutape assessments of seborrhea were significantly improved, on the right and left cheeks, after one treatment cycle, and on the forehead after three treatment cycles. These improvements increased steadily and were much larger at the end of Cycle 6. Acne grades were significantly improved after three and six treatment cycles. VAS scores in response to questions dealing with self-esteem and self-confidence were significantly improved after three cycles and in some cases after just one cycle. The women's views of their skin and hair (greasiness) were correspondingly significantly improved. Subjective assessments indicated that after one, three and six cycles, 69%, 93% and 98%, respectively, of women were satisfied or very satisfied with the DSG-OC. CONCLUSION: In women with facial seborrhea and mild or moderate acne, the use of DSG-OC appears to improve seborrhea after just one cycle and acne grades after three cycles. These improvements are accompanied by increases in self-esteem and confidence.

[Biological role of a neurotrophic factor fragment from pigment epithelium: structure-functional homology with a differentiation factor for the HL-60 cell line]. / Biologicheskaia rol' fragmenta neirotrfnogo faktor iz pigmentnogo épiteliia: strukturno-funktsional'naia gomologiia s faktorom differentsirovki kletok linii HL-60.

It was shown that the full-size neurotrophic factor from pigment epithelium (PEDF) induces the cell differentiation of the human promyelocyte leukemia cell line HL-60. A structural analysis of PEDF revealed in its C-terminal region a six-membered peptide fragment PEDF-(352-357) (PEDF-6) whose sequence is highly homologous to the 41-46 fragment of the active site of the human leukocyte differentiation factor HLDF (HLDF-6). The biological effect of PEDF and synthetic peptides PEDF-6 and HLDF-6 on the HL-60 cells and the early gastrula ectoderm of Xenopus laevis embryos was studied. On the basis of the structural and functional homologies of HLDF, PEDF, and their homologous peptides and the computer models of the spatial structures of the full-size PEDF and the PEDF with the C-terminal fragment split off tby the cleavage of the Leu380-Thr381 bond in the serpin loop, a hypothesis on the functional role of the serpin loop in PEDF was put forward.

[Adjuvant chemotherapy with anthracyclines in comparison with the standard combination of CMF in breast cancer with high risk of relapse]. / Antratsiklin-soderzhashchaia ad''iuvantnaia khimioterapiia v sravnenii s klassicheskoi skhemoi CMF u bol'nykh rakom molochnoi zhelezy s vysokim riskom retsidiva.

The effectiveness of adjuvant therapy with adriablastin and doxorubicin for breast cancer has been compared to that of standard CMF. During 1985-1990, the study included 349 patients with T1-2N2M0 and T3N0-2M0 tumors; mean age--46 yrs; mean follow-up--96.7 months. Overall survival rate in the doxorubicin group was 73%, CMF--62%; relapse-free survival--62.1 and 55%, respectively. The absolute difference in overall survival rates (11%) proved barely significant (p = 0.056). However, the difference in overall survival (p < 0.05) after anthracyclines and CMF in patients with tumors T1-2N2M0 and T3N1M0 was significant and in favor of the former. As far as frequency and degree of side-effects is concerned, their patterns were practically identical in both groups, except for the significantly higher frequency of cardiotoxity and complete alopecia in doxorubicin therapy. Cardiotoxic complication rate was significantly reduced from 13.8 to 3.9% by cardioxane treatment.

[The effectiveness of adjuvant chemotherapy with anthracyclines (adriablastin, doxorubicin) for stage-IIb-IIIa breast cancer]. / Effektivnost' ad''iuvantnoi khimioterapii antratsiklinami (adriablastinom, doksorubitsinom) u bol'nykh rakom molochnoi zhelezy IIb-IIIa stadii.

The effectiveness of adjuvant treatment with anthracyclins (adriablastin, doxorubicin) and standard CMF regimens for breast tumors has been compared. The study included 349 patients with stage IIB-IIIA tumors (T1-2N2M0, T3N0-2M0) (mean age-46 years) during 1985-1990 follow-up-60.38 months. In the doxorubicin group, overall 5-year survival was 73 +/- 8%, in the CMF group-62 +/- 8%. Recurrence-free 5-year survival was 62 +/- 8 and 55 +/- 8%, respectively. The differences are not significant. A stage-related analysis established a significant difference in overall survival in patients with T1-2N2M0 tumors (c-sqare 9.92, p < 0.01). However, due to a small number of cases, the phenomenon requires further study. Although adriablastin treatment involved a significantly higher frequency of carciotoxic symptoms, complete alopecia and dyspeptic complication, a systemic administration of cardioxan and effective antiemetic drugs was lacking.

Inductive capacity of living eye tissues from adult frogs.

The aim of the present work has been to demonstrate the inducing capacity of living homogenous undamaged tissues from adult frogs. Tissues from the eyes of adult frogs Xenopus laevis: retina (R), pigmented epithelium (PE), lens epithelium (LE), and the forebrain (B) as a control, were tested for their inducing capacity using early gastrula ectoderm. To exclude the possibility of ad-mixture of inducing cells in early gastrula ectoderm the transfilter induction technique was used throughout. The results show that the tissues used in the cases of most intense induction tended to induce similar cell types: both R and PE induce R + PE together with adjoining neural cells and secondary lens cells. LE induces lentoids (L) and B cells induce neuroids. In each case epidermis surrounds the explants filled with ectomesenchyme (EM) and melanophores (M). Immunofluorescence reactions clarified the nature of lens cells. This discovery indicates that cells of adult tissues continue throughout life producing substances which are able to promote the appearance of cells of the same type during development. Probably they also serve to mediate interrelations between cells of these tissues, regulating the stability of their differentiation in the adult state, as well.

[Breast-preserving (conservative) therapy of breast cancer]. / Organosokhraniaiushchee (konservativnoe) lechenie raka molochnoi zhelezy.

Conservative surgery (sectoral or segmental + axillary dissection) was performed in 278 patients with breast cancer (T1-2N0M0) at the Institute Clinic in 1990-1995. Following thorough morphological examination. 148 patients (53.2%) were selected to form a clinical study group for an investigation of the role of postoperative radiotherapy in the conservative treatment of breast cancer. Two groups-irradiation of the remaining breast tissue and controls-were formed on the basis of randomized data. Follow-up continued 3-60 months (average duration-37.7 months). Local recurrence was detected in 3 out of 73 (4.2%) patients of group I. A similar relapse was detected in 6 out of 75 (8.0%) patients of group II. No significant difference in total survival rates in the two groups was observed (97.3 and 96.0%; p > 0.05).

[Preliminary results of the Russia (St.Petersburg)/WHO program for the evaluation of the effectiveness of breast self-examination]. / Promezhutochnye rezul'taty programmy Rocciia (Sankt-Peterburg)/VOZ po otsenke éffektivnosti samoobsledovaniia molochnykh zhelez.

Although an absolute difference of 10% (65,4 vs. 54,9%) in 5- and 9-year survival in breast cancer patients was recorded between the self-examination and control groups a large-scale randomized population-controlled study of 122,471 females has failed to provide significant differences (Log-rank - 0,774, p > 0.05). No significant decrease in mortality was observed in the self-examination group as compared with the untrained controls. As a result of providing more information to the population on risk factors. twice as many of the trained females consulted oncologists. Also, the number of early detection of breast tumor (T1-2NOMO) in both groups was 1,5-2,5 times that recorded elsewhere. Since 3,55 per 1,000 patients with breast tumors per year, aged 50-59, died of cardio-vascular disease, i.e. 3,1 times the expected 1,16 per 1,000, more attention should be focused on timely diagnosis and treatment of concomitant cardio-vascular pathology.

Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer.

BACKGROUND: A phase III randomized trial was activated to evaluate the efficacy of preoperative combined chemotherapy and radiotherapy as compared to preoperative radiation therapy alone, in patients with breast cancer presenting with a clinical stage of IIb-IIIa (TNM classification). PATIENTS AND METHODS: From 1985 to 1990, 271 patients, aged 27-55 years, with stage IIb-IIIa breast cancer were randomized to receive either one or two courses of thiotepa 20 mg (i.m. injection) on the days 1, 3, 5, 7, 9, 11 (total dose per course 120 mg), methotrexate 40 mg/m2, i.v. on days 1 and 8, and 5-fluorouracil 500 mg/m2, i.v. on days 1 and 8 (TMF regimen) plus radiotherapy (Group I, 137 patients), or preoperative radiation therapy only (Group II, 134 patients). After the preoperative treatment all patients underwent mastectomy and complete axillary clearance, and then received 4-6 courses of TMF. The trial was conducted in a single institution (N.N. Petrov Research Institute of Oncology, St. Petersburg). RESULTS: Histopathological assessment of the mastectomy specimens showed complete regression of the tumour in 29.1% of the patients in group I and in 19.4% of the patients e.c. in group II. The estimated 5-year overall survival percentages were 86.1% for group I, and 78.3% for group II (P > 0.05). 5-year disease-free survival percentages were 81.0% and 71.6%, respectively (p < 0.05). CONCLUSIONS: Despite the low number of the patients included in the trial, we were able to detect a significant improvement in treatment results with a combination of chemotherapy and radiation therapy given prior to mastectomy over those of local therapy alone with radiation therapy followed by mastectomy, for average- and high-risk patients with operable breast cancer.

[Neoadjuvant chemotherapy in combined treatment of breast cancer]. / Neoad''iuvantnaia khimioterapiia v kompleksnom lechenii raka molochnoi zelezy.

The paper deals with results of complex treatment of 387 patients with stage III breast cancer assigned to either neoadjuvant chemotherapy and preoperative radiotherapy or radiation alone. A study of immediate and end results showed combination of the two modalities to be more effective than each method alone in terms of degree of regression of primary tumor and, particularly, lymph node metastases and duration of recurrence-free period.

[The adjuvant chemotherapy of breast cancer]. / Ad''iuvantnaia khimioterapiiaraka molochnoi zhelezy.

A clinical trial undertaken at Surgical Department No. I of the Institute included the data on 569 cases of stage I-III breast cancer treated in 1985-1989. Adjuvant CMF or TMF chemotherapy failed to improved 5-year survival (chemotherapy 2--285.2%, no chemotherapy--84.8%) in patients with stage I-IIa (TO-2NOMO) disease. Adjuvant treatment with adrioblastin proved superior over CMF and TMF in terms of 5-year overall survival in patients with stage III (T3NO-IMO; TO-3N2MO) cancer (71.0 and 55.0%, respectively).