The matrix-dependent 3D spheroid model of the migration of non-small cell lung cancer: a step towards a rapid automated screening.

In vitro 3D cell culture systems utilizing multicellular tumor spheroids (MCTS) are widely used in translational oncology, including for studying cell migration and in personalized therapy. However, early stages of cellular migration from MCTS and cross-talk between spheroids are overlooked, which was addressed in the current study. Here, we investigated cell migration from MCTS derived from human non-small cell lung cancer (NSCLC) cell line A549 cultured on different substrates, collagen gel or plastic, at different time points. We found that migration starts at 4-16 h time points after the seeding and its speed is substrate-dependent. We also demonstrated that co-culture of two NSCLC-derived MCTS on collagen gel, but not on plastic, facilitates cell migration compared with single MTCS. This finding should be considered when designing MCTS-based functional assays for personalized therapeutic approach and drug screenings. Overall, our work characterizes the in vitro 3D cell culture model resembling NSCLC cell migration from the clusters of CTCs into surgical wound, and describes microscopy-based tools and approaches for image data analysis with a potential for further automation. These tools and approaches also might be used to predict patterns of CTCs migration based on ex vivo analysis of patient biopsy in a 3D culture system.

Can trans resveratrol plus d-chiro-inositol and myo-inositol improve maternal metabolic profile in overweight pregnant patients?

OBJECTIVE: To investigate the effect of trans-resveratrol from Polygonum cuspidatum/magnesium hydroxide complex, trademark Revifast®, plus D-chiro-inositol (DCI) and Myo-inositol (MI) during spontaneous pregnancies in overweight patients in a pilot study. STUDY DESIGN: A one-year, prospective, randomized, double-blinded, placebo-controlled single center clinical study was carried out on overweight pregnant women. 110 patients were randomized in 3 groups to receive: Revifast® with DCI/MI (group I), DCI/MI alone (group II) or control group (group III) for 30 and 60 days. The main outcomes were to explore the lipid profile (total cholesterol, LDL, HDL, TG) and glucose levels, after 30 and 60 days of therapy. RESULTS: No difference in systolic and diastolic parameters among 3 groups during study. All blood chemistry parameters improved compared to placebo at 30 days already, but significantly to 60 days, respect placebo. By comparing the two treatment groups, group I demonstrates significantly improved lipid and glucose parameters than group II, which are at 30 to 60 days of treatment. CONCLUSIONS: The supplementation of Trans-resveratrol, Revifast® in addition to DCI/MI in overweight pregnant woman with an elevated fasting glucose improves glucose levels, Total Cholesterol, LDL and TG.

[An experimental validation of hyaluronidase electrophoresis for the prevention of postoperative adhesions]. / Eksperimental'noe obosnovanie élektroforeza gialuronidazy dlia profilaktiki posleoperatsionnykh spaek.

The experiments on 50 animals were made to evaluate efficacy of electrophoresis of hyaluronidase (from actinohyal solution) against adhesions. Model abdominal adhesions in rats were exposed to hyaluronidase coming from anode and cathode for 20 min. There were altogether 10 daily procedures. The control animals received the solvent from the same poles or were not exposed to electrophoresis. The results demonstrate that hyaluronidase introduction from anode and cathode significantly decreases the occurrence and density of postoperative adhesions compared to controls.

[Role of local fibrinolytic activity of the uterine horns in rats in the pathogenesis of formation of postoperative adhesions]. / Rol' lokal'noi fibrinoliticheskoi aktivnosti matochnykh rogov u krys v patogeneze formirovaniia posleoperatsionnykh spaek.

Experimental models were used to examine the impact of corrections of the uterine horns on the activity of tissue plasminogen activator (tPA). The application of sutures was shown to suppress the activity of tPA in the uterine horns to a greater extent than other surgical techniques. With this, the use of catgut caused the highest suppression of tPA activity and increases in the frequency and density of formation of postoperative adhesions. Depleted tPA reserves and its higher inhibitor levels were found to lead to depressed fibrinolysis, which is a pathogenetic factor for developing an adhesive process.

Myo-inositol, D-chiro-inositol, folic acid and manganese in second trimester of pregnancy: a preliminary investigation.

DESIGN AND PURPOSE: The supplemental administration of myo-inositol, D-chiro-inositol, folic acid and manganese (MDFM) was tested in a prospective, randomized, double-blind, placebo controlled clinical trial, pilot study, to test the hypothesis that its supplemental administration in the second trimester of pregnancy would improve glucose and glycemic parameters and blood pressure. SUBJECTS AND METHODS: Non-obese uniparous healthy pregnant women between 13th and 24th week of pregnancy were divided into two groups: group I, control group with placebo, and the group II, women in treatment with myo-inositol, D-chiro-inositol, folic acid and manganese. The main outcome measures were the comparative analysis of the parameters analyzed at time 0, after 30 days and 60 days; secondary outcome measure was the overall analysis of investigated parameters. RESULTS: 24 women were allocated to receive MDFM and 24 the placebo. The two groups did not significantly differ for demographic, lipidic and glycemic parameter and blood pressure. After 30 days, significantly lower cholesterol (p = 0.0001), significantly lower LDL (p = 0.0013), lower TG (p < 0.0001) and lower glycemia (p = 0.0021) were observed all favoring group II. No significant difference was observed for HDL, diastolic and systolic blood pressure. After 60 days, significant difference was observed for cholesterol (p = 0.0001), LDL (p = 0.0001), HDL (p = 0.0001), TG (p = 0.0001), glycemia (p = 0.0064), all favoring the group treated with MDFM. No significant differences were observed for systolic (p = 0.12) and diastolic blood pressure (p = 0.42). When examining for overall differences between the two groups, a significant difference was observed for examined parameters at time 0 and at time 60; cholesterol (p = 0.0001), LDL (p = 0.0001), HDL (p = 0.047), TG (p = 0.0001) and glycemia (p = 0.019) were reduced in the MDFM group. A significant reduction was also observed in group II for systolic blood pressure after 60 days of intervention (p = 0.0092), but not for diastolic blood pressure (p = 0.29). CONCLUSIONS: MDFM administration after 30 days in pregnancy improved glycemic and lipidic parameters, with significant gain after 60 days, without affecting diastolic blood pressure levels.

Occiput posterior position diagnosis: vaginal examination or intrapartum sonography? A clinical review.

The occiput posterior (OP) position is one of the most frequent malposition during labor. During the first stage of labor, the fetal head may stay in the OP position in 30% of the cases, but of these only 5-7% remains as such at time of delivery. The diagnosis of OP position in the second stage of labor is made difficult by the presence of the caput succedaneum or scalp hair, both of which may give some problem in the identification of fetal head sutures and fontanels and their location in relationship to maternal pelvic landmarks. The capability of diagnosing a fetus in OP position by digital examination has been extremely inaccurate, whereas an ultrasound approach, transabdominal, transperineal and transvaginal, has clearly shown its superior diagnostic accuracy. This is true not only for diagnosis of malpositions, detected in both first and second stage of labor, but also in cases of marked asynclitism.

[Macroscopic and functional evaluation of the effectiveness of restoration of the ovary using fibrin glue and various suture materials after wedge ovarian resection]. / Makroskopicheskaia i funktsional'naia otsenka éffektivnosti vosstanovleniia iaichnika s pomoshch'iu fibrinovogo kleia i razlichnykh shovnykh materialov posle ego klinovidnoi rezektsii.

30 rabbits were operated on by sigmoidal ovarian resection during which one side was treated with fibrin glue, and alternative with different suturing materials (prolene 7/0, catgut 3/0). Macroscopic investigations and determination of generative functions of postoperative animals, in a 3 weeks after coupling with male rabbits, were carried out. It was discovered that the application of fibrin glue promotes the reduction of in inflammatory and sclerotic changes. The frequency of occurred postoperative adhesions and preservation of increasing the ovarian size and weight tendency with the maintained functional conditions in comparison with those treated with suture materials. Prolene has certain advantages when compared with catgut, like macroscopic changes in the ovarian tissues, resulting in decrease of ovarian size and weight, increase of formation of postoperative adhesions and unbalance the whole generative system. In clinics fibrin glue was applied to 7 patients during different operations on ovary. Preliminary clinical data confirmed the experimental results.

[Functional evaluation of the effectiveness of experimental reconstructive and plastic operations on the uterine horns]. / Funktsional'naia otsenka éffektivnosti rekonstruktivnykh i plasticheskikh operatsii na matochnykh rogakh v éksperimente.

In the given experimental model, tubo-plastic surgery was done with the use of locally produced fibrin glue (Fk-1), and commercial product "Beriplast" (FRG). In the control group microsurgical technique was adopted in the uterine horn of rats. It was proved that Fibrin glue reduces the frequency of post operative adhesion formation in the area of anastomosis and the chance of pregnancy is increased in comparison to microsurgical techniques.

[Reproductive function after surgery of the horn of uterus in rats]. / Generativnaia funktsiia posle operatsii na matochnykh rogakh krys.

A model of tuboplasty with the use of biologic glues (FK) and microsuturing material was created in experiments with 63 rats. Clinically commercial fibrin glue Beriplast FK manufactured by Bering (Germany) and FK-1 (USSR) were used in 15 patients during various gynecologic operations. The patency of uterine horn anastomoses, the formation of adhesions and other changes at the site of anastomosis were assessed, as was the incidence of the resultant pregnancy. Clinically early control laparoscopy was carried out on days 4-5 after surgery. The results evidence the efficacy of FK in reconstructive surgery on the uterine tubes. Preliminary analysis of the clinical data has confirmed the experimental data.

[Evaluation of the effectiveness of the use of various anti-adhesion agents in an experiment]. / Otsenka éffektivnosti primeneniia razlichnykh protivospaechnykh sredstv v éksperimente.

The study of the efficacy of the use of different materials recommended for the adhesion prevention was carried out in 15 white rats. On the parietal front-lateral peritoneum of the abdomen, adhesion formation was induced using an adhesion induction model of 10--nodes suture (catgut 3/0) both sides. In the experimental group, fibrin glue FG1 produced at the Surgery Centre of the Russian Academy of Medical Sciences, and oxidized cellulose barrier-Interceed, manufactured by the Johnson & Johnson company (USA); were applied while the control group was made up of the untreated rodents. 5 days after the operation, these animals were opened and the degree of the spread, type, intensity and rigidity of the formed adhesion were studied using the grade system. It was observed, that fibrin glue and Interceed barrier never caused any tissue reaction; a reduction in the frequency of adhesion formation was also noted in the treated group.

[The effect of a natural complex of cytokines on oxygen-dependent function of rat vaginal phagocytes]. / Vliianie estestvennogo kompleksa tsitokinov na kislorod-zavisimuiu funktsiiu fagotsitov vlagalishcha krys.

Our investigation consisted in 10-days treatment of vaginal mucous membrane wounds in white not inbred rats by introduction of natural cytokines complex into the vagina. At the same time the dynamics of vaginal phagocytes oxygen-depended function change was studied. We have ascertained the activating influence of the cytokines complex on the phagocytes chemiluminescence (CL) that found expression in 2.5-7 times fold augmentation of the CL intensity in comparison with control level (an equal portion of Medium--199 was introduced in the vagina of control-group rats). Having ended the application of the cytokines complex we have observed a rather fast normalization of the cells' activity (by the 15-17 days), consequently the cytokines did not have a distant effect on the oxygen-depended phagocytes function. We consider the activation of the phagocytes in wound as well as the bactericidal effect of the oxygen free radicals generated by the phagocytes as positive result.

[An alternative approach to the surgical correction of tubal infertility]. / Al'ternativnyi pokhod k khirurgicheskoi korrektsii trubnogo besplodiia.

The authors compare the efficacy of surgical treatment of tubal sterility using laparoscopy (133 cases) and microsurgical techniques (120 cases). The results were assessed with due consideration for the dissemination of adhesions (first-second and third-fourth degrees), status of the uterine tubes, and presence or absence of chlamydial infection. Surgical correction via an endoscopic access was found to be preferable in adhesions of the first-second degree, whereas in adhesions of the third-fourth degree surgical interventions are inadvisable.

Coagulation and fibrinolysis in rats after surgery with monopolar electrical scalpel.

Blood coagulation, fibrinolysis in plasma and peritoneal fluid, and activity of tissue plasminogen activator in the peritoneum and uterine horns were studied in albino rats after surgery on the uterine horns with a monopolar electrical scalpel. This instrument induced severe inflammatory reaction and disturbances in the fibrinolysis and coagulation systems.

[Use of fibrin glue in gynecologic operations]. / Primenenie fibrinovogo kleia pri ginekologicheskikh operatsiiakh.

Anastomosing of the uterine horns in 98 experimental rats has employed a fibrin glue FK-1 (USSR) and Beriplast (FRG) or microsurgical techniques in a control group. Intactness and sealing of the anastomoses and the incidence of pelvic adhesions were assessed at 5 minutes, 1 hour and 1, 2, 3, 4, 5, and 6 days following the operation. The fibrin glue Beriplast was used clinically in 6 patients during reconstructive-plastic operations. The results with seamless anastomosing of uterine horns in rats using the fibrin glue and preliminary clinical evidence suggests a high effectiveness of the glue in gynecologic reconstructive plastic surgery.