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Short-term cell culturing on basement membrane matrix is a common and very convenient in vitro model of angiogenesis. We studied the possibility of interaction of multipotent stromal cells from the umbilical cord and Ea.hy926 endothelial cells on this model at the early and late periods of the experiment. Multipotent stromal cells alone and in combination with endothelial cells formed an unstable tubular network. Clusters formed after its disassembling later became the sprouting centers in co-culture of the two cell types, but not in pure culture of multipotent stromal cells. Multipotent stromal cells with CD31+ phenotype constitute the structural basis of newly formed stable 3D capillary-like network. Prolongation of the time of culturing and combination of the two in vitro models of angiogenesis (tubulogenesis and sprouting) allowed more complete assessment of the angiogenic potential of multipotent stromal cells.

Intrasplenic allogeneic transplantation of multipotent stromal cells from the umbilical cord stimulates hepatocyte proliferation and promotes recovery of liver weight in rats after subtotal resection (80% organ weight). It can be hypothesized that this effect of multipotent stromal cells is due to more rapid recovery of the number of mitochondria and normalization of mitochondrial function of liver hepatocytes.

The role of the lungs and kidneys in liver regeneration after subtotal hepatectomy was studied on a rat model. It was found that production of hepatocyte growth factor (HGF) in the lungs and kidneys and expression of cytokine genes Il1b, Il6, Il10, and tnfa significantly increased. Analysis of the dynamics of lung macrophage population showed that accumulation of HGF and the increase in the expression of cytokine genes in the lungs were accompanied by simultaneous increase in the number of CD68+ cells, which attested to the leading role of macrophages in activation of HGF synthesis in the lungs. Macrophage content in the kidneys after subtotal hepatectomy did not increase.

2-(2-furyl)phenanthro[9,10-d]oxazole was synthesized by the reaction of 9,10-phenanthrenequinoneimine and furan-2-carbaldehyde in ethanol. Reactions of electrophilic substitution of this compound were investigated (nitration, bromination, sulfurization, formylation, acylation). Depending on the reaction conditions the electrophile attacks either the furan ring or the phenanthrene fragment.

The theoretical premises and experimental results of phase control in high-power microwave oscillators with nanosecond pulse duration are presented. In experiments, two-channel backward wave oscillators (BWOs) for both steady state (100-150 cycles) and super-radiance (SR) mode operation (10-20 cycles) are discussed. For the phase control, the shift of the moment with fastest current rise is provided in the sections of nonlinear transmission lines with axially biased ferrites. The voltage pulse sharpening and shift of group velocity depend on the dc axial magnetic field. In SR mode, two-channel source is capable of producing 2 × 0.3 GW pulses with duration of 2 ns and the center frequency of 10 GHz. The source operates at the repetition rate up to 100 pps with electronic control of the phase in one channel relative to another. The last experiment is carried out using two synchronized compact RADAN-type drivers with two parallel Ka-band BWOs (100 MW, 2 ns, 37 GHz). The controllable shift of interference picture is a proof of the coherency in the aggregated radiation. At the maximum of the pattern in the far zone, the detector indicateds fourfold increase in power density over that measured from single channel.

The coherent composition of the wave beams of two relativistic nanosecond backward-wave tubes (BWTs) with an 8-mm range and peak power in each channel of up to 230 MW is implemented. A specific feature of this experiment was power supply of explosive-emission cathodes by split pulses supplied by a completely solid-phase SOS modulator with reduced amplitude scatter. The voltage growth rate was increased compared to previous experiments, which made it possible to transition to the region of weaker magnetic fields ∼2 T, which was less than cyclotron resonance field, while retaining stable emission of the electron beams. As a result, a standard deviation of phase scatter between the channels of 0.5 ps was found on the time scale.

Background Mesenchymal stromal/stem cells derived from human umbilical cord (UC-MSCs) uniquely combine properties of embryonic and postnatal MSCs and may be the most acceptable, safe, and effective source for allogeneic cell therapy e.g. for therapeutic angiogenesis. In this report we describe pro-angiogenic properties of UC-MSCs as manifested in vitro. Methods UC-MSCs were isolated from human Wharton’s jelly by enzymatic digestion. Presence of soluble forms of VEGF-A in UC-MSC-conditioned media was measured by ELISA. Effects of the conditioned media on human umbilical vein-derived endothelial EA.hy926 cells proliferation were measured by MTT-assay; changes in cell motility and directed migration were assessed by scratch wound healing and transwell chamber migration assays. Angiogenesis was modeled in vitro as tube formation on basement membrane matrix. Progressive differentiation of MSCs to endothelioid progeny was assessed by CD31 immunostaining. Results Although no detectable quantities of soluble VEGF-A were produced by UC-MSCs, the culture medium, conditioned by the UC-MSCs, effectively stimulated proliferation, motility, and directed migration of EA.hy926 cells. In 2D culture, UC-MSCs were able to acquire CD31+ endothelial cell-like phenotype when stimulated by EA.hy926-conditioned media supplemented with VEGF-A165. UC-MSCs were capable of forming unstable 2D tubular networks either by themselves or in combinations with EA.hy926 cells. Active spontaneous sprouting from cell clusters, resulting from disassembling of such networks, was observed only in the mixed cultures, not in pure UC-MSC cultures. In 3D mode of sprouting experimentation, structural support of newly formed capillary-like structures was provided by UC-MSCs that acquired the CD31+ phenotype in the absence of exogenous VEGF-A. Conclusion These data suggest that a VEGF-A-independent paracrine mechanism and at least partially VEGF-A-independent differentiation mechanism are involved in the pro-angiogenic activity of UC-MSCs.

The possibility of in-phase excitation of two independent nanosecond-pulsed relativistic 37-GHz backward-wave oscillators (BWOs) with high-current electron beams has been studied. This regime can be achieved using BWO switching with a picosecond precision. It is shown that long-term (up to 100–200 periods of the field) phase locking in each channel is stably reproduced from pulse to pulse, which ensures coherent summation of the output wave beams at a megawatt power.

To study morphofunctional tissue changes during perforation of the tympanic membrane using blood plasma enriched with platelet growth factors in the experiment.Examined 36 rats (72 tympanic membranes), which were divided into 2 groups, experimental (1st) and control (2nd). Injected blood plasma enriched with platelet-derived growth factors into the external auditory canal once by application after perforation of the tympanic membrane in the rats of the experimental group. Sacrificed rats on the 5th, 10th, 15th day after surgery (6 animals in each group at each stage). Evaluated the condition of the tympanic membrane otoscopically during the experiment. Evaluated the signs of acute otitis media, the presence of 'dry' perforation of the tympanic membrane (without signs of inflammation), and the closure of perforation of the tympanic membrane.In the experimental group, on the 5th day after the surgery, there were no signs of acute otitis media, closure of perforation of the tympanic membrane was identified in 4 cases, 'dry' perforation of the tympanic membrane (without signs of inflammation) was preserved in 8 cases. In the control group, on the 5th day after the surgery, the signs of acute otitis media were identified in 9 cases, cases of closure of the perforation of the tympanic membrane were not noted, 'dry' perforation of the tympanic membrane was preserved in 3 cases. In the 1st group, on the 10th day after surgery, the signs of acute otitis media were identified in 1 case, 'dry' perforation of the tympanic membrane was preserved in 1 case, closure of perforation of the tympanic membrane was identified in 10 cases. At the same time in the 2nd group, the signs of acute otitis media were identified in 6 cases, the 'dry' perforation of the tympanic membrane was preserved in 6 cases, there were no cases of closure of the perforation of the tympanic membrane. In the 1st group, on the 15th day after the surgery, there were no signs of acute otitis media, 'dry' perforation of the tympanic membrane was preserved in 1 case, closure of perforation of the tympanic membrane was identified in 11 cases. In the 2nd group, on the 15th day after surgery the signs of acute otitis media was identified in 1 case, 'dry' perforation of the tympanic membrane was preserved in 10 cases, the closure of perforation of the tympanic membrane was noted in 1 case.Preliminary results show a favorable effect of blood plasma enriched with platelet growth factors on the regeneration of the tympanic membrane under conditions of its traumatic perforation in the rat experiment, which is manifested in a decrease in the incidence of acute otitis media on the 5th day after perforation and in an increase in the incidence of closure of tympanic membrane perforation both on the 10th and 15th day, and in general in the experimental group.Цель исследования - изучить морфофункциональные изменения тканей при перфорации барабанной перепонки с использованием плазмы крови, обогащенной тромбоцитарными факторами роста, в эксперименте. Материал и методы. Обследовали 36 крыс (72 барабанных перепонки), которых поделили на две группы, экспериментальную (1-я) и контрольную (2-я). В экспериментальной группе после перфорации барабанной перепонки однократно аппликационно в наружный слуховой проход вводили плазму крови, обогащенную тромбоцитарными факторами роста, крыс выводили из эксперимента на 5, 10, 15-е сутки после операции (по 6 голов в каждой группе на каждом этапе). В процессе эксперимента отоскопически оценивали состояние барабанной перепонки. Оценивали признаки острого среднего отита, наличие 'сухой' перфорации барабанной перепонки (без признаков воспаления), закрытие перфорации барабанной перепонки. Результаты. В экспериментальной группе на 5-е сутки после операции признаков острого отита не было, закрытие перфорации барабанной перепонки выявили в 4 случаях, 'сухая' перфорация барабанной перепонки (без признаков воспаления) сохранилась в 8 случаях. В контрольной группе на 5-е сутки после операции признаки острого отита выявили в 9 случаях, случаев закрытия перфорации барабанной перепонки не отметили, 'сухая' перфорация барабанной перепонки сохранилась в 3 случаях. На 10-e сутки после операции в 1-й группе развитие острого отита выявили в 1 случае, 'сухая' перфорация барабанной перепонки сохранилась в 1 случае, закрытие перфорации барабанной перепонки выявили в 10 случаях. В те же сроки во 2-й группе развитие острого отита выявили в 6 случаях, 'сухая' перфорация барабанной перепонки сохранилась в 6 случаях, случаев закрытия перфорации барабанной перепонки не было. На 15-е сутки после операции в 1-й группе не было признаков острого среднего отита, 'сухая' перфорация барабанной перепонки сохранилась в 1 случае, закрытие перфорации барабанной перепонки выявили в 11 случаях. На 15-е сутки после операции во 2-й группе наличие признаков острого среднего отита определили в 1 случае, 'сухая' перфорация барабанной перепонки сохранилась в 10 случаях, закрытие перфорации барабанной перепонки отметили в 1 случае. Заключение. Предварительные результаты свидетельствуют о благоприятном влиянии плазмы крови, обогащенной тромбоцитарными факторами роста, на регенерацию барабанной перепонки в условиях ее травматической перфорации в эксперименте на крысах, что проявляется в уменьшении частоты развития острого среднего отита на 5-й день после перфорации и увеличении частоты закрытия перфорации барабанной перепонки как на 10-й и 15-й дни, так и в общем в экспериментальной группе.

The proliferation and death of hemopoietic cells in the regenerating liver of 17-day outbred albino rat fetuses were studied during 2 days after resection of 20% of the organ. The mitotic index of hemopoietic cells in the resected liver increased signifi cantly 24 h after the operation in comparison with the control fetuses. No increase in the counts of apoptotic hemopoietic cells was detected in the regenerating liver. Hence, resection of 20% of the liver in rat fetuses stimulated the proliferation of hemopoietic cells and did not stimulate their apoptosis.

Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing–remitting multiple sclerosis. We randomly assigned 1326 patients in an approximate 1:1:1 ratio to receive one of two cumulative doses of cladribine tablets (either 3.5 mg or 5.25 mg per kilogram of body weight) or matching placebo, given in two or four short courses for the first 48 weeks, then in two short courses starting at week 48 and week 52 (for a total of 8 to 20 days per year). The primary end point was the rate of relapse at 96 weeks. Among patients who received cladribine tablets (either 3.5 mg or 5.25 mg per kilogram), there was a significantly lower annualized rate of relapse than in the placebo group (0.14 and 0.15, respectively, vs. 0.33 ; P

Summary Background Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis (RRMS), but no published randomised trials have directly compared these two drugs. Our aim in the REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS. Methods In this multicentre, randomised, comparative, parallel-group, open-label study, patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were randomised to receive 44 μg subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse. A subpopulation of 460 patients (230 from each group) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume. Treatments were assigned by a computer-generated randomisation list that was stratified by centre. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00078338. Findings Between February and December, 2004, 764 patients were randomly assigned: 386 to interferon beta-1a and 378 to glatiramer acetate. After 96 weeks, there was no significant difference between groups in time to first relapse (hazard ratio 0·94, 95% CI 0·74 to 1·21; p=0·64). Relapse rates were lower than expected: 258 patients (126 in the interferon beta-1a group and 132 in the glatiramer acetate group) had one or more relapses (the expected number was 460). For secondary outcomes, there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions, although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions (0·24 vs 0·41 lesions per patient per scan, 95% CI −0·4 to 0·1; p=0·0002). Safety and tolerability profiles were consistent with the known profiles for both compounds. The overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial during the 96 weeks. Interpretation There was no significant difference between interferon beta-1a and glatiramer acetate in the primary outcome. The ability to predict clinical superiority on the basis of results from previous studies might be limited by a trial population with low disease activity, which is an important consideration for ongoing and future trials in patients with RRMS. Funding EMD Serono; Pfizer.

The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria.

Expression of il1b, il6, il10, tnfa, hgf, tgfb, vegf, and fgf2 genes in the lungs and kidneys was examined on rat model of liver regeneration after subtotal hepatectomy. Enhanced expression of il6, il10, tnfa, hgf, and fgf2 genes was detected at the early terms after 80% liver resection.

In the liver of rats subjected to subtotal liver resection (80% organ weight), the expression of sox9 gene and SOX9 protein content increased and cells with hepatocyte morphology expressing SOX9 appeared; the proportion of cells expressing cytokeratin-19 also increased. Based on these data, we cannot completely exclude the involvement of resident progenitor cells and hepatocyte reprogramming in liver regeneration after subtotal resection, however, the contribution of these processes seems to be insignificant. The leading mechanism of liver mass recovery after subtotal resection is proliferation of hepatocytes.

First version of relativistic BWO with TM 02 operating mode has been tested also in [1]. The cyclotron-resonance mode selection was used. In this case, because of requirement to the defined values of magnetic field and e-beam radius, the efficiency of oscillator was not very high (approximately 10%). Now, the different electrodynamic codes are available to optimize the geometry of Slow Wave Structure (SWS) and reflector for TM 02 mode with small re-emission to TM 01 . Then other techniques of mode selection such as the e-beam pre-modulation near the reflector [2], sectioning of SWS and diffractive losses at the coaxial magnetically-insolated diode can be used. So, refusing the cyclotron-type discrimination of TM 01 mode, we studied approaches of mode selection with higher magnetic field to increase the BWO efficiency, including the idea of self-modulated e-beam emission [3].

The results of theoretical and experimental studies allowing the use of Cherenkov superradiance for the generation of electromagnetic pulses with a peak power higher than electron flow power are reported. For an injection current of 2.6 kA and a particle energy of 330 keV, the power of a microwave pulse with a carrier frequency of 9.3 GHz and a duration of 0.5 ns attained 1.2 GW.