Drainless robot-assisted minimally invasive oesophagectomy-randomized controlled trial (RESPECT).

BACKGROUND: The purpose of this randomized trial is to evaluate the early removal of postoperative drains after robot-assisted minimally invasive oesophagectomy (RAMIE). Evidence is lacking about feasibility, associated pain, recovery, and morbidity. METHODS/DESIGN: This is a randomized controlled multicentric trial involving 72 patients undergoing RAMIE. Patients will be allocated into two groups. The "intervention" group consists of 36 patients. In this group, abdominal and chest drains are removed 3 h after the end of surgery in the absence of contraindications. The control group consists of 36 patients with conventional chest drain management. These drains are removed during the further postoperative course according to a standard algorithm. The primary objective is to investigate whether postoperative pain measured by NRS on the second postoperative day can be significantly reduced in the intervention group. Secondary endpoints are the intensity of pain during the first week, analgesic use, number of postoperative chest X-ray and CT scans, interventions, postoperative mobilization (steps per day as measured with an activity tracker), postoperative morbidity and mortality. DISCUSSION: Until now, there have been no trials investigating different intraoperative chest drain strategies in patients undergoing RAMIE for oesophageal cancer with regard to perioperative complications until discharge. Minimally invasive approaches combined with enhanced recovery after surgery (ERAS) protocols lower morbidity but still include the insertion of chest drains. Reduction and early removal have been proposed after pulmonary surgery but not after RAMIE. The study concept is based on our own experience and the promising current results of the RAMIE procedure. Therefore, the presented randomized controlled trial will provide statistical evidence of the effectiveness and feasibility of the "drainless" RAMIE. TRIAL REGISTRATION: ClinicalTrials.gov NCT05553795. Registered on 23 September 2022.

[Results of carotid endarterectomy in the acutest period of ischemic stroke]. / Rezul'taty karotidnoi endarterektomii v ostreishem periode ishemicheskogo insul'ta.

OBJECTIVE: Analysis of the results of carotid endarterectomy (CEE) in the acute period of ischemic stroke (IS). MATERIAL AND METHODS: This retrospective study included 128 patients (mean age 65.2±4.7 years, 84 (65.6%) men) who underwent CEE in the acute period. Inclusion criteria were: an ischemic focus in the brain with a diameter of no more than 2.5 cm according to MRI; mild neurological deficit (from 3 to 8 points on NIHSS); ≤3 points on the modified Rankin Scale (mRS); stenosis of ICA over 60%. Exclusion criteria were: severe neurological deficit; presence of decompensated comorbid dependence; contraindications to CEE. RESULTS: In the hospital postoperative period, 3.9% of patients were diagnosed with hemorrhagic transformation of the ischemic focus in the brain with progression of neurological deficit and level of consciousness to coma II. In 3.1% cases, a lethal outcome developed on 4-7 days after the operation. In 2.3% patients after CEE, the progression of neurological deficit was noted with the development of new ischemic foci according to postoperative neuroimaging. The probable cause of this event was a distal embolism that developed during the installation of a temporary shunt. Myocardial infarction was diagnosed in 3.9% of patients. The combined end point (death + myocardial infarction + ischemic stroke + hemorrhagic transformation) was 10.1%. CONCLUSION: CEE in the most acute period of ischemic stroke is accompanied by a high risk of hemorrhagic transformation, myocardial infarction, and death, which characterizes this revascularization option as unsafe.

[Long-term results of carotid endarterectomy and carotid artery stenting in patients with high bifurcation of common carotid artery: a multiple-center study]. / Otdalennye rezul'taty karotidnoi endarterektomii i karotidnoi angioplastiki so stentirovaniem u patsientov s vysokim raspolozheniem bifurkatsii obshchei sonnoi arterii. Rezul'taty mnogotsentrovogo issledovaniya.

OBJECTIVE: To analyze in-hospital and long-term results of eversion carotid endarterectomy (CEE), carotid endarterectomy with patch repair and carotid artery stenting (CAS) in patients with high bifurcation of common carotid artery. MATERIAL AND METHODS: A retrospective multiple-center open study included 1983 patients who underwent internal carotid artery (ICA) repair for severe stenosis between 2010 and 2021. Three groups of patients were distinguished depending on revascularization option: group 1 (n=638) - eversion CEE; group 2 (n=351) - CEE with patch repair; group 3 (n=994) - CAS. RESULTS: In-hospital postoperative mortality and incidence of stroke and myocardial infarction were similar. All bleedings (n=39) occurred after CEE. ICA thrombosis was diagnosed in groups 1 and 2 due to intimal detachment after insertion of temporary bypass tube. Incidence of laryngeal paresis, neuropathy of hypoglossal and glossopharyngeal nerves, Horner syndrome, damage to salivary glands was comparable in groups 1 and 2. Long-term mortality was the highest (n=10; 2.8%) after CEE with patch repair due to fatal stroke. In turn, the highest incidence of ICA restenosis and restenosis-induced ischemic stroke was observed after CEE with patch repair and CAS. CONCLUSION: 1. Classical and eversion CEE in patients with high CCA bifurcation is followed by high in-hospital incidence of damage to cranial nerves and salivary glands, laryngeal paresis, Horner syndrome, bleeding and risk of ICA thrombosis. 2. In patients with high CCA bifurcation, CAS and CEE with patch repair are accompanied by high incidence of ICA restenosis, restenosis-induced stroke and mortality in long-term postoperative period. 3. Eversion CEE demonstrates the lowest rates of all adverse cardiovascular events in long-term follow-up period.

MICROBIOME AND UVEITIDES. A REVIEW.

Microorganisms inhabiting all surfaces of mucous membranes and skin and forming a complex ecosystem with the host is called microbiota. The term microbiome is used for the aggregate genome of microbiota. The microbiota plays important role in the mechanisms of number of physiological and pathological processes, especially of the hosts immune system. The origin and course of autoimmune diseases not only of the digestive tract, but also of the distant organs, including the eye, are significantly influenced by intestinal microbiota. The role of microbiota and its changes (dysbiosis) in the etiopathogenesis of uveitis has so far been studied mainly in experimental models. Reduction of severity of non-infectious intraocular inflammation in germ-free mice or in conventional mice treated with broad-spectrum antibiotics was observed in both the induced experimental autoimmune uveitis model (EAU) and the spontaneous R161H model. Studies have confirmed that autoreactive T cell activation occurs in the intestinal wall in the absence of retinal antigen. Recent experiments focused on the effect of probiotic administration on the composition of intestinal microbiota and on the course of autoimmune uveitis. Our study group demonstrated significant prophylactic effect of the administration of the probiotic Escherichia coli Nissle 1917 on the intensity of inflammation in EAU. To date, only a few studies have been published investigating intestinal dysbiosis in patients with uveitis (e.g., in Behcets disease or Vogt-Koyanagi-Harada syndrome). The results of preclinical studies will be presumably used in clinical practice, mainly in the sense of prophylaxis and therapy, such as change in the lifestyle, diet and especially the therapeutic use of probiotics or the transfer of faecal microbiota.

IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW.

Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.

[Effect of retinal protective therapy on optical coherence tomography angiography (pilot study)]. / Vliyanie retinoprotektornoi terapii na pokazateli opticheskoi kogerentnoi tomografii s funktsiei angiografii (pilotnoe issledovanie).

PURPOSE: To assess the influence of the frequency of retinal protective therapy courses on the indicators of regional hemodynamics of the eye. MATERIAL AND METHODS: The study included 17 patients (34 eyes) with a diagnosis of primary open-angle glaucoma (POAG), advanced stage. The patients were divided into 2 groups: the first group received a course of retinal protective therapy with Retinalamin every 3 months, the second group received a course of retinal protective therapy with Retinalamin every 6 months. All patients underwent standard ophthalmological examination including standard automatic perimetry according to the 24-2 program, optical coherence tomography angiography (OCT-A) of the macular area and optic disc. RESULTS: The comparison of hemodynamic parameters of all vascular plexuses of the retina at the beginning and at the end of the study, as well as intergroup comparison did not reveal any statistically significant differences (p>0.05). However, when studying the density and fractal dimension of the vascular bed, multidirectional trends were observed. Specifically, in the peripapillary region, there was a decrease in the length from 19.8 (1/mm) to 19.0 (1/mm) (p=0.37) and the density from 36.6% to 35.7% (p=0.63) of the vascular bed of the peripapillary capillary plexus of the retina in patients of the first group. In the superficial vascular plexus, the trend in the density of the vascular bed in both groups slightly changed (in group 1 - 38.1% and 38.3%, p=0.97; group 2 - 37.8% and 38.7%, p=0.46). The fractal dimension of the vascular bed in the first group tended to increase during treatment from 18.8 (1/mm) to 19.1 (1/mm) (p=0.5), while in the second group, on the contrary, it had tendency to decrease from 18.6 (1/mm) to 17.9 (1/mm) (p=0.63). In the deep vascular plexus, the density of the vascular bed trended to decrease in both groups, but in group 2 (42.5% and 42.4%, p=1.0) it was more pronounced than in the first group (42.5% and 42.6%, p=0.82). However, the fractal dimension of the vascular bed increased in group 1 (21.0 (1/mm) and 21.3 (1/mm), p=0.43) and showed a slight tendency to decrease in group 2 (21.5 (1/mm) and 21.0 (1/mm), p=0.86). CONCLUSION: The general trend of changes in hemodynamic parameters demonstrates a potential positive effect, especially in the data related to the deep vascular plexus.

IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW.

Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.

IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW.

Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.

IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW.

Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.

Ocular Manifestations of Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA), formerly known as Wegeners granulomatosis, is an autoimmune vasculitis of small vessels, presenting as necrotizing granulomatous inflammation especially of the upper and lower respiratory tract and necrotizing glomerulonephritis. GPA affects more often Caucasians in northern states, predominantly is affected the age-range group of 50 - 60 years. GPA may affect any organ; the eye symptoms are stated in the range of 16-78 %. The eye symptoms are very variable, and in up to 27 % they are the first sign of undiagnosed GPA. The etiology of GPA was not until now explained. Anti-neutrophil cytoplasmic antibodies (ANCA) play important role in the pathogenesis of this disease. GPA is ranked among ANCA associated vasculitis. The GPA is diagnosed on the basis of clinical signs and symptoms of systemic vasculitis, laboratory and histological tests and imaging studies. Immunomodulative therapy made a contribution to the improvement of GPA prognosis in the last decades; biological treatment reaches the prominence of the GPA treatment procedures. Good collaboration with other specialties is necessary for the early diagnosis and treatment of this life and vision threating disease. The ophthalmologist in the collaboration with specialists of other medical branches may take an important part in the GPA diagnostics, monitoring of the diseases course, or adverse affects of the medication. This paper pays attention to the eye symptoms of the GPA; the literature is supplemented with own photographs of GPA eye symptoms in patients followed up at the Department of Ophthalmology, First medical faculty, Charles University and General Faculty Hospital in Prague, Czech Republic, E.U. Key words: Granulomatosis with polyangiitis (GPA), orbit, scleritis, peripheral ulcerative keratitis (PUK), immunomodulation.

Metronidazole Attenuates the Intensity of Inflammation in Experimental Autoimmune Uveitis.

Autoimmune uveitis is a serious sightthreatening disease that in many cases fails to respond to conventional immunosuppressive or biological therapy. Experimental models used in research allow more detailed study of pathogenesis of the autoimmune process and testing new therapeutic strategies. Recent results show that infection can trigger autoimmune diseases, and some commensal microorganisms are essential in causing disease activity. The aim of this work was to assess the effect of broadspectrum antibiotics - combination of metronidazole and ciprofloxacin or metronidazole alone - on the intensity of intraocular inflammation in experimental autoimmune uveitis (EAU). EAU was induced in mouse strain C57BL/6J by interphotoreceptor retinoid- binding protein in complete Freund's adjuvant and pertussis toxin. The grade of uveitis was assessed clinically and histologically in haematoxylin and eosin- stained tissues. Lymphocytes and macrophages were detected in cryosections using the immunoperoxidase method with antibodies. The therapy was commenced one week before EAU induction and continued throughout the experiment. In addition, metronidazole treatment was also started two weeks before EAU induction. Antibiotics significantly reduced the intensity of uveitis compared to the control group (P < 0.05). The effects of combination of ciprofloxacin and metronidazole and of metronidazole alone were similar when the therapy started one week before EAU induction (P < 0.05). Metronidazole commenced two weeks before EAU induction and throughout the experiment suppressed the intensity of EAU with even higher statistical significance (P < 0.0001). It can be assumed that the high protective effect of metronidazole on EAU intensity may be due not only to its antimicrobial effect, but also to its immunomodulatory activity.

[Efficacy of primary prevention for atherosclerosis-induced diseases in patients with high cardiovascular risk in Russia and other European countries (Part 1)].

RELEVANCE: Evaluation of the effectiveness of risk management in persons with high cardiovascular risk is an important element in reducing the death rate of the population from cardiovascular diseases (CVD). AIM: Analysis of the prevalence and level of risk factors control in patients with high CV risk CVD from the Russian centers of the primary care unit of the EUROASPIRE IV study in comparison with the general population of the study. MATERIALS AND METHODS: In this cross-sectional study, 14 European countries, including the Russian Federation, participated. Patients aged 18 to 79 years were included in the study, without clinical manifestations of atherosclerosis, who were prescribed antihypertensive therapy and/or lipid lowering therapy and/or treatment for diabetes between the ages of ≥6 months and.

[TATTOO-ASSOCIATED UVEITIS]. / UVEITIDA ASOCIOVANÁ S TETOVÁNÍM.

The clinical case of tattoo-associated uveitis was first described by Lubeck and Epstein in 1952. Uveitis is accompanied by induration and hyperemia of tattoo skin, which can precede, follow or manifest simultaneously with uveitis. The diagnosis is determined on clinical grounds after exclusion of other causes. Uveitis is usually bilateral, chronic and vision impairment is variable. Tattoo-associated uveitis should be remembered in differential diagnosis due to the growing interest in tattoo.Key words: uveitis, tattoo, masquerade syndrome.

[Efficiency of primary prevention for diseases caused by atherosclerosis in patients at high cardiovascular risk in Russia and other European countries (Part 2)].

BACKGROUND: The picture of primary prevention obtained from real-life practice makes possible scheduling measures for prevention improvement. AIM: To analyze features of drug and non-drug therapy aimed at decreasing cardiovascular risk in Russian patients with a high risk (HR) of CVD compared with the study general population. MATERIALS AND METHODS: 14 European countries, including the Russian Federation, participated in this cross-sectional study. The study included patients aged 18-80 without clinical signs of atherosclerosis who have received antihypertensive and/or lipid-lowering therapy and/or therapy for diabetes mellitus (DM) within >6 to.

Population structure and historical demography of South American sea lions provide insights into the catastrophic decline of a marine mammal population.

Understanding the causes of population decline is crucial for conservation management. We therefore used genetic analysis both to provide baseline data on population structure and to evaluate hypotheses for the catastrophic decline of the South American sea lion (Otaria flavescens) at the Falkland Islands (Malvinas) in the South Atlantic. We genotyped 259 animals from 23 colonies across the Falklands at 281 bp of the mitochondrial hypervariable region and 22 microsatellites. A weak signature of population structure was detected, genetic diversity was moderately high in comparison with other pinniped species, and no evidence was found for the decline being associated with a strong demographic bottleneck. By combining our mitochondrial data with published sequences from Argentina, Brazil, Chile and Peru, we also uncovered strong maternally directed population structure across the geographical range of the species. In particular, very few shared haplotypes were found between the Falklands and South America, and this was reflected in correspondingly low migration rate estimates. These findings do not support the prominent hypothesis that the decline was caused by migration to Argentina, where large-scale commercial harvesting operations claimed over half a million animals. Thus, our study not only provides baseline data for conservation management but also reveals the potential for genetic studies to shed light upon long-standing questions pertaining to the history and fate of natural populations.

[The Clinical Signs of Experimental Autoimmune Uveitis]. / Klinické projevy experimentální autoimunitní uveitidy.

INTRODUCTION: Autoimmune uveitis is a sight threatening disease which in many cases fails to respond to conventional immunosuppressive or biological therapy. The research in experimental models of autoimmune uveitis helps to find new therapeutical strategies. The aim of this study is to present the clinical and histological signs of experimental autoimmune uveitis (EAU) in mice. METHODS: EAU was induced in C57BL/6 mice by subcutaneous application of IRBP (interphotoreceptor retinoid binding protein) in complete Freunds adjuvant and intraperitoneal application of pertussis toxin. Clinical evaluation of uveitis was performed in vivo using special imaging system with otoscope. Histological evaluation of uveitis was performed at day 35 post induction of EAU on hematoxylin and eosin stained frozen sections. Clinical and histological grading was used to assess the inflammation intensity of EAU. RESULTS: The intensity of inflammation is depicted on representative fundus images and histological images of retina at day 35 post induction. CONCLUSION: The model of EAU is robust and reproducible and allows us to study the immunopathological mechanisms of inflammation and its regulation. The inflammatory signs in our model are similar to findings of posterior uveitis of autoimmune etiology in humans, thus we may apply our experimental results in human medicine.

[Repetitive DNA sequences as an indicator of the level of genetic isolation in fish].

Although the functional role is still unknown for most types of nuclear noncoding repetitive sequences, some of them proved to provide adequate phylogenetic and taxonomic markers for studying the genetic relationships of organisms at the species and within-species levels. Several markers were used in this work. First, microsatellite markers were used to examine populations varying in the extent of genetic subdivision in marine and anadromous fish, including the Chilean jack mackerel Trachurus murphyi, anadromous brown trout Salmo trutta, and isolated and anadromous char populations. Locus polymorphism was proportional to the gene flow between populations in all cases. Second, satellite DNA was used to study the phylogenetic relationships within the genera Salmo, Oncorhynchus, Salvelinus, and Coregonus. Genetic distances agreed well with the taxonomic relationships based on morphological traits and various biochemical markers and correlated with the evolutionary ages estimated for the groups by other markers. Third, RAPD PCR with a set of 20-mer primers was performed to study the genus Coregonus and anadromous and isolated populations and species of the genus Salvelinus. The resulting phylogenetic trees may help to resolve some disputable taxonomic issues for the groups. A comparison showed that several RAPD-detected sequences contain conserved fragments of coding sequences and polymorphic repeats (minisatellites) from intergenic regions or introns. The finding point to a nonrandom nature of repetitive DNA divergence and may reflect the evolution of the fish groups examined. Heterochromatic satellite repeats were assumed to contribute to generating a reproductive barrier.

Global population structure and demographic history of the grey seal.

Although the grey seal Halichoerus grypus is one of the most familiar and intensively studied of all pinniped species, its global population structure remains to be elucidated. Little is also known about how the species as a whole may have historically responded to climate-driven changes in habitat availability and anthropogenic exploitation. We therefore analysed samples from over 1500 individuals collected from 22 colonies spanning the Western and Eastern Atlantic and the Baltic Sea regions, represented by 350 bp of the mitochondrial hypervariable region and up to nine microsatellites. Strong population structure was observed at both types of marker, and highly asymmetrical patterns of gene flow were also inferred, with the Orkney Islands being identified as a source of emigrants to other areas in the Eastern Atlantic. The Baltic and Eastern Atlantic regions were estimated to have diverged a little over 10 000 years ago, consistent with the last proposed isolation of the Baltic Sea. Approximate Bayesian computation also identified genetic signals consistent with postglacial population expansion across much of the species range, suggesting that grey seals are highly responsive to changes in habitat availability.

Mycophenolate mofetil and cyclophosphamide treatments suppress inflammation intensity in an experimental model of autoimmune uveitis.

In human, autoimmune uveitis is a leading cause of visual disability and ranks with diabetic retinopathy as a major source of blind registrations in developed countries. Since most cases of non-infectious uveitis are considered to be autoimmune or at least immune-mediated, the management of such patients has rested on appropriate immunosuppression. Some patients, however, despite maximal immunotherapy, fail to respond or are seriously intolerant of the drug therapies. Since its establishment 20 years ago, the model of experimental autoimmune uveoretinitis has served as a useful template for novel therapeutic approaches. The aim of our study was to compare the efficacy of mycophenolate mofetil and cyclophosphamide and golimumab treatment in the mouse model of experimental autoimmune uveitis. The intensity of intraocular inflammation was evaluated histologically in the treatment and control groups. Experimental autoimmune uveitis has been induced in mouse strain C57BL/6 by subcutaneous application of interphotoreceptor retinoid binding protein in complete Freund's adjuvant and pertussis toxin. The treatment was commenced on the day of uveitis induction. Cyclophosphamide was applied intraperitoneally in a single dose (100 mg/kg), mycophenolate mofetil intraperitoneally daily (30 mg/kg or 50 mg/kg), golimumab subcutaneously weekly (70 mg/kg). Sham intraperitoneal injection of a placebo (aqua pro injectione) and untreated mice with experimental autoimmune uveitis served as controls. The results show statistically significant suppression of experimental uveitis both with mycophenolate mofetil and with cyclophosphamide, and thus support its use in human medicine.

[Features of expression and functional activity of P2X7 receptors in bone marrow cells under the action of doxorubicin].

Mechanisms of the myelotoxic action of doxorubicin associated with changes in the expression and functional activity of P2X7 receptors have been assessed. The acute and subacute exposure of bone marrow cells to doxorubicin in vivo changed the expression of P2X7, altered the intracellular and extracellular ATP concentrations, and modulated the process of programmed cell death. These changes were associated with transformed susceptibility of hemopoietic cells to the apoptogenic action of ATP. Various possible mechanisms of realization of the apoptogenic action of ATP during acute and subacute exposure to doxorubicin are discussed.