Effect of apple cider vinegar on plasma lipids (model experiment in mice)

Model experiment was carried out to investigate the effect of apple cider vinegar (ACV) on the blood and liver cholesterol (Ch), triglycerides (TG) and one of a marker of antioxidant status of blood (FRAP) in laboratory mice. Animals consumed a basal mice diet (Control) served as the control group. The same diet was supplemented either 1% cholesterol (Ch) or 1% edible sunflower oil (SFO). All groups were duplicated and their animals were supplied drinking water containing ACV (50 mg l-1)(groups: Control+ACV, Chol+ACV, SFO+ACV).The feeding and drinking was ad libitum for 21 days. At the end of experiment the animals were exterminated. Blood and liver samples were analyzed for total cholesterol (tCh), triglycerides (TG) and ferric reducing antioxidant power (FRAP). The results show that the Ch supplemented group stored higher concentration of tCh in the liver (P<0.01) than SFO treated animals. The cholesterol reserves were less in ACV treated groups. The alterations of plasma tCh showed no significant changes by cholesterol or SFO supplementation and drinking ACV containing water. The concentration of plasma and liver TG remained in the same range in all groups independently by different treatments. Animals of SFO supplemented groups (SFO and SFO+ACV) got more fatten than Control and Ch groups and their liver/body mass ratio (%) decreased (P<0.05). The ACV exerted a decreasing effect on the level of plasma tCh and TG markedly (P<0.05) but only in that group (Control+ACV) which consumed the basal diet. This lowering effect could be demonstrated only in the case of TG in the liver. The groups receiving ACV showed decreasing FRAP values. This means a lower antioxidative capacity of plasma. The ACV can helps in the lowering of plasma lipids (tCh and TG) and can depress their liver storage in the case of normal level of lipid consumption. When the lipid input was elevated this benefit not occurred

Humán alkalikus foszfatázt termelő transzgenetikus nyulak előállítása lentivirus géntranszferrel = Creating human alkaline phosphatase producing transgenic rabbits by lentiviral gene transfer

SIV lentivírus vektorral GFP-t expresszáló transzgenikus alapító nyulakat állítottunk elő. Legjobb tudásunk szerint lentivírussal elsőként sikerült transzgenikus nyulat előállítanunk világszerte. Mivel azonban az alapító nyulak különböző mértékben mozaikosak, élő zöld utódnyúl nem született. Emiatt az előre nem látható fajspecifikus különbség miatt, a pályázatban eredetileg tervezett emlőszövetspecifikus promóter - humán szöveti nemspecifikus foszfatáz transzgenikus nyulak előállítására lentivírus transzgenezissel nem került sor. Az előmag mikroinjektálással korábban előállított transzgenikus nyulak tejéből, három különböző módon próbáltunk tisztított rekombináns humán szöveti nemspecifikus foszfatáz fehérjét izolálni. A tisztított rekombináns fehérje biológiai hatásának igazolása szepszis egérmodellen folyamatban van. | GFP expressing transgenic rabbits were created with SIV lentiviral vector. To our knowledge those are the first lentiviral transgenic rabbits worldwide. Since the founder rabbits were expressing the transgene in mosaic pattern to different extent, alive green rabbit did not born from any of the founders. Due to this species specific difference in the efficiency of lentiviral transgenesis, we did not try to establish lentiviral transgenic rabbits with the planned mammary gland specific promoter - human tissue non-specific alkaline phosphatase lentiviral construct. From the milk of the human tissue non-specific alkaline phosphatase expressing transgenic rabbits, which were created by pronuclear microinjection we tried to isolate the recombinant protein on three different ways. Evaluation of the biological activity of the purified recombinant human tissue non-specific alkaline phosphatase is in progress

Onkoreumatológia: a daganatos és mozgásszervi kórképek összefüggései

Az onkoreumatológia a daganatképződés és a reumatológiai kórképek kapcsolatát jelenti. Számos összefüggés van a két orvosi szakterület között. Ezek egy része a reumatológiai kórképben szenvedő betegben jelentkező daganatokat, a másik fele pedig a daganatos betegen fellépő mozgásszervi jelenségeket foglalja magában. Az előbbi csoport kere-tében a reumatológiai betegségekben jelentkező szekunder tumorokat, a tumorasszociált antigének reumatológiai szerepét, a mozgásszervi betegségek kezelésére használt hagyományos és célzott terápiák esetleges onkogenitását és a korábban vagy jelenleg daganatos, mozgásszervi betegek fizioterápiáját tárgyaljuk. A másik nagy csoport magában foglalja a paraneoplasiás szindrómákat, az onkológiai kezelések (kemoterápia és immunterápia) lehetséges autoim-mun-reumatológiai mellékhatásait, a hormondeprivatiós kezelés csonthatásait és a mozgásszervrendszer primer és szekunder daganatai

FcRn Overexpression in Transgenic Mice Results in Augmented APC Activity and Robust Immune Response with Increased Diversity of Induced Antibodies

Our previous studies have shown that overexpression of bovine FcRn (bFcRn) in transgenic (Tg) mice leads to an increase in the humoral immune response, characterized by larger numbers of Ag-specific B cells and other immune cells in secondary lymphoid organs and higher levels of circulating Ag-specific antibodies (Abs). To gain additional insights into the mechanisms underlying this increase in humoral immune response, we further characterized the bFcRn Tg mice. Our Western blot analysis showed strong expression of the bFcRn transgene in peritoneal macrophages and bone marrow derived dendritic cells; and a quantitative PCR analysis demonstrated that the expression ratios of the bFcRn to mFcRn were 2.6- and 10-fold in these cells, respectively. We also found that overexpression of bFcRn enhances the phagocytosis of Ag-IgG immune complexes (ICs) by both macrophages and dendritic cells and significantly improves Ag presentation by dendritic cells. Finally, we determined that immunized bFcRn mice produce a much greater diversity of Ag-specific IgM, whereas only the levels, but not the diversity, of IgG is increased by overexpression of bFcRn. We suggest that the increase in diversity of IgG in Tg mice is prevented by a selective bias towards immunodominant epitopes of ovalbumin, which was used in this study as a model antigen. These results are also in line with our previous reports describing a substantial increase in the levels of Ag-specific IgG in FcRn Tg mice immunized with Ags that are weakly immunogenic and, therefore, not affected by immunodominance

Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn

The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes an active role in phagocytosis, and delivers antigen for presentation. We have previously shown that overexpression of FcRn in transgenic mice significantly improves the humoral immune response. Because rabbits are an important source of polyclonal and monoclonal antibodies, adaptation of our FcRn overexpression technology in this species would bring significant advantages. We cloned the full length cDNA of the rabbit FcRn alpha-chain and found that it is similar to its orthologous analyzed so far. The rabbit FcRn - IgG contact residues are highly conserved, and based on this we predicted pH dependent interaction, which we confirmed by analyzing the pH dependent binding of FcRn to rabbit IgG using yolk sac lysates of rabbit fetuses by Western blot. Using immunohistochemistry, we detected strong FcRn staining in the endodermal cells of the rabbit yolk sac membrane, while the placental trophoblast cells and amnion showed no FcRn staining. Then, using BAC transgenesis we generated transgenic rabbits carrying and overexpressing a 110 kb rabbit genomic fragment encoding the FcRn. These transgenic rabbits – having one extra copy of the FcRn when hemizygous and two extra copies when homozygous - showed improved IgG protection and an augmented humoral immune response when immunized with a variety of different antigens. Our results in these transgenic rabbits demonstrate an increased immune response, similar to what we described in mice, indicating that FcRn overexpression brings significant advantages for the production of polyclonal and monoclonal antibodies

Transgenic rabbits that overexpress the neonatal Fc receptor (FcRn) generate higher quantities and improved qualities of anti-thymocyte globulin (ATG).

Immune suppression with rabbit anti-thymocyte globulin (rATG) is a well-established therapeutic concept for preventing host rejection of transplanted organs and graft versus host disease. Increasing the efficiency of rATG production by reducing the number of animals would be highly beneficial to lower cost and to improve quality standards. We have developed transgenic (Tg) mice and rabbits that overexpress the neonatal Fc receptor (FcRn) and have shown an augmented humoral immune response in these animals. To test whether our FcRn Tg rabbits produced rATG more efficiently, we immunized them and their New Zealand White controls with live Jurkat cells. By day 21 after immunization, Tg animals produced significantly, 1.5 times higher amount of total IgG compared to their wt littermates. Also, the binding efficiency of Tg sera to Jurkat cells and their complement-mediated cytotoxicity was significantly higher. The purified Tg IgG preparation contained 2.6 the amount of Jurkat specific IgG as the wt preparation analyzed by complement-mediated lysis, suggesting greater antigen-specific B cell activation in the Tg rabbits. To test this hypothesis, immunization with ovalbumin and human α1-antitrypsin was performed, resulting in significantly greater numbers of antigen-specific B-cells in the FcRn Tg rabbits as compared with wt controls. The shift towards significantly larger populations of antigen-specific B cells relative to the non-specific B cell pool is further corroborated by our previous findings in FcRn Tg mice. Consequently, our FcRn Tg rabbits have the potential to offer substantial qualitative and quantitative improvements for the production of rATG and other polyclonal or monoclonal antibodies

Low titer lentiviral transgenesis in rodents with simian immundeficiency virus vector

Efficient production of transgenic animals using low-titer lentiviral constructs remains challenging. Here we demonstrate that microinjection of simian immundeficiency virus-derived lentiviral constructs can produce transgenic mice and rats with high efficiency even when using low-titer virus preparations

Kinetics of Jurkat specific immune response in Tg and wt rabbits.

<p><b>A.</b> Total IgG concentrations of serum samples collected from rabbit FcRn transgenic (Tg) and wild type (wt) rabbits immunized with Jurkat T cells (determined by ELISA assay). <b>B.</b> Development of immune response to Jurkat T cell surface antigens during immunization (determined by flow cytometry binding assay of 1∶250-fold diluted individual rabbit serum samples). Each dot represents one animal as an average of three measurements; (* <i>P</i><0.05; ** <i>P</i><0.01).</p