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1
Abukova, R. A. "Hypogammaglobulinemia and therapeutic use of gamma globulin." Kazan medical journal 43, no. 3 (October 29, 2021): 82–85. http://dx.doi.org/10.17816/kazmj84095.
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In the Soviet Union, gammaglobulin was first obtained in 1946 by Kholchev and Kolesnikova from the blood serum of donors. At first, it was used to prevent measles, and then, as the content of various antibodies in it was studied, it began to be used for poliomyelitis (Leitman, Strakhova, Denisenko, Bogdanov), Botkin's disease (Ananiev, Grachev, Fabrikantov), whooping cough (Khropetskaya), scarlet fever ( Kaushanskaya, Zhagullo, Mauerman). Gammaglobulins were also obtained from the blood serum of animals, which were successfully used for rabies (Selimov, Durasova, Kovalevskaya. Kobrinsky, Chun-syun), plague (Semenova, Ponomareva), smallpox (Mirosennikova). Gammaglobulin in industrial conditions is prepared from the placental serum of healthy women in labor.
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Lazarenko, A. A., L. M. Alimbarova, E. Yu Mordvintseva, and I. F. Barinsky. "Development of the suppository form of human immunoglobulin preparation with high titers of antibodies to herpes simplex virus types 1 and 2 for the treatment of chronic forms of herpetic disease." Problems of Virology, Russian journal 62, no. 1 (February 20, 2017): 36–41. http://dx.doi.org/10.18821/0507-4088-2017-62-1-36-41.
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In spite of the vast arsenal of therapeutic agents, therapy of herpes virus infection (HVI) is very difficult, particularly in pregnant women, newborns and children in the first years of life, as well as in patients with immune deficiency. In this regard, possibility of using immunoglobulins for the treatment of HVI is currently attracting the attention of doctors. The aim of this work was to develop a suppository form of the drug containing donor immunoglobulins with high levels of neutralizing antibodies to herpes simplex virus types 1 and 2 for the treatment of chronic forms of herpetic disease. The study included the following steps: 1) selection of gamma-globulins with high antibody titer for HSV-1 and HSV-2 ELISA test; 2) determination of the level of neutralizing antibodies in the selected series of gamma-globulins in tests in tissue cultures and animals; 3) lyophilization of immunoglobulins; 4) development of the suppository form of the preparation containing gamma-globulin donors with high levels of neutralizing antibodies to HSV-1 and HSV-2; 5) study of the safety of the activity of neutralizing antibodies to HSV-1 and HSV-2 in the suppository form of the drug with hyaluronic acid used as immunomodulator. As the result of this work, immunoglobulin preparation in the suppository form was developed. The developed preparation meets the requirements for safety and efficacy. It is not toxic or pyrogenic. The problems of clinical use of this drug as a method of HVI therapy are discussed.
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Ramesh, Sujatha, and Stanley A. Schwartz. "Therapeutic Uses of Intravenous Immunoglobulin (IVIG) in Children." Pediatrics In Review 16, no. 11 (November 1, 1995): 403–10. http://dx.doi.org/10.1542/pir.16.11.403.
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Introduction HISTORY Immunologists have been aware of the existence of protective humoral substances in the serum of patients after an infectious episode for a long time. Serum harvested from large animals after their immunization with specific pathogens was injected into humans for the prophylaxis and treatment of serious infections. The concept of immunoglobulin (also called gamma globulin) therapy originated from these early experiments. Subsequently, Paul Ehrlich produced antitoxin to diphtheria in 1897. To avoid complications such as serum sickness with the use of animal serums, attempts were made to concentrate the antibody-containing fractions of human serum. In 1936, placental immunoglobulin samples were used for prophylaxis of measles. In 1952, Bruton recognized that an 8-year-old child who had serious recurrent infections despite conventional therapy was incapable of making significant quantities of immunoglobulin. This was the first time primary immunodeficiency was diagnosed and treated successfully with intramuscular immunoglobulin. Since then, and until 1981, intramuscular gamma globulin or, alternatively, fresh frozen plasma has been the mainstay of treatment of hypogammaglobulinemia and other primary immune deficiencies. In 1981, intravenous immunoglobulin (IVIG) became available commercially in the United States. The advantages of IVIG over intramuscular gamma globulin are: 1) administration is relatively painless; 2) higher doses can be given, resulting in rapid achievement of therapeutic levels, because volume is not a limitation: 3) its absorption is good: 4) it does not undergo local degradation during infusion; and 5) it does not aggregate and activate complement.
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Shabaldin, A. V., N. S. Deeva, А. S. Sukhikh, G. V. Vavin, and P. M. Kryukov. "Altered expression of cell membrane HLA-G molecules in mothers of children with inborn heart defects upon exposure to plasma gamma-globulin from multiparous women." Russian Journal of Immunology 24, no. 3 (July 15, 2021): 373–76. http://dx.doi.org/10.46235/1028-7221-987-aeo.
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High incidence of newborns with inborn heart defects (HD) and sufficient contribution of this disorder into perinatal, infant and pediatric mortality, as well as disability levels, even after radical surgical treatment determine significance of search for novel methods of prediction and prevention of appropriate HD risks at the stage of pregnancy planning. HLA-G is among key molecules participating in immune interactions between maternal microenvironment and embryos. Maximal antibody titers for HLA antigens is detected in multiparous women. However, the question remains open, which HLA molecules participate in blockage of immune inflammation in the mother-embryo system: either by maternal antibodies, or by donor immune globulins. Hence, the aim of our study was to obtain enriched γ-globulin preparation from blood of multiparous women and evaluation of its activity towards female HLA-G molecules. The γ-globulin fraction (GGF) was obtained from blood plasma of muliparous women by means of affine chromatography using DEAE Affi-Gel Blue system (BioRad, USA). We have formed 2 groups: a control group (14 healthy males), and experimental group of 14 women who gave birth to the children with inborn heart defects.The changes of HLA-G expression on lymphocytes exposed to GGF were evaluated according to a flow cytometry protocol with calculation of percentage values using appropriate quotients. Evaluation of functional activity exerted by the GGF concentrate in control group showed inhibition of HLA-G expression on CD3+ and CD--lymphocytes against effects of autologous serum. GGF effects in experimental group upon HLA-G expression were differently directed, e.g., GGF sufficiently inhibited membrane HLA-G expression on the CD3-negative lymphocytes, compared to control group. Meanwhile, GGF showed stimulatory effect upon CD3+-lymphocytes, or it did not show any inhibitory action. The preparation obtained may serve as prototype for intravenous infusion. Moreover, in future one may use such immunoglobulin preparations, both for immune prophylaxis of non-syndromal sporadic HDs at the pregragravidary stage, as well as at early terms of pregnancy. The therapeutic effect will achieved due to blockage of embryoblast HLA molecules available to recognition.
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Byakova and Pilip. "THE ANTIOXIDANT IN THE COMPOSITIONOF ANTIPARASITIC PASTE FOR HORSES." THEORY AND PRACTICE OF PARASITIC DISEASE CONTROL, no. 20 (May 14, 2019): 161–66. http://dx.doi.org/10.31016/978-5-9902340-8-6.2019.20.161-166.
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The long-running parasitic process adversely affects the viability of the antioxidant defense system, which is reflected in an increase in the onset of the maximum signal reduction and a decrease in the AOA. For the treatment of equine helminth infections, drugs are needed that combine high anthelmintic efficacy with a simultaneous immunostimulating effect. The use of antioxidants in the composition of antiparasitic drugs increases the effectiveness of deworming. The use of the antiparasitic drug alezan containing ivermectin, praziquantel and antioxidant santohin in helminthiases of horses once at the rate of 1 g of paste per 100 kg of animal weight in a therapeutic dose ensured the complete elimination of worms from the host's body by the 10th day of research. The drug is used for therapeutic and prophylactic purposes. Significant changes in the content of total protein, alpha- and gamma-globulins, AlAt and AsAt by the 28th day of research indicate that there is no negative effect of deworming. Information was obtained on the positive effect of the antiparasitic paste with antioxidant on the light sum (S) and maximum flare (Imax), which is characterized by a decrease in the level of free radical lipid oxidation with a decrease in the light sum of radicals by 14.6% and an increase in the antioxidant activity of horse serum by 26.5% on the 7th day. By the 14th day, the radical sum of radicals decreased by 16.9%, the maximum luminescence intensity – by 34.3%, and on the 28th day the light sum index was 26.73, which corresponded to the standard data. With chronic parasitic invasion, a low AOA was observed.
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Cowchock, S. "Prevention of Fetal Death in the Antiphospholipid Antibody Syndrome." Lupus 5, no. 5 (October 1996): 467–72. http://dx.doi.org/10.1177/096120339600500528.
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The first treatment of pregnant women with antiphospholipid antibody syndrome (APLS) employed high doses of corticosteroids, plus low dose aspirin, with the goal of suppressing production of the autoantibody. Corticosteroids (usually prednisone), even when much lower doses are used, and even when tapered after midpregnancy, have been associated with significant maternal and obstetric risks and side effects: the most important are osteomalacia and preterm delivery (often precipitated by premature rupture of the membranes). Since the publication of a randomized trial demonstrating equivalent live birth rates of about 75% whether heparin or prednisone was used for treatment (plus low dose aspirin), the use of adjusted doses of heparin, together with low dose aspirin, has replaced prednisone for treatment of pregnant women; although prednisone may still be needed to treat manifestations of associated autoimmune disorders. A recent randomized trial has shown that the addition of heparin to aspirin is probably superior to treatment with aspirin alone. To achieve prophylactic levels of plasma heparin equivalent to those measured in patients who are not pregnant and are treated with the usual dose of standard heparin of 5000 IU every 12 h, the heparin dose required for treatment of pregnant women is usually higher. For that reason, heparin doses should be adjusted using the nadir APTT, or better plasma heparin measured by a factor Xa inhibition assay at the 2 h post-injection peak. Although low molecular weight heparin has been shown to be useful in prevention of fetal resorption in a mouse model, and appears to be equally safe for treatment of pregnant women, we still have no published data to show therapeutic equivalency, with respect to treatment of APLS-complicated pregnancy, to standard heparin preparations, and none that demonstrate any lower risk for the complication of most concern when heparin is given to pregnant women—osteopenia. Similarly, intravenous infusion of gamma globulins (IVG) appears on the basis of case reports to be effective additional treatment in cases where standard therapy has failed. Gamma globulin preparations contain anti-idiotypic antibodies that have been shown to bind to patient antiphospholipid antibodies. The place for the addition of IVG to standard therapy has not been defined, but clinically significant and corticosteroid-resistant thrombocytopenia complicating antiphospholipid antibody syndrome might be one indication for primary treatment with IVG ± low dose aspirin. Overall, live birth rates in most treatment studies are in the range of 70–80%. The reported birth rate information, however, cannot be compared between studies. None of the studies reported have used tools such as logistic regression analysis to allow for such significant predictors of live birth as the number of prior miscarriages, maternal age, medical history, or a history of fetal death (loss of a viable and chromosomally normal fetus after the 10th gestational week).
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Metlin, A. E., A. D. Botvinkin, A. L. Elakov, and K. N. Gruzdev. "СASES OF HUMAN CONVALESCENCE FROM RABIES AND LIFETIME DIAGNOSTICS OF LYSSAVIRUS ENCEPHALITIS." Problems of Virology, Russian journal 64, no. 1 (February 20, 2019): 42–48. http://dx.doi.org/10.18821/0507-4088-2019-64-1-42-48.
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Notwithstanding the availability of effective vaccines, 40 - 60 thousand rabies cases in humans are reported every year. Almost always the disease is fatal because therapeutic treatment of lyssavirus encephalitis has not been developed. Since 1970 the number of reports on rare cases of convalescence including those using experimental treatment protocols has been gradually increasing 20 cases of convalescence, “partial” convalescence or long-term survival of humans (1970-2015) were selected as they were complaint with laboratory criteria of active lyssavirus infection. Children and teenagers were predominant in the analyzed group (85%). The cases were irregularly spread between the continents: Asia - 6 cases, North America - 6 cases, Africa - 2 cases and Europe - 1 case. India and the USA were on the top of the list of countries by the number of described cases. More than 60% humans were infected from dogs, three cases got infection from bats and 2 cases were allegedly associated with an unknown lyssavirus and an unidentified infection source. 70% cases were vaccinated and 10% cases were treated with gamma globulin before the disease onset. Serological tests for detection of antibodies to lyssaviruses in cerebrospinal fluid of infected humans were typically used for diagnostic laboratory verification. Less than 30% IFA and PCR positives were obtained. Lyssaviruses were never detected. Only 4 convalescent patients were treated using experimental protocols. 80% cases demonstrated severe neurological consequences, four (may be more) patients died afterwards within the period from two months to four years. Different perspectives on prospects of Milwaukee protocol use and other therapeutic techniques are given.
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Latov, Norman, Vinay Chaudhry, Carol Lee Koski, Robert P. Lisak, Brian R. Apatoff, Angelika F. Hahn, and James F. Howard Jr. "Use of intravenous gamma globulins in neuroimmunologic diseases☆☆☆." Journal of Allergy and Clinical Immunology 108, no. 4 (October 2001): S126—S132. http://dx.doi.org/10.1067/mai.2001.118300.
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Marquez, Audrey de Souza, Adriana Pardini Vicentini Moreira, Paula Cesar Leonello, Fernanda Akemi Nakanishi, and Eiko Nakagawa Itano. "Serum proteins and fractions, HDL-cholesterol and total IgG and IgE levels in cases of acute and chronic paracoccidioidomycosis." Revista da Sociedade Brasileira de Medicina Tropical 42, no. 3 (June 2009): 245–49. http://dx.doi.org/10.1590/s0037-86822009000300002.
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This study evaluated serum protein fractions, HDL-cholesterol, total immunoglobulin G and total immunoglobulin E levels in patients with acute and chronic paracoccidioidomycosis, by means of electrophoresis, enzymatic reaction and immunoenzymatic assay. The results demonstrated elevated levels of total immunoglobulin G, total immunoglobulin E, alpha-2 and gamma-globulins, which were more evident in acute than in chronic PCM, but no increase in HDL-cholesterol levels. There was a correlation between the levels of total immunoglobulin E and gamma-globulins and the alpha-2 and beta-globulin fractions in the acute form and between beta and gamma-globulins in both the acute and the chronic form. In conclusion, changes in total immunoglobulin G and immunoglobulin E levels and in the electrophoretic profile may be important markers for the prognosis and therapeutic follow-up of PCM cases, especially because protein electrophoresis is a simple laboratory test that can be applied when specific PCM serological tests are not available. In addition, levels of the gamma-globulin fraction greater than 2.0g/dl may suggest that the patient is developing a more severe form of PCM.
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Ferreira, Hugo Henrique de Freitas, Alessandra Suelen Jardim Silva, Lenilton Silva DA Silva Júnior, Gustavo Henrique de Medeiros Oliveira, Maria das Graças Pereira Araujo, Victor lima Soares, Frank Bahia, et al. "Multiple Myeloma Course with Renal Insufficiency in Young Patient: Case Report." Blood 136, Supplement 1 (November 5, 2020): 26. http://dx.doi.org/10.1182/blood-2020-143302.
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Introduction: Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells in the bone marrow (OM). The average age of patients diagnosed with MM is approximately 70 years, being relatively uncommon in younger individuals. Objective: To report a case of a young patient with multiple myeloma. Case Description: A 42-year-old male patient presented with continuous and progressive low back pain for 3 months, associated with adynamia, weight loss (10 kg), episodes of constipation and bleeding in the oral cavity in this period. Examinations at the first appointment revealed moderate anemia (Hb 7.4 g / dL), leukocytosis, thrombocytopenia, hypercalcemia, and altered renal function (Cr 5.9 and Ur 178), chest tomography indicating vertebral fracture in T6, T11, L2 and L4. Referred for specialized follow-up, he performed electrophoresis of serum proteins with the presence of a monoclonal peak in the gamma globulin fraction. The immunofixation test confirmed monoclonality for IgA isotype and Kappa light chain (IgA / Kappa). The myelogram showed plasmacytosis of more than 50% of mononuclear cells in the bone marrow. He developed renal failure (with dosage of creatinine of 10.1 mg/ dL. and urea of 208 mg/dL) and hypercalcemia requiring dialysis therapy on the third day of hospitalization, having undergone chemotherapy with Bortezomib, cyclophosphamide and dexamethasone. During this period, infection by the multisensitive S. aureus in catheter occurred and, despite being treated with specific antibiotic therapy, it evolved with clinical worsening and hemodynamic instability and was referred to the Intensive Care Unit, going to death after 2 days. Conclusion: Young patients with MM may study with more aggressive characteristics. Despite the use of new therapeutic agents, more effective treatment strategies need to be studied more for patients in this age group. Disclosures No relevant conflicts of interest to declare.
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Fouché, Nathalie, Claudia Graubner, and Judith Howard. "Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals." Veterinary Journal 202, no. 2 (November 2014): 384–86. http://dx.doi.org/10.1016/j.tvjl.2014.08.013.
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Sun, Hao, Huimin Lu, and Yunhong Wu. "Efficacy of Gamma Globulins in Children with Kawasaki Disease and Factors Influencing Children’s Short-Term Prognosis." Computational and Mathematical Methods in Medicine 2022 (July 30, 2022): 1–6. http://dx.doi.org/10.1155/2022/5137874.
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Purpose. To explore and analyze the therapeutic effect of gamma globulins (GG) on Kawasaki disease (KD) in children and the influencing factors of short-term prognosis. Methods. First, 90 pediatric KD patients admitted between January 2019 and January 2021 were selected and divided into a control group ( n = 40 ) and a research group ( n = 50 ) according to the difference in treatment. In addition to routine treatment and nursing given to both groups, control group was given aspirin (ASA), based on which research group was supplemented with GG therapy. The treatment outcome and adverse events (AEs) of the two cohorts of patients were analyzed and compared, and the influencing factors of children’s short-term prognosis were analyzed by logistics multivariate analysis. Results. Research group had a statistical higher overall response rate than control group, with significantly fewer cases suffering from AEs such as nausea and vomiting, diarrhea, rash, dizziness and headache, and coronary artery injury. On the other hand, logistics multivariate analysis identified that gender, body mass index (BMI), onset time, platelet (PLT), and treatment mode all independently influence the short-term prognosis of children with KD. Conclusions. GG therapy is effective in treating pediatric KD patients and can effectively prevent AEs. In addition, gender, BMI, onset-to-treatment time, PLT, C-reactive protein (CRP), and treatment methods are independent risk factors for short-term prognosis of children with KD.
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Ligidova, M. M., M. I. Kalabekov, A. A. Gusev, and L. P. Padilo. "THERAPEUTIC EFFICACY OF ENTRIKIM IN CALF MYCOPLASMOSIS." Scientific Life 15, no. 11 (2020): 1534–43. http://dx.doi.org/10.35679/1991-9476-2020-15-11-1534-1543.
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In the acute course of mycoplasmosis in calves of 10-30 days of age, the incidence per 1000 heads is 94.7 heads, and the mortality rate is 28.9 heads with a mortality rate of 30.5%. In the chronic course of mycoplasmosis in calves of 10-30 days of age, the incidence per 1000 heads is 61.4 heads, and the mortality rate is 14.58 heads with a mortality rate of 23.7%. As a therapeutic drug, calves were administered a 5 % solution of entrikim orally at a dose of 0.5 cm3/10 kg of body weight twice a day for 7 consecutive days. Blood was taken from calves before and after the treatment (3 days after the end of the course) for complex laboratory tests. The total number of red blood cells and white blood cells in calves treated with entrikim increased by 25.4% and 16.9%, respectively (p <0.05). The leukogram parameters did not have significant differences. The content of gamma globulins in sick calves was low. After the treatment, there was a significant increase in o gamma globulin by 14.5% (p <0.05). It is also worth noting an increase in total blood protein by 11.9% (p <0.05). BASC increased by 28.3%, LASC by 11.0%, FA by 4.6%, FI by 14.2%. NST test scores were also more pronounced in calves after treatment. The functional activity of neutrophils in the NST test after therapy had higher indicators, both in the spontaneous and stimulated variants. Its level increased by 43.8% and 33.3%, respectively. The content of immunoglobulins increased by 26.5% higher. In the calves treated, there was also a tendency to increase the total number of T - and B - lymphocytes. The number of T - lymphocytes increased by 48.3% (p <0.05). The content of B - lymphocytes in calves also became higher by 33.3% (p <0.05). The therapeutic effectiveness of entrikim in the acute course was 85.7%, in the chronic course-62.5%, which is significantly higher than in the treatment with enrofloxacin or trimethoprim or tilmicosin alone.
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Lippi, I., F. Perondi, S. Ross, V. Marchetti, G. Lubas, and G. Guidi. "Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome." Open Veterinary Journal 5, no. 2 (2015): 108. http://dx.doi.org/10.5455/ovj.2015.v5.i2.p108.
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A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. The dog received three double filtration plasmapheresis treatments on day 0, 7 and 22 after presentation. A significant (p<0.05) reduction in serum total protein, alpha-2 and gamma globulins was found following each treatment. These reductions were accompanied by a complete resolution, although temporary, of the clinical signs of hyperviscosity syndrome. The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma.
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V. G. Semenov, D. A. Baimukanov, I. A. Alekseev, R. A. Yegorov, A. F. Kuznetsov, V. G. Sofronov, A. H. Volkov, K. Zh. Iskhan, and A. K. Nesipbayeva. "RESISTANCE, PRODUCTIVITY, AND QUALITY OF VEAL WHEN USING BASULIFOR PROBIOTIC FEED ADDITIVE." BULLETIN 1, no. 383 (February 15, 2020): 56–63. http://dx.doi.org/10.32014/2020.2518-1467.7.
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Against the background of the use of a probiotic feed additive at a rate of 0.3 g/kg and 0.4 g/kg of fodder, in experimental calves, compared with the controlanalogs, there was a significant increase in the average daily weight gain on the 15th day of the experiment by 4.60-4.90%, on the 30th day - by 5.87 - 6.34%, on the 60th day - by 7.48 - 7.81%, in the blood of animals the number of red blood cells increased by 3.69 - 4.54%, leukocytes - by 1.48 - 1.75%, hemoglobin - by 6.39 - 7.59%, in blood serum the level of total protein - by 3.28 - 3.31% (P<0.05), albumin - by 2.08 - 2.69% (P<0.05), globulins - by 3.70 - 4.20% (P<0.05), gamma globulins - by 12.41 - 12.91 % (P<0.01). Introduction to the diet of calves of the specified probiotic feed additive promoted a slight increase of immunoglobulins A in blood serum in the experimental calves, in relation to the control analogues, in both experimental groups of animals by 5.00% (P<0.05), immunoglobulins M - by 4.43 - 5.64% (P<0.01), immunoglobulins G - by 5.69 - 5.90% (P<0.05), increasing the preservation of calves - by 3.22 - 3.69% (P<0.05).
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Verçosa Junior, Durval, Neide Judith Faria de Oliveira, Eduardo Robson Duarte, Gabriela Almeida Bastos, Ana Cláudia Maia Soares, Geovanni Dantas Cassali, Benito Soto-Blanco, and Marília Martins Melo. "Serum hepatic biochemistry and electrophoretic protein profile of healthy and Ehrlich tumor-bearing mice treated with extracts of Agaricus blazei Murill." Semina: Ciências Agrárias 37, no. 2 (April 26, 2016): 763. http://dx.doi.org/10.5433/1679-0359.2016v37n2p763.
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Compounds isolated from Agaricus blazei Murill represent a group of promising natural immunomodulators for use in the treatment of neoplasms. We have evaluated the serum biochemical profile of healthy and Ehrlich tumor-bearing mice treated with different extracts of A. blazei. Total, supernatant, and polysaccharide extracts of A. blazei were obtained from suspensions (at acidic or neutral pH) kept in a water bath at 60 °C or in an ultrasonic bath at 37 °C. After oral administering the extracts to mice for 21 days, blood samples were collected for determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), urea, total protein, albumin, globulins, and alpha-, beta- and gamma-globulin fractions. The presence of the tumor led to a significant increase in serum CK and AST activities and in the concentrations of total globulin and the gamma-globulin fraction, and to a decrease in the albumin and alpha2-globulin levels. The polysaccharide extracts of A. blazei reduced the serum AST and ALT activities, probably due to a hepatoprotective effect. In addition, polysaccharide and supernatant extracts inhibited the tumor-induced increase in gamma-globulin levels. Thus, the supernatant and polysaccharide fractions of the extract of A. blazei have potential for use in complementary antineoplastic treatments.
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Hemming, V. G., G. A. Prince, J. R. Groothuis, and G. R. Siber. "Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections." Clinical Microbiology Reviews 8, no. 1 (January 1995): 22–33. http://dx.doi.org/10.1128/cmr.8.1.22.
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Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.
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Shakhov, A. G., L. Yu Sashnina, K. V. Tarakanova, N. V. Karmanova, and Yu Yu Vladimirova. "EFFECT OF THE PREPARATION «PROSTIMUL» ON IMMUNE STATUS, PRODUCTIVITY AND SAFETY OF RETARDED IN GROWTH PIGS." Transactions of the educational establishment “Vitebsk the Order of “the Badge of Honor” State Academy of Veterinary Medicine 57, no. 2 (2021): 133–37. http://dx.doi.org/10.52368/2078-0109-2021-57-2-133-137.
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The article presents the results of studies on the effect of Prostimul containing cytokines of the type 1, vitamins A, E, and C on the immune status, productivity, and safety of pigs that lag behind in growth and development. It was found that the drug, administered twice with an interval of 48 hours was followed by an increase in the immune status of animals, which was manifested by increasing in the serum the level of total protein, gamma globulins, total immunoglobulins, lysozymic and complementary activity, as well as the absorptive and digestive function of phagocytes, and a decrease in the level of circulating immune complexes and their pathogenicity. The use of Prostimul, accompanied by an increase in the immune status of pigs that retard in growth and devel-opment, had a positive effect on their productivity and safety. This allows the drug to be recommended for a wide use in industrial pig farming.
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Okulova, I. I., I. A. Domsky, Yu A. Berezina, and Z. N. Beltyukova. "THE EFFECT OF «ARCUSIT» ON BIOCHEMICAL AND IMMUNOLOGICAL PARAMETERS BLOOD SERA IN SILVER-BLACK FOX (SILVER-BLACK FOX)." Scientific Notes Kazan Bauman State Academy of Veterinary Medicine 247, no. 3 (September 5, 2021): 192–97. http://dx.doi.org/10.31588/2413-4201-1883-247-3-192-197.
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The use of «Arkusit» at a dose of 20 μg / kg of body weight indicates a beneficial effect on the factors of nonspecific resistance of the silver-black fox. The concentration of alkaline phosphatase in the blood serum in the experimental group decreased by 1.8 times (P <0.001), the ALT index - by 1.2 (P <0.05). The concentration of glucose in the experimental group increased 2 times (P <0.05) compared with the control group. In animals of the experimental group, the lysozyme activity of blood serum increased 1.3 times (P <0.05), the OPR reaction and the phagocytic index - 1.4 times (P <0.05), the bactericidal activity of blood serum - 1.8 times (P <0.05). «Arcusit» stimulates the synthesis of gamma globulins, increases the opsonophagocytic, bactericidal activity of blood serum. Thus, the analysis of experimental data indicates that the drug «Arcusit» has a pronounced immunostimulating effect, providing the activation of factors of nonspecific resistance of the body of the silver-black fox.
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Somerville, K. Troy. "Antibody Agents in Solid Organ Transplantation." Journal of Pharmacy Practice 16, no. 6 (December 2003): 388–400. http://dx.doi.org/10.1177/0897190003259835.
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Antibody agents play an important role in the pharmacotherapy of solid organ transplantation. These agents can be either monoclonal or polyclonal, derived from an animal source or genetically engineered utilizing human antibody sequences. This reviewpresents basic pharmacology and therapeutic issues related to the antibody preparations utilized in transplantation including equine and rabbit antithymocyte globulins, muromonab-CD3, daclizumab, and basiliximab. The parameters covered for these agents include mechanism of action, pharmacokinetics, pharmacodynamic monitoring strategies, clinical dosing, adverse effects, and clinical trials. The brief overviewof current clinical data related to these agents focuses on kidney transplantation. The use of these very powerful agents in different patient populations needs to be individualized based on certain risks and these data are presented to help in the decision-making process, especially for renal allograft recipients.
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Sheremeta, M. S., A. A. Trukhin, and M. O. Korchagina. "The use of radioactive substances in medicine — history and development prospects." Problems of Endocrinology 67, no. 6 (October 3, 2021): 59–67. http://dx.doi.org/10.14341/probl12824.
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Nuclear medicine (NM) is a medical specialty that uses radionuclides (radioactive tracers) and ionising radiation for diagnostic and therapeutic (theranostic) purposes. Nuclear medicine arose and developed at the intersection of physics, chemistry and clinical medicine. The radiation emitted by radioisotopes can consist of gamma-, beta- and alpha emission, or it’s combination. Radioisotope of choice for medical purposes should have futher requirements: low radiotoxicity, suitable type of radiation, energy and half-life (several minutes to several hours and days), and also convenient detection of gamma ray radiation. The radionuclide is part of radiopharmaceutical (RP) and acts as its indicator. RP accumulates in morphological structures, becomes a carrier of coordinated information from patient to gamma camera or other equipment and reflects the dynamics of processes occurring in the examined organ. In 2021 NM celebrates its 80th anniversary. The trajectory of NM combines modern methods of radiotheranostics and applied genomic and post-genomic technologies.
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Nikiforov, Vladimir Vladimirovich, T. V. Sologub, I. I. Tokin, V. V. Tsvetkov, M. K. Erofeeva, and V. V. Zarubaev. "The possibility of the use of interferon-gamma in Influenza infection." Epidemiology and Infectious Diseases 20, no. 3 (June 15, 2015): 11–16. http://dx.doi.org/10.17816/eid40849.
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Interferon-gamma (IFN-y) is a pleiotropic lymphokine that have multiple effects on the growth and differentiation of various types of cells associated with innate immunity. IFN-y induces differentiation ofmyeloid cells, stimulates the expression of major histocompatibility complex (MHC) class II and class I antigens, it is a potent activator of macrophages which destroy antigenic molecules penetrating the cell. IFN-y is widely used for the treatment of infectious diseases, cancer, autoimmune and allergic diseases. Studies conducted in Research Institute ofInfluenza indicate that drugs IFN-y can be successfully usedfor prevention of influenza and acute respiratory infection (ARI) during the rise of incidence, as well as for the treatment - the first few days/ hours of the onset. The concomitant use of drugs as IFN-a and IFN-y on influenza and ARI can greatly improve the prophylactic and therapeutic efficacy.
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Kulmakova, Nataliya, Victor Orlov, Alexander Ivanitskiy, Nadezhda Sevastyanova, and Sayana Mongush. "Pork production technology optimization based on mathematical modelling." E3S Web of Conferences 91 (2019): 06009. http://dx.doi.org/10.1051/e3sconf/20199106009.
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One of the ways to enhance sow productivity is to use various food supplements to stimulate digestion and uptake of the elements required for the accelerated development of animals. The list of such supplements is expanding every year and, according to experiments conducted, they yield good results. However, their controversial manifestation in the pork production process should be noted. The used supplements clearly affect this process optimality both in terms of the output and financial outlays. This work addresses the influence of protein-vitamin-mineral supplements (PVMS) on sow productivity, metabolism, and pork quality. The mathematical model has been used to substantiate the optimal alternative of the pork production technology for the PVMS under study. Addition of Provimi supplements to the pig diet has been found to enhance litter heaviness, sow milking capacity, the viability of piggery by the time of weaning, and to promote the growth of the young stock. In the bodies of piggery and sows, the use of supplements normalizes cobalt, manganese, and copper metabolism, increases the content of gamma globulins in the piggery serum, and improves pork nutritional and biological value.
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Horner, Thierry J., Jeffry A. Siegel, Roxanne C. Jewell, Gary J. Lunger, Nancy L. Young, Brian R. Wynne, Vanessa C. Williams, et al. "Comparison of Dosimetry and Gamma Camera Methods for Evaluation of Biodistribution Prior to Administration of the Therapeutic Dose of Tositumomab and Iodine I 131 Tositumomab (Bexxar Therapeutic Regimen)." Blood 116, no. 21 (November 19, 2010): 4916. http://dx.doi.org/10.1182/blood.v116.21.4916.4916.
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Abstract Abstract 4916 Introduction: The Bexxar® Therapeutic Regimen for relapsed/refractory follicular lymphoma (FL) is administered in 2 steps: a dosimetric dose and a therapeutic dose. Radioactive counts, obtained from sequential gamma camera scans of the whole body at several time points after the dosimetric dose, determine the patient (pt)-specific clearance (total body residence time, TBRT) and, along with pt body size, allow determination of the prescribed activity (PA) of the therapeutic dose. Pts do not receive the therapeutic dose if TBRT is outside 50 to 150 hrs and/or gamma camera images show altered biodistribution. TBRT is used to calculate the mCi of I-131 (PA) required to deliver the appropriate therapeutic dose of 65 or 75 cGy to the total body, depending on platelet count. Our aims were 1) to evaluate an alternative, inexpensive sodium iodide probe (probe) detector-based method of measuring radioactive counts for determination of TBRT and 2) to evaluate the clinical benefit of visually assessing gamma camera images for altered biodistribution. Methods: We retrospectively compared probe and gamma camera methods from a phase II study (RIT-II-001) and evaluated altered biodistribution assessed by gamma camera images from a post-marketing observational study. Forty-one of 47 FL pts enrolled in RIT-II-001 from December 1995 to November 1996 were included in the retrospective analysis of TBRT and PA. Pts received a median of 5 prior chemotherapies (range 2–13). Thirty of 41 (73%) pts had low-grade B-NHL, 90% had stage III or IV disease, 51% had bone marrow involvement, 88% had an International Prognostic Index score ≥ 2, and 16 of 34 (47%) pts had bulky disease >500 g. Dosimetry analysis was performed at 3 time points (Day 0; Day 2, 3, or 4; and Day 6 or 7) after dosimetric dose, as currently required for determining PA. The PAs of the therapeutic dose using TBRTs derived from probe and gamma camera counts were compared. Also, we retrospectively evaluated cases of altered biodistribution in an observational post-marketing study (BEX114606) of 2,649 pts who received a dosimetric dose from June 2003 to February 2010. Dosimetry and gamma camera images were independently reviewed from reported cases of altered biodistribution to evaluate the clinical benefit of visually assessing gamma camera images. Results: The mean TBRTs from the clinical study were 94.5 and 95.0 hrs from the probe and gamma camera methods, respectively, and individual TBRTs were highly correlated (r = 0.98). The mean PAs of the therapeutic dose, derived from probe and gamma camera TBRTs, were 85.8 mCi and 85.3 mCi, respectively. The point estimate for the ratio of the PA was 0.995 and the 90% CI (0.984, 1.006) was well within the typical range of 0.80 to 1.25 for demonstrating bioequivalence. The observational study found that only 5 of 2,649 (0.2%) pts did not receive the therapeutic dose due to suspected altered biodistribution. Dosimetry data and gamma camera images were available for 3 pts. Independent review confirmed that all 3 pts had accurately determined TBRTs, but only 1 pt had confirmed altered biodistribution by visual assessment of gamma camera images and TBRTs. Conclusion: TBRTs derived from probe and gamma camera counts were highly comparable. Thus, the probe and gamma camera methods to determine TBRT and calculate the PA of the therapeutic dose of Bexxar appear equivalent. Altered biodistribution prevented only 5 of 2,649 (0.2%) pts from receiving the therapeutic dose of Bexxar. Only 1 pt (0.04%) was independently confirmed to have altered biodistribution by visual assessment of gamma camera images, consistent with the TBRT. Therefore, visual assessment of gamma camera images added no benefit beyond TBRT in determining whether to administer the therapeutic dose of Bexxar. These data indicate that either sequential probe or gamma camera-based dosimetry is sufficient for determining whether to administer the therapeutic dose, and that visual assessment of gamma camera images does not appear to be necessary to detect the rare instance of an altered biodistribution. Disclosures: Horner: GlaxoSmithKline: Employment. Off Label Use: The BEXXAR therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) is indicated for the treatment of patients with CD20 antigen-expressing relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin's lymphoma. Siegel: GlaxoSmithKline: Consultancy. Jewell: GlaxoSmithKline: Employment. Lunger: GE Healthcare: Employment. Young: GlaxoSmithKline: Employment. Wynne: GlaxoSmithKline: Employment. Williams: GlaxoSmithKline: Employment. Lin: GlaxoSmithKline: Employment. Kaminski: GlaxoSmithKline: Patents & Royalties, Research Funding. Wahl: GlaxoSmithKline: Consultancy, Patents & Royalties; Nihon Medi Physics: Consultancy; Spectrum Pharmaceuticals: Consultancy; Naviscan PET systems: Consultancy; Threshold Pharmaceuticals: Equity Ownership. Vleisides: GlaxoSmithKline: Employment.
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Checler, Frédéric. "P4-317 Gamma-secretase inhibitors: a critical evaluation of their potential therapeutic use in Alzheimer disease." Neurobiology of Aging 25 (July 2004): S565. http://dx.doi.org/10.1016/s0197-4580(04)81875-x.
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Korschunov, V. M., V. V. Smeyanov, B. A. Efimov, N. P. Tarabrina, A. A. Ivanov, and A. E. Baranov. "Therapeutic use of an antibiotic-resistant Bifidobacterium preparation in men exposed to high-dose gamma-irradiation." Journal of Medical Microbiology 55, no. 12 (December 1, 2006): 1759. http://dx.doi.org/10.1099/0022-1317-55-12-1759.
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Dudarchuk, A. N. "Peculiarities of sheep pathogenesis at associative invasions of gastrointestinal tract." Proceedings of the National Academy of Sciences of Belarus. Agrarian Series 59, no. 1 (February 9, 2021): 81–89. http://dx.doi.org/10.29235/1817-7204-2021-59-1-81-89.
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In the Republic of Belarus, primarily in farms with imperfect technology, parasitic diseases of sheep are widespread, including: nematodes of gastrointestinal tract, strongyloidosis, eimeriosis, monieziosis, trichocephalosis, cryptosporidiosis, etc. Study of impact of associative parasitosis of sheep on the immunobiological reactivity of animal body has recently become more and more theoretical and practical for rational use of drugs in treatment of these diseases. The purpose of research is to study peculiarities of sheep pathogenesis at associative invasions of gastrointestinal tract. The study was carried out at farm “Villia-agro”, Kobrin district, Brest region. Lambs of 2-4 months of age spontaneously infested with parasites of gastrointestinal tract have been selected. Parameters of cellular immunity were determined: number of leukocytes, monocytes, neutrophils, eosinophils, level of rosette-forming T- and B-lymphocytes and humoral immunity: circulating immune complexes, total protein, protein fractions, including proteins of C3 complement system and immunoglobulins, macro and microelements (calcium, phosphorus and iron) in blood serum. With spontaneous invasion of sheep by associations of parasites of gastrointestinal tract, the following changes have been determined: significant decrease in number of lymphocytes, T-lymphocytes, concentration of total protein, albumin, - β- and g-globulins, calcium and phosphorus. Significant increase in leukocytes: Eosinophils and stab neutrophils, a1-globulins , circulating immune complexes. All this together indicates disturbance in functioning of body’s immunity and requires immediate appropriate treatment aimed both at destroying associations of parasites of gastrointestinal tract and restoring immune system of animal’s body. These studies will form basis for development of rational system for therapeutic and preventive measures for associative parasitosis of sheep in the Republic of Belarus, which will reduce economic damage from these diseases and improve quality of livestock products.
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Prosyanyi, S., and V. Horiuk. "Influence of non-ionizing radiation on protein metabolism in chickens." Naukovij vìsnik veterinarnoï medicini, no. 2 (168) (December 9, 2021): 136–46. http://dx.doi.org/10.33245/2310-4902-2021-168-2-136-146.
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In practical terms, the idea of using an artificial magnetic field is of particular interest, which corresponds in its physical characteristics to the geomagnetic field of the Earth to combat the negative effects of hypogeomagnetic field. Further development of this idea is associated with the use and selection of hypo-, hypermagnetic fields acting on the body with experimental pathology. In this regard, the issue of influence of different duration of irradiation with an alternating pulsed electromagnetic field of ultra-low frequency (APEMF ULF) on the indicators that characterize metabolic processes in the body is insufficiently clarified. Therefore, the aim of research has been to study the effect of alternating pulsed electromagnetic field of ultra-low frequency on protein content and protein metabolism in the body of experimental chickens of the Dominant D959 cross. For this purpose, four experimental and control groups of 120-day-old chickens have been formed – 20 heads in each. The poultry has been kept in a specially equipped room with an alternating pulsed electromagnetic field of ultra-low frequency. The total protein content has been determined by the biuret method; protein fractions (albumins, globulins: alpha-1, alpha-2, beta, gamma) – by diffuse polyacrylamide gel (PAAG) electrophoresis; the content of creatinine, urea and uric acid has been performed by spectrophotometry using standard techniques. According to the results of research, it has been established that by selecting different regimens and duration of action of APEMF ULF, it is possible to influence protein metabolism in the body of chickens. Thus, on the 80th day of continuous irradiation of experimental chickens with APEMF ULF, regardless of the level of protein in the diet, in their blood revealed an increase in total protein, the relative content of globulin fraction mainly due to γ-globulins, and an increase in creatinine, urea and uric acids. When the period of continuous irradiation has been increased to 5 months, a negative effect on protein metabolism has been revealed, which has been manifested by a decrease in total protein content, relative albumin content, decrease in creatinine, urea and uric acid in the serum of experimental chickens. The combination of long-term (for 150 days) daily 60 minutes with weekly intervals of irradiation of chickens with APEMF ULF and their feeding with a 15% increase in protein levels in the diet caused a stimulating effect on protein metabolism and resistance of experimental chickens, with increasing, the relative content of globulins due to the γ-globulin fraction, as well as the main indicators of protein metabolism – creatinine, urea, uric acid. Key words: electromagnetic influence, chicken of Dominant D959 cross, total protein, protein fractions, creatinine, urea, uric acid.
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Novakovska, V. "Hematological profile of pig blood for feeding cellulose amylolytic additive." Tehnologìâ virobnictva ì pererobki produktìv tvarinnictva, no. 1(156) (May 25, 2020): 125–31. http://dx.doi.org/10.33245/2310-9270-2020-157-1-125-131.
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The level of provision of animals with basic nutrients, feeding conditions, physiological condition, age, sex was assessed according to blood parameters. Researched the content of total blood protein, albumin, globulins, glucose, calcium, phosphorus, hemoglobin, erythrocyte count and hematocrit, also calculated blood indices using a set of hematological techniques. The aim was to clarify the biochemical and morphological parameters of the blood of pigs for fattening, by adding additives to the diet. The eff ect of feeding cellulose amylolytic enzyme additive on the productive qualities of pigs for fattening was studied. The cellulose amylolytic additive comprises 0.5% of the enzyme cellulase, 1 gram of which provides 2700 units of activity, and 0.1% of the enzyme α-amylase, 1 gram of which provides 9342 units of activity, with an activity ratio of 1: 4, respectively. Studies in pigs were performed in two stages: the equalization period (15 days) and the main (71 days). Grain fodder grown directly on the farm - barley, wheat, soybeans - was used for feeding pigs. The diet of the control group consisted of 63% barley grain, 27.5% wheat grain, 9% soybean meal 0.5% mineral supplement. Pigs of the experimental group were fed cellulose amylolytic feed additive at the rate of 5 g of cellulase and 1 g of amylase per 1 kg of feed. The use of the above additive in the diets of pigs was observed to increase the immunity of animals due to an increase in gamma globulin in blood proteins by 9%. The increase in the amount of hemoglobin by 8% and erythrocytes by 14% during fattening, due to improved housing conditions and external antigenic stimulation of physiological processes. Decisions on the appropriateness of the inclusion of cellulose amylolytic additive in the diet are made on the basis of production tests of the proposed drug, which increased the average daily gain of live weight by 19.7% during the period of fattening pigs. Key words: pigs, blood, erythrocytes, hemoglobin, hematocrit, leukocytes, thrombocytes, albumins, globulins.
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Landreth, G. "S.12.05 Therapeutic use of peroxisome proliferator-activated receptors (PPAR) gamma agonists in the treatment of Alzheimer's disease." European Neuropsychopharmacology 19 (September 2009): S195—S196. http://dx.doi.org/10.1016/s0924-977x(09)70244-5.
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Gyöngyösi, Adrienn, and László Nagy. "Potential Therapeutic Use of PPARγ-Programed Human Monocyte-Derived Dendritic Cells in Cancer Vaccination Therapy." PPAR Research 2008 (2008): 1–10. http://dx.doi.org/10.1155/2008/473804.
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Dendritic cells (DCs) can regulate all elements of the immune system, and therefore are an ideal target for vaccination. During the last two decades, as a result of extensive research, DCs became the primary target of antitumor vaccination as well. A critical issue of antitumor vaccination is the phenotype of the dendritic cell used. It has been recently shown that several nuclear hormone receptors, and amongst them the lipid-activated nuclear receptor and peroxisome proliferator-activated receptor gamma (PPARγ), have important roles in effecting the immunophenotype of human dendritic cells. It regulates primarily lipid metabolism and via this it influences the immunophenotype of DCs by altering lipid antigen uptake, presentation, and also other immune functions. In this review, we summarize the principles of antitumor vaccination strategies and present our hypothesis on how PPARγ-regulated processes might be involved and could be exploited in the design of vaccination strategies.
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Lewandowska, Hanna, Andrzej Eljaszewicz, Izabela Poplawska, Marlena Tynecka, Alicja Walewska, Kamil Grubczak, Jordan Holl, et al. "Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice." International Journal of Molecular Sciences 22, no. 16 (August 6, 2021): 8467. http://dx.doi.org/10.3390/ijms22168467.
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Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM; however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential.
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Graves, Edward E., Andrea Pirzkall, Tracy R. Mcknight, Daniel B. Vigneron, David A. Larson, Lynn J. Verhey, Michael Mcdermott, Susan Chang, and Sarah J. Nelson. "USE OF PROTON MAGNETIC RESONANCE SPECTROSCOPIC IMAGING DATA IN PLANNING FOCAL RADIATION THERAPIES FOR BRAIN TUMORS." Image Analysis & Stereology 21, no. 2 (May 3, 2011): 69. http://dx.doi.org/10.5566/ias.v21.p69-76.
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Advances in radiation therapy for malignant neoplasms have produced techniques such as Gamma Knife radiosurgery, capable of delivering an ablative dose to a specific, irregular volume of tissue. However, efficient use of these techniques requires the identification of a target volume that will produce the best therapeutic response while sparing surrounding normal brain tissue. Accomplishing this task using conventional computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) techniques has proven difficult because of the difficulties in identifying the effective tumor margin. Magnetic resonance spectroscopic imaging (MRSI) has been shown to offer a clinically-feasible metabolic assessment of the presence and extent of neoplasm that can complement conventional anatomic imaging. This paper reviews current Gamma Knife protocols and MRSI acquisition, reconstruction, and interpretation techniques, and discusses the motivation for including magnetic resonance spectroscopy findings while planning focal radiation therapies. A treatment selection and planning strategy incorporating MRSI is then proposed, which can be used in the future to assess the efficacy of spectroscopy-based therapy planning.
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Liakopoulou, E., CA Blau, Q. Li, B. Josephson, JA Wolf, B. Fournarakis, V. Raisys, G. Dover, T. Papayannopoulou, and G. Stamatoyannopoulos. "Stimulation of fetal hemoglobin production by short chain fatty acids." Blood 86, no. 8 (October 15, 1995): 3227–35. http://dx.doi.org/10.1182/blood.v86.8.3227.3227.
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Abstract Butyrate, a four-carbon fatty acid, and its two-carbon metabolic product, acetate, are inducers of gamma-globin synthesis. To test whether other short-chain fatty acids share this property, we first examined whether propionic acid, a three-carbon fatty acid that is not catabolized to acetate, induces gamma-globin expression. Sodium propionate increased the frequency of fetal hemoglobin containing erythroblasts and the gamma/gamma + beta mRNA ratios in adult erythroid cell cultures and F reticulocyte production in a nonanemic juvenile baboon. Short-chain fatty acids containing five (pentanoic), six (hexanoic), seven (heptanoic), eight (octanoic), and nine (nonanoic) carbons induced gamma-globin expression (as measured by increase in gamma-positive erythroblasts and gamma/gamma + beta mRNA ratios) in adult erythroid burst-forming unit cultures. There was a clear-cut relationship between the concentration of fatty acids in culture and the degree of induction of gamma-globin expression. Three-, four-, and five-carbon fatty acids were better inducers of gamma globin in culture as compared with six- to nine-carbon fatty acids. These results suggest that all short-chain fatty acids share the property of gamma-globin gene inducibility. The fact that valproic acid, a derivative of pentanoic acid, also induces gamma-globin expression suggests that short-chain fatty acid derivatives that are already approved for human use may possess the property of gamma-globin inducibility and may be of therapeutic relevance to the beta-chain hemoglobinopathies.
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Liakopoulou, E., CA Blau, Q. Li, B. Josephson, JA Wolf, B. Fournarakis, V. Raisys, G. Dover, T. Papayannopoulou, and G. Stamatoyannopoulos. "Stimulation of fetal hemoglobin production by short chain fatty acids." Blood 86, no. 8 (October 15, 1995): 3227–35. http://dx.doi.org/10.1182/blood.v86.8.3227.bloodjournal8683227.
Full textAbstract:
Butyrate, a four-carbon fatty acid, and its two-carbon metabolic product, acetate, are inducers of gamma-globin synthesis. To test whether other short-chain fatty acids share this property, we first examined whether propionic acid, a three-carbon fatty acid that is not catabolized to acetate, induces gamma-globin expression. Sodium propionate increased the frequency of fetal hemoglobin containing erythroblasts and the gamma/gamma + beta mRNA ratios in adult erythroid cell cultures and F reticulocyte production in a nonanemic juvenile baboon. Short-chain fatty acids containing five (pentanoic), six (hexanoic), seven (heptanoic), eight (octanoic), and nine (nonanoic) carbons induced gamma-globin expression (as measured by increase in gamma-positive erythroblasts and gamma/gamma + beta mRNA ratios) in adult erythroid burst-forming unit cultures. There was a clear-cut relationship between the concentration of fatty acids in culture and the degree of induction of gamma-globin expression. Three-, four-, and five-carbon fatty acids were better inducers of gamma globin in culture as compared with six- to nine-carbon fatty acids. These results suggest that all short-chain fatty acids share the property of gamma-globin gene inducibility. The fact that valproic acid, a derivative of pentanoic acid, also induces gamma-globin expression suggests that short-chain fatty acid derivatives that are already approved for human use may possess the property of gamma-globin inducibility and may be of therapeutic relevance to the beta-chain hemoglobinopathies.
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Rosenthal, FM, K. Cronin, R. Bannerji, DW Golde, and B. Gansbacher. "Augmentation of antitumor immunity by tumor cells transduced with a retroviral vector carrying the interleukin-2 and interferon-gamma cDNAs." Blood 83, no. 5 (March 1, 1994): 1289–98. http://dx.doi.org/10.1182/blood.v83.5.1289.1289.
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Abstract Therapeutic models using gene transfer into tumor cells have pursued three objectives: (1) to induce rejection of the tumor transduced with therapeutic genes, (2) to induce immune-mediated regression of metastatic disease, and (3) to induce long-lasting immunity to protect against challenge with tumor cells or clinical regrowth of micrometastatic disease. Because in vivo therapy for patients with cancer using gene transfer would, as a first step, attempt to eliminate the existing tumor, we have investigated whether antitumor immunity induced by tumor cells secreting a single cytokine could be increased by cotransfer of a second cytokine gene. To test this approach, CMS-5, a murine fibrosarcoma, was transduced with retroviral vectors carrying interleukin-2 (IL-2), interferon-gamma (IFN-gamma), or granulocyte- macrophage-colony-stimulating factor (GM-CSF) cDNA alone or IL-2 cDNA in combination with IFN-gamma or GM-CSF cDNA. Single cytokine-secreting clones were selected to match levels of cytokine production by double cytokine-secreting clones so that similar amounts of cytokine were secreted. IFN-gamma- and IL-2/IFN-gamma-secreting CMS-5 cells showed increased levels of major histocompatability complex class I expression compared with IL-2- and GM-CSF-secreting or parental CMS-5 cells, IL- 2/IFN-gamma-secreting CMS-5 cells were always rejected by syngeneic mice, whereas the same number of CMS-5 cells secreting only one of these cytokines or mixtures of single cytokine-secreting CMS-5 cells were not rejected. In vivo depletion of CD4+, CD8+, or natural-killer effector cell subpopulations showed that CD8+ cytotoxic T cells were primarily responsible for rejection of IL-2/IFN-gamma-transduced tumor cells. Our data show the successful use of a single retroviral vector to stably transduce two cytokine genes into the same tumor cell, leading to an increased effect on the in vivo induction of antitumor immunity.
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Rosenthal, FM, K. Cronin, R. Bannerji, DW Golde, and B. Gansbacher. "Augmentation of antitumor immunity by tumor cells transduced with a retroviral vector carrying the interleukin-2 and interferon-gamma cDNAs." Blood 83, no. 5 (March 1, 1994): 1289–98. http://dx.doi.org/10.1182/blood.v83.5.1289.bloodjournal8351289.
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Therapeutic models using gene transfer into tumor cells have pursued three objectives: (1) to induce rejection of the tumor transduced with therapeutic genes, (2) to induce immune-mediated regression of metastatic disease, and (3) to induce long-lasting immunity to protect against challenge with tumor cells or clinical regrowth of micrometastatic disease. Because in vivo therapy for patients with cancer using gene transfer would, as a first step, attempt to eliminate the existing tumor, we have investigated whether antitumor immunity induced by tumor cells secreting a single cytokine could be increased by cotransfer of a second cytokine gene. To test this approach, CMS-5, a murine fibrosarcoma, was transduced with retroviral vectors carrying interleukin-2 (IL-2), interferon-gamma (IFN-gamma), or granulocyte- macrophage-colony-stimulating factor (GM-CSF) cDNA alone or IL-2 cDNA in combination with IFN-gamma or GM-CSF cDNA. Single cytokine-secreting clones were selected to match levels of cytokine production by double cytokine-secreting clones so that similar amounts of cytokine were secreted. IFN-gamma- and IL-2/IFN-gamma-secreting CMS-5 cells showed increased levels of major histocompatability complex class I expression compared with IL-2- and GM-CSF-secreting or parental CMS-5 cells, IL- 2/IFN-gamma-secreting CMS-5 cells were always rejected by syngeneic mice, whereas the same number of CMS-5 cells secreting only one of these cytokines or mixtures of single cytokine-secreting CMS-5 cells were not rejected. In vivo depletion of CD4+, CD8+, or natural-killer effector cell subpopulations showed that CD8+ cytotoxic T cells were primarily responsible for rejection of IL-2/IFN-gamma-transduced tumor cells. Our data show the successful use of a single retroviral vector to stably transduce two cytokine genes into the same tumor cell, leading to an increased effect on the in vivo induction of antitumor immunity.
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Barrales-Cureño, Hebert Jair, César Reyes-Reyes, Maximino Diaz-Bautista, Adrián Gómez-de Jesús, Salvador Chávez-Salinas, and Luis Germán López-Valdez. "Therapeutic effects of interferons in human viral infections." Mexican Journal of Biotechnology 3, no. 4 (October 1, 2018): 19–32. http://dx.doi.org/10.29267/mxjb.2018.3.4.19.
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The interferon (IFN) is a cytokine produced by immunocompetent cells in response to various stimuli. Five types of IFNs are identified: alpha, beta, gamma, tau and omega 1. In particular, interferons inhibit viral replication directly by antiviral mechanisms, as they do so indirectly by amplifying immune responses to viral proteins. Likewise, they are also essential elements in clinical oncology. They are used in the treatment of chronic myelocytic and hairy cell leukemia, multiple myeloma, non-Hodgkin's lymphoma, melanoma, renal carcinoma, and Kaposi's sarcoma, as well as in the papilloma. They are also used in diseases of viral origin such as hepatitis B and C, acute respiratory syndrome, and HIV (experimentally in the latter), as well as in neurodegenerative diseases, including multiple sclerosis or amyotrophic lateral sclerosis. The combination of interferons with other therapies is contributing to enhance its antiviral and antitumor activity. This work aims to present an updated reference on the use of interferons in the medical field.
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Marina A. Frolova, Svetlana A. Gryn, Elana I. Kovaleva, Aleksey I. Albulov, Roman N. Melnik, Vladimir I. Eremets, Vera M. Popova, and Irina N. Matveeva. "Study of radioprotective properties of chitosan at gamma-irradiation." International Journal of Research in Pharmaceutical Sciences 11, no. 2 (April 13, 2020): 1734–37. http://dx.doi.org/10.26452/ijrps.v11i2.2076.
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The objective of this study was the analysis of adaptogenic effects of chitosan at gamma-irradiation. The study of radioprotective properties of chitosan was carried out on male mice having the weight of 20-25 g, exposed to gamma-irradiation at the doses of up to 800 bar at the Gamma Panorama unit (radiation source – Cs137, gamma dose rate – 14 R/min, duration of irradiation – 58.5 min). 4 experimental and 2 control groups with 7 animals in each have been formed. The medicine dose schedule, allowing to identify both the prophylactic effect and the therapeutic effect of chitosan, was used in the experiment. It was found out in experiments on white mice, with the purpose of determining 50% lethal dose (LD50) that chitosan belongs to the substances of hazard class 4 because its LD50 considerably exceeds 5000 mg/kg; at this, the toxicity of chitosan decreases parallel to its molecular weight decrease. The prophylactic and therapeutic effect of low-molecular chitosan (molecular weight 5-10 kDa) as abdominal injection at the doses of 200 mg/kg of body weight. It has been demonstrated that the mice from the experimental group I that received chitosan 3 days before the irradiation remained alive throughout the entire observation period (30 days). In the animals of II, III, IV experimental groups that received chitosan in 3, 9 and 22 days after the irradiation, the survival rate by the experiment end was 86, 43 and 29%, respectively, with the 100% death of animals in the control group I (irradiated animals without the use of chitosan) and full safety of animals in the control group II (non-irradiated animals).
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Wagner, Nicole, and Kay-Dietrich Wagner. "PPAR Beta/Delta and the Hallmarks of Cancer." Cells 9, no. 5 (May 4, 2020): 1133. http://dx.doi.org/10.3390/cells9051133.
Full textAbstract:
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. Three different isoforms, PPAR alpha, PPAR beta/delta and PPAR gamma have been identified. They all form heterodimers with retinoic X receptors to activate or repress downstream target genes dependent on the presence/absence of ligands and coactivators or corepressors. PPARs differ in their tissue expression profile, ligands and specific agonists and antagonists. PPARs attract attention as potential therapeutic targets for a variety of diseases. PPAR alpha and gamma agonists are in clinical use for the treatment of dyslipidemias and diabetes. For both receptors, several clinical trials as potential therapeutic targets for cancer are ongoing. In contrast, PPAR beta/delta has been suggested as a therapeutic target for metabolic syndrome. However, potential risks in the settings of cancer are less clear. A variety of studies have investigated PPAR beta/delta expression or activation/inhibition in different cancer cell models in vitro, but the relevance for cancer growth in vivo is less well documented and controversial. In this review, we summarize critically the knowledge of PPAR beta/delta functions for the different hallmarks of cancer biological capabilities, which interplay to determine cancer growth.
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Belem, Wendimi Fatimata, Ching-Hsuan Liu, Yee-Tung Hu, Thierry Burnouf, and Liang-Tzung Lin. "Validation of Viral Inactivation Protocols for Therapeutic Blood Products against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2)." Viruses 14, no. 11 (October 31, 2022): 2419. http://dx.doi.org/10.3390/v14112419.
Full textAbstract:
Therapeutic blood products including convalescent plasma/serum and immunoglobulins concentrated from convalescent plasma, such as intravenous immunoglobulins or hyperimmune globulins, and monoclonal antibodies are passive immunotherapy options for novel coronavirus disease 2019 (COVID-19). They have been shown to improve the clinical status and biological and radiological parameters in some groups of COVID-19 patients. However, blood products are still potential sources of virus transmission in recipients. The use of pathogen reduction technology (PRT) should increase the safety of the products. The purpose of this study was to determine the impact of solvent/detergents (S/D) procedures on SARS-COV-2 infectivity elimination in the plasma of donors but also on COVID-19 convalescent serum (CCS) capacity to neutralize SARS-COV-2 infectivity. In this investigation, S/D treatment for all experiments was performed at a shortened process time (30 min). We first evaluated the impact of S/D treatments (1% TnBP/1% TritonX-45 and 1% TnBP/1% TritonX-100) on the inactivation of SARS-COV-2 pseudoparticles (SARS-COV-2pp)-spiked human plasma followed by S/D agent removal using a Sep-Pak Plus C18 cartridge. Both treatments were able to completely inactivate SARS-COV-2pp infectivity to an undetectable level. Moreover, the neutralizing activity of CCS against SARS-COV-2pp was preserved after S/D treatments. Our data suggested that viral inactivation methods using such S/D treatments could be useful in the implementation of viral inactivation/elimination processes of therapeutic blood products against SARS-COV-2.
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Coroian, Cristian Ovidiu, Vioara Miresan, Camelia Raducu, Claudia Costea, Radu Constantinescu, Aurelia Coroian, Mihai Iacob Bentea, et al. "Oxidative Stress and Haematological Response in Rainbow Trout (Oncorhynchus Mykiss) Fed With Brewer Yeast (Saccharomyces Cerevisiae) as Nutritional Supplement." Revista de Chimie 70, no. 10 (November 15, 2019): 3727–33. http://dx.doi.org/10.37358/rc.19.10.7634.
Full textAbstract:
Production of freshwater fish evolved constantly over the past decades in parallel with increasing the amount of ingredients conventionally used to feed these fish. From the main ingredients, those protein based are the most expensive and increasingly difficult to obtain. Fishmeal demands valuable alternative ingredients to replace it and yeasts seem to offer new protein sources, but not only, acting as probiotics in fish feed. We tested productive and physiological benefits of brewer yeast (Saccharomyces cerevisiae) added 1.5% in standard rainbow trout (Oncorhynchus mykiss) nutrition with Coppens fodder (2 mm granulation) with 45% crude protein (CP) over a period of 45 days, starting at an average live weight of 56.86 gramsin a classical system of breeding. Production parameters as average daily gain (ADG), total live gain (TLG) and feed conversion rate (FCR) but also hematologic and biochemical blood parameters have been evaluated. Yeast fed batch presented higher productive indices but not statistically represented. Significant differences were observed in hematological parameters for hemoglobin, very significant response of yeast fed batch regarding gamma globulins (GGL) level and significant changes were also recorded for total proteins (TP). Significantly lower values for amylase were revealed, while enzymatic profile shown significant differences in alkaline phosphatase (PAL) and creatinine phosphokinase (CPK). Overall, 1.5% of dried brewer yeast added to standard fodder in rainbow trout das led to a better use of feed and a strengthening of immunity.
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Chateauvieux, Sébastien, Franck Morceau, Mario Dicato, and Marc Diederich. "Molecular and Therapeutic Potential and Toxicity of Valproic Acid." Journal of Biomedicine and Biotechnology 2010 (2010): 1–18. http://dx.doi.org/10.1155/2010/479364.
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Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.
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Krakauer, Teresa, Stephen F. Little, and Bradley G. Stiles. "Bacillus anthracis Edema Toxin Inhibits Staphylococcus aureus Enterotoxin B Effects In Vitro: a Potential Protein Therapeutic?" Infection and Immunity 73, no. 10 (October 2005): 7069–73. http://dx.doi.org/10.1128/iai.73.10.7069-7073.2005.
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ABSTRACT Various in vitro effects of staphylococcal enterotoxin B (SEB) on human peripheral blood mononuclear cells were mitigated by Bacillus anthracis edema toxin. In particular, levels of some SEB-induced cytokines (tumor necrosis factor alpha, gamma interferon) and chemokines (monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha [MIP-1α], MIP-1β) were significantly diminished or even nonexistent, depending upon the timing of edema toxin administration. Overall, these results suggest a novel use of B. anthracis edema toxin against a bacterial superantigen.
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Madhunapantula, SubbaRao V., and Gavin P. Robertson. "Therapeutic Implications of Targeting AKT Signaling in Melanoma." Enzyme Research 2011 (March 23, 2011): 1–20. http://dx.doi.org/10.4061/2011/327923.
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Identification of key enzymes regulating melanoma progression and drug resistance has the potential to lead to the development of novel, more effective targeted agents for inhibiting this deadly form of skin cancer. The Akt3, also known as protein kinase B gamma, pathway enzymes regulate diverse cellular processes including proliferation, survival, and invasion thereby promoting the development of melanoma. Accumulating preclinical evidence demonstrates that therapeutic agents targeting these kinases alone or in combination with other pathway members could be effective for the long-term treatment of advanced-stage disease. However, currently, no selective and effective therapeutic agent targeting these kinases has been identified for clinical use. This paper provides an overview of the key enzymes of the PI3K pathway with emphasis placed on Akt3 and the negative regulator of this kinase called PTEN (phosphatase and tensin homolog deleted on chromosome 10). Mechanisms regulating these enzymes, their substrates and therapeutic implications of targeting these proteins to treat melanoma are also discussed. Finally, key issues that remain to be answered and future directions for interested researchers pertaining to this signaling cascade are highlighted.
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Novotný, Josef, Josef Novotný, Václav Spĕvác˘ek, Pavel Dvor˘ák, Tomás˘ Cechák, Roman Lis˘c˘ák, Gustav Broz˘ek, Jaroslav Tintĕra, and Josef Vymazal. "Application of polymer gel dosimetry in gamma knife radiosurgery." Journal of Neurosurgery 97 (December 2002): 556–62. http://dx.doi.org/10.3171/jns.2002.97.supplement_5.0556.
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Object. The purpose of this study was to investigate the use of a polymer gel—based dosimeter for the evaluation of geometric and dosimetric inaccuracies during gamma knife radiosurgery and during the irradiation of an experimental animal. Methods. A polymer gel dosimeter, based on acrylic monomers, was used for experiments conducted in this study. The accuracy of the dosimeter was evaluated on a Siemens EXPERT 1-tesla scanner in the transmitter/receiver head coil with the use of a multiecho sequence with 16 echoes, TE 22.5 to 360 msec, TR 2000 msec, slice thickness 2 mm, field of view 255 mm, and a pixel size of 0.5 × 0.5 mm2. Two experiments were conducted. First, the head phantom containing the polymer gel dosimeter was irradiated using 4-, 8-, 14-, and 18-mm isocenters. Second, a specially designed rat phantom was irradiated by four 4-mm isocenters. The dose profiles in the x, y, and z axes were calculated in the treatment planning system and measured with the polymer gel dosimeter and the results were compared. There was good agreement between the measured and calculated dose profiles. The maximum deviation in the spatial position of the center of measured and calculated dose profiles was 0.5 mm in the head phantom and 1 mm in the rat phantom. The maximum deviation in the width of the selected reference isodose of measured profiles was 1.2 mm in the head phantom and 1.1 mm in the rat phantom. Conclusions. The use of the polymer gel—based dosimeter for the verification of stereotactic procedures has advantages compared with other dosimetric systems. The dosimeter itself is tissue equivalent. Three-dimensional dose distributions can be measured and the dosimeter allows simulation of the therapeutic procedures.
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Musa, Ahmed Sadeq, Muhammad Fahmi Rizal Abdul Hadi, Nabeel Ibrahim Ashour, and Nurul Ab Aziz Hashikin. "Theranostic Investigation of Gadolinium-159 for Hepatocellular Carcinoma: Monte Carlo Simulation Study." Applied Sciences 12, no. 23 (December 3, 2022): 12396. http://dx.doi.org/10.3390/app122312396.
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Gadolinium-159 (159Gd) is a beta emitter with appropriate energy for therapeutic application. However, this radioisotope additionally emits gamma rays, enabling the distribution of 159Gd to be detected by a gamma camera after each therapeutic administration. The current research is innovative in the investigation of 159Gd as a theranostic radioisotope in the radioembolization of HCC using Monte Carlo (MC) simulation. For 159Gd therapeutic investigation, various patient scenarios including varying tumour involvement (TI), tumour-to-normal liver uptake ratio (T/N), and lung shunting (LS) were simulated using Geant4 MC to estimate the absorbed doses to organs at risk. For 159Gd planar imaging investigation, the SPECTHead example from GATEContrib (GitHub) was utilized, and inside a liver a tumour was created and placed inside a torso phantom and simulated using GATE MC simulation. The majority of 159Gd absorbed doses by normal liver and lungs were less than the maximum dose limitations of 70 Gy and 30 Gy, respectively. Absorbed doses to other organs were observed to be below 1 Gy. The utilization of 58 keV and 363.54 keV photopeaks in combination produced optimal planar imaging of 159Gd. This research gives new insights into the use of 159Gd as a theranostic radioisotope, with the potential to be used as an Yttrium-90 (90Y) alternative for liver radioembolization.
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Waterman, Hayley, Heather Howie, Xiaohong Wang, and James C. Zimring. "Use of Monoclonal Antibodies to RBC Antigens As a Therapeutic to Allow Incompatible Transfusion." Blood 126, no. 23 (December 3, 2015): 1140. http://dx.doi.org/10.1182/blood.v126.23.1140.1140.
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Abstract Background: Transfusion of RBCs is an essential therapy to treat myriad diseases. In excess of 340 different RBC alloantigens have now been described; thus, every non-autologous unit of RBCs constitutes a foreign alloantigen. Once a patient makes an alloantibody, in many cases, they can no longer receive RBCs expressing the recognized alloantigen. For chronically transfused patients, who make multiple alloantibodies, identifying sufficient compatible RBC units can become difficult, leading to morbidity, and in some cases, mortality. Thus alloimmunization is a significant clinical problem. As the vast majority of RBC alloantigens are single amino acid polymorphisms, they presumably constitute small epitopes. We hypothesized that monoclonal antibodies against human blood group antigens, engineered so as to lack effector function, would bind to the offending alloantigen in a fashion that would both block binding of recipient alloantibody and allow normal RBC circulation. Methods: Wild-type mice were alloimmunized with transgenic RBCs expressing Kell (K1), splenocytes were fused with myeloma lines, and monoclonal antibodies were isolated. An antibody with specificity for the K1 antigen was isolated (PUMA1). The cDNA for both heavy and light chains were cloned and the variable regions were ligated upstream of constant regions of mouse IgG1, IgG2a, IgG2b, and IgG3. Each anti-K1 IgG subtype was expressed by transfecting constructs into COS cells and antibodies were purified by protein A/G chromatography. The purified antibodies were passively administered to wild type mice, which were then transfused with K1 RBCs. RBC survivals were monitored by flow cytometry. PUMA1 was also humanized with both naturally occurring human IgG constant regions and also a mutant IgG lacking binding sites for complement and Fc-gamma-receptors. Results: Each of the IgGs cleared K1 transgenic RBCs (but not wild-type RBCs); however, clearance potency varied with IgG subtype, with a rank order of IgG2a>IgG1>IgG2b>IgG3. To test the ability of the less hemolytic forms to block clearance by the more hemolytic forms, wild-type mice were infused with PUMA1 IgG2a. K1 RBCs were pre-incubated with PBS, 10ug IgG2b or 10ug IgG3 and then transfused. Alternatively, PBS, 10ug IgG2b or 10ug IgG3 was infused into the recipient mice, right before transfusion of K1 RBCs. Both approaches yielded similar results. Experimental animals that received IgG2a followed by IgG2b or IgG3 (either incubation or infusion) had a 24hr K1 RBC recovery ranging from 72-82%, while mice that received IgG2a followed by PBS had a 41-44% recovery. The humanized forms have been expressed and maintain specific binding to the K1 alloantigen. Conclusions: Together, the data presented herein demonstrate the ability of less hemolytic forms of anti-K1 alloantibodies to serve as a therapeutic to decrease delayed hemolytic transfusion reactions by more hemolytic forms, in a murine model using murine IgG forms of PUMA1. Ongoing in vivo murine studies are assessing the humanized and mutated forms of PUMA1 to serve as a therapeutic reagent that can block access of hemolytic anti-K1 alloantibodies to incompatible RBCs, both in wild-type mice and also in mice with humanized Fc-gamma receptors. The ultimate goal of these studies is the development of therapeutic modified antibodies that can allow safe and effective incompatible transfusion in patients alloimmunized to RBC antigens. For a multiply alloimmunized patient, being able to block one or two antibodies would allow identification of units that were negative for other antibody specificities; thus, therapeutics of this type against a limited number of common alloantigens would have substantial impact. Disclosures Zimring: BloodworksNW: Patents & Royalties: Patent Application filed on technology in this abstract - no royalties; Immucor Inc.: Research Funding.
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Michon, J., S. Moutel, J. Barbet, JL Romet-Lemonne, YM Deo, WH Fridman, and JL Teillaud. "In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody." Blood 86, no. 3 (August 1, 1995): 1124–30. http://dx.doi.org/10.1182/blood.v86.3.1124.1124.
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Abstract Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.
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Michon, J., S. Moutel, J. Barbet, JL Romet-Lemonne, YM Deo, WH Fridman, and JL Teillaud. "In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody." Blood 86, no. 3 (August 1, 1995): 1124–30. http://dx.doi.org/10.1182/blood.v86.3.1124.bloodjournal8631124.
Full textAbstract:
Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.