1.Serum immunoglobulin fused interferon-alpha inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells.
Jun Sung KIM ; Kyeong Nam YU ; Mi Suk NOH ; Min Ah WOO ; Sung Jin PARK ; Jin Hong PARK ; Jin HUA ; Hyun Sun CHO ; Soon Kyung HWANG ; Eun Sun LEE ; Youn Sun CHUNG ; In Young CHOI ; Se Chang KWON ; Myung Haing CHO
Journal of Veterinary Science 2008;9(1):45-50
Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 x : 30 microgram/kg and 50 x : 150 microgram/kg). A slight anti-tumoral effect was observed in all 10 x groups compared to the control. In the 50 x groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-beta. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition.
Adenocarcinoma/*drug therapy
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Alanine Transaminase/blood
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Animals
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Antineoplastic Agents/chemistry/pharmacology
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Blood Urea Nitrogen
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Dose-Response Relationship, Drug
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Immunoglobulins/*chemistry/*pharmacology
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Interferon Alfa-2a/chemistry/pharmacology
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Interferon-alpha/*chemistry/*pharmacology
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Mice
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Mice, Nude
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Neoplasms, Experimental/*drug therapy
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Polyethylene Glycols/chemistry/pharmacology
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Recombinant Fusion Proteins/chemistry/pharmacology
2.Kidney Transplantation in Sensitized Recipients; A Single Center Experience.
Sun Moon KIM ; Chungsik LEE ; Jung Pyo LEE ; Eun Man KIM ; Jongwon HA ; Sang Joon KIM ; Myoung Hee PARK ; Curie AHN ; Yon Su KIM
Journal of Korean Medical Science 2009;24(Suppl 1):S143-S147
A successful transplantation, across a positive crossmatch barrier, is one of the most persistent long- standing problems in the field of kidney transplant medicine. The aim of this study was to describe seven consecutive living renal transplantations in recipients with positive crossmatch for donors or positive for donor specific antibodies (DSAs). A preconditioning regimen including plasmapheresis and intravenous immunoglobulin was delivered three times a week until the crossmatch and/ or DSAs became negative. Mycophenolate mofetil and tacrolimus were started two days before the plasmapheresis. The protocol was modified to include administration of anti-CD 20 antibody (rituximab, 375 mg/m(2)) from the patient number 3 through the patient number 7. All seven patients achieved negative conversion of the crossmatch or DSAs, and the kidney transplantations were successfully performed in all cases. Acute cellular rejection occurred in two patients, which were subclinical and controlled with high dose steroid treatment. Antibody-mediated rejection occurred in one patient, which was easily reversed with plasmapheresis. All recipients attained normal graft function during the 7-24 months of follow up. Our study suggests that sensitized patients can be transplanted successfully with desensitization pretreatment.
Adult
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Antibodies, Monoclonal/pharmacology
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Antigens, CD20/biosynthesis
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Biopsy
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Female
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Graft Rejection
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Graft Survival
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Histocompatibility Testing/methods
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Humans
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Immunoglobulins/chemistry
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Kidney Transplantation/*methods
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Male
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Middle Aged
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Plasmapheresis
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Transplantation Conditioning
3.Effects of fufangdenshen tablets on human atherosclerotic plasma protein using proteomic technique.
Zeng-chun MA ; Yue GAO ; Hong-ling TAN ; Cheng-rong XIAO ; Hong-jin WU ; Sheng-qi WANG
China Journal of Chinese Materia Medica 2006;31(9):766-769
OBJECTIVETo research the effects of fufangdenshen tablets on atherosclerotic plasma protein using proteomic technique and further explore its potential molecular mechanism to cure atherosclerosis.
METHODThe plasma of normal, atherosclerosis and cured group were collected, and the albumin in plasma was removed. Proteomic protocol involved of 2-DE, image analysis and spectrometry detection was used to detect regulated plasma protein by fufangdenshen tablets.
RESULT3 decreased expressed and 6 higher protein in atherosclerotic plasma could be recovered by fufangdenshen tablets. The levels of fibrinogen, Granzyme C and immunoglobulin were decreased by fufangdenshen tablets.
CONCLUSIONThe levels of fibrinogen, Granzyme C in atherosclerotic plasma could be decreased by fufangdenshen tablets. The effects of fufangdenshen tablets on atherosclerosis included that: inhibition of adhesion of monocyte, inhibition of proliferation and migration of VSMC, and weakening of inflammation.
Aged ; Coronary Artery Disease ; blood ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Fibrinogen ; metabolism ; Granzymes ; blood ; Humans ; Immunoglobulins ; blood ; Middle Aged ; Plants, Medicinal ; chemistry ; Proteomics ; Salvia miltiorrhiza ; chemistry ; Tablets
4.Regulating effects of Rosa roxburghii tratt preparation on immune function in arseniasis patients caused by coal burning.
Jun LI ; Ai-hua ZHANG ; Yu-jiang REN ; Zhong-yi LIU ; Xiao-xin HUANG ; Da-ping YANG
Chinese Journal of Preventive Medicine 2013;47(9):783-787
OBJECTIVETo explore the influence of rosa roxburghii tratt preparation on immune function of arseniasis patients caused by burning coal.
METHODSAccording to the diagnosis standard for endemic arseniasis(WS/T 211-2001), 62 cases of arseniasis patients who resided in endemic arseniasis area in Guizhou province were selected and divided stratified randomly into two groups: rosa roxburghii tratt juice treatment group and superoxide dismutase(SOD)-enriched rosa roxburghii tratt juice treatment group, with 31 patients in each group.Each patient took 120 ml/d rosa roxburghii tratt preparation or SOD-enriched rosa roxburghii tratt orally for one month. Another 30 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were selected as controls. A 2 ml blood and 50 ml urine samples were collected from individuals and the urine arsenic contents, peripheral blood T-lymphocyte subsets (CD3(+), CD4(+), CD8(+) T cell), serum immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) were detected. The differences between more than two groups on above indicators were compared. The correlations between urinary arsenic and immune parameters were analyzed.
RESULTSAmong the rosa roxburghii tratt juice group, SOD-enriched rosa roxburghii tratt juice before intervention group and the control group, the levels of urine arsenic were (76.55 ± 23.02) , (72.60 ± 25.91) and (26.33 ± 11.30) µg/g Cr respectively and IgG were (11.31 ± 1.68), (11.35 ± 1.94) and (9.23 ± 1.75) g/L respectively. The differences were statistically significant(F values were 82.01, 13.82, both P values < 0.05). After intervention with rosa roxburghii tratt preparation, the levels of urine arsenic were (53.21 ± 16.51) and (51.72 ± 17.70)µg/g Cr, both decreased than before intervention (t values were 5.80 and 3.78, both P values < 0.05). The levels of CD3(+) were (44.47 ± 7.14)%, (43.44 ± 6.61)% and (70.78 ± 5.26)%, CD4(+) were (29.87 ± 5.67)%, (29.42 ± 5.87)% and (46.08 ± 5.87)%, CD4(+)/CD8(+) were(1.25 ± 0.42), (1.22 ± 0.39) and (1.79 ± 0.26) and C4 were (0.13 ± 0.08), (0.13 ± 0.09) and (0.20 ± 0.11) g/L respectively among the two treatment group before intervention and the control group. The differences were significant (F values were 178.04, 76.71, 23.13 and 5.26, all P values < 0.05). After intervention, the levels of CD3(+) were (59.73 ± 7.38)% and (66.31 ± 7.57)%, CD4(+) were (34.00 ± 7.97)% and (39.11 ± 5.81)%, CD4(+)/CD8(+) were (1.41 ± 0.37) and(1.58 ± 0.26), all increased than before intervention(t values were 12.47, 25.18, 5.41, 10.47, 3.22 and 5.05, all P values < 0.05). The levels of urine arsenic and CD3(+), CD4(+), CD4(+)/CD8(+), C4 were inversely correlated correlation, while positive correlation existed between the level of urine arsenic and IgG(r values were -0.68, -0.56, -0.51, -0.43 and 0.36, all P values < 0.01).
CONCLUSIONSThe level of urinary arsenic level is closely related to immune function suppression in arseniasis patients caused by burning coal, rosa roxburghii tratt preparation can effectively improve immune function of arseniasis patients.
Adult ; Arsenic ; urine ; Arsenic Poisoning ; etiology ; immunology ; China ; Coal ; Complement System Proteins ; immunology ; Female ; Humans ; Immunoglobulins ; immunology ; Male ; Middle Aged ; Plant Extracts ; pharmacology ; Rosa ; chemistry ; Superoxide Dismutase ; pharmacology ; T-Lymphocyte Subsets ; immunology
5.High affinity soluble ILT2 receptor: a potent inhibitor of CD8(+) T cell activation.
Ruth K MOYSEY ; Yi LI ; Samantha J PASTON ; Emma E BASTON ; Malkit S SAMI ; Brian J CAMERON ; Jessie GAVARRET ; Penio TODOROV ; Annelise VUIDEPOT ; Steven M DUNN ; Nicholas J PUMPHREY ; Katherine J ADAMS ; Fang YUAN ; Rebecca E DENNIS ; Deborah H SUTTON ; Andy D JOHNSON ; Joanna E BREWER ; Rebecca ASHFIELD ; Nikolai M LISSIN ; Bent K JAKOBSEN
Protein & Cell 2010;1(12):1118-1127
Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence
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Antigens, CD
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chemistry
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genetics
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pharmacology
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Autoimmunity
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Biological Assay
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Cell Line
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Cytotoxicity, Immunologic
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genetics
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immunology
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Dose-Response Relationship, Immunologic
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Humans
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Immunoglobulins
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immunology
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metabolism
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Immunologic Factors
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chemistry
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genetics
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pharmacology
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Kinetics
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Leukocyte Immunoglobulin-like Receptor B1
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Lymphocyte Activation
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genetics
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immunology
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Major Histocompatibility Complex
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genetics
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immunology
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Molecular Sequence Data
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Molecular Targeted Therapy
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Mutagenesis, Site-Directed
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Peptide Library
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Polyethylene Glycols
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Protein Binding
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genetics
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immunology
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Receptors, Immunologic
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chemistry
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genetics
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Recombinant Fusion Proteins
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genetics
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metabolism
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T-Lymphocytes, Cytotoxic
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immunology
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metabolism
6.Protection of Carassius auratus Gibelio against infection by Aeromonas hydrophila using specific immunoglobulins from hen egg yolk.
Xiao-liang LI ; Jiang-bing SHUAI ; Wei-huan FANG
Journal of Zhejiang University. Science. B 2006;7(11):922-928
Specific immunoglobulin (IgY) from egg yolk against Aeromonas hydrophila was produced by immunization of White Leghorn hens with formalin-killed whole cells of A. hydrophila. ELISA test using A. hydrophila as the coating antigen revealed that the specific antibody titer started to increase in the egg yolk at the 13th day post-immunization (P/N=2.18), reached the peak at the 56th day (P/N=13.82), and remained at high level until day 133 (P/N=7.03). The antibody was purified by saturated ammonium sulphate with a recovery rate of 63.5%. The specific IgY inhibited the growth of A. hydrophila at a concentration of 1.0 mg/ml during the 18 h incubation. Pre-treatment of polyploid gibel carps Carassius auratus Gibelio with specific IgY had a protection rate of 60% (6/10) against challenge with A. hydrophila, while none of the fishes in the control groups receiving sterile phosphate buffered saline (PBS) or non-specific IgY survived the challenge. Treatment of fishes with the specific IgY 4 h after the challenge also had lower mortality (70%, 7/10), a 30% reduction against the control PBS or non-specific IgY groups (10/10). These results indicate that specific IgY antibodies could be obtained easily from hens immunized with an inactivated A. hydrophila and could provide a novel alternative approach to control of diseases in fishes caused by this organism.
Aeromonas hydrophila
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drug effects
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growth & development
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immunology
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Animals
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Antibody Specificity
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Antigen-Antibody Reactions
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Chickens
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immunology
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Dose-Response Relationship, Drug
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Egg Yolk
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chemistry
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Goldfish
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immunology
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microbiology
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Gram-Negative Bacterial Infections
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immunology
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prevention & control
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Immunoglobulins
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pharmacology
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therapeutic use
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Microbial Sensitivity Tests
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Survival Rate
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Time Factors
7.Clinical effect of milkvetch extract oral liquid in preventing and treating children's recurrent respiratory tract infection.
Shan-Pu YANG ; Hong DONG ; Yue-Chao WU
Chinese Journal of Integrated Traditional and Western Medicine 2008;28(6):544-547
OBJECTIVETo explore and compare the clinical effects of three immuno-potentiators and their influence on immune function in preventing and treating recurrent respiratory tract infection (RRI).
METHODSSeventy-two children with RRT were assigned to three groups, the 23 patients in the M group treated with milkvetch extract oral liquid, the 23 in the P group treated by P-transfer factor and the 26 in the U group treated by Utilins injection. Clinical effect was compared among three groups after treatment, and changes of T cell subgroups as well as immune antibodies were detected before and after treatment.
RESULTSThe markedly effective rate in the M, P, and U group was 69.6%, 65.2%, and 73.0% respectively, and the total effective rate 87.0%, 82.6%, and 92.3%, showing an insignificant difference among them (all P>0.05). After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ rose obviously in the three groups (all P<0.05); levels of CD8+ in the M group and the P group lowered significantly (P<0.05, P<0.01), but with no significant difference among three groups in the changes of T cell subgroups (all P>0.05). Serum levels of IgG in all the three groups, IgA in the P group and the M group, and IgM in the M group and the U group rose significantly (P<0.05 or P<0.01), with statistical difference presented in comparing of IgA level in the P group with that in the other two groups (P<0.01).
CONCLUSIONThe clinical effects and the outcomes of immunological indexes' changing are similar in RRI patients treated by the three immuno-potentiators. They all can enhance the immunological function of the organism, strengthen the disease-resistant ability of patients, and reduce the incidence of RRI. Among them, the milkvetch extract oral liquid is worthy of spreading due to its lower cost, simple administration, exemption from painful injection, and good compliance.
Administration, Oral ; Astragalus Plant ; chemistry ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Humans ; Immunoglobulins ; blood ; Infant ; Male ; Respiratory Tract Infections ; blood ; drug therapy ; immunology ; prevention & control ; Retrospective Studies ; Secondary Prevention ; T-Lymphocyte Subsets ; drug effects ; immunology ; Treatment Outcome