Thymus Extract Research Articles

NMR-spectroscopy-based metabonomic study on mouse model of blood deficiency syndrome induced by compound method of bleeding,starved feeding and exhausting and effect of Siwutang

To explore the essence of blood deficiency syndrome and the mechanism of the effects of siwutang based on the characteristic changes in metabolic profiles of C57 mice with blood deficiency induced by compound method of bleeding, starved feeding and exhausting before and after the treatment of Siwutang. Thirty C57 mice were randomly divided into three groups of 10 animals: the control group and two blood deficiency model groups without or with siwutang treatment. The animals were sacrificed after induction by compound method of bleeding,starved feeding and exhausting for 10 days and the blood, spleen, thymus and bone marrow were obtained. The metabolic profiles of serum, aqueous and lipidic extracts of thymus, spleen and bone marrow were investigated using 1H nuclear magnetic resonance spectroscopy (NMR). The NMR spectra were integrated in segments of 0.01, normalized and then analyzed using SIMCA-P software to visualize the similarities and differences in metabolic profiles between these groups. Compared with the control group, the model group contained different levels of lactate, choline, glucose, taurine, alanine, LDL, glycerin, UFA, creatinine, acetoacetate, glutamate and beta-hydroxybutyrate (beta-HB). In the Siwutang treated group, the above-mentioned changes were reversed. The disorder of energy metabolism, damage of lymphocyte, and disorder of immune function were observed in blood deficiency model by NMR-based-metabonomics method, and the Siwutang can improve these effects. Metabonomics may be a valuable tool in the pharmacological evaluation of siwutang.

Does Interleukin 6 Contribute to Renal Hemodynamic Changes During Angiotensin II–Dependent Hypertension?

The role that the adaptive immune system has in the control of blood pressure and pathogenesis of hypertension has been of interest to investigators for several decades. Early evidence on this subject in humans showed an enhanced T-lymphocyte activation during malignant hypertension1 and also implicated a role for B lymphocytes, because autoantibody production was elevated in hypertensive patients.2 In addition, early studies in experimental animal models demonstrated that thymectomy cured hypertension in New Zealand black mice3 or that renal-induced hypertension in rats was associated with thymic hypertrophy.4 Moreover, the transplantation of thymus extracts from Wistar-Kyoto rats or immunosuppressive therapy reduced blood pressure in spontaneously hypertensive rats.5,6 Although these studies strongly implicated immune system dysfunction as an important contributor to the development of hypertension, interest in the role for the immune system in blood pressure control appeared to wane. More recently, an interest in the role of the immune system in the development of hypertension has been renewed. In the past several years it is has been difficult to miss the growing body of evidence supporting a mechanistic role for the adaptive immune system. Guzik et al7 demonstrated recently that angiotensin II (Ang II)–dependent hypertension requires T cells but not B cells using RAG1−/− knockout mice, and Crowley et al8 similarly found an important role for adaptive immunity in Ang II–mediated hypertension using severe combined immunodeficient mice. There have also been several studies showing that inhibiting B- and T-cell proliferation with mycophenolate mofetil lowers blood pressure in experimental animal models of hypertension, such as the Dahl salt-sensitive rat.9 In humans, there is not as much direct evidence available supporting a role for adaptive immunity in the pathophysiology of hypertension; however, a small study in 8 patients with essential hypertension (but also rheumatoid …

Assessment of protective effect of thymus on cadmium chloride that induced nephropathy and neuropathy in rats

This study included twenty seven rats were allowed to acclimate for 1 week in the animal house of veterinary medicine college. Rats were housed three per cage with dimension of (45*35*20). Rats were divided into three groups; the first group represent cadmium chloride (CaCl) treated group which include nine (9) animals denoted by (group A); second group represent thymus and cadmium chloride treated group which include nine animals (9) denoted by (B) and third group which represent control group which also include nine (9) animals denoted by (C). The CaCl was given by drinking water with dose rate (50 PPM) daily; the aqueous extraction of thymus also was given by drinking after adding of CaCl with dose rate (50 PPM) daily. Tissue samples were taken for histopathological study by killing (3) animals from each group at periods of (17, 24 and 31) days after exposure to CaCl. Routine histological technique ending by staining 5 μm with H&E and then examined by light microscope. The histopathological results of group (A) revealed presence of pale area ( a” softening”) in the brain surrounding by edema. The tissue has vacuolated structure, also a number of astrocytes with small round basophilic nuclei and ill- defined cytoplasmic boundaries are present. Finding of hypertrophic reactive astrocytes and alterations of neurofibrils that clumped and twisted into odd shapes like tennis rackets or skeins of wool. The results of group (B) showed the protective effectiveness of Thymus extract against treatment with CACL and the brain tissue looks like normal regeneration occurs mainly at plaque margin and presence of normal white matter. The histopathological results of kidneys of group (A) showed that the most prominent microscopic changes, in particular evident necrosis, especially in proximal tubules. There is atrophy of most of the tubules and the glomerular tuft shows marked increased in cellularity, with obliterated Bowman’s space . The most marked changes are the loss of tubules, and many of these remaining are small and lined by very atrophic epithelium. The results of Group (B) didn’t revealed any effectiveness of thymus extract against toxicity of kidney tissue with CACL. The conclusion that the cadmium chloride may cause severe damage in brain and kidneys of rats and thymus can used as a protective agent against toxicity with cadmium chloride and this protective effect occur obviously in protection of brain tissue against toxic effect of cadmium chloride.

The influence of bovine thymic extract on the immune response in irradiated wistar rats

Immunomodulation is a phenomenon that is based on the influence of different endogenous and exogenous substances on the function of molecules and cells pertaining to the immune system. Some components extracted from the bovine thymus have immunomodulating features and can, both in animals and humans, by suppressing the immune response (humoral and/or cellular) bring about immunostimulation and increased organism resistance. In this paper the effects of bovine thymus extract (Thymex - L) on the parameters of humoral immune response (concentration of antibodies to tetanus toxoid - ATTx) and cellular immune response (interleukin 2 - IL-2, interferon γ - IFN-γ and degree of cutaneus basophyl hypersensitivity - CBHR) in rats previously irradiated by X-rays at a dose of 4 or 6 Gy. The studied thymus extract had shown positive effects on IL-2 and IFN-γ serum concentrations in irradiated rats. In the group of rats irradiated with 4 Gy the effects were evident on the 7th day of the trial. Rats irradiated with the higher dose (6 Gy) experienced the positive effects of thymus extract on the 21st day of the experiment. In the skin PHA hypersensitivity test, a positive effect was also recorded, being more pronounced in rats which received the lower irradiation dose. The tested thymus extract had shown a positive effect on the concentration of ATTx as early as the 14th day of the trial.

Evcil Tavşanlarda Thymus serpyllum’un Koksidiozise Karşı Etkisi: Oosist Atılımı ve Canlı Ağırlık Değişimi

Summary The comparative anticoccidial activity of sulfadimidine and methanolic extract ofThymus serpyllum was examined in rabbits experimentally infected with Eimeria infection in rabbits. This study was to demonstrate the effect of sulfadimidine and methanolic extract of Thymus serpyllum on faecal oocyst excreation and body weight change. The rabbits were divided into three groups each consisting of 6 animals. Group 1 served the as positive control (infected, non-treated), group 2 was the (infected and treated with extract), and rabbits in group 3 was (infected and treated with sulfadimidine). Each rabbit in the all groups was infected with single oral doses of 500.000 oocysts. Rabbits in group 2 and group 3 was treated with single oral doses of 100 mg/kg body weight of methanolic extract and single oral doses of 2 g/kg body weight of sulfadimidine. The overall faecal oocyst counts were ercorded for every consecutive day until day 36 of the study. Faecal oocyst counts were lower in group 2 and 3 than in group 1. Thymus serpyllum treated rabbits in group 2 had higher body weight gain over the day 24 post treatment period than in group 1 and 3. However body weight gain in group 2 was significantly (P<0.05) higher on day 8 only compared to group 1 and 3.

Antibodies to small ribonucleoprotein and to 73-kD heat shock protein: two distinct markers of mixed connective tissue disease.

We set out to discover whether antibodies to small ribonucleoprotein antigens (RNP) and to 73-kD heat shock protein (hsp 73) which have been proposed as markers of mixed connective tissue disease (MCTD) recognize different epitopes. MCTD serum was immunoadsorbed on hsp 73-coupled Sepharose and the affinity retained, and non-retained fractions were checked by immunoblotting for recognition of either purified bovine hsp 73 or calf thymus extract RNPs. The hsp 73 affinity-bound serum fraction recognized hsp 73 but not RNP antigens, the reverse being true for the non-retained fraction. We conclude that anti-hsp 73 and anti-RNPs are distinct markers of MCTD.

Expression of pemphigus-autoantigen desmoglein 1 in human thymus

Desmoglein (Dsg) 1 is a transmembrane glycoprotein of the desmosome allowing cell-cell adhesion between keratinocytes, whose expression is restricted to stratified squamous epithelia-like epidermis. Dsg1 is the target autoantigen of pathogenic autoantibodies produced by pemphigus foliaceus and 50% of pemphigus vulgaris patients in a Dsg1-specific T-cell-dependent pathway. Herewith, we show that mRNA of the DSG1 gene is present in normal human thymus and show by quantitative real-time polymerase chain reaction analysis that the expression of DSG1 transcript increases with age. Although immunoblot analysis on human thymus extracts using different anti-Dsg1 antibodies did not allow to detect the protein, we show by double-immunofluorescence assay that Dsg1 is expressed at protein level by CD19+ CD63+ cells located in the medulla. These data provide another illustration of the thymic expression of a tissue-specific autoantigen involved in an organ-specific autoimmune disease, which may participate in the tolerance acquisition and/or regulation of Dsg1-specific T cells.

Avaliação do uso de extrato de timo (timulina) em pacientes com neoplasia maligna submetidos ao tratamento cirúrgico

OBJETIVO: Avaliar a ação da timulina em pacientes com neoplasia maligna, submetidos ao tratamento, com e sem quimioterapia e radioterapia complementar (QT/RT). MÉTODO: Estudo retrospectivo realizado em 50 pacientes, analisando as variações das taxas de leucócitos, linfócitos totais e da relação de linfócitos CD4/CD8 após imunoestimulação com timulina. RESULTADOS: No grupo submetido à QT/RT ocorreu um aumento do número de leucócitos após seis meses em 43,33% dos casos, e em 83,33% após 12 meses. Com relação aos linfócitos totais, após seis meses, 63,33% apresentaram níveis maiores, e depois de 12 meses isto ocorreu em casos 90% dos casos. A relação de linfócitos CD4/CD8 mostrou um aumento em 66,66%, e em 90% depois após 6 e 12 meses respectivamente. A análise estatística se mostrou significante com o teste de ANOVA one way. No grupo não submetido à QT/RT a elevação dos níveis de leucócitos ocorreu em 85% dos pacientes aos seis meses e em 90% aos 12 meses. As taxas de linfócitos se elevaram em 60% dos casos em seis meses e em 85% após 12 meses. A relação CD4/CD8 se tornou maior tanto aos seis como aos 12 meses em 65%. A análise estatística mostrou relevância com o teste "t" de Student e o de ANOVA one way. Não houve necessidade de interrupção dos ciclos de QT/RT e nenhum paciente referiu intolerância à timulina. CONCLUSÃO: O uso da timulina foi capaz de restaurar a resposta imune, reduzir os danos imunossupressores e colaterais induzidos pela terapia antineoplásica e não apresentou efeitos colaterais.

Evaluation of the Immunomodulatory Properties of a Calf Lipid Thymus Extract and Standardization of a Method for Quantification of its Biological Activity

The aim of this study was to test the immunobiological properties of a new formulation of the lipid thymus calf extract (Thymsol), prepared for in vitro cell culture experiments. At first, we showed that Thymsol enhanced the antigen specific immune response in AO rats in vitro, using Keyhole limpet hemocyanin (KLH). At lower concentrations (0.5-2.5 I¼g mL-1) the extract increased the proliferation of rat spleen lymphocytes in vitro, stimulated with suboptimal concentrations of Concanavalin A (ConA) or anti-T-cell receptor (TCR) monoclonal antibody (mAb), followed by an increase in the production of interleukin-2 (IL-2). Stimulation of IL-2 production was additionally enhanced in the presence of a blocking anti-IL-2 receptor I± mAb. Higher concentrations of Thymsol (20-60 I¼g mL-1) showed a dose-dependent inhibition of lymphocyte proliferation. After testing the variability in IL-2 production by anti-TCR mAb-activated splenocytes, using several stimulatory concentrations of different Thymsol samples, and the production of this cytokine by different cultures of splenocytes treated with the same Thymsol sample, we proposed an IL-2-based method for quantification of the immunobiological activity of the extract.

TrkAIII expression in the thymus

The alternative TrkAIII splice variant is expressed by murine and human thymus. Alternative TrkAIII splicing predominates in postembryonic day E13 (E17 and E18), postnatal murine (3 week and 3 month) and human thymuses, with TrkAIII mRNA expressed by selected thymocyte subsets and thymic epithelial cells (TECs) and a 100 kDa immunoprecipitable TrkAIII-like protein detected in purified thymocyte and whole thymus extracts. FACS and immunohistochemical analysis indicate a non-cell surface localisation for the TrkAIII-like protein in cortical CD4 +/CD8 + double positive and, to a lesser extent, single positive thymocyte subsets at the cortex/medulla boundary and in Hassle's corpuscles, reticular epithelial and dendritic cells of the thymic medulla. TrkA(I/II) expression, on the other hand, predominates in sub-capsular regions of the thymus. TrkAIII-like immunoreactivity at the cortex/medulla boundary associates with regions of thymocyte proliferation and not apoptosis. A potential role for thymic hypoxia in thymocyte alternative TrkAIII splicing is supported by reversal to TrkAI splicing by normoxic but not hypoxic culture and induction of Jurkat T cell alternative TrkAIII splicing by the hypoxia mimic CoCl 2. In contrast, TEC expression of TrkAIII predominates in both normoxic and hypoxic culture conditions. The data support a potential role for TrkAIII in thymic development and function, of particular relevance to intermediate stage CD4 +/CD8 + thymocyte subsets and TECs, which potentially reflects a reversible thymocyte and more permanent TEC adaptation to thymic environment. Since intracellular TrkAIII neither binds nor responds to NGF and can impede regular NGF/TrkA signalling (Tacconelli et al., Cancer Cell, 2004), its expression would be expected to provide an alternative and/or impediment to regular NGF/TrkA signalling within the developing and developed thymus of potential functional importance.

Expression of nerve growth factor is upregulated in the rat thymic epithelial cells during thymus regeneration following acute thymic involution

Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. Nerve growth factor (NGF) is increasingly recognized as a potent immunomodulator, promoting “cross-talk” between various types of immune system cells. The present study describes the expression of NGF during thymus regeneration following acute involution induced by cyclophosphamide in the rat. Immunohistochemical stain demonstrated not only the presence of NGF but also its upregulated expression mainly in the subcapsular, paraseptal, and perivascular epithelial cells, and medullary epithelial cells including Hassall's corpuscles in both the normal and regenerating thymus. Biochemical data obtained using Western blot and RT-PCR supported these results and showed that thymic extracts contain NGF protein and mRNA, at higher levels during thymus regeneration. Thus, our results suggest that NGF expressed in these thymic epithelial cells plays a role in the T lymphopoiesis associated with thymus regeneration during recovery from acute thymic involution.

Isolation of thymus gland fractions and the determination of their biological activity

A calf thymus extract was prepared and fractionated into lipid and non-lipid fractions. The non-lipid fraction was isolated from the calf thymus extract using the Folch method. The components isolated from the non-lipid fraction were characterized by IR, NMR, biuret and HPLC method. The results of the analyses indicated the presence of peptides. The lipid fraction contained phospholipids, glycolipids and neutral lipids. The biological activity of both the isolated lipid and peptide fractions was determined by the in vivo hemolytic plaques method in Wistar rats with an involuted thymus. The peptide and phospholipid fractions of the thymus extract showed a significant increase of hemolytic plaques. The glycolipid and neutral lipid fraction failed to express a significant immunological response.

Pim Kinase Substrate Identification and Specificity

The Pim family of Ser/Thr kinases has been implicated in the process of lymphomagenesis and cell survival. Known substrates of Pim kinases are few and poorly characterized. In this study we set out to identify novel Pim-2 substrates using the Kinase Substrate Tracking and Elucidation (KESTREL) approach. Two potential substrates, eukaryotic initiation factor 4B (eIF4B) and apoptosis inhibitor 5 (API-5), were identified from rat thymus extracts. Sequence comparison of the Pim-2 kinase phosphorylation sites of eIF4B and mouse BAD, the only other known Pim-2 substrate, revealed conserved amino acids preceding the phosphorylated serine residue. Stepwise replacement of the conserved residues produced a consensus sequence for Pim kinase recognition: RXRHXS. Pim-1 and Pim-2 catalyzed the phosphorylation of this recognition sequence 20-fold more efficiently than the original (K/R-K/R-R-K/R-L-S/T-a; a = small chain amino acid) Pim-1 phosphorylation site. The identification of the novel Pim kinase consensus sequence provides a more sensitive and versatile peptide based assay for screening modulators of Pim kinase activity.

Complementary/Alternative Therapies for the Treatment of Breast Cancer. A Systematic Review of Randomized Clinical Trials and a Critique of Current Terminology

The objectives of this study was to evaluate and critically analyze all randomized clinical trials (RCTs) of ''alternative cancer cures'' (ACCs) for breast cancer. The electronic databases Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Allied and Complementary Medicine, Scirus, BIOSIS, CancerLit and CINAHL and for ongoing trials the MetaRegister at http://www.controlled-trials.com/ and the National Research Register at http://www.update-software.com/national/ were searched from their inception. Bibliographies of located studies were scanned. Unpublished or ongoing trials were identified through correspondence with experts in the field. Our own files were hand searched for further RCTs. Review methods included a systematic review of RCTs involving breast cancer patients treated with ACCs, survival, parameters indicative of tumor burden, disease progression, cancer recurrence, and cancer cure. Results were tabulated and summarized. Thirteen RCTs met the inclusion criteria. In most cases their methodological quality is low, with only two RCTs scoring ''4'' and four RCTs scoring ''3'' out of 5 possible points for methodological quality. The treatments tested included various methods of psychosocial support such as group support therapy, cognitive behavioral therapy cognitive existential group therapy, a combination of muscle relaxation training and guided imagery, the Chinese herbal remedy Shi Quan Da Bu Tang, thymus extract, transfer factor, melatonin, and factor AF2. Encouraging but not fully convincing results emerged for melatonin.

Rapid actin monomer–insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1

Actin filaments in cells depolymerize rapidly despite the presence of high concentrations of polymerizable G actin. Cofilin is recognized as a key regulator that promotes actin depolymerization. In this study, we show that although pure cofilin can disassemble Listeria monocytogenes actin comet tails, it cannot efficiently disassemble comet tails in the presence of polymerizable actin. Thymus extracts also rapidly disassemble comet tails, and this reaction is more efficient than pure cofilin when normalized to cofilin concentration. By biochemical fractionation, we identify Aip1 and coronin as two proteins present in thymus extract that facilitate the cofilin-mediated disassembly of Listeria comet tails. Together, coronin and Aip1 lower the amount of cofilin required to disassemble the comet tail and permit even low concentrations of cofilin to depolymerize actin in the presence of polymerizable G actin. The cooperative activities of cofilin, coronin, and Aip1 should provide a biochemical basis for understanding how actin filaments can grow in some places in the cell while shrinking in others.

The chemokine CXCL13 is a key molecule in autoimmune myasthenia gravis

Myasthenia gravis (MG) is associated with ectopic germinal centers in the thymus. Thymectomy and glucocorticoids are the main treatments but they induce operative risks and side effects, respectively. The aim of this study was to propose new therapies more efficient for MG. We hypothesized that molecules dysregulated in MG thymus and normalized by glucocorticoids may play a key role in thymic pathogenesis. Using gene chip analysis, we identified 88 genes complying with these criteria, the most remarkable being the B-cell chemoattractant (CXCL13). Its expression was increased in thymus and sera of glucocorticoid-untreated patients and decreased in response to treatment in correlation with clinical improvement. Normal B cells were actively chemoattracted by thymic extracts from glucocorticoid-untreated patients, an effect inhibited by anti-CXCL13 antibodies. In the thymus, CXCL13 was preferentially produced by epithelial cells and overproduced by epithelial cells from MG patients. Altogether, our results suggest that a high CXCL13 production by epithelial cells could be responsible for germinal center formation in MG thymus. Furthermore, they show that this gene is a main target of corticotherapy. Thus, new therapies targeting CXCL13 could be of interest for MG and other autoimmune diseases characterized by ectopic germinal center formation.

Expression of the onconeural CV2/CRMP5 antigen in thymus and thymoma

Anti-CV2 antibodies (AB) react with the developmentally regulated neural proteins CRMPs and particularly with CRMP5. They occur with small cell lung cancer (SCLC) and thymoma. SCLCs universally express CRMP5. We investigated the expression of CRMPs in thymoma and thymus. In thymoma, none of the CRMPs were detected by immunohistochemistry in tumorous epithelial cells with specific antibodies including CRMP5 but an antibody reacting with a peptide common to the CRMPs labeled a 66-kDa protein in Western blot of rat brain, thymus, and thymoma extracts. Thus, the normal CRMP5 is probably not expressed by tumorous epithelial cells. These results indicate that the mechanisms leading to CRMP5 autoimmunization are different in SCLC and thymoma.

The influence of thymic extract on hematological parameter values in irradiated Wistar rats

In this study, results obtained by following up the changes in hematological parameter values in Wistar rats irradiated with 4 Gy and treated with calves thymic extract Thymex-L are presented. Following irradiation, white blood picture parameters were dramatically decreased and gradually increased from day 14. This elevation was higher in the Thymex-L treated group and the differences were statistically significant for total leukocyte, lymphocyte and neutrophyl granulocyte count starting from day 14. A significant increase of the monocyte count was observed only at day 28. Parameters of the red blood picture (erythrocyte count, hemoglobin concentration and packed red blood cell volume) were increased starting from day 21. We were able to conclude that treatment of irradiated Wistar rats with thymic extract results in a significant improvement of hematological parameter values.

The Immune Modulator FTY720 Inhibits Sphingosine-1-phosphate Lyase Activity

FTY720 is a novel immunomodulatory agent that inhibits lymphocyte trafficking and prevents allograft rejection. FTY720 is phosphorylated in vivo, and the phosphorylated drug acts as agonist for a family of G protein-coupled receptors that recognize sphingosine 1-phosphate. Evidence suggests that FTY720-phosphate-induced activation of S1P1 is responsible for its mechanism of action. FTY720 was rationally designed by modification of myriocin, a naturally occurring sphingoid base analog that causes immunosuppression by interrupting sphingolipid metabolism. In this study, we examined interactions between FTY720, FTY720-phosphate, and sphingosine-1-phosphate lyase, the enzyme responsible for irreversible sphingosine 1-phosphate degradation. FTY720-phosphate was stable in the presence of active sphingosine-1-phosphate lyase, demonstrating that the lyase does not contribute to FTY720 catabolism. Conversely, FTY720 inhibited sphingosine-1-phosphate lyase activity in vitro. Treatment of mice with FTY720 inhibited tissue sphingosine-1-phosphate lyase activity within 12 h, whereas lyase gene and protein expression were not significantly affected. Tissue sphingosine 1-phosphate levels remained stable or increased throughout treatment. These studies raise the possibility that disruption of sphingosine 1-phosphate metabolism may account for some effects of FTY720 on immune function and that sphingosine-1-phosphate lyase may be a potential target for immunomodulatory therapy.

The Immunomodulatory Role of Calf Thymus Extract on Humoral and Cell Mediated Immune Response in Chicken Vaccinated Against New Castle Disease Virus

The effect of administration of calf thymus extract (CTE) with protein concentration of 1.8mg/ml was studied using two groups of day old layer chicks. Both the groups were vaccinated with 'F' and 'R2B' strains of New Castle Disease Virus (NDV) vaccines on 7th day and 8th week respectively. One group was administered with 1.8mg of thymic proteins intraperitoneally, one week prior and one week after each vaccination. The other group remained as vaccinated control group. Humoral and cell mediated responses were evaluated 15 days after each vaccination. Intraperitoneal administration of calf thymus extract markedly and significantly increased the antibody titres against NDV, serum globulin level, and percentage of lymphocytes in the blood. In addition thymus extract resulted in definite and significant cellular immunopotentiation.