Search results for: immunosuppressive

Authors: Xian-Peng Jiang, Catherine C. Baucom, Toby Jiang, Robert L. Elliott

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HLA-G binds to the inhibitory receptors of uterine NK cells and plays an important role in protection of fetal cells from maternal NK lysis. HLA-G also mediates tumor escape, but the immunosuppressive role is often neglected. These studies have focused on the examination of HLA-G expression in human breast carcinoma and HLA-G immunosuppressive role in NK cytolysis. We examined HLA-G expression in breast cell lines by real time PCR, ELISA and immunofluorescent staining. We treated the breast cancer cell lines with anti-human HLA-G antibody or progesterone. Then, NK cytolysis was measured by using MTT assay. We find that breast carcinoma cell lines increase the expression of HLA-G mRNA and protein, compared to normal cells. Blocking HLA-G of the breast cancer cells by the antibody increases NK cytolysis. Progesterone upregulates HLA-G mRNA and protein of human breast cancer cell lines. The increased HLA-G expression suppresses NK cytolysis. In summary, human breast carcinoma overexpress HLA-G immunosuppressive molecules. Blocking HLA-G protein by antibody improves NK cytolysis. In contrast, upregulation of HLA-G expression by progesterone impairs NK cytolytic function. Thus, HLA-G is a new immunosuppressive checkpoint and potential cancer immunotherapeutic target.

Keywords: HLA-G, Breast carcinoma, NK cells, Immunosuppressive checkpoint

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

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Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

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Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

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Authors: Zahra Tolou-Ghamari

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Introduction: After allogeneic organ transplantation, in order to lower the rate of rejectiontacrolimus is given. In fact, infection is reported as the most complication of tacrolimus that might be associated with higher susceptibility by its’ long term use. Aim: This study aims to review the association between the occurrence of infections after organ transplantation following the administration of tacrolims. Materials and Methods: Scientific literature on the pharmacotherapy of tacrolimus after organ transplantation and infections were searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Results: In order to prevent acute and chronic rejection, the potent immunosuppressive drug tacrolimus administered as a calcineurin inhibitor after organ transplantation. Its’ most frequent infectious complication is reported as urinary tract infection. Virulent strain of recombinant Literiamonocytogenes, in addition to an increase in bacterial burden in the liver and spleen tissues, was reported in the animal experimental study. The consequence of aggressive events and recipients total area under the cureve exposure to immunosuppressive could be as considered as surrogate markers for individual infection’s risk evaluation. Conclusion: Transplant surgery and duration of hospital stay could determinate the risk of infection during the first month of organ transplantation. Despite administration of antiviral drugs, opportunistic infection such as cytomegalovirus could increase the risk of infection during month 1 to year after transplantation.

Keywords: transplant, infection, tacrolimus, kidney

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Mir Mohammad Reza Hosseini

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In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

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Authors: Kritin K. Verma, Brian L. Ransdell

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White patches are a symptom of vitiligo, a chronic autoimmune dermatological condition that causes a loss of pigmentation in the skin. Vitiligo can cause issues of self-esteem and quality of life while also progressing the development of other autoimmune diseases. Current treatments in allopathy and homeopathy exist; some treatments have been found to be toxic, whereas others have been helpful. Allopathy has seemed to offer several treatment plans, such as phototherapy, skin lightening preparations, immunosuppressive drugs, combined modality therapy, and steroid medications to improve vitiligo. This presentation will review the FDA-approved topical cream, Opzelura, a JAK inhibitor, and its effects on limiting vitiligo progression. Meanwhile, other non-conventional methods, such as Arsenic Sulphuratum Flavum used in homeopathy, will be debunked based on current literature. Most treatments still serve to arrest progression and induce skin repigmentation. Treatment plans may differ between patients due to depigmentation location on the skin. Since there is no gold standard plan for treating patients with vitiligo, the oral presentation will review all topical and systemic pharmacological therapies that fight the depigmentation of the skin and categorize their validity from a systematic review of the literature. Since treatment plans are limited in nature, all treatment methods will be mentioned and an attempt will be made to make a golden standard treatment process for these patients.

Keywords: vitiligo, phototherapy, immunosuppressive drugs, skin lightening preparations, combined modality therapy, arsenic sulphuratum flavum, homeopathy, allopathy, golden standard, Opzelura

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Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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Authors: Fidelis E. Uwumiro, Chimaobi O. Nwevo, Favour O. Osemwota, Victory O. Okpujie, Emeka S. Obi, Omamuyovbi F. Nwoagbe, Ejiroghene Tejere, Joycelyn Adjei-Mensah, Christopher N. Ekeh, Charles T. Ogbodo

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Several risk factors associated with cardiovascular events have been identified as specific to Chronic Kidney Disease (CKD). This study endeavors to validate these CKD-specific risk factors using up-to-date national-level data, thereby highlighting the crucial significance of confirming the validity and generalizability of findings obtained from previous studies conducted on smaller patient populations. The study utilized the nationwide inpatient sample database to identify adult hospitalizations for CKD from 2016 to 2020, employing validated ICD-10-CM/PCS codes. A comprehensive literature review was conducted to identify both traditional and CKD-specific risk factors associated with cardiovascular events. Risk factors and cardiovascular events were defined using a combination of ICD-10-CM/PCS codes and statistical commands. Only risk factors with specific ICD-10 codes and hospitalizations with complete data were included in the study. Cardiovascular events of interest included cardiac arrhythmias, sudden cardiac death, acute heart failure, and acute coronary syndromes. Univariate and multivariate regression models were employed to evaluate the association between chronic kidney disease-specific risk factors and cardiovascular events while adjusting for the impact of traditional CV risk factors such as old age, hypertension, diabetes, hypercholesterolemia, inactivity, and smoking. A total of 690,375 hospitalizations for CKD were included in the analysis. The study population was predominantly male (375,564, 54.4%) and primarily received care at urban teaching hospitals (512,258, 74.2%). The mean age of the study population was 61 years (SD 0.1), and 86.7% (598,555) had a CCI of 3 or more. At least one traditional risk factor for CV events was present in 84.1% of all hospitalizations (580,605), while 65.4% (451,505) included at least one CKD-specific risk factor for CV events. The incidence of CV events in the study was as follows: acute coronary syndromes (41,422; 6%), sudden cardiac death (13,807; 2%), heart failure (404,560; 58.6%), and cardiac arrhythmias (124,267; 18%). 91.7% (113,912) of all cardiac arrhythmias were atrial fibrillations. Significant odds of cardiovascular events on multivariate analyses included: malnutrition (aOR: 1.09; 95% CI: 1.06–1.13; p<0.001), post-dialytic hypotension (aOR: 1.34; 95% CI: 1.26–1.42; p<0.001), thrombophilia (aOR: 1.46; 95% CI: 1.29–1.65; p<0.001), sleep disorder (aOR: 1.17; 95% CI: 1.09–1.25; p<0.001), and post-renal transplant immunosuppressive therapy (aOR: 1.39; 95% CI: 1.26–1.53; p<0.001). The study validated malnutrition, post-dialytic hypotension, thrombophilia, sleep disorders, and post-renal transplant immunosuppressive therapy, highlighting their association with increased risk for cardiovascular events in CKD patients. No significant association was observed between uremic syndrome, hyperhomocysteinemia, hyperuricemia, hypertriglyceridemia, leptin levels, carnitine deficiency, anemia, and the odds of experiencing cardiovascular events.

Keywords: cardiovascular events, cardiovascular risk factors in CKD, chronic kidney disease, nationwide inpatient sample

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Authors: Stefan Bradu, Daniel Siegel, Jameson Loyal, Andrea Leaf, Alana Kurtti, Usha Alapati, Jared Jagdeo

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Compared with all other variants of nodular melanoma, patients with polypoid nodular melanoma have the lowest 5-year survival rate. The pathophysiology and management of polypoid melanoma are scarcely reported in the literature. Although surgical excision is the cornerstone of melanoma management, treatment of polypoid melanoma is complicated by several negative prognostic factors, including early metastasis. This report demonstrates the successful treatment of a rapidly developing red nodular polypoid melanoma with metastasis using surgery and adjuvant nivolumab in a SARS-CoV-2-positive patient who delayed seeking care due to the COVID-19 pandemic. In addition to detailing the successful treatment approach, the immunosuppressive effects of SARS-2-CoV and its possible contribution to the rapid progression of polypoid melanoma are discussed. This case highlights the complex challenges of melanoma diagnosis and management during the COVID-19 pandemic.

Keywords: covid-19, dermatology, immunotherapy, melanoma, nivolumab

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Authors: Shafieeh Mansoori, Fatemeh Yazdian, Ashrafsadat Hatamian, Majid Azizi

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Monascus purpureus, which has a special metabolite with many therapeutic and medicinal properties including antioxidant, antibiotic, anti-hypercholesterolemia, and immunosuppressive properties, is a traditional Chinese fermentation fungus and is used as a natural dietary supplement. Production of desired metabolites actually determined by optimized growth which is supported by some factors such as substrates and Monascus strains type, moisture content of the fermentation mixture, aeration, and control of contamination issues. In this experiment, M. purpureus PTCC5305 was cultured in both the liquid and solid culture medium. The former medium contain YMP (yeast extract, maltose and peptone), PGC (peptone, glucose complex), and GYP (glucose, yeast extract and peptone) medium. After 8 days, the best medium for the cell production was PGC agar medium on solid culture with 0.28 g dry weight of cell mass whereas the best liquid culture was GYP medium with 3.5 g/l dry weight of cell mass. The lowest cell production was on YMP agar with 0.1 g dry weight of cell mass and then YMP medium with 2.5 g/l dry cell weight.

Keywords: Monascus purpureus, solid state fermentation, submerged culture, Chinese fermentation fungus

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST, and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands, cannabinol, and cannabidiol, were obtained from PubChem. After the necessary process of the obtained files, AutoDock Vina was used to perform molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis, were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands cannabinol and cannabidiol were obtained from PubChem. After a necessary process of the obtained files, AutoDock Vina was used to performing molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: V. Surena, B. Nazemisalman, F. Noghrehkar

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Introduction: Gingival overgrowth (GO) is a common side effect involving users of antiepileptic, immunosuppressive and calcium channel blocker drugs. Cyclosporine and phenytoin are amongst the most widely used drugs associated with GO. Gingival fibroblasts seem to have a significant role in the production of certain enzymes after administration of the drugs contributing to GO. Previous studies have shown a higher prevalence of GO in children and adolescents. The aim of this study was to compare normal human gingival fibroblasts with those exposed to Cyclosporine or phenytoin in measuring the production levels of certain enzymes that could have a possible role in GO. Methods: samples were obtained from the gingival biopsies of seven adult and seven children and were cultured into plates. With the growth of fibroblast cells, they were treated with or without either Cyclosporine or phenytoin. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the expressed levels of R-EGF, cathepsin B,L, Lysyl oxidase, COL1, TGF β1, MMP-1,2, and TIMP1. Results: according to RT-PCR analyses, the expressed levels of R-EGF, cathepsin B, L, Lysyl oxidase, COL1, TGF β1, MMP-1, 2 and TIMP1 were affected by Cyclosporine and phenytoin. TGF-β1, TIMP, Cathepsin B and EGF showed comparable values in the adult and pediatric groups. Conclusions: Different expressed levels of enzymes after treatment of the gingival fibroblasts of adults and pediatrics with phenytoin or Cyclosporine could be the reason for the higher severity of GO in children. More studies need to be performed on the pathogenesis of GO at different age groups.

Keywords: cyclosporine, fibroblasts, phenytoin, gingivae

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Authors: Karissa A. Graham

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Pyoderma gangrenosum (PG) is a prototypic autoinflammatory neutrophilic dermatosis that is a rare disorder. It presents a diagnostic challenge owing to its variable presentation, clinical overlap with other conditions, it is often associated with other systemic conditions, and there is no definitive histological or laboratory characteristic. The Delphai consensus for PG includes the presence of at least one ulcer on the anterior lower limb. Systemic corticosteroids and immunosuppressive therapies are the mainstay treatment for PG. We describe a case report of delayed diagnosis of ulcerative pyoderma gangrenosum in a 44-year-old male on his forearm. The patient presented with an infected ulcer on his right forearm that had been present for over three years. The patient was a Type 2 Diabetic with no personal or family history of inflammatory bowel disease or other autoimmune diseases. The patient was initially investigated for malignancy, but biopsies returned as chronic inflammatory tissue with neutrophilic infiltrate and no malignancy. The patient was commenced on systemic prednisone for the treatment of pyoderma gangrenosum. The diagnosis of ulcerative PG poses a challenge given the vast differential diagnosis for a cutaneous ulcer (i.e., malignant, vascular, autoimmune, trauma, infective, etc.). Diagnostic accuracy is important given that the treatment for PG with steroids does not go without risks and indeed may be contraindicated in other potential causes of the ulcer. Indeed, more common and more sinister causes of ulcers should be investigated first, as death from PG is quite rare.

Keywords: dermatological diagnosis, dermatosis, pyoderma gangrenosum, rare presentation

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Authors: Zakieh Rostamzadeh , Nariman Sepehrvand-Zahra Shirmohamadi

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Background: Cytomegalovirus (CMV) infection is one of the most common infectious problems following kidney transplantation. In this study, we are aimed to investigate the CMV infection in the setting of renal transplant recipients in Urmia-Iran, using both ELISA and polymerase chain reaction (PCR) methods. Methods: Ninety-six renal transplant recipients were selected randomly and enrolled in a cross-sectional study. Blood sampling was done via venipuncture, and all sera were investigated for anti-CMV IgM, and the seropositive cases in association with 14 randomly selected seronegative cases were investigated with PCR assay. Results: Thirty-three patients (34.3%) were seropositive for anti-CMV IgM, 3 patients (3.1%) were in borderline range, and 60 patients (62.5%) were seronegative. By considering the patients with borderline anti-CMV IgM levels as seropositive, 37.5% were seropositive for anti-CMV IgM. Among 36 seropositive cases, the CMV infection was confirmed in 19 (52.7%) of them using PCR. Age (P = 0.40), educational status (P = 0.77), history of pre-transplantation dialysis (0.52), history of blood transfusion (P = 0.52), and immunosuppressive regimen were not statistically different among recipients with positive versus negative CMV PCR study results. Conclusion: The seroprevalence of CMV infection was demonstrated to be high in renal transplant recipients of Urmia-Iran. The rate was higher compared to several previous reports in the literature. ELISA method has an appropriate sensitivity to screen the recipients for CMV infection but considering its relatively low specificity, the seropositive cases are better to be confirmed by further PCR study.

Keywords: cytomegalovirus, renal transplantation, ELISA, IgM, PCR

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Authors: Hsin-Lien Lin, Ju-Hui Fu

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Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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Authors: Iman M. Mansour, Rania A. Zayed, Fadwa S. Abdel-Azim, Lamyaa H. Abdel-Latif

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Background and Objectives: The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Methods: 37 adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. Results: MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (p=0.002 and p<0.001 respectively). A positive correlation was found between IDO expression and Tregs percentage (p value=0.012, r=0.5). Conclusion: In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which has an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

Keywords: acute myeloid leukemia, indoleamine 2, 3-dioxygenase, mesenchymal stem cells, T regulatory cells

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Authors: Moez Elsaadani, Noel Durand, Brice Sorli, Didier Montet

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Governments and international instances are trying to improve the food safety system to prevent, reduce or avoid the increase of food borne diseases. This food risk is one of the major concerns for the humanity. The contamination by mycotoxins is a threat to the health and life of humans and animals. One of the most common mycotoxin contaminating feed and foodstuffs is Ochratoxin A (OTA), which is a secondary metabolite, produced by Aspergillus and Penicillium strains. OTA has a chronic toxic effect and proved to be mutagenic, nephrotoxic, teratogenic, immunosuppressive, and carcinogenic. On the other side, because of their high stability, specificity, affinity, and their easy chemical synthesis, aptamer based methods are applied to OTA biosensing as alternative to traditional analytical technique. In this work, five aptamers have been tested to confirm qualitatively and quantitatively their binding with OTA. In the same time, three different analytical methods were tested and compared based on their ability to detect and quantify the OTA. The best protocol that was established to quantify free OTA from linked OTA involved an ultrafiltration method in green coffee solution with. OTA was quantified by HPLC-FLD to calculate the binding percentage of all five aptamers. One aptamer (The most effective with 87% binding with OTA) has been selected to be our biorecognition element to study its electrical response (variation of electrical properties) in the presence of OTA in order to be able to make a pairing with a radio frequency identification (RFID). This device, which is characterized by its low cost, speed, and a simple wireless information transmission, will implement the knowledge on the mycotoxins molecular sensors (aptamers), an electronic device that will link the information, the quantification and make it available to operators.

Keywords: aptamer, aptasensor, detection, Ochratoxin A

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Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

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Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

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Authors: Pui Hong Chung, Wing Chi Ho, Jun Li, Cyrus Leung, Ek Yeoh

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Background: Cigarette smoking is associated with poor tuberculosis (TB) outcomes in terms of progression of active TB, relapse of TB and TB-related mortality, but the association with latent tuberculosis infection (LTBI) is unclear. The systematic review conducted aimed at studying the association between active smoking and LTBI, and likelihood of dose-response relationship. Methods: Two independent reviewers searched three electronic databases comprising PudMed, Medline by EBSCOHOST, ExcerptaMedica Database (EMBASE), from inception up to 31st Dec 2015 for studies reporting data on current smoking and the LTBI with tuberculin skin test (TST) or interferon-γ release assays (IGRAs) results, comparing the odds ratios (ORs) of outcome measure of TST or IGRAs among current smokers with 95% confidence intervals (CI). Results: Seven studies were identified, including six cross-sectional studies and one longitudinal cohort study. The outcome measures from three studies were in TST, three studies in IGRAs and one for both tests. For TST, OR ranging from 1.39 to 3.40 (95% CI) with all studies shown positive association between cigarette smoking and LTBI. For IGRAs, OR ranging from 0.47 to 1.89 (95% CI) with one study shown the negative association that might be related to impaired interferon-gamma production in immunosuppressive persons. One identified study demonstrated positive dose-response relationship in TST result. Conclusions: Cigarette smoking is likely to be a risk factor of LTBI. There is the important implication for TB and tobacco control program to halt TB by empowering public health policy. Further study is also needed to provide more evidence of the dose-response model/relationship.

Keywords: latent tuberculosis infection, systematic review, active smoking, model

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Authors: Sihyun Chae, Ryoto Arai, Waldo Concepcion, Paula Popescu

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The kidneys perform an important role in the human hormones that regulate the blood pressure, produce an active form of vitamin D and control the production of red blood cells. Kidney disease can cause health problems, such as heart disease. Also, increase the chance of having a stroke or heart attack. There are mainly to types of treatments for kidney disease, dialysis, and kidney transplant. For a better quality of life, the kidney transplant is desirable. However, kidney transplant can cause antibody reaction and patients’ body would be attacked by immune system of their own. For solving that issue, patients with transplanted kidney always take immunosuppressive drugs which can hurt kidney as side effects. Patients willing to do a kidney transplant have a waiting time of 3.6 years in average searching to find an appropriate kidney, considering there are almost 96,380 patients waiting for kidney transplant. There is a promising method to solve these issues: bioartificial kidney. Our membrane is specially designed with unique perforations capable to filter the blood cells separating the white blood cells from red blood cells. White blood cells will not pass through the encapsulated kidney preventing the immune system to attack the new organ and eliminating the need of a matching donor. It is possible to construct life-time long encapsulation without needing pumps or a power supply on the cell’s separation method preventing futures surgeries due the Cross-Channel Flow inside the device. This technology allows the possibility to use an animal kidney, prevent cancer cells to spread through the body, arm and leg transplants in the future. This project aims to improve the quality of life of patients with kidney disease.

Keywords: kidney encapsulation, immunosuppression filter, leukocyte filter, leukocyte

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Authors: Zebiri Saliha

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Ochratoxin A (OTA) is a mycotoxin produced by certain species of the genera Aspergillus and Penicillium, primarily found in cereals, coffee, and grapevine products. Its accumulation in the body can lead to nephrotoxic, teratogenic, immunosuppressive, and carcinogenic effects. The objective of this study is to investigate the contamination of consumed wheat and its derivatives by toxic fungi in Algeria. For this purpose, an analysis of 200 samples was conducted, including 90 samples of durum wheat and common wheat and 110 samples of wheat derivatives collected from mills (semolina and flour manufacturers). The results revealed an average fungal contamination rate ranging from 60% to 100%. The identified fungal isolates primarily belonged to the genera Aspergillus (70%), Penicillium (27.5%), Alternaria (40%), and Mucor (19.4%). The density of the fungal flora was higher in products intended for animal consumption, such as durum wheat flour (2525 CFU/g), wheat scraps (3175 CFU/g), and wheat bran (2950 CFU/g). Conversely, low fungal density was observed in fine semolina (900 CFU/g) and flour (800 CFU/g) intended for human consumption. The genus Penicillium was isolated in 46% of the analyzed samples of durum wheat derivatives and in 62.7% of the analyzed samples of common wheat derivatives. The Aspergillus genus dominated the majority of the analyzed samples. Molecular identification of Aspergillus and Penicillium isolates by sequencing ITS1-5.8S-ITS2 regions of DNAr and a part of the calmodulin (CaM) gene indicated that the species involved in the production of OTA in wheat and its derivatives were mainly Aspergillus ochraceus, A. westerdijkia, A. alliaceus, A. carbonarius, and Penicillium islandicus. The amounts of OTA produced by these species were determined by HPLC-FLD and ranged between 0,8.9 and 3033μg/g. Given that food safety and quality are major concerns today, understanding the microbial biodiversity of wheat is crucial because it is a staple food in Algeria.

Keywords: wheat derivatives, Aspergillus, microbial biodiversity, OTA

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Authors: Sumeyra Sevim, Gulsum Gizem Topal, Mercan Merve Tengilimoglu-Metin, Banu Sancak, Mevlude Kizil

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Aflatoxin M1 (AFM1) represents mutagenic, carcinogenic, hepatotoxic and immunosuppressive properties, and shows adverse effect on human health. Recently the use of probiotics are focused on AFM1 detoxification because of the fact that probiotic strains have a binding ability to AFM1. Moreover, inulin is a prebiotic to improve the ability of probiotic bacteria. Therefore, the aim of the study is to investigate the effect of inulin on AFM1 binding ability of some probiotic bacteria. Yoghurt samples were manufactured by using skim milk powder artificially contaminated with AFM1 at concentration 100 pg/ml. Different samples were prepared for the study as: first sample consists of yoghurt starter bacteria (L. bulgaricus and S. thermophilus), the second sample consists of starter and L. plantarum, starter and B. bifidum ATCC were added to the third sample, starter and B. animalis ATCC 27672 were added to the forth sample, and the fifth sample is a binary culture consisted of starter and B. bifidum and B. animalis. Moreover, the same work groups were prepared with inulin (4%). The samples were incubated at 42°C for 4 hours, then stored for three different time interval (1,5 and 10 days). The toxin was measured by the ELISA. When inulin was added to work groups, there was significant change on AFM1 binding ability at least one sample in all groups except the one with L. plantarum (p<0.05). The highest levels of AFM1 binding ability (68.7%) in samples with inulin were found in the group which B. bifidum was added, whereas the lowest levels of AFM1 binding ability (44.4%) in samples with inulin was found in the fifth sample. The most impressive effect of inulin was found on B.bifidum. In this study, it was obtained that there was a significant effect of storage on AFM1 binding ability in the all groups with inulin except the one with L. plantarum (p<0.05). Consequently, results show that AFM1 detoxification by probiotics have a potential application to reduce toxin concentrations in yoghurt. Besides, inulin has different effects on AFM1 binding ability of each probiotic bacteria strain.

Keywords: aflatoxin M1, inulin, probiotics, storage

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Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

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Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

Procedia PDF Downloads 181

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

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We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Pavel Porubiak, Lukas Kudlacek

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Introduction Transplant tourism is a controversial method of obtaining an organ, and that goes all the more for a country such as China, where sources of evidence point out to the possibility of organs being harvested illegally. This research aimed at listing the individual countries these tourists come from, or which medical companies sell transplant related products in there, with China being used as an example. Materials and methods The methodology of scoping study was used for both parts of the research. The countries from which transplant tourists come to China were identified by a search through existing medical studies in the NCBI PubMed database, listed under the keyword ‘transplantation in China’. The search was not limited by any other criteria, but only the studies available for free – directly on PubMed or a linked source – were used. Other research studies on this topic were considered as well. The companies were identified through multiple methods. The first was an online search focused on medical companies and their products. The Bloomberg Service, used by stock brokers worldwide, was then used to identify the revenue of these companies in individual countries – if data were available – as well as their business presence in China. A search through the U.S. Securities and Exchange Commission was done in the same way. Also a search on the Chinese internet was done, and to obtain more results, a second online search was done as well. The results and discussion The extensive search has identified 14 countries with transplant tourists to China. The search for a similar studies or reports resulted in finding additional six countries. The companies identified by our research also amounted to 20. Eight of them are sourcing China with organ preservation products – of which one is just trying to enter the Chinese market, six with immunosuppressive drugs, four with transplant diagnostics, one with medical robots which Chinese doctors use for transplantation as well, and another one trying to enter the Chinese market with a consumable-type product also related to transplantation. The conclusion The question of the ethicality of transplant tourism may be very pressing, since as the research shows, just the sheer amount of participating countries, sourcing transplant tourists to another one, amounts to 20. The identified companies are facing risks due to the nature of transplantation business in China, as officially executed prisoners are used as sources, and widely cited pieces of evidence point out to illegal organ harvesting. Similar risks and ethical questions are also relevant to the countries sourcing the transplant tourists to China.

Keywords: China, illegal organ harvesting, transplant tourism, organ harvesting technology

Procedia PDF Downloads 106