Displaying publications 521 - 540 of 700 in total

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  1. Farah Wahida I, Aminuddin BS, Munirah S, Chua KH, Fuzina NH, Isa MR, et al.
    Med J Malaysia, 2004 May;59 Suppl B:190-1.
    PMID: 15468882
    This study was to assess collagen type II and collagen type I gene expression in tissue-engineered human auricular: cartilage formed via tissue engineering technique. Large-scale culture expansions were transformed into 3D in vitro construct and were implanted subcutaneously on the dorsal of athymic mice. After 8 weeks, explanted construct was processed in the same manner of native cartilage to facilitate cells for gene expression analysis. Isolated cells from in vivo construct demonstrated expression of type II collagen gene comparable to native cartilage. This study verified that tissue-engineered auricular cartilage expressed cartilage specific gene, collagen type II after in vivo maturation.
    Matched MeSH terms: Cartilage/transplantation
  2. Muhd Fakhruddin BH, Aminuddin BS, Mazlyzam AL, Ruszymah BH
    Med J Malaysia, 2004 May;59 Suppl B:182-3.
    PMID: 15468878
    Skin is the largest organ in human system and plays a vital role as a barrier against environment and pathogens. Skin regeneration is important in tissue engineering especially in cases of chronic wounds. With the tissue engineering technology, these skins equivalent have been use clinically to repair burns and wounds. Consented redundant skin samples were obtained from patients aged 9 to 65 years old. Skin samples were digested with dispase, thus separating the epidermis and the dermis layer. The epidermis layer was trypsinized and cultured in DKSFM in 6-well plate at 37 degrees C and 5% CO2. Once confluent, the culture were trypsinized and the cells were pooled. Cells were counted using haemacytometer. Doubling time and viability were calculated and analysed. From the result, we conclude that doubling time and viability of in vitro keratinocytes cultured in DKSFM media is not age dependant.
    Matched MeSH terms: Skin Transplantation*
  3. Chua KH, Aminuddin BS, Fuzina NH, Ruszymah BH
    Med J Malaysia, 2004 May;59 Suppl B:194-5.
    PMID: 15468884
    We have previously formulated an optimized human chondrocytes growth medium based on 2% fetal bovine serum supplementation. For clinical usage, the animal serum must be replaced by patient own serum. We investigated the effects of human serum concentration for human nasal septum chondrocytes monolayer culture and cartilage reconstruction. Human serum demonstrated a dose dependent manner in promoting chondrocytes growth and cartilage engineering.
    Matched MeSH terms: Cartilage/transplantation*
  4. Ruszymah BH, Chua K, Latif MA, Hussein FN, Saim AB
    Int J Pediatr Otorhinolaryngol, 2005 Nov;69(11):1489-95.
    PMID: 15941595
    Treatment and management of congenital as well as post-traumatic trachea stenosis remains a challenge in pediatric surgery. The aim of this study was to reconstruct a trachea with human nasal septum chondrocytes by using the combination of biodegradable hydrogel and non-biodegradable high-density polyethylene (HDP) as the internal predetermined shape scaffold.
    Matched MeSH terms: Chondrocytes/transplantation*
  5. Dorai AA, Halim AS, Zulmi W
    Med J Malaysia, 2004 Dec;59 Suppl F:42-6.
    PMID: 15941160
    Reconstructive surgeons often encounter complex soft tissue and skeletal defects following oncological surgery. Soft tissue defects after wide resection in upper extremities posses a difficult challenge to find adequate tissue for reconstructing these defects. Paucity of local tissues dictates the requirement of loco-regional or distant flaps for these complex soft tissue defects which often exposes tendons, bones, nerves and joints. The latissimus dorsi muscle is a near ideal flap for the reconstruction because of the long neurovascular pedicle, ease of mobilization and its expendability. It can be rotated, with or without overlying skin, to cover soft tissue defects of the shoulder arm and elbow. Due to the large size of the muscle, it can be used to resurface the soft tissue defects and cover all major structures. Eleven consecutive cases were reviewed in which latissimus dorsi myocutaneous flap was used to reconstruct soft tissue defects of the upper limb following radical tumor resection. Flap survival was 100% with nominal donor site morbidity.
    Matched MeSH terms: Muscle, Skeletal/transplantation*
  6. Lim KL, Teoh HK, Choong PF, Teh HX, Cheong SK, Kamarul T
    Expert Opin Biol Ther, 2016 07;16(7):941-51.
    PMID: 27070264 DOI: 10.1517/14712598.2016.1174211
    INTRODUCTION: Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model.

    AREAS COVERED: Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents.

    EXPERT OPINION: Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

    Matched MeSH terms: Induced Pluripotent Stem Cells/transplantation
  7. Saw KY, Anz A, Jee CS, Ng RC, Mohtarrudin N, Ragavanaidu K
    Arthroscopy, 2015 Oct;31(10):1909-20.
    PMID: 26008951 DOI: 10.1016/j.arthro.2015.03.038
    PURPOSE: To histologically evaluate the quality of articular cartilage regeneration from the medial compartment after arthroscopic subchondral drilling followed by postoperative intra-articular injections of autologous peripheral blood stem cells (PBSCs) and hyaluronic acid with concomitant medial open-wedge high tibial osteotomy (HTO) in patients with varus deformity of the knee joint.
    METHODS: Eight patients with varus deformity of the knee joint underwent arthroscopic subchondral drilling of International Cartilage Repair Society (ICRS) grade 4 bone-on-bone lesions of the medial compartment with concomitant HTO. These patients were part of a larger pilot study in which 18 patients underwent the same procedure. PBSCs were harvested and cryopreserved preoperatively. At 1 week after surgery, 8 mL of PBSCs was mixed with 2 mL of hyaluronic acid and injected intra-articularly into the knee joint; this was repeated once a week for 5 consecutive weeks. Three additional intra-articular injections were administered weekly at intervals of 6, 12, and 18 months postoperatively. Informed consent was obtained at the time of hardware removal for opportunistic second-look arthroscopy and chondral biopsy. Biopsy specimens were stained with H&E, safranin O, and immunohistochemical staining for type I and II collagen. Specimens were graded using the 14 components of the ICRS Visual Assessment Scale II, and a total score was obtained.
    RESULTS: Second-look arthroscopy showed satisfactory healing of the regenerated cartilage. Histologic analysis showed significant amounts of proteoglycan and type II collagen. The total ICRS Visual Assessment Scale II histologic scores comparing the regenerated articular cartilage (mean, 1,274) with normal articular cartilage (mean, 1,340) indicated that the repair cartilage score approached 95% of the normal articular cartilage score. There were no infections, delayed unions, or nonunions.
    CONCLUSIONS: Chondrogenesis with stem cells in combination with medial open-wedge HTO for varus deformity correction of the knee joint regenerates cartilage that closely resembles the native articular cartilage.
    LEVEL OF EVIDENCE: Level IV, therapeutic case series.
    Matched MeSH terms: Stem Cell Transplantation*
  8. Abdul Rahman R, Mohamad Sukri N, Md Nazir N, Ahmad Radzi MA, Zulkifly AH, Che Ahmad A, et al.
    Tissue Cell, 2015 Aug;47(4):420-30.
    PMID: 26100682 DOI: 10.1016/j.tice.2015.06.001
    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (p<0.05 respectively). Both constructs expressed the accumulation of collagen type II, collagen type IX, aggrecan and sox9, showed down-regulation of collagen type I as well as produced relative sGAG content with PLGA/fibrin construct exhibited better gene expression in all profiles and showed significantly higher relative sGAG content at each time point (p<0.05). This study suggested that with optimum in vitro manipulation, PLGA/fibrin when seeded with pluripotent non-committed BMSCs has the capability to differentiate into chondrogenic lineage and may serve as a prospective construct to be developed as functional tissue engineered cartilage.
    Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
  9. Ghods AJ
    Exp Clin Transplant, 2015 Apr;13 Suppl 1:13-7.
    PMID: 25894121
    The Organization of Islamic Cooperation consists of 57 member states whose people are mainly followers of the Islamic religion. During the past several decades, organ transplants have been increasingly used for the treatment of end-stage organ failures worldwide. This study is to investigate the current status of organ transplant in Islamic countries.
    Matched MeSH terms: Organ Transplantation*
  10. Jeyaratnam TS, Ahmad TS, Kassim NM
    Hand Surg, 2001 Jul;6(1):99-102.
    PMID: 11677671
    Matched MeSH terms: Ulnar Artery/transplantation*
  11. Lee KT, Li MK, Cheng WS, Foo KT
    Br J Urol, 1998 May;81(5):705-8.
    PMID: 9634045 DOI: 10.1046/j.1464-410x.1998.00586.x
    OBJECTIVE: To evaluate the impact of the modified ileal neobladder reconstruction on lifestyle, voiding habits and functional outcome in Asian patients.

    PATIENTS AND METHODS: Twenty-seven Asian patients (25 men and two women, mean age 59 years, range 41-76) underwent modified ileal neobladder reconstruction after radical cystectomy for carcinoma of the bladder. The mean (range) follow-up was 21 (3-75) months. All patients were evaluated retrospectively using case notes, reviews, interviews and voiding charts; 18 patients underwent urodynamic studies.

    RESULT: Twenty-five patients (93%) achieved diurnal and 23 (85%) nocturnal continence within 6 months. Of the 19 patients who were in employment before surgery, 15 continued to be economically active afterward; 26 patients (96%) reported no change in their daily living activities. Of 16 men who reported being potent pre-operatively only four retained some residual erectile function. Twenty-three patients were interviewed about their voiding habits and satisfaction with the outcome of surgery. Fourteen patients had no sensation of reservoir fullness and of the 21 men, 13 had to squat or sit to void effectively. The mean (range) voiding frequency was 5 (4-8) during the day and 2 (0-4) during sleep. Twenty-two patients were satisfied with the overall outcome.

    CONCLUSIONS: The modified ileal bladder provides a high urinary continence rate with minimal changes in daily living activities and occupational status. The functional outcome was very satisfactory and accepted well, despite some changes in reservoir sensation, voiding posture and erectile function. The method is a viable option for reconstruction after cystectomy in Asian patients.
    Matched MeSH terms: Ileum/transplantation
  12. Chong PP, Selvaratnam L, Abbas AA, Kamarul T
    J Orthop Res, 2012 Apr;30(4):634-42.
    PMID: 21922534 DOI: 10.1002/jor.21556
    The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri-lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s-GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s-GAG expressions to chondrocytes.
    Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
  13. Alsaeedi HA, Koh AE, Lam C, Rashid MBA, Harun MHN, Saleh MFBM, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Sep;198:111561.
    PMID: 31352000 DOI: 10.1016/j.jphotobiol.2019.111561
    Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.
    Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
  14. Jalalonmuhali M, Carroll RP, Tsiopelas E, Clayton P, Coates PT
    Hum Immunol, 2020 Jul;81(7):323-329.
    PMID: 32327243 DOI: 10.1016/j.humimm.2020.04.002
    BACKGROUND: Blood transfusion during the post-operative period of kidney transplantation is common as part of a life-saving procedure, especially in the event of acute blood loss. However, there have been conflicting opinions since the pre-cyclosporine era. The risk of sensitization post-transfusion remains the main limiting factor following transfusion in kidney transplant recipients. Thus, the objective of this study is to assess the development of de novo HLA-DSA, HLA-Ab and allograft rejection post blood transfusion.

    METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.

    RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).

    CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.

    Matched MeSH terms: Kidney Transplantation*
  15. Abu Bakar K, Mohamad NA, Hodi Z, McCulloch T, Williams A, Christian M, et al.
    Pediatr Nephrol, 2019 12;34(12):2557-2562.
    PMID: 31520127 DOI: 10.1007/s00467-019-04346-z
    BACKGROUND: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known.

    METHODS: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels

    Matched MeSH terms: Kidney Transplantation/adverse effects
  16. Zhao J, Tien HY, Abdullah S, Zhang Z
    Plast Reconstr Surg, 2010 Dec;126(6):2052-2059.
    PMID: 21124145 DOI: 10.1097/PRS.0b013e3181f44994
    BACKGROUND: Second toe-to-thumb transfer is a good alternative to using the great toe for reconstruction of the thumb. It achieves excellent function and reduces morbidity to the donor foot. However, cosmesis is often poor. The second toe has three unattractive features, a narrow "neck," a bulbous tip, and a short nail.

    METHODS: The authors describe a modified second toe transfer that addresses cosmesis in six patients. These include (1) harvesting a flap from the adjacent side of the great toe and insetting it into the volar aspect of the second toe to give more bulk, (2) making skin excisions on each side of the tip to reduce the bulbous appearance, and (3) excising the eponychium to produce apparent lengthening of the nail.

    RESULTS: The mean follow-up period was 18 months (range, 6 to 36 months). The procedure resulted in good function and improved cosmesis in all six cases. Part of the great toe flap was lost in one case. The mean two-point discrimination in the transferred toes was 10.1 mm, with protective sensation present in the flaps. The range of motion of the transferred toe was 14 to 38 degrees at the metatarsophalangeal joint, 16 to 55 degrees at the proximal interphalangeal joints, and 20 to 36 degrees in the distal interphalangeal joints. All patients except one were happy with the appearance of the transferred toe.

    CONCLUSION: This novel approach will allow patients to take advantage of the lower morbidity to the donor site afforded by second toe-to-thumb transfer and provide the patients with a more aesthetic appearance of the new thumb.

    Matched MeSH terms: Toes/transplantation*
  17. Carroll RP, Deayton S, Emery T, Munasinghe W, Tsiopelas E, Fleet A, et al.
    Hum Immunol, 2019 Aug;80(8):573-578.
    PMID: 31014826 DOI: 10.1016/j.humimm.2019.04.005
    High levels of angiotensin receptor antibodies (ATRab) are associated with acute cellular and humoral rejection, vascular occlusion, de novo human leucocyte antigen donor specific antibody (HLA DSA) and poor graft survival in kidney transplant recipients (KTR). Since 2015 we proactively managed patients "at risk" (AR) with ATRab >17 U/ml with perioperative plasma exchange (PLEX) and/or angiotensin receptor blockade (ARB). 44 patients were treated with this protocol. 265 KTR with ATRab ≤17 U/ml deemed "low risk" (LR) were transplanted under standard conditions. PLEX and ARB were not associated with increased risk of: delayed graft function requiring haemodialysis (HDx), hyperkalaemia >5.5 mmol/l requiring HDx, and the combined clinical end-point of severe hypotension, blood transfusion and re-operation for bleeding. Rejection rates were similar at 90 days: 8/44 (18%) in the AR group and 36/265 (14%) in the LR group (p = 0.350). Death censored graft survival was the same between the AR and LR groups with a 94% 48-month graft survival - hazard ratio (log-rank) 1.16 [95% CI 0.2-5.8] p = 0.844. Proactive treatment of ATRab >17 U/ml with PLEX and/or ARB is not associated with increased rates of perioperative complications and comparable rates of rejection and death censored graft survival at 4 years compared to KTR <17 U/ml ATRab.
    Matched MeSH terms: Kidney Transplantation*
  18. Lee SZ, Halim AS
    Burns, 2019 09;45(6):1386-1400.
    PMID: 31054957 DOI: 10.1016/j.burns.2019.04.011
    INTRODUCTION: Autologous skin grafting is the mainstay of treatment in burn patients. Extensive full thickness burns remains a challenge to the burns surgeon due to the lack of autologous skin donor sites. The conventional split thickness skin grafting (SSG) and the Meek micrografting (Meek) technique are part of the armamentarium of the burns surgeon to curtail the challenge of paucity of donor sites. With advances in burn care, mortality rates of burn patients have reduced. As a result, with more patients surviving acute burn, there is a paradigm shift of research towards assessment of functional outcomes and quality of life of the burn survivors. As there is lack of research regarding the functional outcome of the Meek technique, this study was designed to examine the long term functional outcome of the Meek technique and SSG in burns.

    METHOD: A cross-sectional study was conducted in Hospital Universiti Sains Malaysia to assess patients with burns between 10 to 40% total body surface area (TBSA) and with at least one year after injury. The Burn Specific Health Score-brief (BSHS-B) was utilized to compare the functional outcome whilst the Vancouver Scar Scale (VSS) was used for comparison on the scar outcome of the two skin grafting techniques.

    RESULTS: Forty three patients (Meek,15; SSG,28) were included. The mean current age (years old) of Meek and SSG was 24.7 (range, 7-75) and 25.9 (range, 7-65) respectively. The mean TBSA (%) of the Meek group was 26.7 (range, 13-40) while that of the SSG group was 16.1 (range, 10-32). A simplified domain structure was used for the BSHS-B questionnaire. The work and sexuality subscale were analyzed separately due to missing data. There mean scores of affect and relations was higher in Meek compared to SSG (Meek, 3.86; SSG, 3.75; p > 0.05). Function domain was also better in Meek compared to SSG (Meek, 3.88; SSG, 3.73; p > 0.05). The Meek group displayed superior scar outcome compared to SSG as evidenced by the statistically significant difference in score for the pigmentation, pliability, height and total VSS score.

    CONCLUSION: The Meek group showed more favorable BSHS-B scores compared to the SSG group. The scar outcome of the Meek technique is significantly superior to SSG. Therefore, the Meek technique is superior in the management of burns because the long term scar and functional outcome of this technique is better compared to conventional SSG.

    Matched MeSH terms: Skin Transplantation/methods*
  19. Wong LP
    Clin Transplant, 2011 Jan-Feb;25(1):E22-31.
    PMID: 20718827 DOI: 10.1111/j.1399-0012.2010.01312.x
    Malaysia's organ and tissue donation rates are among the lowest in the world. The study aims to explore the knowledge, attitudes, practices and behaviors regarding deceased organ donation and transplantation in the diverse ethnic communities in the state of Selangor, Malaysia.
    Matched MeSH terms: Organ Transplantation*
  20. Hamzah S, Teh LK, Siew JS, Ahmad G, Wong HS, Zakaria ZA, et al.
    Can J Physiol Pharmacol, 2014 Jan;92(1):50-7.
    PMID: 24383873 DOI: 10.1139/cjpp-2013-0128
    Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.
    Matched MeSH terms: Kidney Transplantation/rehabilitation*
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