Displaying publications 21 - 40 of 43 in total

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  1. Eng HS, Mohamed Z, Calne R, Lang CC, Mohd MA, Seet WT, et al.
    Kidney Int, 2006 May;69(10):1858-64.
    PMID: 16612333
    Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.
    Matched MeSH terms: Cyclosporine/pharmacokinetics*; Cyclosporine/pharmacology
  2. Keck CM
    Int J Pharm, 2010 May 5;390(1):3-12.
    PMID: 19733647 DOI: 10.1016/j.ijpharm.2009.08.042
    The influence of optical parameters, additional techniques (e.g. PIDS technology) and the importance of light microscopy were investigated by comparing laser diffraction data obtained via the conventional method and an optimized analysis method. Also the influence of a possible dissolution of nanocrystals during a measurement on the size result obtained was assessed in this study. The results reveal that dissolution occurs if unsaturated medium or microparticle saturated medium is used for the measurements. The dissolution is erratic and the results are not reproducible. Dissolution can be overcome by saturating the measuring medium prior to the measurement. If nanocrystals are analysed the dispersion medium should be saturated with the nanocrystals, because the solubility is higher than for coarse micro-sized drug material. The importance of using the optimized analysis method was proven by analysing 40 different nanosuspensions via the conventional versus the optimized sizing method. There was no large difference in the results obtained for the 40 nanosuspensions using the conventional method. This would have led to the conclusion, that all the 40 formulations investigated are physically stable. However, the analysis via the optimized method revealed that from 40 formulations investigated only four were physically stable. In conclusion an optimized analysis saves time and money and avoids misleading developments, because discrimination between "stable" and "unstable" can be done reliably at a very early stage of the development.
    Matched MeSH terms: Cyclosporine/administration & dosage; Cyclosporine/chemistry
  3. Chow SK
    Asia Pac Allergy, 2012 Apr;2(2):149-60.
    PMID: 22701866 DOI: 10.5415/apallergy.2012.2.2.149
    This guideline is a result of a consensus reached during the 19th Asian-Australasian Regional Conference of Dermatology by the Asian Academy of Dermatology and Venereology Study Group in collaboration with the League of Asian Dermatological Societies in 2010. Urticaria has a profound impact on the quality of life in Asia and the need for effective treatment is required. In line with the EAACI/GA(2)LEN/EDF/WAO guideline for the management of urticaria the recommended first-line treatment is new generation, non-sedating H1-antihistamines. If standard dosing is ineffective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of non-sedating H1-antihistamines, it is recommended that therapies such as H2-antihistamine, leukotriene antagonist, and cyclosporine A should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are the most important considerations.
    Matched MeSH terms: Cyclosporine
  4. Ismail AS, Taharin R, Embong Z
    Int Med Case Rep J, 2012;5:33-7.
    PMID: 23754920 DOI: 10.2147/IMCRJ.S29960
    Here, a case of vision threatening blepharokeratoconjunctivitis that responded well to topical cyclosporin is reported. A 9-year-old Malay girl with a history of bilateral blepharokeratoconjunctivitis was regularly treated with lid scrubbing using diluted baby shampoo, fusidic acid gel, and topical steroids as well as an intermittent course of oral doxycycline for the past year. She developed acute onset bilateral eye redness associated with poor vision in her right eye. Both eyes showed marked diffuse hyperemic conjunctiva with corneal vascularization. The presence of corneal vascularization obscured the visual axis in the right eye. The condition did not improve with regular intensive lid hygiene using diluted baby shampoo, fusidic acid gel, and topical steroids. She was started on topical cyclosporin A 0.5% every 6 hours. There was a dramatic regression of corneal vascularization after 3 days on topical cyclosporin, with marked improvement in visual acuity. This is a single case in which cyclosporin improved the status of the ocular surface. A large cohort study is required to justify its effectiveness in treating blepharokeratoconjunctivitis and to test its potential as an alternative immunosuppressive agent in comparison to conventional corticosteroids.
    Matched MeSH terms: Cyclosporine
  5. Meera Kuppusamy, Tarita Taib
    We report a case of a 13-year-old boy who presented with acute onset of generalised erythematous skin and patchy areas of pustules for one week duration. He was well until one month ago when he started having small scaly plaques on his scalp and extensors of his legs. During the acute episode, he also had joint pain and bilateral conjunctivitis. Skin biopsy confirmed pustular psoriasis. He developed leucocytosis and transaminitis during the acute phase of the pustular eruption while on acitretin, which was then withheld. Subsequently, treatment with oral cyclosporine induced remission of his skin and joint disease. The case is hereby reported because of rarity of presentation and clinical features. Oral cyclosporine should be considered in patients with generalised pustular psoriasis complicated with transaminitis.
    Matched MeSH terms: Cyclosporine
  6. Albela H, Begum S, Leong KF
    J Dermatolog Treat, 2021 Mar 11.
    PMID: 33706651 DOI: 10.1080/09546634.2021.1899111
    Generalized Pustular Psoriasis (GPP) is a rare, severe, life-threatening form of psoriasis and accounts for up to 13.1% of all childhood psoriasis. Common first-line systemic treatment for pediatric patients with GPP include oral acitretin, cyclosporin and methotrexate which have varying efficacy and side effects but multiple interventions are often needed to induce remission and maintain long term control. Recently, the anti IL 17 A monoclonal antibody secukinumab have been shown to be effective in adult patients with GPP; however, there is lack of evidence of its usage in the pediatric population. We describe a case series of 4 pediatric patients with GPP who were treated with off-label use of secukinumab. All four patients had marked clearance and reduction in Generalized Pustular Psoriasis Area & Severity Score (GPPASI) within first 48 h of first injection with subsequent almost complete to complete clearance of skin lesions by 1 month follow up. In conclusion, secukinumab was found to be successful in inducing remission, with rapid clearance and maintaining remission, with or without combination with other systemic agents for pediatric GPP.
    Matched MeSH terms: Cyclosporine
  7. Al-Bayaty, F.H., Al-Tay, B.O., Al-Kushali, S.S., Mahmmod, L.
    ASM Science Journal, 2009;3(1):45-50.
    MyJurnal
    A study was undertaken to estimate the histological changes of gingival enlargement induced by
    Cyclosporin A (CsA) and Nifedipine, separately and in combination. Twelve adult rabbits were divided equally into four main groups. The first group received 10 mg/kg/day Nifedipine, the second received 10 mg/kg/day CsA, and the third received a combination of 10 mg/kg /day Nifedipine and CsA by gastric feeding. The fourth was regarded as a control group. Animals were given the drugs from day 1 of the experiment until day 70. They were then sacrificed for histological purposes. Results showed increase in the thickness of the epithelium with keratosis and acanthosis, and also increased vascularity. Collagen fibres and fibroblasts at different rates in the three histological groups were observed. Significant alveolar bone resorption with increased marrow spaces filled with fatty tissue were found in the CsA group. Non-significant changes in the alveolar bone of the Nifedipine group while subsequent bone resorption and bone deposition were seen in the combination group. These changes could be due to the effect of both drugs. Significant changes in the gingiva and the alveolar bone were shown in the three experimental groups compared with the control group.
    Matched MeSH terms: Cyclosporine
  8. Meera Kuppusamy, Tarita Taib
    MyJurnal
    We report a case of a 13-year-old boy who presented with acute onset of generalised erythematous skin and patchy areas of pustules for one week duration. He was well until one month ago when he started having small scaly plaques on his scalp and extensors of his legs. During the acute episode, he also had joint pain and bilateral conjunctivitis. Skin biopsy confirmed pustular psoriasis. He developed leucocytosis and transaminitis during the acute phase of the pustular eruption while on acitretin, which was then withheld. Subsequently, treatment with oral cyclosporine induced remission of his skin and joint disease. The case is hereby reported because of rarity of presentation and clinical features. Oral cyclosporine should be considered in patients with generalised pustular psoriasis complicated with transaminitis.
    Matched MeSH terms: Cyclosporine
  9. Hamizah R, Norlinah MI, Tan HJ, Soehardy Z, Halim AG, Rohana AG, et al.
    Med J Malaysia, 2006 Dec;61(5):633-5.
    PMID: 17623968 MyJurnal
    A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.
    Matched MeSH terms: Cyclosporine/therapeutic use
  10. Goh BL, Tan SY
    Transplant Proc, 1998 Nov;30(7):3594-5.
    PMID: 9838575
    Matched MeSH terms: Cyclosporine/therapeutic use
  11. Tan YC, Abdul Sattar M, Ahmeda AF, Abdul Karim Khan N, Murugaiyah V, Ahmad A, et al.
    PLoS One, 2020;15(4):e0231472.
    PMID: 32298299 DOI: 10.1371/journal.pone.0231472
    Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.
    Matched MeSH terms: Cyclosporine/toxicity*
  12. Tumian NR, Wong CL
    Taiwan J Obstet Gynecol, 2015 Aug;54(4):432-7.
    PMID: 26384065 DOI: 10.1016/j.tjog.2014.11.023
    Hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by uncontrolled mature histiocyte proliferation, hemophagocytosis, and hypercytokinemia. We describe a previously healthy pregnant patient who presented in the third trimester of pregnancy with HLH.
    Matched MeSH terms: Cyclosporine/administration & dosage
  13. Wong WF, Looi CY, Kon S, Movahed E, Funaki T, Chang LY, et al.
    Eur J Immunol, 2014 Mar;44(3):894-904.
    PMID: 24310293 DOI: 10.1002/eji.201343496
    Runx1 transcription factor is a key player in the development and function of T cells. Runx1 transcripts consist of two closely related isoforms (proximal and distal Runx1) whose expressions are regulated by different promoters. Which Runx1 isoform is expressed appears to be tightly regulated. The regulatory mechanism for differential transcription is, however, not fully understood. In this study, we investigated the regulation of the proximal Runx1 promoter in T cells. We showed that proximal Runx1 was expressed at a low level in naïve T cells from C57BL/6 mice, but its expression was remarkably induced upon T-cell activation. In the promoter of proximal Runx1, a highly conserved region was identified which spans from -412 to the transcription start site and harbors a NFAT binding site. In a luciferase reporter assay, this region was found to be responsive to T-cell activation through Lck and calcineurin pathways. Mutagenesis studies and chromatin immunoprecipitation assay indicated that the NFAT site was essential for NFAT binding and transactivation of the proximal Runx1 promoter. Furthermore, TCR signaling-induced expression of proximal Runx1 was blocked by treatment of cells with cyclosporin A. Together, these results demonstrate that the calcineurin-NFAT pathway regulates proximal Runx1 transcription upon TCR stimulation.
    Matched MeSH terms: Cyclosporine/pharmacology
  14. Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE
    Eur J Drug Metab Pharmacokinet, 2017 Dec;42(6):993-1004.
    PMID: 28536776 DOI: 10.1007/s13318-017-0420-3
    BACKGROUND AND OBJECTIVE: Mycophenolic acid (MPA) provides effective treatment for lupus nephritis patients. Owing to its large pharmacokinetic variability, it is questionable whether standard fixed dose therapy can achieve optimal MPA exposure. The aim of this study was to develop a population pharmacokinetic model of MPA and its metabolite, 7-O-MPA-β-glucuronide (MPAG), to identify important covariate influences and better predict patient dosing requirements.
    METHODS: MPA and MPAG concentration-time profiles were collected from 25 patients receiving mycophenolate mofetil (MMF) with or without cyclosporine (CsA) co-therapy. Samples were collected pre-dose and at 1, 2, 4, 6 and 8 h post-dose on one or two occasions.
    RESULTS: A total of 225 and 226 concentration-time measurements of MPA and MPAG, respectively, were used to develop the model, utilizing NONMEM® software. A two-compartment model with first-order absorption and elimination for MPA and a one-compartment model with first-order elimination and enterohepatic circulation (EHC) for MPAG best described the data. Apparent clearance of MPAG (CL/F MPAG) significantly decreased with reducing renal function and extent of EHC was reduced with concomitant CsA use. Simulations using the final model showed that a 70-kg subject with a creatinine clearance of 90 mL/min receiving concomitant CsA would require 1.25 g of MMF twice daily while a similar subject who did not receive concomitant CsA would require 0.75 g twice daily to achieve a MPA area under the concentration-time curve from 0 to 12 h (AUC0-12) of 45 mg·h/L.
    CONCLUSION: A 'tiered' dosing approach considering patient renal function and CsA co-therapy, rather than a 'one dose fits all' approach, would help individualize MMF therapy in adult lupus nephritis patients to ensure more patients have optimal MPA exposure.
    Study site: Nephrology and Systemic Lupus Erythematosus (SLE) Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Cyclosporine/pharmacology
  15. Choong, Yi Fong, Chaw, Su Hlaing, Aye, Aye Mya Min, Chee, Geap Tay, Lai, Choo Ong, Hany Ariffin
    Neurology Asia, 2015;20(3):275-281.
    MyJurnal
    Background & Objective: Posterior reversible encephalopathy syndrome (PRES) is associated with
    immunosuppressive agents used in children with haemato-oncological diseases. There are no reports
    to date from the South Asia and South East Asia region. We report a Malaysian tertiary centre case
    series of children with haemato-oncological disease who developed PRES. Methods: Retrospective
    study of children seen with haemato-oncology diseases seen at the University Malaya Medical Centre
    Kuala Lumpur who developed PRES from 2011 – 2013. Clinical details were obtained from medical
    records and brain neuroimaging was reviewed. Results: Five patients met the inclusion criteria. All
    5 patients had significant hypertension acutely or subacutely prior to neurology presentation. Four
    presented with acute seizures and the remainder 1 presented with encephalopathy.Three patients
    were on chemotherapy, 1 had renal impairment and 1 had prior immunosupression for bone marrow
    transplantation. A full recovery was seen in 4 patients and 1 patient had mild residual quadriplegia.
    Conclusion: Our case series expands the clinico-radiological spectrum of PRES in children with
    underlying haemato-oncological disorders. It is the first to show that prior cyclosporin intake as long
    as 2 months is a potential risk factor for PRES. Clinicians need to be vigilant for development of
    PRES and closely monitor the blood pressure in these children who are receiving or recently had
    immunosuppressive drugs and present with acute neurological symptoms.
    Matched MeSH terms: Cyclosporine
  16. Hor SM, Norshamsiah md, Mushawiahti M, Hazlita MI
    MyJurnal
    A 23-year-old lady presented with both eye progressive painless blurring of vision for two weeks in 2011. Prior to that she had malar rash, hair loss, photosensitivity and bilateral leg swelling. Ocular examination showed that visual acuity on the right was 6/60 and on the left was 6/24. Both optic disc were swollen with extensive peripapillary cotton wool spot (CWS), flame shape haemorrhages, dilated and tortuous vessels with macular oedema. Systemic examination revealed blood pressure of 176/111 mmHg, malar rash and alopecia. Diagnosis of grade 4 hypertensive retinopathy secondary to SLE was made. The diagnosis was confirmed by positive ANA/ dsDNA, low C3/ C4 and renal biopsy showed lupus nephritis. She was treated with oral prednisolone, hydroxychloroquine and cyclosporin A. Throughout the monitoring for hydroxychloroquine toxicity, vision over both eyes were 6/9, but serial visual fields showed non-progressive left superior and inferior scotoma while right eye showed inferior scotoma. The intraocular pressure was normal with pink optic disc and cup disc ratio of 0.3. Optical coherence tomography (OCT) showed temporal and nasal retinal nerve fiber layer thinning bilaterally. However, macula OCT, fundus fluorescein angiography and autofluorescence were normal. The visual field defect was concluded secondary to CWS indicating microinfarction of the retinal nerve fiber secondary to previous hypertensive retinopathy. Non-progressive visual field defects may occur after the appearance of CWS in hypertensive retinopathy and it should not be overlooked when diagnosing glaucoma or hydroxychloroquine toxicity.
    Matched MeSH terms: Cyclosporine
  17. Lau BW, Lim DZ, Capon F, Barker JN, Choon SE
    Int J Dermatol, 2017 Apr;56(4):392-399.
    PMID: 28194751 DOI: 10.1111/ijd.13489
    BACKGROUND: Limited information exists regarding juvenile generalized pustular psoriasis (GPP). We aim to determine the clinical profile and outcome of Malaysians with juvenile GPP.

    METHODS: Review of hospital case notes on patients with juvenile GPP.

    RESULTS: Twenty-seven patients with juvenile GPP were identified. Female to male ratio was 1.4:1. The median age at onset of GPP was 6.5 years. Ten patients had prior psoriasis with a median pre-pustular duration of 2.7 years. Onset of GPP was earlier in patients without prior psoriasis (5.1 years vs. 12.0 years, P = 0.002). Precipitating factors identified included stress, upper respiratory tract infection, systemic steroid use, vaccination, and pregnancy. A positive family history of psoriasis and GPP was present in six and one patient(s), respectively. Twenty-one patients had acute, five annular, and one localized variant of GPP. Arthritis was present in 22.2%. Fever, leukocytosis, and transaminitis were mainly seen in patients with acute GPP at 80.9, 72.2, and 11.1%, respectively. Among 20 patients screened, eight carry IL36RN variants and one has CARD14 mutation. IL36RN-positive patients have more severe disease characterized by early onset, low prevalence of prior plaque psoriasis, high prevalence of systemic inflammation, and need for continuous long-term systemic therapy. Acitretin and cyclosporine were effective in aborting acute GPP in 100% of 16 and 66.7% of six patients treated, respectively. However, relapses were common. Only three of the 17 patients whose initial acute GPP was controlled with systemic agents were successfully weaned off treatment.

    CONCLUSIONS: Juvenile GPP is a chronic recalcitrant disease. IL36RN-positive patients have more severe disease.

    Matched MeSH terms: Cyclosporine
  18. Chia TY, Sattar MA, Abdulla MH, Rathore HA, Ahmad Fu, Kaur G, et al.
    Ren Fail, 2013 Aug;35(7):978-88.
    PMID: 23822648 DOI: 10.3109/0886022X.2013.809563
    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p 
    Matched MeSH terms: Cyclosporine/pharmacology*
  19. Chong FW, Chakravarthi S, Nagaraja HS, Thanikachalam PM, Lee N
    Malays J Pathol, 2009 Jun;31(1):35-43.
    PMID: 19694312
    Cyclosporine A (CsA), a calcineurin inhibitor produced by the fungi Trichoderma polysporum and Cylindrocarpon lucidum, is an immunosuppressant prescribed in organ transplants to prevent rejection. Its adverse effect on renal dysfunction has limited its use in a clinical setting. Apigenin (4',5',7'-Trihydroxyflavone), a herbal extract, with anti-inflammatory and anti-tumour properties, has been investigated for properties to reverse this adverse effect. This research was conducted to establish a standard protocol for immunohistochemical estimation of Transforming Growth Factor beta (TGF-beta) expression, as an indicator of Cyclosporine A induced damage, and to observe whether apoptotic index and TGF-beta expression can be used to assess effects of Apigenin on CsA induced renal dysfunction. Six groups of 5 male Sprague-Dawley albino rats each were dosed once daily for 21 days, as follows: (1) negative control--oral corn oil, (2) positive control--Cyclosporine A (25 mg/kg), (3) Group 3--Apigenin (20 mg/kg), (4) Group 4--Cyclosporine A (25 mg/kg) +Apigenin (10 mg/kg), (5) Group 5--Cyclosporine A (25 mg/kg) +Apigenin (15 mg/kg) and (6) Group 6--Cyclosporine A (25 mg/kg) +Apigenin (20 mg/kg). Cyclosporine A was administered intra-peritoneally while Apigenin was given orally. The rat kidneys were harvested and examined microscopically to assess the apoptotic index, and stained by immunohistochemistry for multifunctioning polypeptide TGF-beta expression. A high apoptotic index and TGF-beta intensity was observed in the Cyclosporine A group. Apigenin significantly reduced the both apoptotic index and TGF-beta intensity. The apoptotic index correlated with TGF-beta intensity, especially in glomeruli. This study indicates that Cyclosporine A can enhance the TGF-beta expression in rat kidney, signifying accelerated apoptosis. TGF-beta and apoptotic index may be used to assess Apigenin and its effect on Cyclosporine A induced renal damage.
    Matched MeSH terms: Cyclosporine/toxicity*
  20. Lee WS, Lum SH, Lim CB, Chong SY, Khoh KM, Ng RT, et al.
    Hepatol Int, 2015 Apr;9(2):292-302.
    PMID: 25788179 DOI: 10.1007/s12072-014-9558-0
    BACKGROUND: Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population.

    METHODS: Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia.

    RESULTS: At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012].

    CONCLUSIONS: Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.
    Matched MeSH terms: Cyclosporine/therapeutic use
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