Potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus

PubMed Central

Ha, Dong-Ho; Pathak, Shiva; Yong, Chul Soon; Kim, Jong Oh; Jeong, Jee-Heon; Park, Jun-Beom

2016-01-01

The aim of the present study is to evaluate the potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus. Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres were prepared using electrospraying technique. In vitro release study of tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres was performed in phosphate-buffered saline (pH 7.4). Gingiva-derived stem cells were isolated and incubated with tacrolimus or tacrolimus-loaded microspheres. Release study of the microspheres revealed prolonged release profiles of tacrolimus without any significant initial burst release. The microsphere itself did not affect the morphology of the mesenchymal stem cells, and cell morphology was retained after incubation with microspheres loaded with tacrolimus at 1 μg/mL to 10 μg/mL. Cultures grown in the presence of microspheres loaded with tacrolimus at 1 μg/mL showed the highest mineralization. Alkaline phosphatase activity increased with an increase in incubation time. The highest expression of pSmad1/5 was achieved in the group receiving tacrolimus 0.1 μg/mL every third day, and the highest expression of osteocalcin was achieved in the group receiving 1 μg/mL every third day. Biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization. Microspheres loaded with tacrolimus may be applied for increased osteoblastic differentiation. PMID:27721434

Effects of traditional chinese medicine Wuzhi capsule on pharmacokinetics of tacrolimus in rats.

PubMed

Wei, Hua; Tao, Xia; Di, Peng; Yang, Yingbo; Li, Jingxian; Qian, Xiaofeng; Feng, Jin; Chen, Wansheng

2013-07-01

Wuzhi capsule (WZC) is a preparation of an ethanol herbal extract of Schisandra sphenanthera (Nan-Wuweizi), with its main active ingredients that include schisandrin, schizandrol B, schisantherin A, schisanhenol, and deoxyschizandrin. WZC and tacrolimus are often coadministered for the treatment of drug-induced hepatitis in organ transplant recipients in China. Recently, it was reported that WZC could significantly increase the blood concentration of tacrolimus. The purpose of this study was to investigate whether and how WZC affects the pharmacokinetics of tacrolimus in rats. Liquid chromatography-tandem mass spectrometry method was used to determine the plasma concentration of tacrolimus. The results showed that WZC increased the mean plasma concentration of tacrolimus. Compared with administration of tacrolimus alone [maximum plasma concentration (C(max)), 18.87 ± 10.29 ng/ml; area under the plasma concentration-time curve from time zero to last sampling time (AUC(0→t)), 40.98 ± 37.07 ng h/ml], a single intragastric administered dose of WZC increased the pharmacokinetic parameters of tacrolimus (C(max), 59.42 ± 30.32 ng/ml; AUC(0→t), 239.71 ± 28.86 ng h/ml) by 5-fold in rat plasma. After pretreatment with WZC for 12 days, there were still significant increases in AUC(0→t) (from 40.98 ± 37.07 to 89.21 ± 26.39 ng h/ml; P < 0.05) and C(max) (from 18.87 ± 10.29 to 43.16 ± 10.61 ng/ml; P < 0.05) of tacrolimus, compared with oral of tacrolimus alone, suggesting that WZC increased the exposure of tacrolimus by one or more mechanisms. The increase in tacrolimus C(max) by WZC was dose-dependent. The effect of WZC on tacrolimus AUC(0→t) also increased with dose, with a maximal effect observed at 450 mg/kg (825.34 ng h/ml). No further increases in tacrolimus AUC(0→t) were observed at WZC dose above 450 mg/kg. It is suggested that, because of the effect of WZC on the pharmacokinetics of tacrolimus, the herb-drug interaction between WZC and tacrolimus

A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients.

PubMed

Bloom, R D; Trofe-Clark, J; Wiland, A; Alloway, R R

2013-01-01

An exploratory, post hoc analysis was performed using data from a prospective, multicenter, open-label, randomized, two-period (14 d per period), two-sequence, crossover, steady-state pharmacokinetic study comparing generic tacrolimus (Sandoz) vs. reference tacrolimus in stable renal transplant patients receiving their pre-study twice-daily dose. Pharmacokinetic parameters were compared in 68 patients according to gender, African American ethnicity, the presence or absence of diabetes, and use of steroids. The ratios of tacrolimus AUC0-12 h , Cmax , and C12 with generic vs. reference tacrolimus were calculated using the geometric mean (GM) of dose-normalized values at days 14 and 28. Mean (SD) tacrolimus dose at baseline was 5.7 (4.2) mg/d. There were no consistent differences in dose-normalized AUC0-12 h , C12 , Cmax, or tmax between the generic and reference preparations within subpopulations. The 90% confidence intervals (CI) for the ratios of dose-normalized AUC0-12 h and C12 with generic vs. reference tacrolimus were within 80-125% for all subpopulations, as were 90% CIs for Cmax other than for females, African Americans, and non-diabetics, which is not unexpected given the wide variability of tacrolimus Cmax and the small subpopulation sizes. These exploratory results suggest that this generic tacrolimus preparation would be expected to offer comparable bioavailability to the reference drug in these patient subpopulations. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability.

PubMed

Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken-Ichi; Sako, Kazuhiro; Hakomori, Tadashi; Higaki, Kazutaka

2017-12-01

We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG). Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG. Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study. We successfully developed the formulation exhibiting a significant reduction in C max , the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy. © 2017 Royal Pharmaceutical Society.

Generic tacrolimus in solid organ transplantation.

PubMed

Taube, D; Jones, G; O'Beirne, J; Wennberg, L; Connor, A; Rasmussen, A; Backman, L

2014-05-01

The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which are similar in quality, safety, and efficacy to their approved innovator drugs. There are data available for three generic brands, tacrolimus (Intas), tacrolimus (PharOS), and tacrolimus (Sandoz). Bioequivalence has been demonstrated for generic tacrolimus (Sandoz) within a narrow therapeutic range to its innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other SOT patients, including lung and heart recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

PubMed

Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

2013-03-01

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Interpreting Tacrolimus Concentrations During Pregnancy and Postpartum

PubMed Central

Hebert, Mary F.; Zheng, Songmao; Hays, Karen; Shen, Danny D.; Davis, Connie L.; Umans, Jason G.; Miodovnik, Menachem; Thummel, Kenneth E.; Easterling, Thomas R.

2012-01-01

Summary Pregnancy following solid organ transplantation, although considered high risk for maternal, fetal and neonatal complications, has been quite successful. Tacrolimus pharmacokinetic changes during pregnancy make interpretation of whole blood trough concentrations particularly challenging. There are multiple factors that can increase the fraction of unbound tacrolimus, including but not limited to low albumin concentration and low RBC count. The clinical titration of dosage to maintain whole blood tacrolimus trough concentrations in the usual therapeutic range can lead to elevated unbound concentrations and possibly toxicity in pregnant women with anemia and hypoalbuminemia. Measurement of plasma or unbound tacrolimus concentrations for pregnant women might better reflect the active form of the drug, though these are technically-challenging and often unavailable in usual clinical practice. Tacrolimus crosses the placenta with in utero exposure being approximately 71% of maternal blood concentrations. The lower fetal blood concentrations are likely due to active efflux transport of tacrolimus from the fetus toward the mother by placental P-glycoprotein. To date, tacrolimus has not been linked to congenital malformations, but can cause reversible nephrotoxicity and hyperkalemia in the newborn. In contrast, very small amounts of tacrolimus are excreted in the breast milk and are unlikely to elicit adverse effects in the nursing infant. PMID:23274970

Topical tacrolimus for atopic dermatitis.

PubMed

Cury Martins, Jade; Martins, Ciro; Aoki, Valeria; Gois, Aecio F T; Ishii, Henrique A; da Silva, Edina M K

2015-07-01

Atopic dermatitis (AD) (or atopic eczema) is a chronic inflammatory skin condition that affects children and adults and has an important impact on quality of life. Topical corticosteroids (TCS) are the first-line therapy for this condition; however, they can be associated with significant adverse effects when used chronically. Tacrolimus ointment (in its 2 manufactured strengths of 0.1% and 0.03%) might be an alternative treatment. Tacrolimus, together with pimecrolimus, are drugs called topical calcineurin inhibitors (TCIs). To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments. We searched the following databases up to 3 June 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 5, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and the Global Resource of Eczema Trials (GREAT database). We searched six trials registers and checked the bibliographies of included studies for further references to relevant trials. We contacted specialists in the field for unpublished data.A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE on 30 July 2013. We also scrutinised the U.S. Food and Drug Administration (FDA) websites for adverse effects information. All randomised controlled trials (RCTs) of participants with moderate to severe atopic dermatitis (both children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments. Two authors independently screened and examined the full text of selected studies for compliance with eligibility criteria, risk of bias, and data extraction. Our three prespecified primary outcomes were physician's assessment, participant's self-assessment of improvement, and adverse effects. Our secondary outcomes included assessment of improvement of the disease by validated or objective measures, such as

Increased bioavailability of tacrolimus after rectal administration in rats.

PubMed

Sakai, Masayuki; Hobara, Norio; Hokama, Nobuo; Kameya, Hiromasa; Ohshiro, Susumu; Sakanashi, Matao; Saitoh, Hiroshi

2004-09-01

The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

A multicenter experience with generic tacrolimus conversion.

PubMed

McDevitt-Potter, Lisa M; Sadaka, Basma; Tichy, Eric M; Rogers, Christin C; Gabardi, Steven

2011-09-27

The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.

Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review.

PubMed

Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

2018-06-01

TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

Overview of extended release tacrolimus in solid organ transplantation

PubMed Central

Patel, Neha; Cook, Abigail; Greenhalgh, Elizabeth; Rech, Megan A; Rusinak, Joshua; Heinrich, Lynley

2016-01-01

Tacrolimus (Prograf©, Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf©, Astagraf XL©) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient’s due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher. PMID:27011912

Overview of extended release tacrolimus in solid organ transplantation.

PubMed

Patel, Neha; Cook, Abigail; Greenhalgh, Elizabeth; Rech, Megan A; Rusinak, Joshua; Heinrich, Lynley

2016-03-24

Tacrolimus (Prograf(©), Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf(©), Astagraf XL(©)) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient's due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher.

Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

PubMed Central

Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G.

2014-01-01

Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement. PMID:24639902

Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization.

PubMed

Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G

2014-01-01

Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

PubMed Central

Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

2013-01-01

Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

The calcineurin inhibitor tacrolimus as a new therapy in severe cherubism.

PubMed

Kadlub, Natacha; Vazquez, Marie-Paule; Galmiche, Louise; L'Herminé, Aurore Coulomb; Dainese, Linda; Ulinski, Tim; Fauroux, Brigitte; Pavlov, Ioana; Badoual, Cécile; Marlin, Sandrine; Deckert, Marcel; Leboulanger, Nicolas; Berdal, Ariane; Descroix, Vianney; Picard, Arnaud; Coudert, Amélie E

2015-05-01

Cherubism is a rare genetic disorder characterized by extensive growth of a bilateral granuloma of the jaws, resulting in facial disfigurement. Cherubism is caused by gain-of-function mutations in the SH3BP2 gene, leading to overactivation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-dependent osteoclastogenesis. Recent findings in human and mouse cherubism have suggested that calcineurin inhibitors might be drug candidates in cherubism medical treatment. A 4-year-old boy with aggressive cherubism was treated with the calcineurin inhibitor tacrolimus for 1 year, and clinical, radiological, and molecular data were obtained. Immunohistologic analysis was performed to compare preoperative and postoperative NFATc1 staining and tartrate resistant acid phosphatase (TRAP) activity. Real-time PCR was performed to analyze the relative expression levels of OPG and RANKL. After tacrolimus therapy, the patient showed significant clinical improvement, including stabilization of jaw size and intraosseous osteogenesis. Immunohistologic analyses on granuloma showed that tacrolimus caused a significant reduction in the number of TRAP-positive osteoclasts and NFATc1 nuclear staining in multinucleated giant cells. Molecular analysis showed that tacrolimus treatment also resulted in increased OPG expression. We present the first case of effective medical therapy in cherubism. Tacrolimus enhanced bone formation by stimulating osteogenesis and inhibiting osteoclastogenesis. © 2014 American Society for Bone and Mineral Research.

Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review

PubMed Central

Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

2018-01-01

Abstract Rationale: TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Patient concerns: Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. Diagnoses: In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients’ laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. Interventions and outcomes: In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. Lessons: This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome. PMID:29879072

Tacrolimus Topical

MedlinePlus

... ointment is used to treat the symptoms of eczema (atopic dermatitis; a skin disease that causes the ... use other medications for their condition or whose eczema has not responded to another medication. Tacrolimus is ...

Population pharmacokinetics of tacrolimus in paediatric systemic lupus erythematosus based on real-world study.

PubMed

Wang, D-D; Lu, J-M; Li, Q; Li, Z-P

2018-05-15

Different population pharmacokinetics (PPK) models of tacrolimus have been established in various populations. However, the tacrolimus PPK model in paediatric systemic lupus erythematosus (PSLE) is still undefined. This study aimed to establish the tacrolimus PPK model in Chinese PSLE. A total of nineteen Chinese patients with PSLE from real-world study were characterized with nonlinear mixed-effects modelling (NONMEM). The impact of demographic features, biological characteristics, and concomitant medications was evaluated. Model validation was assessed by bootstrap and prediction-corrected visual predictive check (VPC). A one-compartment model with first-order absorption and elimination was determined to be the most suitable model in PSLE. The typical values of apparent oral clearance (CL/F) and the apparent volume of distribution (V/F) in the final model were 2.05 L/h and 309 L, respectively. Methylprednisolone and simvastatin were included as significant. The first validated tacrolimus PPK model in patients with PSLE is presented. © 2018 John Wiley & Sons Ltd.

Safety and efficacy of conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation: randomized controlled trial in adult renal transplantation.

PubMed

Oh, Chang-Kwon; Huh, Kyu Ha; Lee, Jong Soo; Cho, Hong Rae; Kim, Yu Seun

2014-09-01

The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.

Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients.

PubMed

Kim, In-Wha; Moon, Yoo Jin; Ji, Eunhee; Kim, Kyung Im; Han, Nayoung; Kim, Sung Ju; Shin, Wan Gyoon; Ha, Jongwon; Yoon, Jeong-Hyun; Lee, Hye Suk; Oh, Jung Mi

2012-05-01

The purpose of this study was to characterize the effects of clinical and genetic variables on the pharmacokinetics and complications of tacrolimus during the first year after kidney transplantation. One hundred and thirty-two Korean kidney recipients who received tacrolimus were genotyped for ABCB1 (exons 12, 21, and 26) and CYP3A5 (intron 3). Tacrolimus trough levels, dose, or dose-adjusted trough levels and complications were compared among patients during the early stage (3, 7, 14, 30, and 90 days) and up to 1 year according to the genotypes. A donor source-adjusted linear mixed model with multilevel analysis adjusting for age, body weight, hematocrit, and serum creatinine showed that CYP3A5 genotype is associated with dose-adjusted level of tacrolimus (p < 0.001). The influence of ABCB1 polymorphisms on the pharmacokinetics or complications of tacrolimus was less certain in our study. The incidence of acute rejections was significantly higher in recipients of cadaveric donor kidney (p < 0.05). A generalized estimating equation model analysis showed that alopecia and hyperlipidemia were associated with dose-adjusted level of tacrolimus (p < 0.001). Genotype of CYP3A5 variants along with significant clinical covariates may be useful in individualizing tacrolimus therapy in kidney transplantation patients.

Nationwide conversion to generic tacrolimus in pediatric kidney transplant recipients.

PubMed

Naicker, Derisha; Reed, Peter W; Ronaldson, Jane; Kara, Tonya; Wong, William; Prestidge, Chanel

2017-11-01

Bioequivalence between Tacrolimus Prograf® and generic tacrolimus formulations has been demonstrated in adult populations, however clinical experience and safety data regarding generic tacrolimus in pediatric transplant recipients is limited. This study aimed to evaluate conversion from Tacrolimus Prograf® to Sandoz® in pediatric renal transplant recipients nationwide. The primary outcome was a change in mean trough tacrolimus concentration. Additionally, changes in tacrolimus intra-patient coefficient of variation (CoV), allograft function, requirement for dose adjustments, and episodes of biopsy-proven rejection were evaluated. Retrospective cohort study in 37 pediatric renal transplant recipients who switched to Tacrolimus Sandoz®. Each patient had three pre-conversion tacrolimus trough and creatinine concentrations within the 4 months prior and three post-conversion concentrations on day 3, 10, and the next subsequent level. Mean pre- and post-conversion tacrolimus trough concentrations and glomerular filtration rate (eGFR) were calculated. Tacrolimus concentration, CoV, and creatinine differences were compared by paired t test. Thirty-seven patients (41% females, age 3-18 years) were included. Average intra-patient difference in trough tacrolimus concentration was 0.05μg/l (95% CI -0.37 to 0.47). Average intra-patient difference in eGFR was -1.20 ml/min/1.73 2 (95% CI -3.53 to 1.13). Three patients had acute rejection during 12 months post-conversion compared to none during 12 months pre-conversion. Pediatric renal transplant recipients can be converted from Tacrolimus Prograf® to Sandoz® with negligible change in trough concentration, dose adjustments, or immediate allograft function. Of concern was the number of acute rejection episodes, however non-adherence contributed to at least one episode and this difference was determined clinically and statistically not significant.

Development of a Simple and Rapid Method to Measure the Free Fraction of Tacrolimus in Plasma Using Ultrafiltration and LC-MS/MS.

PubMed

Stienstra, Nicolaas A; Sikma, Maaike A; van Dapperen, Anouk L; de Lange, Dylan W; van Maarseveen, Erik M

2016-12-01

Tacrolimus is an immunosuppressant mainly used in the prophylaxis of solid organ transplant rejection. Therapeutic drug monitoring of tacrolimus is essential for avoiding toxicity related to overexposure and transplant rejection from underexposure. Previous studies suggest that unbound tacrolimus concentrations in the plasma may serve as a better predictor of tacrolimus-associated nephrotoxicity and neurotoxicity compared to tacrolimus concentration in whole blood. Monitoring the plasma concentrations of unbound tacrolimus might be of interest in preventing tacrolimus-related toxicity. Therefore, the aim was to develop a method for the measurement of total and unbound tacrolimus concentrations in plasma. The sample preparation for the determination of the plasma concentrations of unbound tacrolimus consisted of an easy-to-use ultrafiltration method followed by solid-phase extraction. To determine the total concentration of tacrolimus in plasma, a simple method based on protein precipitation was developed. The extracts were injected into a Thermo Scientific HyPurity C18 column using gradient elution. The analytes were detected by liquid chromatography-tandem mass spectrometry with positive ionization. The method was validated over a linear range of 1.00-200 ng/L for unbound tacrolimus concentrations in plasma and 100-3200 ng/L for total plasma concentrations. The lower limit of quantification was 1.00 ng/L in ultrafiltrate and 100 ng/L in plasma. The inaccuracy and imprecision for the determination of unbound tacrolimus concentrations in ultrafiltrate and plasma showed a maximum coefficients of variation (CV) of 11.7% and a maximum bias of 3.8%. A rapid and easy method based on ultrafiltration and liquid chromatography-tandem mass spectrometry was established to measure the total and unbound tacrolimus concentrations in plasma. This method can facilitate further investigations on the relationship between plasma concentrations of unbound tacrolimus and clinical

Multi-site analytical evaluation of the Abbott ARCHITECT tacrolimus assay.

PubMed

Wallemacq, Pierre; Goffinet, Jean-Sebastien; O'Morchoe, Susan; Rosiere, Thomas; Maine, Gregory T; Labalette, Myriam; Aimo, Giuseppe; Dickson, Diana; Schmidt, Ed; Schwinzer, Reinhard; Schmid, Rainer W

2009-04-01

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Tacrolimus immunoassay. Proficiency panels and specimens from a population of organ transplant recipients were analyzed in 6 clinical laboratories in Europe and the United States, and the results were compared with other methods. The ARCHITECT assay requires a whole blood specimen pretreatment step with methanol/zinc sulfate to precipitate protein and extract the drug, followed by a 30-minute immunoassay using anti-tacrolimus antibody-coated paramagnetic microparticles and an acridinium-tacrolimus tracer. The assay was free from hematocrit interference in the range 25%-55% and from interference by extremes of cholesterol, triglycerides, bilirubin, total protein, and uric acid. The total percent of coefficient of variations of the assay were 4.9%-7.6% at 3 ng/mL, 2.9%-4.6% at 8.6 ng/mL, and 3.1%-8.2% at 15.5 ng/mL. Limit of detection was < or =0.5 ng/mL and limit of quantification (LOQ) ranged from 0.69 to 1.07 ng/mL across the 6 sites (based on the upper 95% confidence interval concentrations). The 2007 European Consensus Conference on Tacrolimus Optimization recommended the use of assay methods with an LOQ around 1 ng/mL, based upon the need to measure trough tacrolimus blood concentrations precisely down to 3 ng/mL during low-dose tacrolimus regimens. Tacrolimus International Proficiency Testing Scheme samples were measured by the ARCHITECT immunoassay at 5 sites and showed an average bias of -0.28 to +0.85 ng/mL versus IMx Tacrolimus II immunoassay historical values and -0.21 to +0.68 ng/mL versus liquid chromatography/tandem mass spectrometry (LC-MSMS) Tacrolimus historical values. Method comparison studies were performed with the ARCHITECT Tacrolimus immunoassay on patient specimens with the following results: ARCHITECT Tacrolimus assay versus the Abbott IMx Tacrolimus II immunoassay (4 sites) yielded average biases between -0.94 and +0.26 ng/mL; ARCHITECT assay

Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.

PubMed

Borba-Santos, Luana P; Reis de Sá, Leandro F; Ramos, Juliene A; Rodrigues, Anderson M; de Camargo, Zoilo P; Rozental, Sonia; Ferreira-Pereira, Antonio

2017-01-01

Calcineurin inhibitors - such as the clinically used drug tacrolimus - are active against important fungal pathogens, particularly when combined with azoles. However, tacrolimus has not been tested against sporotrichosis, an endemic subcutaneous mycosis with worldwide distribution. Here, we evaluated the activity of tacrolimus and cyclosporine A in vitro - as monotherapy and in combination with itraconazole or fluconazole - against yeasts of Sporothrix brasiliensis and S. schenckii , the main sporotrichosis agents in Brazil. We also analyzed the effect of tacrolimus treatment on intracellular neutral lipid levels, which typically increase after azole treatment. Tacrolimus inhibited the growth of yeasts from S. brasiliensis and S. schenckii reference isolates, with minimum inhibitory concentration (MIC) values (required for ≥50% growth inhibition) of 1 and 2 mg/L, respectively. Importantly, the combination of tacrolimus and azoles exhibited high synergy toward reference Sporothrix isolates. Tacrolimus combined with itraconazole significantly increased neutral lipid accumulation in S. brasiliensis , but not in S. schenckii . Clinical isolates of S. brasiliensis and S. schenckii were more sensitive to tacrolimus as monotherapy than feline-borne isolates, however, synergy between tacrolimus and azoles was only observed for feline-borne isolates. Cyclosporine A was effective against S. brasiliensis and S. schenckii as monotherapy (MIC = 1 mg/L), but exhibited no synergy with itraconazole and fluconazole. We conclude that tacrolimus has promising antifungal activity against sporotrichosis agents, and also increases the activity of the current anti-sporotrichosis therapy (itraconazole and fluconazole) in combination assays against S. brasiliensis feline-borne isolates.

Limited interaction between tacrolimus and P-glycoprotein in the rat small intestine.

PubMed

Saitoh, Hiroshi; Saikachi, Yuko; Kobayashi, Mikako; Yamaguchi, Michiko; Oda, Masako; Yuhki, Yoshimitsu; Achiwa, Kazuhito; Tadano, Koji; Takahashi, Yasushi; Aungst, Bruce J

2006-05-01

The significance of intestinal P-glycoprotein (P-gp) in determining the oral bioavailability of tacrolimus has been still controversial. In this study, we reevaluated the interaction of tacrolimus with P-gp in the rat small intestine, by evaluating its absorption from the rat small intestine and its modulating effect on the absorption of known P-gp substrates (digoxin, methylprednisolone, and vinblastine). Intestinal absorption of tacrolimus itself was as extensive as other P-gp modulators such as cyclosporine and verapamil. While cyclosporine and verapamil significantly increased the absorption of methylprednisolone and vinblastine through potent inhibition of intestinal P-gp, tacrolimus failed to achieve this. When cyclosporine and tacrolimus were intravenously administered to rats, digoxin absorption was significantly increased by cyclosporine but not by tacrolimus. When tacrolimus was coadministered with clotrimazole, a specific CYP3A inhibitor, into the rat small intestine, the area under the curve of tacrolimus blood concentrations increased more than seven-fold compared with that of tacrolimus alone. Our present results strongly suggest that the interaction between tacrolimus and P-gp is limited in the rat small intestine and that extensive metabolism by CYP3A enzymes is more responsible for the low oral bioavailability of tacrolimus. It was considered that the extensive absorption of cyclosporine and verapamil was closely associated with their potent ability to inhibit intestinal P-gp.

Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats.

PubMed

Tamura, Shigeki; Ohike, Atsuo; Ibuki, Rinta; Amidon, Gordon L; Yamashita, Shinji

2002-03-01

The objective of this study is to investigate the role of P-glycoprotein (P-gp), a membrane efflux pump associated with multidrug resistance (MDR) and a known substrate for tacrolimus, in determining the regional intestinal permeability of tacrolimus in rats. Thus, isolated segments of rat jejunum, ileum, or colon were perfused with tacrolimus solutions containing polyethoxylated hydrogenated castor oil 60 surfactant, and with or without verapamil, a P-gp substrate used to reverse the MDR phenotype. The results indicated that the intrinsic permeability of tacrolimus in the jejunum, calculated on the basis of the concentration of non-micellized free tacrolimus, was quite high ( approximately 1.4 x 10(-4) cm/s). The apparent permeability (P(app)) in the jejunum was unaffected by the presence of verapamil; however, the P(app) in the ileum and the colon increased significantly in the presence of verapamil and were similar to the values observed in the jejunum. The results suggest that systemic absorption of tacrolimus from the gastrointestinal tract could be significantly affected by P-gp efflux mechanisms. It is also possible that differences in P-gp function at various intestinal sites in a subject or at a given intestinal site in various subjects could lead to large intra- and interindividual variability in bioavailability of tacrolimus following oral administration. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association .

21 CFR 862.1678 - Tacrolimus test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tacrolimus test system. 862.1678 Section 862.1678 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... quantitatively determine tacrolimus concentrations as an aid in the management of transplant patients receiving...

Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.

PubMed Central

Borba-Santos, Luana P.; Reis de Sá, Leandro F.; Ramos, Juliene A.; Rodrigues, Anderson M.; de Camargo, Zoilo P.; Rozental, Sonia; Ferreira-Pereira, Antonio

2017-01-01

Calcineurin inhibitors – such as the clinically used drug tacrolimus – are active against important fungal pathogens, particularly when combined with azoles. However, tacrolimus has not been tested against sporotrichosis, an endemic subcutaneous mycosis with worldwide distribution. Here, we evaluated the activity of tacrolimus and cyclosporine A in vitro – as monotherapy and in combination with itraconazole or fluconazole – against yeasts of Sporothrix brasiliensis and S. schenckii, the main sporotrichosis agents in Brazil. We also analyzed the effect of tacrolimus treatment on intracellular neutral lipid levels, which typically increase after azole treatment. Tacrolimus inhibited the growth of yeasts from S. brasiliensis and S. schenckii reference isolates, with minimum inhibitory concentration (MIC) values (required for ≥50% growth inhibition) of 1 and 2 mg/L, respectively. Importantly, the combination of tacrolimus and azoles exhibited high synergy toward reference Sporothrix isolates. Tacrolimus combined with itraconazole significantly increased neutral lipid accumulation in S. brasiliensis, but not in S. schenckii. Clinical isolates of S. brasiliensis and S. schenckii were more sensitive to tacrolimus as monotherapy than feline-borne isolates, however, synergy between tacrolimus and azoles was only observed for feline-borne isolates. Cyclosporine A was effective against S. brasiliensis and S. schenckii as monotherapy (MIC = 1 mg/L), but exhibited no synergy with itraconazole and fluconazole. We conclude that tacrolimus has promising antifungal activity against sporotrichosis agents, and also increases the activity of the current anti-sporotrichosis therapy (itraconazole and fluconazole) in combination assays against S. brasiliensis feline-borne isolates. PMID:28966608

Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats.

PubMed

Egashira, Kanoko; Sasaki, Hitoshi; Higuchi, Shun; Ieiri, Ichiro

2012-01-01

Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo.

Trends in the biosynthesis and production of the immunosuppressant tacrolimus (FK506).

PubMed

Barreiro, Carlos; Martínez-Castro, Miriam

2014-01-01

The current off-patent state of tacrolimus (FK506) has opened the hunting season for new generic pharmaceutical formulations of this immunosuppressant. This fact has boosted the scientific and industrial research on tacrolimus for the last 5 years in order to improve its production. The fast discovery of tacrolimus producer strains has generated a huge number of producers, which presents the biosynthetic cluster of FK506 as a high promiscuous genetic region. For the first time, the current state-of-the-art on the tacrolimus biosynthesis, production improvements and drug purification is reviewed. On one hand, all the genes involved in the tacrolimus biosynthesis, in addition to the traditional PKS/NRPS, as well as their regulation are analysed. On the other hand, tacrolimus direct and indirect precursors are reviewed as a straight manner to improve the final yield, which is a current trend in the field. Twenty years of industrial and scientific improvements on tacrolimus production are summarised, whereas future trends are also drafted.

Tacrolimus placental transfer at delivery and neonatal exposure through breast milk.

PubMed

Zheng, Songmao; Easterling, Thomas R; Hays, Karen; Umans, Jason G; Miodovnik, Menachem; Clark, Shannon; Calamia, Justina C; Thummel, Kenneth E; Shen, Danny D; Davis, Connie L; Hebert, Mary F

2013-12-01

The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml(-1)) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml(-1)). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml(-1)) and unbound drug concentrations (0.003 ± 0.001 ng ml(-1)) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema.

PubMed

Jin, Hyunju; Kim, Jeong-Min; Kim, Gun-Wook; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Byung-Soo

2017-06-01

The limited efficacy of topical tacrolimus may result from insufficient frequency of application or amount applied in eczema patients. To investigate the frequency of application and amount of use of topical tacrolimus in patients with various types of eczema. The frequency of application and the applied amount of topical tacrolimus were assessed over two weeks. A total of 200 eczema patients completed this study. The average number of applications per day was 1.75 ± 0.53, despite instructions to apply the topical tacrolimus twice daily. With respect to the frequency of application, 147 (73.5%) and 122 (61.0%) of patients followed the prescription in the first and second weeks, respectively. The average amount applied per 2% of total body surface area (TBSA) was 0.54 ± 0.52 g. Only 53 (26.5%) patients applied between 80 and 120% of expected amount of topical tacrolimus. The frequency of application was self-reported, possibly resulting in limited accuracy. Korean patients with eczema tend to apply topical tacrolimus less frequently and in inappropriate amounts. Clear instructions regarding both the frequency and amount of application are needed to improve the therapeutic outcome with treatment with topical tacrolimus.

Mechanisms of lower maintenance dose of tacrolimus in obese patients.

PubMed

Sawamoto, Kazuki; Huong, Tran T; Sugimoto, Natsumi; Mizutani, Yuka; Sai, Yoshimichi; Miyamoto, Ken-ichi

2014-01-01

A retrospective analysis suggested that blood tacrolimus concentrations were consistent among patients with a body mass index (BMI) that was lean (<18.5), normal (≥ 18.5 and <25) or overweight/obese (≥ 25). The average maintenance dose of tacrolimus in patients with BMI ≥ 25 was significantly lower compared with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed a normal diet were given tacrolimus intravenously or orally. The blood concentrations of tacrolimus in obese rats were significantly higher than those in lean rats after administration via both routes. The moment analysis has suggested that CLtot and Vdss of tacrolimus were not significantly different between lean and obese rats. The bioavailability was higher in obese rats, compared with that in lean rats. The protein expression of Cyp3a2 in the liver was significantly decreased in obese rats, compared with lean rats, while P-gp in the small intestine was also significantly decreased in obese rats. These results suggested that the steady-state trough concentration of tacrolimus in obese patients was well maintained by a relatively low dose compared with that in normal and lean patients, presumably due to increased bioavailability.

The evaluation of potential pharmacokinetic interaction between sirolimus and tacrolimus in healthy volunteers.

PubMed

Tortorici, Michael A; Parks, Virginia; Matschke, Kyle; Korth-Bradley, Joan; Patat, Alain

2013-04-01

Sirolimus and tacrolimus are immunosuppressive compounds that have been used concomitantly in renal transplant patients. Both drugs are dosed orally and have common intestinal and hepatic metabolism and intestinal transport mechanisms. As such, there is a potential for pharmacokinetic drug interaction. A single-dose, open-label, four-period, four-treatment, randomized crossover study was conducted in 27 healthy fasting volunteers. Each subject received a 15-mg oral dose of sirolimus alone, a 10-mg oral dose of tacrolimus alone, sirolimus and tacrolimus administered simultaneously, and tacrolimus administered 4 h before sirolimus. Whole blood and plasma samples for sirolimus and tacrolimus testing were analyzed by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were assessed using noncompartmental methods and were compared using analysis of variance (ANOVA). The geometric mean ratio and 90 % confidence interval (CI) area under the concentration-time curve from time 0 to infinity (AUCinf) for sirolimus administered simultaneously with tacrolimus versus sirolimus alone were 97 and 89-106, respectively, and, when administered in a staggered approach versus sirolimus alone, 107 and 98-117, respectively. The geometric mean ratio (%) and 90 % CI AUCinf for tacrolimus administered simultaneously with sirolimus versus tacrolimus alone were 92 and 82-102, respectively, and, when administered in a staggered approach versus tacrolimus alone, 94 and 84-105, respectively. The results of this study demonstrate a lack of any clinically important drug interaction between sirolimus and tacrolimus in healthy subjects after single-dose administration. However, due to the complexity of anti-rejection immunosuppressive therapy dosing, we suggest that sirolimus and tacrolimus concentration monitoring be performed when changes in dosing are made for either drug regimen.

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

PubMed

Szeto, C-C; Kwan, B C-H; Lai, F M-M; Tam, L-S; Li, E K-M; Chow, K-M; Gang, W; Li, P K-T

2008-11-01

The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling.

PubMed

Størset, Elisabet; Holford, Nick; Hennig, Stefanie; Bergmann, Troels K; Bergan, Stein; Bremer, Sara; Åsberg, Anders; Midtvedt, Karsten; Staatz, Christine E

2014-09-01

The aim was to develop a theory-based population pharmacokinetic model of tacrolimus in adult kidney transplant recipients and to externally evaluate this model and two previous empirical models. Data were obtained from 242 patients with 3100 tacrolimus whole blood concentrations. External evaluation was performed by examining model predictive performance using Bayesian forecasting. Pharmacokinetic disposition parameters were estimated based on tacrolimus plasma concentrations, predicted from whole blood concentrations, haematocrit and literature values for tacrolimus binding to red blood cells. Disposition parameters were allometrically scaled to fat free mass. Tacrolimus whole blood clearance/bioavailability standardized to haematocrit of 45% and fat free mass of 60 kg was estimated to be 16.1 l h−1 [95% CI 12.6, 18.0 l h−1]. Tacrolimus clearance was 30% higher (95% CI 13, 46%) and bioavailability 18% lower (95% CI 2, 29%) in CYP3A5 expressers compared with non-expressers. An Emax model described decreasing tacrolimus bioavailability with increasing prednisolone dose. The theory-based model was superior to the empirical models during external evaluation displaying a median prediction error of −1.2% (95% CI −3.0, 0.1%). Based on simulation, Bayesian forecasting led to 65% (95% CI 62, 68%) of patients achieving a tacrolimus average steady-state concentration within a suggested acceptable range. A theory-based population pharmacokinetic model was superior to two empirical models for prediction of tacrolimus concentrations and seemed suitable for Bayesian prediction of tacrolimus doses early after kidney transplantation.

Beneficial effects of topical tacrolimus on recalcitrant erosions of pemphigus vulgaris.

PubMed

Gach, J E; Ilchyshyn, A

2004-05-01

We report a case of pemphigus vulgaris in which a recalcitrant area of erosion on the cheek cleared only when topical tacrolimus was used in addition to a regime of systemic therapy consisting of cyclophosphamide and prednisolone. Clinical improvement occurred within 10 days of applying topical tacrolimus with healing of erosions and reduction in pain and burning sensations. Topical tacrolimus may inhibit local activation of T lymphocytes through altered expression of cytokines such as interleukin-1, -4 and -5, tumour necrosis factor-alpha and interferon-gamma. Some of these cytokines may also contribute directly to increasing keratinocyte fragility in the aetiology of pemphigus vulgaris erosions. This case illustrates that topical tacrolimus may be a useful adjunct in the management of patients with pemphigus vulgaris.

Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

PubMed

Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

2018-02-20

The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Analysis of tacrolimus and creatinine from a single dried blood spot using liquid chromatography tandem mass spectrometry.

PubMed

Koop, Dennis R; Bleyle, Lisa A; Munar, Myrna; Cherala, Ganesh; Al-Uzri, Amira

2013-05-01

Long term therapeutic drug monitoring and assessment of renal function are required in renal transplant recipients on immunosuppressant therapy such as tacrolimus. Dry blood spots (DBS) have been used successfully in the clinic for many years and offers a convenient, simple and non-invasive method for repeated blood tests. We developed and performed a preliminary validation of a method for the analysis of tacrolimus and creatinine from a single DBS using liquid chromatography-tandem mass spectrometric (LC-MS/MS). Tacrolimus and creatinine were extracted from a 6mm punch with a mixture of methanol/acetonitrile containing ascomycin and deuterated creatinine as internal standards. A 10 μl aliquot of the extract was analyzed directly after dilution for creatinine with normal phase high performance liquid chromatography and multiple reaction monitoring. The remainder of the extract was processed and analyzed for tacrolimus. The lower limit of quantification for tacrolimus was 1 ng/ml with accuracy of 0.34% bias and precision (CV) of 11.1%. The precision ranged from 1.33% to 7.68% and accuracy from -4.44% to 11.6% bias for the intra- and inter-day analysis. The lower limit of quantification of creatinine was 0.01 mg/dL with precision of 7.94%. Accuracy was based on recovery of additional creatinine spiked into whole blood samples and ranged from -2.45% bias at 5 mg/dL to 3.75% bias at 0.5 mg/dL. Intra- and inter-day precision was from 3.48 to 4.11%. The assay was further validated with DBS prepared from pediatric renal transplant recipients. There was excellent correlation between the levels of tacrolimus and creatinine obtained from the clinical laboratory and the DBS method developed. After additional validation, this assay may have a significant impact on compliance with medication intake as well as potentially lowering the cost associated with intravenous blood draws in clinical laboratories. Copyright © 2013 Elsevier B.V. All rights reserved.

Efficacy of tacrolimus/mycophenolate mofetil as acute graft-versus-host disease prophylaxis and the impact of subtherapeutic tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation.

PubMed

Offer, Katharine; Kolb, Michelle; Jin, Zhezhen; Bhatia, Monica; Kung, Andrew L; George, Diane; Garvin, James H; Robinson, Chalitha; Sosna, Jean; Karamehmet, Esra; Satwani, Prakash

2015-03-01

Only a few studies in children have evaluated the efficacy of prophylactic regimens using tacrolimus on acute graft-versus-host disease (aGVHD). As a result, optimal tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation (alloHCT) are not well defined. We measured the association between subtherapeutic levels (<10 ng/mL) during weeks 1 to 4 after alloHCT and the cumulative incidence of grades II to IV aGVHD in children. Additionally, we identified optimal lower cutoff levels for tacrolimus. Sixty patients (median age, 8 years) received tacrolimus/mycophenolate mofetil between March 2003 and September 2012. Twenty-three had a malignant disease and 37 nonmalignant disorders. The stem cell source included peripheral blood stem cells (n = 12) and bone marrow or cord blood (n = 48). Conditioning regimen varied. Specifically, 38.3% received a myeloablative regimen, 36.7% receiving a reduced-toxicity regimen, and 25% receiving a reduced-intensity regimen. Tacrolimus was initiated at .03 mg/kg/day via continuous i.v. infusion or .12 mg/kg/day orally. The dose was adjusted to maintain daily steady state concentrations within a range of 10 to 20 ng/mL. The overall incidence of grades II to IV aGVHD was 33.3%. On multivariate analysis, a mean tacrolimus level < 10 ng/mL during week 3 (P = .042; 95% confidence interval, 1.051 to 14.28) was significantly associated with increased incidence of grades II to IV aGVHD. Using weekly receiver operator curves, the optimal lower cutoff for tacrolimus levels was 10 to 11.2 ng/mL. Further prospective studies are warranted to study the incidence of aGVHD comparing the conventional tacrolimus levels of 5 to 15 versus 10 to 15 ng/mL. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Successful treatment of plasma cell cheilitis with topical tacrolimus: report of two cases.

PubMed

Hanami, Yuka; Motoki, Yoshikazu; Yamamoto, Toshiyuki

2011-02-15

Plasma cell cheilitis is an uncommon chronic inflammatory dermatitis that presents with flat to slightly elevated erosive erythematous plaques. It is histologically characterized by plasma cell infiltrates into the mucosa. Other than the lip, genital areas are often involved, which is called plasma cell balanitis or vulvitis. Plasma cell cheilitis is sometimes resistant to conventional topical corticosteroid therapy. Other choices include oral griseofulvin, topical cyclosporine, and intralesional corticosteroid injection, all of which occasionally fail to produce satisfactory results. Recent reports show that topical calcineurin inhibitors are effective for plasma cell cheilitis, balanitis, and vulvitis. However, there are so far only 2 reports of plasma cell cheilitis successfully treated with topical pimecrolimus and tacrolimus. We present herein two cases of plasma cell cheilitis, in which topical tacrolimus showed beneficial effects, suggesting that this immunomodulatory agent is a promising option for plasma cell cheilitis.

Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

PubMed Central

Abdel Jalil, Mariam H; Hawwa, Ahmed F; McKiernan, Patrick J; Shields, Michael D; McElnay, James C

2014-01-01

Aims To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation. Methods The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates. Results The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%. Conclusion Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance. PMID:23738951

Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

PubMed

Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

2016-08-01

Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Involvement of CYP 3A5 In the Interaction Between Tacrolimus and Nicardipine: A Case Report.

PubMed

Sassi, Mouna B; Gaies, Emna; Salouage, Issam; Trabelsi, Sameh; Lakhal, Mohamed; Klouz, Anis

2015-01-01

Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and secondarily by CYP3A5. Several drugs can modify tacrolimus blood levels as calcium channel blockers (CCBs). Interaction with nicardipine was reported in some cases. A man with a history of malignant arterial hypertension treated with nicardipine, underwent kidney transplantation. After transplantation, he was treated with tacrolimus, mycophenolate mofetil and corticoids. Therapeutic drug monitoring of tacrolimus was done regularly showing a mean trough concentration (C0) of 24.39 ng/mL with some concentrations reaching 52 ng/mL. After changing nicardipine by prazosine, the first tacrolimus C0 after stopping nicardipine was 3.2 ng/mL. Increase of tacrolimus trough concentrations is due to the inhibition of CYP3A4. Very high levels of tacrolimus suggest the non expression of CYP3A5. Thus, because of the possible lack of the secondary pathway, therapeutic drug monitoring of tacrolimus is highly recommended at the introduction of CCBs and also at its stopping.

Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

PubMed

Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

2013-03-01

Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

Unraveling Nutritional Regulation of Tacrolimus Biosynthesis in Streptomyces tsukubaensis through omic Approaches.

PubMed

Ordóñez-Robles, María; Santos-Beneit, Fernando; Martín, Juan F

2018-05-01

Streptomyces tsukubaensis stands out among actinomycetes by its ability to produce the immunosuppressant tacrolimus. Discovered about 30 years ago, this macrolide is widely used as immunosuppressant in current clinics. Other potential applications for the treatment of cancer and as neuroprotective agent have been proposed in the last years. In this review we introduce the discovery of S. tsukubaensis and tacrolimus, its biosynthetic pathway and gene cluster ( fkb ) regulation. We have focused this work on the omic studies performed in this species in order to understand tacrolimus production. Transcriptomics, proteomics and metabolomics have improved our knowledge about the fkb transcriptional regulation and have given important clues about nutritional regulation of tacrolimus production that can be applied to improve production yields. Finally, we address some points of S. tsukubaensis biology that deserve more attention.

Distinct effects of omeprazole and rabeprazole on the tacrolimus blood concentration in a kidney transplant recipient.

PubMed

Takahashi, Kazushige; Yano, Ikuko; Fukuhara, Yuga; Katsura, Toshiya; Takahashi, Takeshi; Ito, Noriyuki; Yamamoto, Shingo; Ogawa, Osamu; Inui, Ken-ichi

2007-12-01

Proton-pump inhibitors (PPIs, e.g. omeprazole and rabeprazole) are often administered to transplant patients as a treatment or prophylaxis for ulcers after surgery. Since tacrolimus and PPIs share the CYP3A4 system for metabolism, pharmacokinetic interactions are anticipated when they are administered simultaneously. We present a Japanese male patient who underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. The concentration/dose (C/D) ratio for tacrolimus was markedly higher during the period of treatment with omeprazole than ranitidine or rabeprazole. The results of liver functional tests were within the normal range during the use of these three antacid drugs. Since the higher C/D ratio for tacrolimus when omeprazole was being administered did not result from a decrease in the elimination of tacrolimus due to hepatic dysfunction, drug interaction between omeprazole and tacrolimus was strongly suspected. The present case indicates that rabeprazole can be used safely in place of omeprazole in kidney transplant recipients receiving tacrolimus.

A Low Concentration of Tacrolimus/Semifluorinated Alkane (SFA) Eyedrop Suppresses Intraocular Inflammation in Experimental Models of Uveitis.

PubMed

De Majumdar, S; Subinya, M; Korward, J; Pettigrew, A; Scherer, D; Xu, H

2017-01-01

Corticosteroids remain the mainstay therapy for uveitis, a major cause of blindness in the working age population. However, a substantial number of patients cannot benefit from the therapy due to steroids resistance or intolerance. Tacrolimus has been used to treat refractory uveitis through systemic administration. The aim of this study was to evaluate the therapeutic potential of 0.03% tacrolimus eyedrop in mouse models of uveitis. 0.03% tacrolimus in perfluorobutylpentane (F4H5) (0.03% Tacrolimus/SFA) was formulated using a previously published protocol. Tacrolimus suspended in PBS (0.03% Tacrolimus/PBS) was used as a control. In addition, 0.1% dexamethasone (0.1% DXM) was used as a standard therapy control. Endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) were induced in adult C57BL/6 mice using protocols described previously. Mice were treated with eyedrops three times/day immediately after EIU induction for 48 h or from day 14 to day 25 post-immunization (for EAU). Clinical and histological examinations were conducted at the end of the experiment. Pharmacokinetics study was conducted in mice with and without EIU. At different times after eyedrop treatment, ocular tissues were collected for tacrolimus measurement. The 0.03% Tacrolimus/SFA eyedrop treatment reduced the clinical scores and histological scores of intraocular inflammation in both EIU and EAU to the levels similar to 0.1% DXM eyedrop treatment. The 0.03% Tacrolimus/PBS did not show any suppressive effect in EIU and EAU. Pharmacokinetic studies showed that 15 min after topical administration of 0.03% Tacrolimus/SFA, low levels of tacrolimus were detected in the retina (48 ng/g tissue) and vitreous (2.5 ng/ml) in normal mouse eyes, and the levels were significantly higher in EIU eyes (102 ng/g tissue in the retina and 24 ng/ml in the vitreous). Tacrolimus remained detectable in intraocular tissues of EIU eyes 6 h after topical administration (68 ng/g retinal tissue, 10

Different Influences on Tacrolimus Pharmacokinetics by Coadministrations of Zhi Ke and Zhi Shi in Rats

PubMed Central

Lin, Shiuan-Pey; Wu, Ping-Ping; Hou, Yu-Chi; Tsai, Shang-Yuan; Wang, Meng-Ju; Fang, Shih-Hua; Chao, Pei-Dawn Lee

2011-01-01

Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these two Citrus herbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased the C max and AUC0−t of tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection. PMID:21318106

A single-centre comparison of the clinical outcomes at 6 months of renal transplant recipients administered Adoport® or Prograf® preparations of tacrolimus

PubMed Central

Connor, Andrew; Prowse, Andrew; Newell, Paul; Rowe, Peter A.

2013-01-01

Background The use of generic formulations of immunosuppressive drugs in place of brand name drugs offers considerable cost savings. Brand name tacrolimus (Prograf®) came off patent in April 2008. However, published evidence supporting therapeutic equivalence of generic formulations of tacrolimus in solid organ transplantation is lacking. The South West Transplant Centre switched from administering Prograf® to a generic formulation (Adoport®) for de novo transplant recipients in November 2010. This study sought to compare the clinical outcomes of renal transplant recipients administered Prograf® with those receiving Adoport®. Methods Data regarding patient characteristics and clinical outcomes were collected retrospectively for all patients undergoing renal transplantation at the South West Transplant Centre between 8 November 2009 and 8 November 2011 to whom tacrolimus was prescribed. Results A total of 48 patients received Prograf® and 51 received Adoport®. At 6 months, no statistically significant differences were identified in the rates of patient survival, graft survival, acute allograft rejection, delayed graft function, calcineurin inhibitor toxicity or cytomegalovirus infection occurring within the two groups. Conclusions This is the first study to compare the clinical outcomes of patients receiving Adoport® with those receiving brand name tacrolimus. We report comparable clinical outcomes at 6 months in patients receiving either Prograf® or Adoport® from the time of renal transplantation. These early outcome data therefore support the use of Adoport® in place of Prograf® as a potential cost-saving measure. PMID:27818747

Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation.

PubMed

Calvo, Pier Luigi; Serpe, Loredana; Brunati, Andrea; Nonnato, Antonello; Bongioanni, Daniela; Olio, Dominic Dell'; Pinon, Michele; Ferretti, Carlo; Tandoi, Francesco; Carbonaro, Giulia; Salizzoni, Mauro; Amoroso, Antonio; Romagnoli, Renato; Canaparo, Roberto

2017-06-01

The aim of the present study was to investigate the influence of the cytochrome P450 (CYP) 3A4/5 genotype in paediatric liver transplant recipients and donors, and the contribution of age and gender to tacrolimus disposition on the first day after transplantation. The contribution of the CYP3A4/5 genotype in paediatric liver transplant recipients and donors to the tacrolimus blood trough concentrations (C 0 ) and the tacrolimus concentration/weight-adjusted dose ratio on day 1 was evaluated in 67 liver-transplanted children: 33 boys and 34 girls, mean age 4.5 years. Donor CYP3A5 genotype appears to be significantly associated with tacrolimus disposition on the first day after liver transplantation (P < 0.0002). Other physiological factors, such as recipient age and donor gender may also play a role and lead to significant differences in tacrolimus C 0 and tacrolimus concentration/weight-adjusted dose ratio on day 1. However, according to the general linear model, only recipient age appears to be independently associated with tacrolimus disposition on the first day after liver transplantation (P < 0.03). Indeed, there was a faster tacrolimus metabolism in children under 6 years of age (P < 0.02). Donor CYP3A5 genotype, recipient age and, to a lesser extent, donor gender appear to be associated with tacrolimus disposition on day 1 after transplant. This suggests that increasing the starting tacrolimus doses in paediatric patients under 6 years of age who receive a graft from a male extensive metabolizer may enhance the possibility of their tacrolimus levels reaching the therapeutic range sooner. © 2017 The British Pharmacological Society.

Differences in Peripheral Blood Lymphocytes between Brand-Name and Generic Tacrolimus Used in Stable Liver Transplant Recipients.

PubMed

Kim, Jong Man; Kwon, Choon Hyuck David; Joh, Jae-Won; Sinn, Dong Hyun; Choi, Gyu-Seong; Park, Jae Berm; Kang, Eun-Suk; Lee, Suk-Koo

2017-01-01

In this study, peripheral blood lymphocytes were compared between a brand-name and a generic tacrolimus group in stable liver transplant recipients. Sixteen patients who underwent ABO-compatible living donor liver transplants between 2012 and 2013 and had stable graft function were included in this study. Ten patients received brand-name tacrolimus and 6 patients received generic tacrolimus. CD3, CD4, CD8, γδ, CD4+FoxP3+, and CD3-CD56+ T cells were analyzed in peripheral blood obtained preoperatively and 4, 8, 12, and 24 weeks after liver transplantation. Categorical variables were compared using a χ2 test or Fisher exact test, and continuous variables were compared using the Mann-Whitney U test. Regarding the baseline and perioperative characteristics, there were no statistically significant differences between the 2 groups. Immunosuppression also was not different. Subtype analysis of T-cell populations carried out in parallel showed similar levels of CD3, CD4, CD8, and γδT cells with brand-name tacrolimus and generic tacrolimus in stable liver transplant recipients. However, the levels of CD4+Foxp3+ and CD3-CD56+ T cells were higher in the brand-name tacrolimus group than in the generic tacrolimus group 8 weeks after transplantation (p < 0.05). The level of CD4+Foxp3+ T cells was higher in the brand-name tacrolimus group than in the generic tacrolimus group after transplantation. This finding showed that brand-name tacrolimus could have more potential immunosuppressive activity than generic tacrolimus regarding the contribution of CD4+Foxp3+ T cells to graft tolerance in liver transplant recipients. © 2017 S. Karger AG, Basel.

The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report.

PubMed

Becker, Jürgen C; Houben, Roland; Vetter, Claudia S; Bröcker, Eva B

2006-01-11

Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA) as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema). Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. Oral lichen planus (OLP) was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these pathways had also been altered subsequent to tacrolimus therapy.

The Pittsburgh Randomized Trial of Tacrolimus Compared to Cyclosporine for Hepatic Transplantation

PubMed Central

Fung, John J.; Eliasziw, Michael; Todo, Satoru; Jain, Ashok; Demetris, Anthony J.; McMichael, John P.; Starzl, Thomas E.; Meier, Paul; Donner, Allan

2009-01-01

Background Tacrolimus (formerly FK 506) was first used clinically in 1989 to successfully replace cyclosporine in hepatic transplant recipients who were experiencing intractable rejection or as the baseline drug from the time of operation. After extensive pilot experience, an institutional review board-mandated clinical trial comparing cyclosporine with tacrolimus was performed. Study Design From February 16, 1990 to December 26, 1991, 154 patients were recruited. The competing drugs were combined with equal induction doses of prednisone in both arms of the study for the first 81 patients and with subsequently higher doses of prednisone in the remaining 35 patients who received cyclosporine and were entered into the trial. Drug crossover was permitted for lack of efficacy or adverse events. End points were rejection confirmed by biopsy and treatment failure leading to retransplantation or death. Results Seventy-nine patients were randomized to the tacrolimus arm and 75 to the cyclosporine arm during 1990 and 1991. All patients were available for follow-up throughout the trial, which terminated on May 30, 1995. The mean duration of follow-up was four years. Patients randomized to the tacrolimus arm were less likely to experience acute rejection than were those receiving cyclosporine, with 36.2 percent of the patients receiving tacrolimus and 16.8 percent of the patients receiving cyclosporine showing freedom from rejection at one year (p=0.003, likelihood ratio test). Survival of patients over the course of the study was virtually the same in the two groups. Conclusions Tacrolimus was more effective than cyclosporine in preventing acute rejection. PMID:8696542

Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

PubMed Central

Guerra, Augusto Afonso; Silva, Grazielle Dias; Andrade, Eli Iola Gurgel; Cherchiglia, Mariângela Leal; Costa, Juliana de Oliveira; Almeida, Alessandra Maciel; Acurcio, Francisco de Assis

2015-01-01

OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective. PMID:25741648

Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil.

PubMed

Guerra Júnior, Augusto Afonso; Silva, Grazielle Dias; Andrade, Eli Iola Gurgel; Cherchiglia, Mariângela Leal; Costa, Juliana de Oliveira; Almeida, Alessandra Maciel; Acurcio, Francisco de Assis

2015-01-01

OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. Moreover, regimens containing cyclosporine were more cost-effective [corrected].

De novo use of generic tacrolimus in liver transplantation - a single center experience with one-yr follow-up.

PubMed

Dannhorn, E; Cheung, M; Rodrigues, S; Cooper, H; Thorburn, D; Patch, D; Burroughs, A K; O'Beirne, J

2014-12-01

Use of generic tacrolimus in liver transplantation (LT) could result in cost savings. Generic tacrolimus has been shown to be bioequivalent to innovator tacrolimus in healthy volunteers and renal transplant patients. There are limited data on the de novo use of generic tacrolimus in LT. This study aimed to determine whether the de novo use of generic tacrolimus (Adoport, Sandoz,UK) was associated with differences in outcomes, safety, and cost compared with innovator tacrolimus (Prograf, Astellas, Japan). Patients were studied before and after a programmatic change from de novo IS with Prograf to Adoport. Outcomes, tacrolimus levels, doses, and costs were compared for the first-yr post-LT. Ninety-four patients were studied, 46 Prograf, 48 Adoport. No significant differences in rejection, cytomegalovirus infection, acute kidney injury, sepsis, or graft loss were observed between groups. Tacrolimus costs were significantly reduced with the de novo use of Adoport. Day 14 dose normalized levels in Adoport patients showed significant variation but at the day 30 and one yr, there were no significant differences in the doses or levels of tacrolimus between groups. Adoport is safe and effective compared to Prograf when used de novo in LT patients. Tacrolimus costs were significantly reduced by the use of Adoport. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of Topical Tacrolimus and Topical Pimecrolimus in Four European Countries: A Multicentre Database Cohort Study.

PubMed

Kuiper, Josephina G; van Herk-Sukel, Myrthe P P; Castellsague, Jordi; Pottegård, Anton; Berglind, Ingegärd Anveden; Dedman, Daniel; Gutierrez, Lia; Calingaert, Brian; Hallas, Jesper; Sundström, Anders; Gallagher, Arlene M; Kaye, James A; Pardo, Carolina; Rothman, Kenneth J; Perez-Gutthann, Susana

2018-05-07

Despite the concerns about a potential increased risk of skin cancer and lymphoma with the use of topical tacrolimus and pimecrolimus, no population-based studies have given an overview of the use of these drugs in Europe. To assess the use of topical tacrolimus and pimecrolimus in children and adults in Europe. Multicentre database cohort study comprising data from the Netherlands, Denmark, Sweden and the UK. We analysed users of topical tacrolimus and pimecrolimus starting from the date of first availability (between 2002 and 2003) or start establishment of the prescription database in Sweden (2006) through 2011. Use was assessed separately for children (≤ 18 years) and adults. 32,052 children and 104,902 adults were treated with topical tacrolimus, and 32,125 children and 58,280 adults were treated with topical pimecrolimus. The number of users increased rapidly after first availability, especially for topical tacrolimus. Topical tacrolimus was more frequently used in all countries except Denmark. For both drugs, there was a decrease in users after 2004 in the Netherlands and Denmark and after 2005 in the UK, especially among children. This decrease was largest in Denmark. The decrease in the number of users was temporary for topical tacrolimus, while use remained relatively low for topical pimecrolimus. The number of topical tacrolimus and pimecrolimus users increased rapidly after regulatory approval. A transient reduction in topical tacrolimus use and a persistent reduction in topical pimecrolimus use was seen after 2004 in the Netherlands and Denmark and after 2005 in the UK.

Topical tacrolimus in alopecia areata.

PubMed

Price, Vera H; Willey, Andrea; Chen, Bryan K

2005-01-01

Eleven patients with alopecia areata affecting 10% to 75% of the scalp, average duration 6 years, had no terminal hair growth in response to tacrolimus ointment 0.1% applied twice daily for 24 weeks. Treatment failure may reflect insufficient depth of penetration of the ointment formulation and less than optimal patient selection.

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers.

PubMed

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-11-01

The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. © 2014 The British Pharmacological Society.

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

PubMed Central

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-01-01

Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation.

PubMed

Benítez, C E; Puig-Pey, I; López, M; Martínez-Llordella, M; Lozano, J J; Bohne, F; Londoño, M C; García-Valdecasas, J C; Bruguera, M; Navasa, M; Rimola, A; Sánchez-Fueyo, A

2010-10-01

We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier: NCT00436722. © 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Lactobacillus Fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.

PubMed

Toral, Marta; Romero, Miguel; Rodríguez-Nogales, Alba; Jiménez, Rosario; Robles-Vera, Iñaki; Algieri, Francesca; Chueca-Porcuna, Natalia; Sánchez, Manuel; de la Visitación, Néstor; Olivares, Mónica; García, Federico; Pérez-Vizcaíno, Francisco; Gálvez, Julio; Duarte, Juan

2018-05-30

Our aim was to analyse whether the probiotic Lactobacillus fermentum CECT5716 (LC40) could prevent endothelial dysfunction and hypertension induced by tacrolimus in mice. Tacrolimus increased systolic blood pressure (SBP) and impaired endothelium-dependent relaxation to acetylcholine and these effects were partially prevented by LC40. Endothelial dysfunction induced by tacrolimus was related to both increased NADPH oxidase (NOX2) and uncoupled eNOS driven-superoxide production and Rho-kinase mediated eNOS inhibition. LC40 treatment prevented all the aortic changes induced by tacrolimus. LC40 restored the imbalance between T-helper 17 (Th17)/ regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and spleen. Tacrolimus induced gut dysbiosis, i.e. it decreased microbial diversity, increased Firmicutes/Bacteroidetes ratio and decreased acetate- and butyrate-producing bacteria and these effects were prevented by LC40. Fecal microbiota transplantation from LC40 treated mice to control mice prevented the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus. LC40 treatment prevented hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects were associated with a reduction in vascular oxidative stress, mainly through NOX2 down-regulation and prevention of eNOS-uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cobicistat Significantly Increases Tacrolimus Serum Concentrations in a Renal Transplant Recipient with Human Immunodeficiency Virus Infection.

PubMed

Han, Zhe; Kane, Brenna M; Petty, Lindsay A; Josephson, Michelle A; Sutor, Jozefa; Pursell, Kenneth J

2016-06-01

Cobicistat is a pharmacokinetic booster in several fixed-dose combination products for treatment of human immunodeficiency virus (HIV) infection. As a potent inhibitor of cytochrome P450 (CYP) 3A enzymes, significant drug-drug interactions are expected between cobicistat and medications that are metabolized primarily through the CYP3A pathway, including calcineurin inhibitors (e.g., tacrolimus and cyclosporine). We describe a case of tacrolimus toxicity due to supratherapeutic tacrolimus concentrations when Stribild (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate) was initiated for newly diagnosed HIV infection in a 50-year-old renal transplant recipient who was previously receiving a stable tacrolimus regimen. Drug-drug interaction via CYP3A inhibition was acknowledged, and weekly labs were ordered to allow for close monitoring of renal function and tacrolimus serum concentrations as recommended by Stribild prescribing information. The patient reported headache, insomnia, stomachache, and decreased urine output within 1 week of starting Stribild and was found to have acute kidney injury (serum creatinine [S cr ]concentration increasing from 1.5-2.3 mg/dl) and a serum tacrolimus concentration of 111.2 ng/ml at 1 week follow-up (goal trough level 4-6 ng/ml). Both tacrolimus and Stribild were withheld. In 15 days, the patient's tacrolimus serum concentration returned to goal. In the interim, he required twice/week clinic visits for laboratory assessments and an emergency department visit for management of hyperkalemia (potassium 6.5 mEq/L). Triumeq (abacavir, dolutegravir, and lamivudine) was started about 4 weeks later after S cr returned to baseline, and his tacrolimus serum trough concentrations subsequently remained stable. To our knowledge, this is the first case report describing the extent, significance, and onset of cobicistat and tacrolimus drug-drug interaction in clinical practice. As more fixed-dose combination products

A simple and highly sensitive on-line column extraction liquid chromatography-tandem mass spectrometry method for the determination of protein-unbound tacrolimus in human plasma samples.

PubMed

Bittersohl, Heike; Schniedewind, Björn; Christians, Uwe; Luppa, Peter B

2018-04-27

Therapeutic drug monitoring (TDM) of the immunosuppressive drug tacrolimus is essential to avoid side effects and rejection of the allograft after transplantation. In the blood circulation, tacrolimus is largely located inside erythrocytes or bound to plasma proteins and less than 0.1% is protein-unbound (free). One basic principle of clinical pharmacology is that only free drug is pharmacologically active and monitoring this portion has the potential to better reflect the drug effect than conventional measurements of total tacrolimus in whole blood. To address this, a highly sensitive and straightforward on-line liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, validated and applied to patient plasma samples. The sample preparation included ultracentrifugation and addition of the stable isotope labeled drug analogue D2,13C-tacrolimus, followed by on-line sample extraction and measurement using a Sciex QTRAP ® 6500 in the multiple reaction monitoring mode. Due to very low concentrations of protein-unbound tacrolimus, it was important to develop a highly sensitive, precise and accurate assay. Here, we first report the efficient formation of tacrolimus lithium adduct ions, which greatly increased assay sensitivity. A lower limit of quantification (LLOQ) of 1 pg/mL (10 fg on column) was achieved and the assay was linear between 1 and 200 pg/mL. There was no carry-over detected. The inaccuracy ranged from -9.8 to 7.4% and the greatest imprecision was 7.5%. The matrix factor was found to be smaller than 1.1%. In summary, this method represents a suitable tool to investigate the potential clinical value of free tacrolimus monitoring in organ transplant recipients. Copyright © 2018 Elsevier B.V. All rights reserved.

Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

PubMed

TruneČka, P; Klempnauer, J; Bechstein, W O; Pirenne, J; Friman, S; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Mönch, C; Brown, M; Undre, N; Tisone, G

2015-07-01

DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

PubMed

Liu, Jin-Yu; Song, Ming; Guo, Min; Huang, Feng; Ma, Bing-Jun; Zhu, Lan; Xu, Gang; Li, Juan; You, Ru-Xu

Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

PubMed Central

Shokati, Touraj; Bodenberger, Nicholas; Gadpaille, Holly; Schniedewind, Björn; Vinks, Alexander A.; Jiang, Wenlei; Alloway, Rita R.; Christians, Uwe

2015-01-01

The calcineurin inhibitor tacrolimus is the cornerstone of most immunosuppressive treatment protocols after solid organ transplantation in the United States. Tacrolimus is a narrow therapeutic index drug and as such requires therapeutic drug monitoring and dose adjustment based on its whole blood trough concentrations. To facilitate home therapeutic drug and adherence monitoring, the collection of dried blood spots is an attractive concept. After a finger stick, the patient collects a blood drop on filter paper at home. After the blood is dried, it is mailed to the analytical laboratory where tacrolimus is quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in combination with a simple manual protein precipitation step and online column extraction. For tacrolimus analysis, a 6-mm disc is punched from the saturated center of the blood spot. The blood spot is homogenized using a bullet blender and then proteins are precipitated with methanol/0.2 M ZnSO4 containing the internal standard D2,13C-tacrolimus. After vortexing and centrifugation, 100 µl of supernatant is injected into an online extraction column and washed with 5 ml/min of 0.1 formic acid/acetonitrile (7:3, v:v) for 1 min. Hereafter, the switching valve is activated and the analytes are back-flushed onto the analytical column (and separated using a 0.1% formic acid/acetonitrile gradient). Tacrolimus is quantified in the positive multi reaction mode (MRM) using a tandem mass spectrometer. The assay is linear from 1 to 50 ng/ml. Inter-assay variability (3.6%-6.1%) and accuracy (91.7%-101.6%) as assessed over 20 days meet acceptance criteria. Average extraction recovery is 95.5%. There are no relevant carry-over, matrix interferences and matrix effects. Tacrolimus is stable in dried blood spots at RT and at +4 °C for 1 week. Extracted samples in the autosampler are stable at +4 °C for at least 72 hr. PMID:26575262

Early alteration of kidney function in nonuremic type 1 diabetic islet transplant recipients under tacrolimus-mycophenolate therapy.

PubMed

Gillard, Pieter; Rustandi, Maria; Efendi, Achmad; Lee, Da Hae; Ling, Zhidong; Hilbrands, Robert; Kuypers, Dirk; Mathieu, Chantal; Jacobs-Tulleneers-Thevissen, Daniel; Gorus, Frans; Pipeleers, Daniel; Keymeulen, Bart

2014-08-27

Transplant patients on tacrolimus therapy exhibit a reduced glomerular filtration rate (GFR). The type of graft and immune treatment protocol may influence the extent and reversibility of this side effect. The present single-center study is conducted in 48 nonuremic type 1 diabetic recipients of an intraportal islet-cell graft under maintenance immunosuppression (IS) with tacrolimus and mycophenolate mofetil. Estimated GFR (eGFR) and albuminuria were followed up to 5 years posttransplantation. Mean eGFR values decreased by 19 mL/min/1.73 m after 1 to 2 weeks of IS (P<0.0001) and then remained stable throughout the complete treatment period. The decrease was related to predose trough tacrolimus concentrations or doses and disappeared upon its discontinuation; it was also associated with the presence of albuminuria at the time of transplantation. Tacrolimus treatment resulted in a reduction of albuminuria; its discontinuation restored albuminuria to the initial levels. The use of tacrolimus in our islet-cell transplant protocol caused an initial 20% reduction in eGFR, which was reversible following its discontinuation, at least within the 5-year follow-up period. The associated reduction in albuminuria was also reversible, compatible with a tacrolimus-induced preglomerular vasoconstriction. These observations support further use of our tacrolimus regimen in this patient population.

Ranolazine, tacrolimus, and diltiazem might be a hazardous combination in a transplant patient.

PubMed

Patni, Hitesh; Gitman, Michael; Hazzan, Azzour; Jhaveri, Kenar D

2012-01-01

We report a case of a renal transplant patient who was maintained on tacrolimus and diltiazem therapy and developed tacrolimus toxicity leading to reversible acute kidney injury when started on ranolazine. A 62-year-old Caucasian male status post renal transplant in 2009 (on prednisone and tacrolimus) was evaluated for ischemic heart disease and was initiated on ranolazine 500 mg tablets twice daily, which was later increased to 1000 mg twice daily. After 2 weeks, he developed fatigue, loss of appetite, tremors, and decreased urine output and was admitted to our hospital. His other significant medications included enalapril 2.5 mg and diltiazem 240 mg daily. The patient was awake and alert, but lethargic. He was found to be bradycardic with a heart rate of 42/min. The rest of his physical examination was benign. His electrocardiogram revealed sinus bradycardia. Laboratory studies revealed serum creatinine of 2.4 mg/dL from a baseline of 1.5 mg/dL (stable for the past 2 years). The tacrolimus trough was elevated at 14 ng/mL, which decreased after stopping ranolazine, reaching 7 ng/mL after 3 days, while continuing the same dose of tacrolimus. His creatinine trended downward and reached his baseline of 1.5 mg/dL over the next 2 days. His bradycardia and other symptoms resolved after cessation of ranolazine. He was discharged to follow up, to initiate an alternate agent for ischemic heart disease. Specific pharmacokinetic studies are warranted to study these drug interactions, and tacrolimus levels should be closely monitored in transplant patients who initiate ranolazine treatment.

Tacrolimus treatment of atopic eczema/dermatitis syndrome.

PubMed

Thestrup-Pedersen, Kristian

2003-10-01

Atopic dermatitis is today the most common chronic disease of children in Europe, the US and Japan. The 'golden standard' of therapy is topical glucocorticosteroids and emollients. The steroids have been on the market for four decades, are efficacious, but only advised for short-term treatment due to their risks of side effects. More than 16,000 persons suffering from atopic dermatitis have been enrolled in clinical studies of tacrolimus. One third of patients with moderate to severe atopic dermatitis experience over 90% improvement in their disease over a 12-week treatment period and up to 70% of patients have over 50% improvement. A 1-year treatment leads to more than 90% improvement in 75% of patients. The most pronounced side effect is a burning sensation occurring in up to 60% of patients. Atopic dermatitis is a chronic skin disease leading to a demand for long-term treatment control. Such treatment options have not previously been available--except for emollients which are not efficacious for controlling skin inflammation. Tacrolimus and pimecrolimus are new treatment options, free from the potential side effects of topical steroids, which are known for their efficacy in short-term treatment. The new treatment modalities prevent the eczema from relapsing and at the same time they control active eczema. The future will see a shift towards the long-term use of tacrolimus which is able to control the skin inflammation and, hopefully, shorten the course of the eczema.

A high performance liquid chromatography tandem mass spectrometry for the quantification of tacrolimus in human bile in liver transplant recipients.

PubMed

Tron, Camille; Rayar, Michel; Petitcollin, Antoine; Beaurepaire, Jean-Marie; Cusumano, Caterina; Verdier, Marie-Clémence; Houssel-Debry, Pauline; Camus, Christophe; Boudjema, Karim; Bellissant, Eric; Lemaitre, Florian

2016-12-02

Tacrolimus whole-blood concentrations imperfectly reflect concentrations at the effect site. Tacrolimus concentrations in the transplanted organ could be more relevant to predict rejection events. Because liver biopsy cannot be repeatedly performed after liver transplantation, we suggested measuring tacrolimus in the bile to have a cost-effective and clinically implementable surrogate marker of intra-hepatic tacrolimus concentration. We developed and fully validated a liquid chromatography-tandem mass spectrometry method for the determination of tacrolimus in human bile. Sample purification was achieved using protein precipitation and liquid-liquid extraction with ethyl-acetate. Gradient elution was performed using a C18 analytical column with a 5min run-time. The method was linear from 0.5ng/mL to 20ng/mL. In this concentration range, within-day and between-day precisions as well as overall bias were within ±15%. Matrix effect was fully corrected by the internal standard (ascomycin). The assay was optimized to achieve good selectivity in this complex biological matrix. Tacrolimus was found to be stable in bile stored 6 months at -80°C, after 3 freeze and thaw cycles, 20h at room temperature and 24h in extracts kept at 15°C in the auto-sampler. The method was applied to quantify tacrolimus in bile from liver transplant recipients. It allowed getting preliminary data about tacrolimus excretion profile in bile and showed the lack of correlation between tacrolimus whole blood concentration and tacrolimus liver exposition. This alternative and innovative analytical approach of tacrolimus bio-analysis appears suitable for further studies evaluating relevance of biliary tacrolimus concentration as a new pharmacological marker of immunosuppressive activity. Copyright © 2016 Elsevier B.V. All rights reserved.

The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report.

PubMed

Morita, Mayu; Asoda, Seiji; Tsunoda, Kazuyuki; Soma, Tomoya; Nakagawa, Taneaki; Shirakawa, Masayori; Shoji, Hirofumi; Yagishita, Hisao; Nishikawa, Takeji; Kawana, Hiromasa

2017-04-01

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

PubMed Central

Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

2016-01-01

Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

PubMed Central

Provenzani, Alessio; Santeusanio, Andrew; Mathis, Erin; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Provenzani, Ambra; Polidori, Carlo; Vizzini, Giovanni; Polidori, Piera; D’Alessandro, Natale

2013-01-01

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus; also, unlike phenotypic tests, the genotype is a stable characteristic that needs to be determined only once for any given gene. However, prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication. At present, research has been able to reliably show that the CYP3A5 genotype, but not the CYP3A4 or ABCB1 ones, can modify the pharmacokinetics of tacrolimus. However, it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity. For these reasons, pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing. PMID:24409044

Tacrolimus hydrate ointment inhibits skin plasma extravasation in rats induced by topical m-xylene but not capsaicin.

PubMed

Goto, Shiho; Kondo, Fumio; Ikai, Yoshitomo; Miyake, Mio; Futamura, Masaki; Ito, Komei; Sakamoto, Tatsuo

2009-04-17

Tacrolimus ointment is used to treat various chronic inflammatory skin diseases. However, the effect of this ointment on acute neurogenic inflammation in the skin remains to be fully elucidated. Topical capsaicin and m-xylene produce tachykinin release from sensory nerves in the skin, resulting in skin plasma leakage. We investigated the effect of tacrolimus ointment (0.1%) on skin microvascular leakage induced by topical capsaicin (10 mM) and m-xylene (neat), and intracutaneous compound 48/80 (c48/80) (10 microg/ml, 50 microl/site) in two groups of rats pretreated with excessive capsaicin or its vehicle. The amount of leaked Evans blue dye reflected skin plasma leakage. Capsaicin, m-xylene or c48/80 was applied to the shaved abdomens of rats 8 h after topical application of tacrolimus ointment or its base. Desensitization with capsaicin reduced the skin response to capsaicin and m-xylene by 100% and 65%, respectively, but not to c48/80. Tacrolimus ointment significantly inhibited the skin response induced by m-xylene and c48/80, regardless of pretreatment with capsaicin. However, topical tacrolimus did not influence the skin response induced by capsaicin. We also evaluated whether topical capsaicin and m-xylene, and intracutaneous c48/80 cause mast cell degranulation in skin treated with tacrolimus. Mast cell degranulation was microscopically assessed. Topical tacrolimus only significantly suppressed degranulation induced by m-xylene and c48/80. Our data shows that tacrolimus ointment partially inhibits plasma leakage and mast cell degranulation in rat skin induced by m-xylene and c48/80 but not capsaicin, suggesting that the inhibitory effect is not associated with a reduction in neurogenic-mediated mechanisms.

Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine.

PubMed

Navas-López, Víctor Manuel; Blasco-Alonso, Javier; Girón Fernández-Crehuet, Francisco; Serrano Nieto, Maria Juliana; Gallego-Gutiérrez, Silvia; Luque Pérez, Silvia; Sierra Salinas, Carlos

2014-08-01

Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2-5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.

The cost effectiveness of tacrolimus versus microemulsified cyclosporin: a 10-year model of renal transplantation outcomes.

PubMed

Orme, Michelle E; Jurewicz, Wieslaw A; Kumar, Nagappan; McKechnie, Tracy L

2003-01-01

In 1983, the launch of cyclosporin was a significant clinical advance for organ transplant recipients. Subsequent drug research led to further advances with the introduction of cyclosporin microemulsion (cyclosporin ME) and tacrolimus. This paper presents the results from a long-term model comparing the clinical and economic outcomes associated with cyclosporin ME and tacrolimus immunosuppression for the prevention of graft rejection following renal transplantation. A model was developed to project the costs and outcomes over a 10-year period following transplantation. The model was based on the results of a prospective, randomised study of 179 renal transplantation recipients receiving either cyclosporin ME or tacrolimus, which was conducted by the Welsh Transplantation Research Group (median follow-up: 2.7 years). The short-term costs and outcomes were the averages from the actual head-to-head trial data. From this, the long-term costs and outcomes were extrapolated based on the rate of change in patient and graft survival at 3, 5 and 10 years post transplant, as reported in the 1995 United Kingdom Transplant Support Service Authority Renal Transplant Audit. PERSPECTIVE AND YEAR OF COST DATA: The analysis was conducted from the perspective of a UK transplant unit. Costs were at 1999 prices (pounds sterling 1 = dollars US 1.42 = Euro 1.5) and costs and outcomes were discounted at 6% and 1.5%, respectively. The model estimated that 10 years after transplantation, the proportion of patients surviving was 56% of the cyclosporin ME cohort and 64% of the tacrolimus cohort. The cumulative cost of maintenance therapy at 10 years was pounds sterling 23204 per patient maintained on cyclosporin ME versus pounds sterling 23803 per patient on tacrolimus. The cost per survivor at 10 years was pounds sterling 37000 (tacrolimus) versus pounds sterling 41000 (cyclosporin ME) and the cost per patient with a functioning graft was pounds sterling 39000 versus pounds sterling 45000

Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis.

PubMed

Hamel, Blaise; Wu, May; Hamel, Elizabeth O; Bass, Dorsey M; Park, K T

2018-01-01

Severe colitis flare from ulcerative colitis (UC) or Crohn's disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis. A retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol. Twelve patients (10 UC, two CD; median age 16 years; three female) received at least one dose of vedolizumab 10 mg/kg (max of 300 mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks. We report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.

Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

PubMed

Liu, Jin-Yu; You, Ru-Xu; Guo, Min; Zeng, Lu; Zhou, Pu; Zhu, Lan; Xu, Gang; Li, Juan; Liu, Dong

2016-01-01

Tacrolimus and cyclosporine are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of cyclosporine and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection, and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and quality-adjusted life years gained and incremental cost-effectiveness. Altogether, 6137 patients from 27 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of patient mortality, graft loss, acute rejection, and hypercholesterolemia. Nevertheless, tacrolimus increased the risk of new-onset diabetes. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events following renal transplant. Tacrolimus is an effective and safe immunosuppressive agent and it may be more cost-effective than cyclosporine for the primary prevention of graft rejection in renal transplant recipients. However, new-onset diabetes should be closely monitored during the medication period.

Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo.

PubMed

Mina, Mary; Elgarhy, Lamia; Al-Saeid, Hanan; Ibrahim, Zeinab

2018-03-12

Several treatment modalities had been used for the treatment of vitiligo, but the optimal treatment has not yet been identified. To study the efficacy of microneedling with 5-flurouracil vs its efficacy with tacrolimus in the treatment of vitiligo. Twenty-five patients with vitiligo were subjected to microneedling of 2 patches of vitiligo with dermapen, then application of 5-fluorouracil to 1 patch and tacrolimus on the other patch. This procedure was repeated every 2 weeks for every patient for maximum 6 months (12 sessions). The patients were followed up for 3 months after the last session. The overall repigmentation was significantly higher in 5-fluorouracil-treated patches compared with tacrolimus. Excellent improvement occurred in 48% of 5- flurouracil-treated patches while only in 16% of tacrolimus-treated patches. In the acral parts, 40% of the patches treated with 5-fluorouracil achieved excellent improvement (repigmentation >75%), while no patch in the acral parts achieved excellent improvement with tacrolimus. However, there was significant difference between the 2 drugs,regarding inflammation, ulceration, and hyperpigmentation which occurred with 5-fluorouracil. Microneedling combined with 5-fluorouracil or tacrolimus is safe and effective treatment of vitiligo. However, 5-fluorouracil achieved a greater percentage of repigmentation than tacrolimus particularly in the acral parts. © 2018 Wiley Periodicals, Inc.

Topical tacrolimus for parastomal pyoderma gangrenosum: a report of two cases.

PubMed

Altieri, Maria; Vaziri, Khashayar; Orkin, Bruce A

2010-09-01

Pyoderma gangrenosum (PG) is an idiopathic, ulcerative, inflammatory dermatologic condition that occurs in patients with systemic diseases such as inflammatory bowel disease (IBD). This inflammatory skin disorder is presumably caused by an autoimmune mechanism and the diagnosis is one of exclusion. PG is not a common condition but it is thought to account for approximately 50% of chronic parastomal ulcers. Refractory parastomal PG (PPG) occurs in patients with inactive disease or after bowel resection. Multiple medical treatments, ranging from topical agents for mild disease to systemic immunosuppressive therapy for severe disease, have been used with varying rates of success. Using topical tacrolimus, an immunosuppressant that inhibits T-lymphocyte proliferation, and meticulous stoma care can result in successful treatment. Two women (ages 59 and 62 years) with a history of ulcerative colitis and colon resection presented with parastomal ulcers consistent with PPG. The 59-year patient presented with a painful 2 cm x 2 cm parastomal ulcer that improved following daily application of topical tacrolimus 0.1%. The 62-year old woman first was prescribed daily appliance changes and application of topical triamcinolone 0.5% to her 3-cm ulcer. The ulcer increased in size and treatment was changed to daily application of tacrolimus 0.1%. After 2 months and a reduction in ulcer size and severity, the dosage was changed to daily application of tacrolimus 0.03%. Both patients reported resolution of pain and itching, the most common symptoms of PPG, and no adverse effects were observed. The encouraging results observed in these two cases confirm that tacrolimus helps resolve PPG lesions even at concentrations previously thought to be ineffective. Additional studies to help clinicians optimize care of these painful lesions are needed.

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival.

PubMed

Gallagher, Harry M; Sarwar, Ghulam; Tse, Tracy; Sladden, Timothy M; Hii, Esmond; Yerkovich, Stephanie T; Hopkins, Peter M; Chambers, Daniel C

2015-11-01

Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation. We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died. Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005). Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluation of gingival alterations in rats medicated with cyclosporine A, tacrolimus and sirolimus: a stereological study.

PubMed

Pamuk, F; Cetinkaya, B O; Ayas, B; Keles, G C; Gacar, A

2015-10-01

It has previously been shown that both cyclosporine A and tacrolimus cause gingival overgrowth in the rat. We proposed that sirolimus may play an important role in decreasing the severity of gingival overgrowth. Therefore, the aim of this study was to evaluate the gingival changes induced by immunosuppressants, in the presence and absence of sirolimus, using histopathology and stereological methods. Thirty-six male Sprague-Dawley rats were distributed into six treatment groups, each containing six rats, as follows: (i) cyclosporine A for 8 wk; (ii) tacrolimus for 8 wk; (iii) sirolimus for 8 wk; (iv) cyclosporine A + sirolimus for 8 wk; (v) tacrolimus + sirolimus for 8 wk; and (vi) distilled water for 8 wk. Histomorphometric analyses included measurements of epithelial thickness and connective tissue width and height. Stereological analyses included measurements of volumetric densities of fibroblasts (Vf ), collagen fibers (Vcf ) and blood vessels (Vbv ). Connective tissue width and height were significantly increased in cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05), and epithelial thickness was significantly increased in the cyclosporine A group and tacrolimus group compared with the control group (p < 0.05). Vf was significantly increased in the cyclosporine A group and the tacrolimus group compared with the control group (p < 0.05), whereas Vcf and Vbv were significantly increased in the cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05). The results of the study suggest that sirolimus seems not to be associated with gingival overgrowth, and combined usage of sirolimus and immunosuppressants decreases the severity of gingival overgrowth. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sirolimus Associated with Tacrolimus at Low Doses in Elderly Kidney Transplant Patients: A Prospective Randomized Controlled Trial.

PubMed

Kojima, Cristiane Akemi; Nga, Hong Si; Takase, Henrique Mochida; Bravin, Ariane Moyses; Martinez Garcia, Márcia de Fátima Faraldo; Garcia, Paula Dalsoglio; Contti, Mariana Moraes; de Andrade, Luis Gustavo Modelli

2018-06-01

There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimus-mycophenolate (23 patients). Cytomegalovirus infection rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.

Immunophenotype of infiltrating cells in protocol renal allograft biopsies from tacrolimus-versus cyclosporine-treated patients.

PubMed

Serón, Daniel; O'Valle, Francisco; Moreso, Francesc; Gomà, Montse; Hueso, Miguel; Grinyó, Josep M; Garcia del Moral, Raimundo

2007-03-15

The prevalence of subclinical rejection is lower in patients receiving tacrolimus than in patients treated with cyclosporine. However, it is not known whether this difference is related to the modulation of a specific cell immunophenotype. We perform a two case-one control study in patients treated with tacrolimus (n=44) or cyclosporine (n=22) with a protocol biopsy performed at 4 to 6 months. Immunophenotype of infiltrating cells was evaluated with monoclonal antibodies directed against CD45 (all leukocytes), CD3 (T lymphocytes), CD68 (monocytes/macrophages), and CD20 (B lymphocytes) and expressed as interstitial positive cells/mm(2). The number of interstitial CD45 (290+/-209 vs. 696+/-560; P<0.01), CD3 (121+/-84 vs. 208+/-104; P<0.01), and CD68 (155+/-232 vs. 242+/-280; P<0.05) but not CD20 (137+/-119 vs. 197+/-154) positive cells was lower in tacrolimus-treated patients. T lymphocytes and macrophages interstitial infiltration was reduced in tacrolimus treated patients evaluated with protocol biopsies in comparison to cyclosporine-treated patients.

Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: a Retrospective Study.

PubMed

Strohbehn, Garth W; Pan, Warren W; Petrilli, Christopher M; Heidemann, Lauren; Larson, Sophia; Aaronson, Keith D; Johnson, Matt; Ellies, Tammy; Heung, Michael

2018-04-30

Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the pre-analytical phase of the inpatient tacrolimus TDM process at their institution. Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study. Times of tacrolimus administration and laboratory study collection were extracted and time distribution plots for each step in the inpatient TDM process were generated. Trough levels were drawn appropriately in 25.9% of the cases. Timing between doses was consistent, with 91.9% of the following dose administrations occurring 12 +/- 2 hours after the previous dose. Only 38.1% of the drug administrations occurred within one hour of laboratory study collection. Tacrolimus-related patient safety events were reported at a rate of 1.9 events per month while incorrect timing of TDM sample collection occurred approximately 200 times per month. Root cause analysis identified a TDM process marked by a lack of communication and coordination of drug administration and TDM sample collection. Extrapolating findings nationwide, we estimate $22 million in laboratory costs wasted annually. Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes.

Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored.

PubMed

González, Fernando; López, René; Arriagada, Elizabeth; Carrasco, René; Gallardo, Natalia; Lorca, Eduardo

2017-01-01

Background . Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. Methods . Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. Results . Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL ( p < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. Conclusion . Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians.

Tacrolimus potently inhibits human osteoclastogenesis induced by IL-17 from human monocytes alone and suppresses human Th17 differentiation.

PubMed

Yago, Toru; Nanke, Yuki; Kawamoto, Manabu; Yamanaka, Hisashi; Kotake, Shigeru

2012-08-01

Tacrolimus (FK506, Prograf®) is an orally available, T cell specific and anti-inflammatory agent that has been proposed as a therapeutic drug in rheumatoid arthritis (RA) patients. It has been known that T cells have a critical role in the pathogenesis of RA. Recent studies suggest that Th17 cells, which mainly produce IL-17, are involved in many autoimmune inflammatory disease including RA. The present study was undertaken to assess the effect of tacrolimus on IL-17-induced human osteoclastogenesis and human Th17 differentiation. Human CD14(+) monocytes were cultured in the presence of macrophage-colony stimulating factor (M-CSF) and IL-17. From day 4, tacrolimus was added to these cultures. Osteoclasts were immunohistologically stained for vitronectin receptor 10days later. IL-17 production from activated T cells stimulated with IL-23 was measured by enzyme-linked immunosorbent assay (ELISA). Th17 differentiation from naïve T cells was assayed by flow cytometry. Tacrolimus potently inhibited IL-17-induced osteoclastogenesis from human monocytes and osteoclast activation. Addition of tacrolimus also reduced production of IL-17 in human activated T cells stimulated with IL-23. Interestingly, the population of human IL-17(+)IFN-γ(-) CD4 T cells or IL-17(+)TNF-α(+) CD4 T cells were decreased by adding of tacrolimus. The present study demonstrates that the inhibitory effect of tacrolimus on IL-17-induced osteoclastogenesis from human monocytes. Tacrolimus also inhibited expression of IL-17 or TNF-α by reducing the proportion of Th17, suggesting that therapeutic effect on Th17-associated disease such as RA, inflammatory bowel disease, multiple sclerosis, psoriasis, or allograft rejection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dyslipidaemia among renal transplant recipients: cyclosporine versus tacrolimus.

PubMed

Fazal, Muhammad Asim; Idrees, Muhammad Khalid; Akhtar, Syed Fazal

2014-05-01

To compare new onset dyslipidaemia in live-related renal transplant recipients taking cyclosporine versus tacrolimus after 3 months of therapy. The randomised controlled trial was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Karachi, from September 2010 to April 2011, and included 182 End Stage Renal Disease patients on maintenance haemodialysis with pre-transplant normal lipid profile. The patients, who had live-related renal transplant, were randomly allocated to two equal groups using lottery. Group A received cyclosporine (3 mg/kg) and group B was treated with tacrolimus (0.1 mg/kg). All patients had pre-transplant fasting lipid profile checked when they were on maintenance haemodialysis and 3 months after renal transplantation. Serum fasting lipid profile was collected by taking 5 ml blood by venipuncture after an overnight fast of 9-12 hours. SPSS 10 was used for statistical analyses. Of the 182 patients, 144 (79.1%) were males and 38 (20.9%) were females. The overall mean age was 30.18 +/- 9.57 years, and the mean weight was 54.41 +/- 11.144 kg. Significant difference was not observed between the two groups regarding age and weight of the patients. Dyslipidaemia was found in 115(63.2%) subjects; 61(67%) in group A and 54 (59.3%) in group B. There was no statistical difference (p=0.28) when comparison was done after 3 months of therapy. The occurrence of new onset hyperlipidaemia is similar in renal transplant recipients receiving either cyclosporine or tacrolimus in first 3 months post-transplant, but there is room for more research in this field as dyslipidaemia following successful renal transplantation is a frequent and persistent complication.

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

PubMed

Chen, W-Y; Lee, C-Y; Lin, P-Y; Hsieh, C-E; Ko, C-J; Lin, K-H; Lin, C-C; Ming, Y-Z; Chen, Y-L

2017-03-01

Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts. Copyright © 2016 Elsevier Inc. All rights reserved.

[The therapeutic drug monitoring network server of tacrolimus for Chinese renal transplant patients].

PubMed

Deng, Chen-Hui; Zhang, Guan-Min; Bi, Shan-Shan; Zhou, Tian-Yan; Lu, Wei

2011-07-01

This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.

Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.

PubMed

Miles, Clifford D; Skorupa, Jill Y; Sandoz, John P; Rigley, Theodore H; Nielsen, Kathleen J; Stevens, R Brian

2011-01-01

Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 μg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications. © 2010 John Wiley & Sons A/S.

Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored

PubMed Central

López, René; Arriagada, Elizabeth; Carrasco, René; Gallardo, Natalia; Lorca, Eduardo

2017-01-01

Background. Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. Methods. Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. Results. Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL (p < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. Conclusion. Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians. PMID:28246556

Artificial neural network model for predicting the bioavailability of tacrolimus in patients with renal transplantation

PubMed Central

Thishya, Kalluri; Vattam, Kiran Kumar; Naushad, Shaik Mohammad; Raju, Shree Bhushan

2018-01-01

The objective of the current study was to explore the role of ABCB1 and CYP3A5 genetic polymorphisms in predicting the bioavailability of tacrolimus and the risk for post-transplant diabetes. Artificial neural network (ANN) and logistic regression (LR) models were used to predict the bioavailability of tacrolimus and risk for post-transplant diabetes, respectively. The five-fold cross-validation of ANN model showed good correlation with the experimental data of bioavailability (r2 = 0.93–0.96). Younger age, male gender, optimal body mass index were shown to exhibit lower bioavailability of tacrolimus. ABCB1 1236 C>T and 2677G>T/A showed inverse association while CYP3A5*3 showed a positive association with the bioavailability of tacrolimus. Gender bias was observed in the association with ABCB1 3435 C>T polymorphism. CYP3A5*3 was shown to interact synergistically in increasing the bioavailability in combination with ABCB1 1236 TT or 2677GG genotypes. LR model showed an independent association of ABCB1 2677 G>T/A with post transplant diabetes (OR: 4.83, 95% CI: 1.22–19.03). Multifactor dimensionality reduction analysis (MDR) revealed that synergistic interactions between CYP3A5*3 and ABCB1 2677 G>T/A as the determinants of risk for post-transplant diabetes. To conclude, the ANN and MDR models explore both individual and synergistic effects of variables in modulating the bioavailability of tacrolimus and risk for post-transplant diabetes. PMID:29621269

Tacrolimus Improves Symptoms of Children With Myasthenia Gravis Refractory to Prednisone.

PubMed

Liu, Chanchan; Gui, Mengcui; Cao, Yayun; Lin, Jing; Li, Yue; Ji, Suqiong; Bu, Bitao

2017-12-01

Myasthenia gravis tends to affect children in China. Oral pyridostigmine and prednisone could effectively improve the symptoms, but multiple side effects become a major concern after long-term oral prednisone. To avoid the long-term complications of prednisone therapy and to obtain more satisfactory improvement, we tested the efficacy and safety of tacrolimus in children with myasthenia gravis. Children with myasthenia gravis who had not achieved satisfactory improvement or who experienced severe side effects after prednisone therapy were recruited between January 2015 and December 2016 at Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily and the dose was adjusted on the basis of the clinical response and the serum concentration. The dosage of prednisone, the severity of symptoms, blood samples, the serum concentration of tacrolimus, and titers of antiacetylcholine receptor antibodies were evaluated every four weeks. Fourteen children were enrolled. One child withdrew two weeks after the enrollment. Thirteen children have completed the therapy for one year. At the end point, the dosage of prednisone was significantly decreased (P < 0.05), the symptoms were evaluated by the quantitative myasthenia gravis score, and myasthenia gravis-specific manual muscle testing and myasthenia gravis-activities of daily living scores were significantly improved (P < 0.05, P < 0.05, and P < 0.01, respectively). More importantly, ten (76.9%) patients had completely discontinued prednisone, and the major side effects were nearly reversed. The mean titer of antiacetylcholine receptor antibodies significantly dropped from 1.96±2.62 nmol/L to 0.70±1.04 nmol/L (P < 0.05). No severe adverse events were reported. Our results suggest that tacrolimus is a promising agent for children with refractory myasthenia gravis. Randomized clinical trials are needed to confirm the observation. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test.

PubMed

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-10-01

To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm(2). The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window.

Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids.

PubMed

Mourad, Michel; Mourad, Georges; Wallemacq, Pierre; Garrigue, Valérie; Van Bellingen, Christophe; Van Kerckhove, Valérie; De Meyer, Martine; Malaise, Jacques; Eddour, Djamila Chaib; Lison, Dominique; Squifflet, Jean Paul; Haufroid, Vincent

2005-10-15

CYP3A5 and MDR1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements. The aim is to determine whether these polymorphisms also affect sirolimus trough concentrations and dose requirements after kidney transplantation. Eighty-five renal transplant recipients receiving sirolimus were included. Twenty-four were treated with a combined sirolimus-tacrolimus regimen. Eighty-one patients received steroids. Sirolimus and tacrolimus were adjusted to a target therapeutic window. CYP3A5 (intron 3) and MDR1 (exons 12, 21, 26) genotypes were correlated to the adjusted trough concentrations and dose requirements for both sirolimus and tacrolimus. There were no significant correlation between adjusted sirolimus trough concentrations or dose requirements and genetic polymorphisms. In a multiple regression model, adjusted-prednisone dose was involved with a positive or negative effect when considering sirolimus dose requirements or adjusted concentrations, respectively. In the subgroup of patients treated by tacrolimus and sirolimus, adjusted tacrolimus doses were higher in patients carrying at least one CYP3A5 *1 allele (median 0.083 vs. 0.035 mg/kg for CYP3A5*3/*3 patients, P<0.05). Adjusted-prednisolone dose and CYP3A5 polymorphism explained up to 61% of the variability in tacrolimus dose requirements. Unlike tacrolimus, sirolimus adjusted trough concentrations and dose requirements seem not affected by CYP3A5 and MDR1 polymorphisms. Adjusted-prednisone dose has a significant impact on tacrolimus and sirolimus dose requirements.

Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region

PubMed Central

Qin, Xuzhen; Rui, Jianzhong; Xia, Yong; Mu, Hong; Song, Sang Hoon; Raja Aziddin, Raja Elina; Miles, Gabrielle; Sun, Yuli

2018-01-01

Background The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs). Methods This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow). Results Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types. Conclusions The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types. PMID:29214751

High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients

PubMed Central

Goodall, Dawn L.; Willicombe, Michelle; McLean, Adam G.; Taube, David

2017-01-01

Background Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol. Methods We retrospectively analyzed the outpatient tacrolimus levels of kidney-only transplant patients taken between 6 and 12 months posttransplant. IPV was determined using the coefficient of variance. Results Six hundred twenty-eight patients with a mean number of 8.98 ± 3.81 tacrolimus levels and a mean follow-up of 4.72 ± 2.19 years were included. Multivariate analysis showed death was associated with increasing age (1.04 [1.01-1.07], P = 0.0055), diabetes at time of transplant (2.79 [1.44-5.41], P = 0.0024), and rejection (2.34 [1.06-5.19], P = 0.036). Variables associated with graft loss included the highest variability group (2.51 [1.01-6.27], P = 0.048), mean tacrolimus level less than 5 ng/mL (4.32 [1.94-9.63], P = 0.0003), a high clinic nonattendance rate (1.10 [1.01-1.20], P = 0.03), and rejection (9.83 [4.62-20.94], P < 0.0001). Independent risk factors for rejection were de novo donor-specific antibody (3.15 [1.84-5.39], P < 0.0001), mean tacrolimus level less than 5 ng/mL (2.57 [1.27-5.19], P = 0.00860, and a high clinic nonattendance rate (1.11 [1.05-1.18], P = 0.0005). Conclusions This study shows that high tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival. Interventions to minimize the causes of high variability, particularly nonadherence are essential to improve long-term allograft outcomes. PMID:28795143

Personalized tacrolimus doses determined by CYP3A5 genotype for induction and maintenance phases of kidney transplantation.

PubMed

Vannaprasaht, Suda; Reungjui, Sirirat; Supanya, Darika; Sirivongs, Dhavee; Pongskul, Cholatip; Avihingsanon, Yingyos; Tassaneeyakul, Wichittra

2013-11-01

Cytochrome P450 (CYP) 3A4 and 3A5 are major isoforms involved in the metabolism of tacrolimus, with the CYP3A5 gene being more polymorphic. It is hypothesized that individual variation in the metabolism of tacrolimus drug may result from genetic polymorphism of CYP3A5. It has been reported that the clearance of tacrolimus in patients with the CYP3A5*1 allele was ~2.5-fold greater than that in those with the CYP3A5*3/*3 genotype. Recent data have also shown that polymorphism in exon 26 (C3435T) of the multidrug resistance gene (MDR1) was correlated with the expression level and function of P-glycoprotein in the lower duodenum, making the relationship between polymorphism of MDR1 and the effective dose of tacrolimus a source of controversy. This study investigated the influence of genetic polymorphisms of CYP3A5 and MDR1 on the dose requirements for the induction and maintenance phases of tacrolimus therapy in kidney transplant recipients. Sixty-eight kidney transplant recipients were enrolled, and their clinical and laboratory data were retrospectively reviewed after 6 months of tacrolimus administration. Genotypes of CYP3A5*1 and CYP3A5*3 and exon 26 of MDR1 (C3435T) were determined by the single-nucleotide polymorphism genotyping method. The frequencies of CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1 were 44.1%, 35.3%, and 20.6%, respectively. The mean dose of tacrolimus required for the induction phase was significantly greater in the CYP3A5*1/*1 group (0.142 [0.050] mg/kg/d) than that required in the CYP3A5*1/*3 group (0.097 [0.040] mg/kg/d; P = 0.072) and in the CYP3A5*3/*3 group (0.077 [0.020] mg/kg/d; P = 0.005). The maintenance dose of tacrolimus required in the CYP3A5*1/*1 group (0.12 [0.03] mg/kg/d) was 1.3-fold higher than that in the CYP3A5*1/*3 group (0.09 [0.03] mg/kg/d; P = 0.018) and 2.4-fold higher than in the CYP3A5*3/*3 group (0.05 [0.02] mg/kg/d; P < 0.0001). No statistically significant relationship was observed between the doses of tacrolimus

Adult Heart Transplantation Under Tacrolimus (FK506) Immunosuppression: Histopathologic Observations and Comparison to a Cyclosporine-based Regimen with Lympholytic (ATG) Induction

PubMed Central

Tsamandas, Athanassios C.; Pham, Si M.; Seaberg, Eric C.; Pappo, Orit; Kormos, Robert L.; Kawai, Akihiko; Griffith, Bartley P.; Zeevi, Adriana; Duquesnoy, Rene; Fung, John J.; Starzl, Thomas E.; Demetris, Anthony J.

2011-01-01

Background Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited. Methods We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared. Results In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tacrolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contrast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat

Successful treatment of eosinophilic pustular folliculitis with topical tacrolimus 0.1 percent ointment.

PubMed

Ng, Shanna Shan-Yi; Tay, Yong-Kwang

2012-02-15

Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi disease, is a rare condition commonly treated with topical glucocorticosteroids. If this fails, oral indomethacin is frequently the next line. Because the condition is recurrent, the use of long term steroids may cause side effects such as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an immunosuppressant that is generally used as a steroid-sparing agent in atopic dermatitis. We report a case of classic EPF, which was recurrent over 5 years that had failed topical glucocorticosteroids but was successfully treated with topical tacrolimus 0.1 percent ointment.

Effects of topical corticosteroid and tacrolimus on ceramides and irritancy to sodium lauryl sulphate in healthy skin.

PubMed

Jungersted, Jakob Mutanu; Høgh, Julie K; Hellegren, Lars I; Jemec, Gregor B E; Agner, Tove

2011-05-01

The skin barrier, located in the stratum corneum, is influenced mainly by the lipid and protein composition of this layer. In eczematous diseases impairment of the skin barrier is thought to be of prime importance. Topical anti-inflammatory drugs and emollients are the most widely used eczema treatments. The aim of this study was to examine the effects of topically applied corticosteroid, tacrolimus and emollient on stratum corneum lipids and barrier parameters. Nineteen healthy volunteers participated in the study. Both forearms of the subjects were divided into four areas, which were treated twice daily for one week with betamethasone, tacrolimus, emollient, or left untreated, respectively. After one week each area was challenged with a 24 h sodium lauryl sulphate patch test. The lipids were collected using the cyanoacrylate method and evaluated by high performance thin layer chromatography. For evaluation of the skin barrier, transepidermal water loss, erythema and electrical capacitance were measured. The ceramide/cholesterol ratio was increased in betamethasone- (p = 0.008) and tacrolimus-treated (p = 0.025) skin compared with emollient-treated skin. No differences in ceramide subgroups were found between treatment regimes. Pretreatment with betamethasone (p = 0.01) or with tacrolimus (p = 0.001) causes a decreased inflammatory response to sodium lauryl sulphate compared with emollient. In conclusion, treatment with betamethasone and tacrolimus has a positive effect on the ceramide/cholesterol ratio and susceptibility to irritant reaction compared with an emollient.

Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

PubMed

Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

2018-04-19

We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

PubMed

Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

2000-12-01

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus.

PubMed

Chen, Wei; Zhou, Yuan; Huang, Fei-Ran; Luo, Dan; Wang, Da-Guang

2018-04-10

Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO 2 ) fractional laser together with tacrolimus. Forty-five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO 2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. The treatment of vitiligo by CO 2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO 2 fractional laser together with tacrolimus. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test

PubMed Central

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-01-01

Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm2. The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window. PMID:21927013

Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation.

PubMed

Fukazawa, Kyota; Nishida, Seigo; Aguina, Luz; Pretto, Ernesto

2011-01-01

Central pontine myelinolysis (CPM) is the most detrimental neurologic complication after liver transplantation. The incidence of CPM after liver transplantation ascends to 17%. Although the precise etiology and pathogenesis of CPM is largely unknown, a growing literature implicates a possible role of immunosuppressive agents, such as Cyclosporine (incidence 30%) on its development. Other immunosuppressive agents also can cause CPM but the frequency of these cases is less compared to Cyclosporine. There is only one case report for Tacrolimus (FK506)-associated speech disorder, which might be an atypical presentation of CPM, and no case reports for Rapamycin. We present a case of Tacrolimus induced CPM. A 62-year-old woman who underwent liver transplantation developed clinical symptoms with radiologic evidence consistent with CPM 7 days after liver transplant. Since the electrolytes in this patient remained normal from her admission, the hypothesis of inmunossupressor neurotoxicity was established and the therapy was switched, resulting in an evident clinical and radiological improvement of her condition in the following days. Five months later, the patient's only neurological deficit was slight dysarthria and a follow-up MRI showed no abnormalities. This case provides evidence of Tacrolimus-associated CPM after transplantation, which presented with a classic "lock-in syndrome" with radiographic confirmation.

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

PubMed Central

Hawwa, Ahmed F; McKiernan, Patrick J; Shields, Michael; Millership, Jeff S; Collier, Paul S; McElnay, James C

2009-01-01

AIMS The aim of this study was to investigate the influence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation. METHODS Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular filtration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes. RESULTS The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (≥30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls, P= 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%, P= 0.057). Carriers of the G2677->T variant allele also had a significant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P= 0.031). Haplotype analysis showed a significant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P= 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were significantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation. CONCLUSIONS These findings suggest that ABCB1 polymorphisms in the native intestine significantly influence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the first year post-transplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and

A rare but important adverse effect of tacrolimus in a heart transplant recipient: diabetic ketoacidosis.

PubMed

Öztürk, Zeynelabidin; Gönç, E Nazlı; Akcan, Leman; Kesici, Selman; Ertuğrul, İlker; Bayrakçı, Benan

2015-01-01

Heart transplantation indications in pediatric population include congenital heart diseases, cardiomyopathies and retransplants. Cardiomyopathy is the primary indication for 11 to 17 years of age. The surveillance after transplantation is a very important issue because of both the rejection risk and the adverse effects due to medications after transplantation. Immunosuppressive agents that are commonly used after heart transplantations have several toxicities. Here we present an adolescent patient diagnosed with dilated cardiomyopathy, performed heart transplantation, treated with tacrolimus and suffered from diabetic ketoacidosis due to tacrolimus. After the diagnosis was made the appropriate fluid and insulin therapy was started immediately and ketoacidosis resolved in the first 24 hours of the therapy. The diagnosis revised as new onset diabetes mellitus after transplantation and the tacrolimus dosage titrated to therapeutic level. After glycemic control the patient discharged with rapid acting insulin, three times daily, before meals; and long acting insulin once daily at night. In ten month follow up time the insulin dosages were progressively reduced.

Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

PubMed

Aridon, Paolo; Ragonese, Paolo; Di Benedetto, Norma; Grasso, Giovanni; Conaldi, Pier Giulio; D'Amelio, Marco; Savettieri, Giovanni

2009-12-01

Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

Effects of Tacrolimus or Sirolimus on the adhesion of vascular wall cells: Controlled in-vitro comparison study.

PubMed

Krüger-Genge, A; Hiebl, B; Franke, R P; Lendlein, A; Jung, F

2017-01-01

In drug eluting stents the cytostatic drugs Sirolimus or Tacrolimus are used to inhibit blood vessel restenosis by limiting the proliferation of smooth muscle cells. However, the cytostatic activity of both drugs was shown to be not cell specific and could also affect the stent endothelialisation, respectively. Currently, only limited in vitro data are available about the impact of Sirolimus and Tacrolimus on endothelial cell proliferation over a broad concentration range. To answer this question the following study was performed.Commercially obtained HUVEC were expanded with DMEM cell culture medium (GIBCO, Germany) supplemented with 5 vol% fetal calf serum on non-coated regular polystyrene-based 24-multiwell plates. For drug testings 2×104 cells/cm2 were seeded and grown for 24 h until 30-40% of the multiwell surfaces were covered and then exposed to Sirolimus (1.0×10-11 - 1.0×10-5 mol/l) or Tacrolimus (2.0×10-8 - 6.2×10-5 mol/l), both dissolved in DMSO. 12, 24 and 48 h after adding the drugs cell numbers per area were quantified by counting the cells in six wells with four fields of view per well, representing 0.6 mm2, using a confocal laser microscope.After 48 h of cell growth in the drug-free cell culture medium, the HUVEC number increased from 2.0×104 to 3.55×104 cells/cm2 (mean cell doubling time: 53.6 h, n = 6). At lower concentrations (≤2.0×10-6 mol/l) Tacrolimus reduced the number of adherent HUVEC significantly less than Sirolimus (p < 0.05). However, at higher concentrations (≥2.07×10-5 mol/l) the effect of Tacrolimus on the number of adherent endothelial cells was significantly greater than that of Sirolimus (p < 0.05). At the highest concentration applied (6.22×10-5 mol/l), Tacrolimus induced detachment of all HUVECs within 12 h after drug application. The number of adherent HUVEC decreased only slightly (about 9%) after Sirolimus application at the highest concentration (1.09×10-5 mol/l).These data

MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients.

PubMed

Mai, Ingrid; Perloff, Elke S; Bauer, Steffen; Goldammer, Mark; Johne, Andreas; Filler, Guido; Budde, Klemens; Roots, Ivar

2004-11-01

This retrospective study investigated the influence of MDR1 haplotypes derived from the polymorphisms 2677G > T (exon 21) and 3435C > T (exon 26) on the pharmacokinetics of the immunosuppressant drug tacrolimus in 73 renal transplant patients. Based on both variants of SNPs 2677 and 3435, four different haplotypes and eight different genotypes were identified in the study sample. Tacrolimus trough concentrations (C(0)) were compared between different SNP variants and genotypes, as well as between carriers and noncarriers of each haplotype. Additionally, CYP3A5 genotype (6956G > A) was determined. No significant differences were observed between groups. Differences in mean tacrolimus C(0) values between carriers and noncarriers of each haplotype ranged from -0.04 microg/litre (95% confidence interval: -0.53 to 0.60) to -23 microg/litre (-1.07 to 1.53). No association was found between CYP3A5*1/*3 genotype and tacrolimus Co concentractions. MDR1 haplotypes derived from the SNPs 2677G > T (exon 21) and 3435C > T (exon 26) do not influence the pharmacokinetics of tacrolimus in renal transplant patients.

EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Lasa, Juan; Olivera, Pablo

2017-01-01

There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: "Inflammatory Bowel Diseases" or "Ulcerative Colitis" and "Calcineurin Inhibitors" or "Tacrolimus" or "FK506". Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

False Elevation of the Blood Tacrolimus Concentration, as Assessed by an Affinity Column-mediated Immunoassay (ACMIA), Led to Acute T Cell-mediated Rejection after Kidney Transplantation.

PubMed

Kono, Momoko; Hasegawa, Jumpei; Ogawa, Hina; Yoshikawa, Kanae; Ishiwatari, Ayumi; Wakai, Sachiko; Tanabe, Kazunari; Shirakawa, Hiroki

2018-05-01

Tacrolimus is the most commonly used immunosuppressant. Because of its narrow therapeutic range, it is necessary to frequently monitor its concentration. We report the case of a 25-year-old man who underwent kidney transplantation whose tacrolimus concentrations, as measured by an affinity column-mediated immunoassay, were falsely elevated. As we reduced the dose of tacrolimus, the recipient developed T cell-mediated rejection. Using the same blood samples, an enzyme-multiplied immunoassay technique showed that the patient's levels of tacrolimus were extremely low. A further examination indicated that the false increase in the tacrolimus concentration was likely due to an unknown interfering substance. We administered methylprednisolone and antithymocyte-globulin. The patient's serum creatinine level decreased and remained stable after these treatments.

Successful treatment of oral lichen planus-like chronic graft-versus-host disease with topical tacrolimus: a case report.

PubMed

Sánchez, Andrés R; Sheridan, Phillip J; Rogers, Roy S

2004-04-01

Bone marrow transplantation (BMT) is a common treatment used for deficiencies of host marrow or in the control of blood malignancies. Post-allogeneic BMT complications include graft-versus-host disease (GVHD). GVHD occurs when immunologically active T lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the donor. In this case report we describe the occurrence of oral lichen planus-like lesions as the first manifestation of chronic GVHD (c-GVHD) and the subsequent management of this disease with topical tacrolimus. Diagnostic aids included routine histology and direct immunofluorescence studies to rule out immunobullous diseases and to confirm the c-GVHD. Treatment consisted of topical application of 0.1% tacrolimus ointment three times a day. Routine histology confirmed the clinical diagnosis of oral lichen planus-like c-GVHD. Treatment with tacrolimus ointment completely resolved the oral lesions after 2 months of therapy. Topical tacrolimus at low concentrations (0.1%) shows promise in the management of oral lichen planus-like c-GVHD. Controlled studies are necessary to assess the efficacy, the duration of therapy required for effective results, and the safety of this treatment over the long-term.

Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes

PubMed Central

2013-01-01

Introduction This study investigated whether the calcineurin inhibitor, tacrolimus, suppresses receptor activator of NF-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLS) through regulation of IL-6/Janus activated kinase (JAK2)/signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling (SOCS3) signaling. Methods The expression of RANKL, JAK2, STAT3, and SOCS3 proteins was assessed by western blot analysis, real-time PCR and ELISA in IL-6 combined with soluble IL-6 receptor (sIL-6R)-stimulated rheumatoid arthritis (RA)-FLS with or without tacrolimus treatment. The effects of tacrolimus on synovial inflammation and bone erosion were assessed using mice with arthritis induced by K/BxN serum. Immunofluorescent staining was performed to identify the effect of tacrolimus on RANKL and SOCS3. The tartrate-resistant acid phosphatase staining assay was performed to assess the effect of tacrolimus on osteoclast differentiation. Results We found that RANKL expression in RA FLS is regulated by the IL-6/sIL-6R/JAK2/STAT3/SOCS3 pathway. Inhibitory effects of tacrolimus on RANKL expression in a serum-induced arthritis mice model were identified. Tacrolimus inhibits RANKL expression in IL-6/sIL-6R-stimulated FLS by suppressing STAT3. Among negative regulators of the JAK/STAT pathway, such as CIS1, SOCS1, and SOCS3, only SOCS3 is significantly induced by tacrolimus. As compared to dexamethasone and methotrexate, tacrolimus more potently suppresses RANKL expression in FLS. By up-regulating SOCS3, tacrolimus down-regulates activation of the JAK-STAT pathway by IL-6/sIL-6R trans-signaling, thus decreasing RANKL expression in FLS. Conclusions These data suggest that tacrolimus might affect the RANKL expression in IL-6 stimulated FLS through STAT3 suppression, together with up-regulation of SOCS3. PMID:23406906

Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients

NASA Astrophysics Data System (ADS)

Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

2017-02-01

Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients.

PubMed

Provenzani, Alessio; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Biondi, Filippo; Sanguedolce, Rosario; Vizzini, Giovanni; Palazzo, Ugo; Polidori, Piera; Triolo, Fabio; Gridelli, Bruno; D'Alessandro, Natale

2009-01-01

Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCB1. We have investigated the effects of possible relevant CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C(0)) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T] and 26 [3435C>T]. 87.5% of the population showed a CYP3A5*3/*3 genotype. For the ABCB1 SNPs, in the case of 3435C>T the total frequency observed for the allelic variant was 50%. For the 2677G>T, the total frequency of the allelic variant was 12.5%, lower than in other Caucasian populations and without any significant linkage with 3435C>T. At 3 and 6 months after transplantation, tacrolimus dose requirements were significantly higher in patients receiving a liver with one copy of the *1 allele compared to those homozygous for the *3 allele (0.111+/-0.057 vs. 0.057+/-0.030 [P<0.05] at 3 month and 0.086+/-0.051 vs. 0.044+/-0.025 [P<0.05] at 6 month). For the recipients' genotypes, the presence of at least one *1 copy tended, though not statistically significantly, to increase tacrolimus doses. With regard to the ABCB1 SNPs, they did not show any influence on tacrolimus dosing requirements. Pharmacogenetic analysis of CYP3A5 in the donor could contribute to determine the appropriate initial dosage of tacrolimus in liver transplant patients.

Alemtuzumab induction with tacrolimus monotherapy in de novo renal transplantation.

PubMed

Villanueva, M E; Muñoz, A S; Casasola, C C; Africa, J B; Danguilan, R A; Ona, E T

2008-09-01

Alemtuzumab is increasingly being used as induction therapy for kidney transplantation, allowing immunosuppression minimization. This study examined the efficacy of alemtuzumab induction followed by low-dose tacrolimus monotherapy in standard risk primary kidney transplant patients. This retrospective cohort of primary standard risk renal transplant recipients were given alemtuzumab induction and low-dose tacrolimus maintenance immunosuppression (target trough 7 to 10 ng/mL for the first 6 months and 5 to 7 ng/mL thereafter). Serum creatinine values, acute rejection episodes, and graft survival were noted at week 1 as well as months 3, 6, 12, and 18. At the time of analysis, 47 patients were at 6 months, 28 at 12 months, and 6 patients at 18 months from transplant. Mean follow-up was 12.53 months (range, 6 to 23). Mean serum creatinine was 1.47 +/- 0.65 mg/dL at 3 months, 1.56 +/- 0.84 at 6 months, 1.45 +/- 0.37 at 12 months, and 1.74 +/- 0.35 at 18 months. The 1-year clinical acute rejection rate was 21% (6/28), occurring at 0 to 3 months in 2 (33%), 4 to 6 months in 1 (17%), and >6 months in 3 patients (50%). Biopsy-proven acute rejection was 14% (4/28). The episodes were classified as borderline in one, Banff 2A in two, and Banff 3 in one patients. One patient had both acute cellular and acute humoral rejection; half responded to steroid pulse therapy. The 1-year patient survival rate was 90%. The 1-year death-censored graft survival rate was 98%. Alemtuzumab induction with tacrolimus monotherapy is an acceptable option in standard risk patients. BPAR was 14%, but renal function remained satisfactory at 18 months posttransplant.

Increased medication compliance of liver transplant patients switched from a twice-daily to a once-daily tacrolimus-based immunosuppressive regimen.

PubMed

Eberlin, M; Otto, G; Krämer, I

2013-01-01

Compliance with immunosuppressive therapy plays a major role in the long-term success of liver transplantation. Thus, the development of strategies to promote compliance of liver transplant patients and its evaluation over time are of particular interest. The main objective of this study was to compare medication compliance rates among liver transplant patients over time after transplantation where switched from a twice- to once-daily tacrolimus-based regimen. Sixty-five liver transplant patients being administered tacrolimus-based therapy were classified into three subgroups with regard to time posttransplantation. Medication compliance with tacrolimus-based therapy was measured using an electronic medication event monitoring system over a 12-month period: for 6 months tacrolimus was administered twice-daily and for 6 months, once-daily. Dosing, taking, and timing compliance as well as drug holidays were compared intra-individually between twice- and once-daily intake and among the three subgroups. In addition, patient compliance and quality of life were evaluated using questionnaires. A per protocol analysis of electronically obtained data showed 63 patients to be eligible. The resulting dosing, taking, and timing compliance rates of the patients were higher during the once-daily dosing period. No significant differences in compliance rates with tacrolimus therapy were observed among three subgroups independent of the dosing regimen. More patients failed the correct timing of the evening compared to the morning dose. Missing doses occurred particularly during weekends. Compliance variables measured by questionnaires (Morisky score, self-report, Medication Experience Scale for Immunosuppressants (MESI) score) and the Hospital Anxiety and Depression Scale score were similar in the two dosing periods. The short-form health survey (SF-36) score was higher with once-daily intake. The high measured compliance rates did not vary significantly dependent upon the time

Physical and microbiological stability of an extemporaneous tacrolimus suspension for paediatric use.

PubMed

Han, J; Beeton, A; Long, P F; Wong, I; Tuleu, C

2006-04-01

An extemporaneous suspension of tacrolimus for paediatric use has recently been developed but poor bioavailability and erratic plasma concentrations were observed during clinical use. It was not clear whether this was due to changes in the physical properties of the suspension during storage. The aim of this work was to investigate the physical and microbiological stability over the recommended 8-week shelf-life of this extemporaneous tacrolimus suspension. Suspensions (0.5 mg/mL) were custom made by a special manufacturer under Good Manufacturing Practice conditions. The procedure involved mixing tacrolimus capsule contents into Ora Plus and Simple Syrup (1 : 1) using a mortar and pestle followed by an homogenization step. The particle sizes of the suspensions were measured using a MasterSizer. A light microscope equipped with polarizers was used to visualize any particle size changes or crystal growth. Viable bacterial and fungal contamination was assessed using standard colony count techniques on solid media. The suspensions were kept at 22-26 degrees C and evaluated weekly. The volume mean diameter d((4,3)) from laser diffraction did not change significantly. Light microscopy did not reveal any significant change in particle size or crystal growth. Contamination by viable and culturable micro-organisms could not be detected. The suspension was physically (particle size) and microbiologically stable during the 8-week study period suggesting other factors including poor dosing could be responsible for the pharmacokinetic variation observed during clinical use which warrants further investigation.

A novel approach for prediction of tacrolimus blood concentration in liver transplantation patients in the intensive care unit through support vector regression.

PubMed

Van Looy, Stijn; Verplancke, Thierry; Benoit, Dominique; Hoste, Eric; Van Maele, Georges; De Turck, Filip; Decruyenaere, Johan

2007-01-01

Tacrolimus is an important immunosuppressive drug for organ transplantation patients. It has a narrow therapeutic range, toxic side effects, and a blood concentration with wide intra- and interindividual variability. Hence, it is of the utmost importance to monitor tacrolimus blood concentration, thereby ensuring clinical effect and avoiding toxic side effects. Prediction models for tacrolimus blood concentration can improve clinical care by optimizing monitoring of these concentrations, especially in the initial phase after transplantation during intensive care unit (ICU) stay. This is the first study in the ICU in which support vector machines, as a new data modeling technique, are investigated and tested in their prediction capabilities of tacrolimus blood concentration. Linear support vector regression (SVR) and nonlinear radial basis function (RBF) SVR are compared with multiple linear regression (MLR). Tacrolimus blood concentrations, together with 35 other relevant variables from 50 liver transplantation patients, were extracted from our ICU database. This resulted in a dataset of 457 blood samples, on average between 9 and 10 samples per patient, finally resulting in a database of more than 16,000 data values. Nonlinear RBF SVR, linear SVR, and MLR were performed after selection of clinically relevant input variables and model parameters. Differences between observed and predicted tacrolimus blood concentrations were calculated. Prediction accuracy of the three methods was compared after fivefold cross-validation (Friedman test and Wilcoxon signed rank analysis). Linear SVR and nonlinear RBF SVR had mean absolute differences between observed and predicted tacrolimus blood concentrations of 2.31 ng/ml (standard deviation [SD] 2.47) and 2.38 ng/ml (SD 2.49), respectively. MLR had a mean absolute difference of 2.73 ng/ml (SD 3.79). The difference between linear SVR and MLR was statistically significant (p < 0.001). RBF SVR had the advantage of requiring only 2

Oromucosal film preparations: classification and characterization methods.

PubMed

Preis, Maren; Woertz, Christina; Kleinebudde, Peter; Breitkreutz, Jörg

2013-09-01

Recently, the regulatory authorities have enlarged the variety of 'oromucosal preparations' by buccal films and orodispersible films. Various film preparations have entered the market and pharmacopoeias. Due to the novelty of the official monographs, no standardized characterization methods and quality specifications are included. This review reports the methods of choice to characterize oromucosal film preparations with respect to biorelevant characterization and quality control. Commonly used dissolution tests for other dosage forms are not transferable for films in all cases. Alternatives and guidance on decision, which methods are favorable for film preparations are discussed. Furthermore, issues about requirements for film dosage forms are reflected. Oromucosal film preparations offer a wide spectrum of opportunities. There are a lot of suggestions in the literature on how to control the quality of these innovative products, but no standardized tests are available. Regulatory authorities need to define the standards and quality requirements more precisely.

Treatment of Sjögren's syndrome dry eye using 0.03% tacrolimus eye drop: Prospective double-blind randomized study.

PubMed

Moscovici, Bernardo Kaplan; Holzchuh, Ricardo; Sakassegawa-Naves, Fernando Eiji; Hoshino-Ruiz, Diego Ricardo; Albers, Marcos Bottene Villa; Santo, Ruth Miyuki; Hida, Richard Yudi

2015-10-01

To describe the clinical efficacy of the treatment of Sjögren's syndrome dry eye using 0.03% tacrolimus eye drop. Prospective double-blind randomized study. Institutional outpatient clinic. Forty-eight eyes of twenty-four patients with dry eye related to Sjögren syndrome were enrolled in this study. The patients were randomized in 2 groups: tacrolimus (n=14) and vehicle (n=10) group. The tacrolimus group received a vial containing tacrolimus 0.03% (almond oil as vehicle) and the other group received the almond oil vehicle. All patients were instructed to use the eye drops every 12h in the lower conjunctival sac. Schirmer I test, break-up-time (BUT), corneal fluorescein and Rose Bengal staining scores were evaluated in all patients one day before the treatment (baseline), 7, 14, 28 and 90 days after treatment with the eye drops. The average fluorescein and Rose Bengal scores improved statistically after 7 days of treatment and even more after 90 days. The average Schirmer I and BUT values were unchanged after 7, 14 and 21 days but did show an improvement relative to baseline after 28 days of treatment. Schirmer I, BUT, fluorescein and Rose Bengal did not show any statistical significance in the vehicle group. Topical 0.03% tacrolimus eye drop improved tear stability and ocular surface status in cases of inflammatory or SS-related dry eye. ClinicalTrials.gov Identifier: NCT01850979. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

The impact of conversion from prograf to generic tacrolimus in liver and kidney transplant recipients with stable graft function.

PubMed

Momper, J D; Ridenour, T A; Schonder, K S; Shapiro, R; Humar, A; Venkataramanan, R

2011-09-01

Bioequivalence of the recently available generic tacrolimus formulation, manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma, Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in transplant patients have not been evaluated. Tacrolimus trough concentrations and indices of liver and kidney function were recorded before and after generic substitution in 48 liver and 55 kidney transplant recipients. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (± SD) was 184.1 (± 123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (± 87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D-ratios in kidney transplant patients were 125.3 (± 92.7) and 110.4 (± 79.2) ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p < 0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver and 0.87 ng/mL in kidney transplant patients following the switch, after accounting for all significant covariates. No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution. These results suggest that transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz-generic product provided trough concentrations are closely monitored following the substitution. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients.

PubMed

Provenzani, Alessio; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Vizzini, Giovanni; Salis, Paola; Caccamo, Chiara; Bertani, Tullio; Palazzo, Ugo; Polidori, Piera; Gridelli, Bruno; D'Alessandro, Natale

2011-12-01

Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T/A] and 26 [3435C>T] in both liver transplant donors and recipients and in kidney transplant recipients. Of the 152 subjects studied, 84.9% showed a CYP3A5*3/*3 genotype. The total frequency of the allelic variant *3 was 93%. For the G2677T/A and C3435T polymorphisms the total frequencies of the allelic variants T/A and T were 44.7 and 46.7%, respectively. At 1, 3 and 6 months after transplantation the dose-adjusted C0 levels were significantly lower in patients with one copy of the *1 allele compared to those homozygous for the *3 allele. In the case of liver transplant patients the tacrolimus dose requirements were dominantly influenced by the polymorphisms of the CYP3A5 gene in the donors. With regard to the ABCB1 SNPs, in general they did not show any appreciable influence on tacrolimus dosing requirements; however, kidney transplant recipients carrying the 2677T/A allele required significantly higher daily tacrolimus doses than subjects homozygous for the wild-type allele. Identification of CYP3A5 single nucleotide polymorphisms prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus in the patients.

Different top-down approaches to estimate measurement uncertainty of whole blood tacrolimus mass concentration values.

PubMed

Rigo-Bonnin, Raül; Blanco-Font, Aurora; Canalias, Francesca

2018-05-08

Values of mass concentration of tacrolimus in whole blood are commonly used by the clinicians for monitoring the status of a transplant patient and for checking whether the administered dose of tacrolimus is effective. So, clinical laboratories must provide results as accurately as possible. Measurement uncertainty can allow ensuring reliability of these results. The aim of this study was to estimate measurement uncertainty of whole blood mass concentration tacrolimus values obtained by UHPLC-MS/MS using two top-down approaches: the single laboratory validation approach and the proficiency testing approach. For the single laboratory validation approach, we estimated the uncertainties associated to the intermediate imprecision (using long-term internal quality control data) and the bias (utilizing a certified reference material). Next, we combined them together with the uncertainties related to the calibrators-assigned values to obtain a combined uncertainty for, finally, to calculate the expanded uncertainty. For the proficiency testing approach, the uncertainty was estimated in a similar way that the single laboratory validation approach but considering data from internal and external quality control schemes to estimate the uncertainty related to the bias. The estimated expanded uncertainty for single laboratory validation, proficiency testing using internal and external quality control schemes were 11.8%, 13.2%, and 13.0%, respectively. After performing the two top-down approaches, we observed that their uncertainty results were quite similar. This fact would confirm that either two approaches could be used to estimate the measurement uncertainty of whole blood mass concentration tacrolimus values in clinical laboratories. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation

PubMed Central

de Mesquita Coutinho, P R; Cristante, A F; de Barros Filho, T E P; Ferreira, R; dos Santos, G B

2016-01-01

Study design: Experimental study with rats. Objective: To evaluate functional and histological effects of tacrolimus (FK 506) and erythropoietin (EPO) after experimental spinal cord contusion injury (SCI). Setting: Brazil. Methods: Wistar rats (n=60) were submitted to SCI with the NYU Impactor system. The control group received saline; the EPO group received EPO; the group EPO+FK 506 received EPO associated with tacrolimus and the group FK 506 received tacrolimus only. The Sham group underwent SCI, but did not receive any drug. Locomotor function was evaluated after SCI by BBB (Basso, Beattie and Bresnahan) weekly and by the motor-evoked potential test in 42 days. The spinal cord was histologically evaluated. Results: There was a significant difference between treated and the control groups from the seventh day on for BBB scores, with no difference between the groups EPO and EPO+FK 506 by the end of the study. There were significant differences between groups for necrosis and bleeding, but not for hiperemia, degeneration and cellular infiltrate. Axon neuron count was different between all groups (P=0.001), between EPO+FK 506 and FK 506 (P=0.011) and between EPO+FK 506 and Sham (P=0.002). Amplitude was significantly different between all groups except between control and sham. For latency, there was no difference. Conclusions: This study did not reveal significant differences in the recovery of locomotor function, or in the histological and electrophysiological analysis in animals treated with EPO and tacrolimus after thoracic SCI. PMID:26481712

A Markov chain model to evaluate the effect of CYP3A5 and ABCB1 polymorphisms on adverse events associated with tacrolimus in pediatric renal transplantation.

PubMed

Sy, Sherwin K B; Heuberger, Jules; Shilbayeh, Sireen; Conrado, Daniela J; Derendorf, Hartmut

2013-10-01

The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.

Conversion from cyclosporine to tacrolimus improves renal function and lipid profile after cardiac transplantation.

PubMed

Garlicki, Mirosław; Czub, Paweł; Labuś, Krzysztof; Ehrlich, Marek P; Rdzanek, Hanna

2006-01-01

Calcineurin inhibitors (CNIs) have become the cornerstone of immunosuppressive regimens following heart transplantation, but their use is associated with nephrotoxicity. The impact on renal function after conversion from cyclosporine (CsA) to tacrolimus (TAC) is reported. Fifteen patients (men age 42 +/- 11 years) after cardiac transplantation (HTX) were switched from CsA to TAC (mean time after HTX 21 +/- 6 months). There were 13 male and 2 female patients. Mean cholesterol and LDL level at the time of conversion were 217 +/- 65 ml/dl and and 136 +/- 51 mg/100 ml respectively. Indication for HTX was ischemic cardiomyopathy (CMP) in 8, congenital in 3 and dilatative CMP in the remaining 4 patients. Mean tacrolimus level (microg/dl) at 1, 3, 6 and 12 months were 8.6 +/- 3.3, 8.6 +/- 1.4, 9.2 +/- 2.8 and 9.8 +/- 2.5 respectively. There was a statistically significant improvement in creatinine levels at 1, 3, 6 and 12 months after conversion from baseline 1.9 +/- 0.7 mg/dl to 1.4 +/- 0.5 mg/dl, 1.4 +/- 0.4 mg/dl, 1.3 +/- 0.4 mg/dl and 1.2 +/- 0.4 mg/dl, respectively (p < 0.05). Furthermore, TAC decreased cholesterol as well as LDL-levels during this one-year time frame. This study shows that conversion from CsA to tacrolimus after orthotopic heart transplantation improves renal function.

Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.

PubMed

Ito, Ayano; Okada, Yuko; Hashita, Tadahiro; Aomori, Tohru; Hiromura, Keiju; Nojima, Yoshihisa; Nakamura, Tomonori; Araki, Takuya; Yamamoto, Koujirou

2017-06-01

The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.

The Preparation and Characterization of Materials.

ERIC Educational Resources Information Center

Wold, Aaron

1980-01-01

Presents several examples illustrating different aspects of materials problems, including problems associated with solid-solid reactions, sintering and crystal growth, characterization of materials, preparation and characterization of stoichiometric ferrites and chromites, copper-sulfur systems, growth of single crystals by chemical vapor…

Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

DTIC Science & Technology

2016-10-01

Chimerism Vascularized Composite Allograft Tolerance Induction Protocol PRINCIPAL INVESTIGATORS: Dr. Curtis L. Cetrulo CONTRACTING ORGANIZATION...Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance...tacrolimus, FK506, vascularized composite allografts , immune rejection, preclinical, transplant, nonhuman primate model, degradable polymer, tyrosine

Efficacy and Safety of Tacrolimus Therapy for Active Ulcerative Colitis; A Systematic Review and Meta-analysis

PubMed Central

Komaki, Yuga; Komaki, Fukiko; Ido, Akio

2016-01-01

Background: Approximately 25% of patients with ulcerative colitis [UC] experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus as a rescue therapy for active UC. Methods: Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short- and long-term clinical response, colectomy free rates, and rate of adverse events in randomised controlled trials [RCTs] and observational studies. Results: Two RCTs comparing high trough concentration [10–15ng/ml] versus placebo [n = 103] and 23 observational studies [n = 831] were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio [RR] = 4.61, 95% confidence interval [CI] = 2.09–10.17, p = 0.15 x 10-3] among RCTs. Rates of clinical response at 1 and 3 months were 0.73 [95% CI = 0.64–0.81] and 0.76 [95% CI = 0.59–0.87], and colectomy-free rates remained high at 1, 3, 6, and 12 months [0.86, 0.84, 0.78, and 0.69, respectively] among observational studies. Among RCTs, adverse events were more frequent compared with placebo [RR = 2.01, 95% CI = 1.20–3.37, p = 0.83 x 10-2], but there was no difference in severe adverse events [RR = 3.15, 95% CI = 0.14–72.9, p = 0.47]. Severe adverse events were rare among observational studies [0.11, 95% CI = 0.06–0.20]. Conclusions: In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC. PMID:26645641

Efficacy and Safety of Tacrolimus Therapy for Active Ulcerative Colitis; A Systematic Review and Meta-analysis.

PubMed

Komaki, Yuga; Komaki, Fukiko; Ido, Akio; Sakuraba, Atsushi

2016-04-01

Approximately 25% of patients with ulcerative colitis [UC] experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus as a rescue therapy for active UC. Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short- and long-term clinical response, colectomy free rates, and rate of adverse events in randomised controlled trials [RCTs] and observational studies. Two RCTs comparing high trough concentration [10-15ng/ml] versus placebo [n = 103] and 23 observational studies [n = 831] were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio [RR] = 4.61, 95% confidence interval [CI] = 2.09-10.17, p = 0.15 x 10(-3)] among RCTs. Rates of clinical response at 1 and 3 months were 0.73 [95% CI = 0.64-0.81] and 0.76 [95% CI = 0.59-0.87], and colectomy-free rates remained high at 1, 3, 6, and 12 months [0.86, 0.84, 0.78, and 0.69, respectively] among observational studies. Among RCTs, adverse events were more frequent compared with placebo [RR = 2.01, 95% CI = 1.20-3.37, p = 0.83 x 10(-2)], but there was no difference in severe adverse events [RR = 3.15, 95% CI = 0.14-72.9, p = 0.47]. Severe adverse events were rare among observational studies [0.11, 95% CI = 0.06-0.20]. In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A differential impact of mycophenolic acid, prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.

PubMed

Barraclough, Katherine A; Staatz, Christine E; Johnson, David W; Gillis, David; Lee, Katie J; McWhinney, Brett C; Ungerer, Jacobus P J; Campbell, Scott B; Isbel, Nicole M

2013-04-01

Soluble CD30 (sCD30) has been associated with rejection and graft loss in kidney transplantation, leading to the suggestion that sCD30 might be a useful biomarker to adjust immunosuppressant medication dosing. However, there has been minimal study of the influence of individual immunosuppressive drugs on sCD30 levels. To evaluate the influence of mycophenolic acid (MPA), prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients. The sCD30 levels were measured pretransplant and 30 days posttransplant. Area under the concentration-time curve (AUC) for each drug was estimated on day 30 using validated, multiple regression-derived limited sampling strategies. One hundred twenty-five subjects were included. Median (interquartile range) sCD30 levels were lower on day 30 posttransplant compared with pretransplant [10.7 (3.7-20.1) pg/mL versus 66.5 (46.0-95.1) pg/mL; P < 0.0001]. On univariate analyses, day 30 sCD30 levels were negatively correlated with MPA exposure and positively correlated with tacrolimus exposure. Using multivariate logistic regression, higher tacrolimus exposure was independently associated with higher day 30 sCD30 levels (2.2 change in odds for an SD increase in tacrolimus AUC 0-12, P = 0.01; 5.5 change in odds for an SD increase in tacrolimus predose concentration, P < 0.0001). In contrast, MPA and total and free prednisolone exposures were not independently associated with sCD30 levels. The sCD30 levels are significantly reduced in the presence of combination immunosuppression but are differentially affected by different immunosuppressant agents. More research is required before introduction of sCD30 measurement into clinical practice can be considered.

Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.

PubMed

Woodworth, Michael H; Kraft, Colleen S; Meredith, Erika J; Mehta, Aneesh K; Wang, Tiffany; Mamo, Yafet T; Dhere, Tanvi; Sitchenko, Kaitlin L; Patzer, Rachel E; Friedman-Moraco, Rachel J

2018-04-01

Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China.

PubMed

Zhou, Lei; Liu, Weibin; Li, Wei; Li, Haifeng; Zhang, Xu; Shang, Huifang; Zhang, Xu; Bu, Bitao; Deng, Hui; Fang, Qi; Li, Jimei; Zhang, Hua; Song, Zhi; Ou, Changyi; Yan, Chuanzhu; Liu, Tao; Zhou, Hongyu; Bao, Jianhong; Lu, Jiahong; Shi, Huawei; Zhao, Chongbo

2017-09-01

To determine the efficacy of low-dose, immediate-release tacrolimus in patients with myasthenia gravis (MG) with inadequate response to glucocorticoid therapy in a randomized, double-blind, placebo-controlled study. Eligible patients had inadequate response to glucocorticoids (GCs) after ⩾6 weeks of treatment with prednisone ⩾0.75 mg/kg/day or 60-100 mg/day. Patients were randomized to receive 3 mg tacrolimus or placebo daily (orally) for 24 weeks. Concomitant glucocorticoids and pyridostigmine were allowed. Patients continued GC therapy from weeks 1-4; from week 5, the dose was decreased at the discretion of the investigator. The primary efficacy outcome measure was a reduction, relative to baseline, in quantitative myasthenia gravis (QMG) score assessed using a generalized linear model; supportive analyses used alternative models. Of 138 patients screened, 83 [tacrolimus ( n = 45); placebo ( n = 38)] were enrolled and treated. The change in adjusted mean QMG score from baseline to week 24 was -4.9 for tacrolimus and -3.3 for placebo (least squares mean difference: -1.7, 95% confidence interval: -3.5, -0.1; p = 0.067). A post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group (68.2%) versus the placebo group (44.7%; p = 0.044). Adverse event profiles were similar between treatment groups. Tacrolimus 3 mg treatment for patients with MG and inadequate response to GCs did not demonstrate a statistically significant improvement in the primary endpoint versus placebo over 24 weeks; however, a post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group versus the placebo group. This study was limited by the low number of patients, the absence of testing for acetylcholine receptor antibody and the absence of stratification by disease duration (which led to a disparity between the two groups). Clinical

Successful treatment with 308-nm monochromatic excimer light and subsequent tacrolimus 0.03% ointment in refractory plasma cell cheilitis.

PubMed

Yoshimura, Kazuhiro; Nakano, Shunji; Tsuruta, Daisuke; Ohata, Chika; Hashimoto, Takashi

2013-06-01

Plasma cell cheilitis is a chronic inflammatory disease that presents with erythema, erosions, ulcers and occasional nodules within the mucosa, including the lips. It is histopathologically characterized by dense plasma cell infiltration in the lamina propria of the mucous membranes. Several treatments for plasma cell cheilitis have been reported, including topical steroids, topical antibiotics or topical tacrolimus. However, 308-nm monochromatic excimer light (MEL) has never been reported as a treatment option, while it was reported to be very effective in treating erosive oral lichen planus. We report a 62-year-old man who had chronic plasma cell cheilitis on the lower lip, which was refractory to topical and systemic corticosteroid. The lesion and severe pain were significantly improved by the treatment with nine sessions of 308-nm MEL twice per week with a total dose of 1120 mJ/cm(2). However, the lesion gradually worsened after treatment frequency was reduced to once per month. Subsequent tacrolimus 0.03% ointment cleared the lesion completely in a month and no recurrence was observed a year later. Refractory plasma cell cheilitis and concomitant severe pain quickly responded to 308-nm MEL when administrated twice per week. Because the long interval between each MEL treatment seemed ineffective to improve the lesion, appropriate frequency and adequate total dose of MEL treatment may be necessary for a successful treatment. © 2013 Japanese Dermatological Association.

Successful management of angiolymphoid hyperplasia with eosinophilia in a split-face trial of topical tacrolimus and timolol solution.

PubMed

Chacon, Anna; Mercer, Jessica

2016-08-01

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign condition characterized by multiple benign angiomatous nodules or plaques. Cutaneous lesions can be painful, pruritic, pulsatile, or potentially disfiguring resulting in significant morbidity. ALHE is a pathologic diagnosis featuring proliferations of capillary-sized vessels with epithelioid endothelial cells surrounded by larger, thick-walled vessels and accompanying eosinophils and lymphocytes. Surgery is generally required, however the skin lesions often recur after excision. ALHE is notoriously difficult to treat and many physicians would prefer a non-invasive treatment of choice. We report a case of ALHE that was successfully treated with the novel use of topical tacrolimus in a split-face trial with topical timolol solution.

A case of vesicular cutaneous lupus erythematosus in a Border collie successfully treated with topical tacrolimus and nicotinamide-tetracycline.

PubMed

Lehner, Georg M; Linek, Monika

2013-12-01

Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period. © 2013 ESVD and ACVD.

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation.

PubMed

Cheung, Chi Yuen; van der Heijden, Jaques; Hoogtanders, Karin; Christiaans, Maarten; Liu, Yan Lun; Chan, Yiu Han; Choi, Koon Shing; van de Plas, Afke; Shek, Chi Chung; Chau, Ka Foon; Li, Chun Sang; van Hooff, Johannes; Stolk, Leo

2008-02-01

Dried blood spot (DBS) sampling and high-performance liquid chromatography tandem-mass spectrometry have been developed in monitoring tacrolimus levels. Our center favors the use of limited sampling strategy and abbreviated formula to estimate the area under concentration-time curve (AUC(0-12)). However, it is inconvenient for patients because they have to wait in the center for blood sampling. We investigated the application of DBS method in tacrolimus level monitoring using limited sampling strategy and abbreviated AUC estimation approach. Duplicate venous samples were obtained at each time point (C(0), C(2), and C(4)). To determine the stability of blood samples, one venous sample was sent to our laboratory immediately. The other duplicate venous samples, together with simultaneous fingerprick blood samples, were sent to the University of Maastricht in the Netherlands. Thirty six patients were recruited and 108 sets of blood samples were collected. There was a highly significant relationship between AUC(0-12), estimated from venous blood samples, and fingerprick blood samples (r(2) = 0.96, P < 0.0001). Moreover, there was an excellent correlation between whole blood venous tacrolimus levels in the two centers (r(2) = 0.97; P < 0.0001). The blood samples were stable after long-distance transport. DBS sampling can be used in centers using limited sampling and abbreviated AUC(0-12) strategy as drug monitoring.

Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial

PubMed Central

Vinks, Alexander A.; Fukuda, Tsuyoshi; King, Eileen C.; Zou, Yuanshu; Jiang, Wenlei; Klawitter, Jelena; Christians, Uwe

2017-01-01

Background Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, “brand”) product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. Methods and findings From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within

Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

PubMed

Alloway, Rita R; Vinks, Alexander A; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; King, Eileen C; Zou, Yuanshu; Jiang, Wenlei; Woodle, E Steve; Tremblay, Simon; Klawitter, Jelena; Klawitter, Jost; Christians, Uwe

2017-11-01

Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug Administration

Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.

PubMed

Rostaing, Lionel; Bunnapradist, Suphamai; Grinyó, Josep M; Ciechanowski, Kazimierz; Denny, Jason E; Silva, Helio Tedesco; Budde, Klemens

2016-04-01

1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR

De novo use of a generic formulation of tacrolimus versus reference tacrolimus in kidney transplantation: evaluation of the clinical results, histology in protocol biopsies, and immunological monitoring.

PubMed

Melilli, Edoardo; Crespo, Elena; Sandoval, Diego; Manonelles, Anna; Sala, Neus; Mast, Richard; Padulles, Ariadna; Grinyo, Josep M; Bestard, Oriol; Cruzado, Josep Maria

2015-11-01

The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport(®) ; Sandoz), replacing the one we were currently using (Prograf(®) ; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5-7 days; 1, 3, and 6 months post-transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD-EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf(®) versus Adoport(®) ), noticing no important differences. We also evaluated the results of protocol biopsies at 6 months in a subgroup of patients, thus verifying the safety and efficacy of this particular generic drug versus the reference product on a histological basis as well. No difference in the development of dnDSA (de novo donor-specific antibody) was found between the two groups. © 2015 Steunstichting ESOT.

Quantitation of tacrolimus in whole blood using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS).

PubMed

Donaldson, Keri J; Shaw, Leslie M

2010-01-01

We describe a multiple reaction monitoring positive ion HPLC/tandem mass spectrometric method for quantification of tacrolimus in human whole blood with online extraction and cleanup. Included in this procedure: API 2000 triple quadrupole mass spectrometer with turbo-ion spray source (Applied Biosystems, Foster City, CA); 10-port diverter/switching valve (Valco, Houston, TX); HPLC system (Agilent Technologies series 1100, Wilmington, DE); 10 mm (C(18)) guard cartridge (Perkin Elmer, Norwalk, CT) used as an extraction column; a Nova-Pak C18 analytical column (2.1 x 150 mm I.D., 4 microm, Waters Corp, Milford, MA); washing solution, methanol: 30 mM ammonium acetate pH 5.1 (80:20); eluting solution, methanol:30 mM ammonium acetate pH 5.1 (97:3); flow rate 0.8 mL/min; and a run-time of 2.8 min. The first and third quadrupoles were set to detect the ammonium adduct ion and a high mass fragment of tacrolimus (m/z 821.5-->768.3), and of an internal standard (ascomycin) (m/z 901.8-->834.4). The lower limit of quantification of this method is 3.75 mg/L. The concentration of drug is determined by comparing peak-area ratios for tacrolimus and internal standard to a standard curve constructed using non-weighted linear through zero regression.

Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

PubMed

Undre, Nasrullah; Dickinson, James

2017-04-04

Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10�

Tacrolimus interaction with nafcillin resulting in significant decreases in tacrolimus concentrations: A case report.

PubMed

Wungwattana, Minkey; Savic, Marizela

2017-04-01

Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Plasma cell cheilitis, successfully treated with topical 0.03% tacrolimus ointment.

PubMed

Jin, Seon Pil; Cho, Kwang Hyun; Huh, Chang Hun

2010-05-01

Plasma cell cheilitis is a rare, idiopathic mucosal condition. The treatment of plasma cell cheilitis is often disappointing. It is often resistant to various topical treatments. We present a 65-year-old woman who had a painful, eroded area on her lower lip, which responded poorly to various topical treatments. A biopsy revealed a band-like infiltration composed mainly of plasma cells in the dermis. She was diagnosed as having plasma cell cheilitis, and was successfully treated with 0.03% topical tacrolimus ointment.

Prediabetes in patients receiving tacrolimus in the first year after kidney transplantation: a prospective and multicenter study.

PubMed

Porrini, Esteban; Moreno, Jose Manuel; Osuna, Antonio; Benitez, Rocio; Lampreabe, Ildefonso; Diaz, Juan Manuel; Silva, Irene; Domínguez, Rosa; Gonzalez-Cotorruelo, Julio; Bayes, Beatriz; Lauzurica, Ricardo; Ibernon, Meritxell; Moreso, Francisco; Delgado, Patricia; Torres, Armando

2008-04-27

Tacrolimus-based immunosuppression, the most widely used regimen in kidney transplantation, increases the risk of new onset diabetes after transplantation (NODAT). However, the prevalence, evolution and risk factors of different prediabetic alterations: impaired fasting glucose, impaired glucose tolerance, and provisional diabetes, have not been established. In this multicenter and prospective study we evaluated 154 nondiabetic kidney transplant recipients receiving tacrolimus, mycophenolate mofetil and low dose steroids. An oral glucose tolerance test was performed 3 and 12 months after transplantation and prediabetes was defined by American Diabetes Association criteria. Prediabetes was highly prevalent and showed little variation between 3 and 12 months (36% and 33%, respectively). Impaired glucose tolerance was the most frequent abnormality observed (23% and 25%, respectively) observed. In addition, 20% of recipients showed NODAT by 1 year. Multivariate analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.004-1.14), pretransplant body mass index (OR: 1.3, CI: 1.09-1.6) and triglyceride/high density lipoprotein-cholesterol ratio, a marker of insulin resistance, (OR: 1.4, CI: 1.05-1.9) were independent risk factors for prediabetes. One in two recipients with tacrolimus-based immunosuppresion showed prediabetes or NODAT by 1 year posttransplantation when properly investigated. Older age and high pretransplant body mass index and triglyceride/high density lipoprotein-cholesterol ratio were risk factors for prediabetes. These findings may help applying early interventions to prevent the disorder.

The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

PubMed Central

Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner

2014-01-01

The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies. PMID:25340655

Preparation and Characterization of PETI-330/Multiwalled Carbon Nanotube

NASA Technical Reports Server (NTRS)

Ghose, Sayata; Watson, Kent A.; Working, Dennis C.; Criss, Jim M.; Siochi, Emilie J.; Connell, John W.

2005-01-01

As part of an ongoing effort to incorporate multifunctionality into advanced composites, blends of PETI-330 and multi-walled carbon nanotubes (MWCNTs) were prepared, characterized and fabricated into moldings. The PETI-330/MWCNT mixtures were prepared at concentrations ranging from 3 to 25 weight percent by dry mixing the components in a ball mill. The resulting powders were characterized for degree of mixing, thermal and rheological properties. Based on the characterization results, PETI-330/MWCNT samples were scaled up to 300 g and used to fabricate moldings 10.2 cm x 15.2 cm x 0.32 cm thick. The moldings were made by injecting the mixtures at 260-280 C into an Invar tool followed by curing for 1 h at 371 C. The tool was designed to impart shear during the injection process in an attempt to achieve some alignment of the MWCNTs in the flow direction. Good quality moldings were obtained that were subsequently characterized for thermal, mechanical and electrical properties. The degree of dispersion and alignment of the MWCNTs were investigated using high-resolution scanning electron microscopy. The preparation and preliminary characterization of PETI-330/MWCNT composites will be discussed. Keywords: phenylethynyl terminated imides, high temperature polymers, nanocomposites, moldings

Pilot Analysis of Late Conversion to Belatacept in Kidney Transplant Recipients for Biopsy-Proven Chronic Tacrolimus Toxicity

PubMed Central

Rosales, Ivy

2018-01-01

Background Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. Methods We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. Results The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months (p = 0.09), 34.1 mL/min at 6 months (p = 0.63), 34.9 mL/min at 12 months (p = 0.57), and 39.6 mL/min at 24 months after conversion (p = 0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. Conclusion While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months. PMID:29854421

Preparation and Characterization of Natural Rubber/Organophilic Clay Nanocomposites

NASA Astrophysics Data System (ADS)

Gonzales-Fernandes, M.; Esper, F. J.; Silva-Valenzuela, M. G.; Martín-Cortés, G. R.; Valenzuela-Diaz, F. R.; Wiebeck, H.

Natural rubber/organophilic clay nanocomposites were prepared and characterized. A brown bentonite from Paraiba's State, Brazil was modified with a sodium salt and treated with quaternary ammonium salt hexadecyltrimethyl ammonium chloride. The clay in its natural state, after cation exchange with sodium and after organophilization was characterized by XRD, IR, SEM, thermal analysis. Nanocomposite samples were prepared containing 10 resin percent of organophilic clay. The vulcanized samples were analyzed by XRD, SEM. The nanocomposites obtained showed improvement in their mechanical properties in comparison with samples without clay.

Randomized Comparison of Topical Betamethasone Valerate Foam, Intralesional Triamcinolone Acetonide and Tacrolimus Ointment in Management of Localized Alopecia Areata

PubMed Central

Kuldeep, CM; Singhal, Himanshu; Khare, Ashok Kumar; Mittal, Asit; Gupta, Lalit K; Garg, Anubhav

2011-01-01

Background: Alopecia areata (AA) is a common, non-scarring, patchy loss of hair at scalp and elsewhere. Its pathogenesis is uncertain; however, auto-immunity has been exemplified in various studies. Familial incidence of AA is 10-42%, but in monozygotic twins is 50%. Local steroids (topical / intra-lesional) are very effective in treatment of localized AA. Aim: To compare hair regrowth and side effects of topical betamethasone valerate foam, intralesional triamcinolone acetonide and tacrolimus ointment in management of localized AA. Materials and Methods: 105 patients of localized AA were initially registered but 27 were drop out. So, 78 patients allocated at random in group A (28), B (25) and C (25) were prescribed topical betamethasone valerate foam (0.1%) twice daily, intralesional triamcinolone acetonide (10mg/ml) every 3 weeks and tacrolimus ointment (0.1%) twice daily, respectively, for 12 weeks. They were followed for next12 weeks. Hair re-growth was calculated using “HRG Scale”; scale I- (0-25%), S II-(26-50%), S III - (51-75%) and S IV- (75-100%). Results: Hair re-growth started by 3 weeks in group B (Scale I: P<0.03), turned satisfactory at 6 weeks in group A and B (Scale I: P<0.005, Scale IV: P<0.001)), good at 9 weeks (Scale I: P<0.0005, Scale IV: P<0.00015), and better by 12 weeks of treatment (Scale I: P<0.000021, Scale IV: P<0.000009) in both A and B groups. At the end of 12 weeks follow-up hair re-growth (>75%, HRG IV) was the best in group B (15 of 25, 60%), followed by A (15 of 28, 53.6%) and lastly group-C (Nil of 25, 0%) patients. Few patients reported mild pain and atrophy at injection sites, pruritus and burning with betamethasone valerate foam and tacrolimus. Conclusion: Intralesional triamcinolone acetonide is the best, betamethasone valerate foam is better than tacrolimus in management of localized AA. PMID:21769231

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial.

PubMed

Nashan, Bjorn; Schemmer, Peter; Braun, Felix; Dworak, Markus; Wimmer, Peter; Schlitt, Hans

2015-03-26

Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients. Hephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in period (3-5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft

Safety and efficacy of the switch to generic mycophenolate mofetil and tacrolimus in heart transplant patients.

PubMed

Söderlund, Carl; Rådegran, Göran

2015-07-01

Generic immunosuppressants may offer economic advantages, but their use is still controversial. At our center, 55 heart transplant patients were switched from CellCept(®) to Myfenax Teva(®) (MT) (n = 51, 18% female, 8.1 ± 6.6 yr post-transplantation) and/or Prograf(®) to Tacrolimus Sandoz(®) (TS) (n = 17, 41% female, 6.6 ± 5.8 yr post-transplantation). We conducted an acute monitoring and a retrospective follow-up with regard to safety and efficacy. Acute cellular rejections (ACRs) on endomyocardial biopsies (EMBs) four wk after the MT switch were specifically compared to a matched retrospective control group. Tacrolimus C0 levels (TS switch) as well as hemoglobin, leukocytes, and thrombocytes (MT switch) did not change (p = NS) during the three wk after each respective switch (8.7 ± 2.9 vs. 8.4 ± 1.9 μg/L, 129.1 ± 12.6 vs. 130.1 ± 12.8 g/L, 6.3 vs. 6.2 × 10(9) /L, and 217.4 ± 56.6 vs. 219.3 ± 61.8 × 10(9) /L, respectively). 0% of the EMBs in the MT switch vs. 3% of the EMBs in the control group showed ACR>grade 1R (p = NS). After six months, survival was 96% (MT switch) and 100% (TS switch), and the frequency of severe ACR was low. Safety parameters measured at the next annual follow-up were also stable following each switch. Switching to MT and/or TS several years after heart transplantation appeared safe in the short-term perspective, showing no detectable changes in tacrolimus C0 levels, safety or efficacy, during an average follow-up of six months. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preparation and Characterization of Cabamazepine Cocrystal in Polymer Solution.

PubMed

Zhang, Hao; Zhu, Ying; Qiao, Ning; Chen, Yang; Gao, Linghuan

2017-12-01

In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected as cocrystal coformers. Cocrystal screening products were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD) techniques. Characterization results show that in ethanol-water solvent mixture, pure CBZ-NIC cocrystal can be prepared, while CBZ-SAC cocrystal cannot be obtained. The addition of PVP can inhibit CBZ-NIC cocrystal formation and facilitate CBZ-SAC cocrystal formation.

Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution

PubMed Central

Zhang, Hao; Zhu, Ying; Chen, Yang; Gao, Linghuan

2017-01-01

In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected as cocrystal coformers. Cocrystal screening products were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD) techniques. Characterization results show that in ethanol-water solvent mixture, pure CBZ-NIC cocrystal can be prepared, while CBZ-SAC cocrystal cannot be obtained. The addition of PVP can inhibit CBZ-NIC cocrystal formation and facilitate CBZ-SAC cocrystal formation. PMID:29194387

Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

PubMed

Nieto, Yago; Patton, Nigel; Hawkins, Timothy; Spearing, Ruth; Bearman, Scott I; Jones, Roy B; Shpall, Elizabeth J; Rabinovitch, Rachel; Zeng, Chan; Barón, Anna; McSweeney, Peter A

2006-02-01

We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.

Preparation and Characterization of PETI-330/Multiwalled Carbon Nanotube Composites

NASA Technical Reports Server (NTRS)

Ghose, Sayata; Watson, Kent A.; Working, Dennis C.; Delozier, Donavon M.; Criss, Jim M.; Siochi, Emilie J.; Connell, John W.

2005-01-01

As part of an ongoing effort to incorporate multi-functionality into advanced composites, blends of PETI-330 and multi-walled carbon nanotubes (MWCNTs) were prepared, characterized and fabricated into moldings. The PETI-330/MWCNT mixtures were prepared at concentrations ranging from 3 to 25 weight percent by dry mixing the components in a ball mill. The resulting powders were characterized for degree of mixing, thermal and rheological properties. Based on the characterization results, PETI-330/MWCNT samples were scaled up to approx. 300 g and used to fabricate moldings 10.2 cm x 15.2 cm x 0.32 cm thick. The moldings were fabricated by injecting the mixtures at 260-280 C into a stainless steel tool followed by curing for 1 h at 371 C. The tool was designed to impart high shear during the injection process in an attempt to achieve some alignment of the MWCNTs in the flow direction. Good quality moldings were obtained that were subsequently characterized for thermal, mechanical and electrical properties. The degree of dispersion and alignment of the MWCNTs were investigated using high-resolution scanning electron microscopy and Raman spectroscopy. The preparation and preliminary characterization of PETI-330/MWCNT composites will be discussed. Keywords: phenylethynyl terminated imides, high temperature polymers, nanocomposites,

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement.

PubMed

Ponnammal, Poovizhi; Kanaujia, Parijat; Yani, Yin; Ng, Wai Kiong; Tan, Reginald B H

2018-03-16

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus ® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus ® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement

PubMed Central

Ponnammal, Poovizhi; Kanaujia, Parijat; Ng, Wai Kiong; Tan, Reginald B. H.

2018-01-01

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w/w. Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage. PMID:29547585

A comparison of the extended-release and standard-release formulations of tacrolimus in de novo kidney transplant recipients: a 12-month outcome study.

PubMed

Fanous, Helen; Zheng, Rebecca; Campbell, Carolyn; Huang, Michael; Nash, Michelle M; Rapi, Lindita; Zaltzman, Jeffrey S; Prasad, G V Ramesh

2013-02-01

BACKGROUND: Limited comparative data are available on the outcomes between extended-release and standard-release tacrolimus when used de novo in kidney transplant recipients (KTRs). METHODS: We identified KTRs transplanted at our institution during 2009-10 routinely prescribed extended-release tacrolimus and compared them with those transplanted during 2008-09 prescribed standard-release tacrolimus. Graft function (eGFR by MDRD-7 equation) at 12 months post-transplant (primary outcome); new-onset diabetes and other cardiovascular risk factors, BK viremia incidence, acute rejection, and graft survival to 12 months (secondary outcomes) were compared by intent-to-treat analysis. Time-to-steady-state concentration and number of dose adjustments required to attain steady state were recorded. RESULTS: There were no important demographic differences between the extended-release (N = 106) and standard-release (N = 95) cohorts. The estimated glomerular filtration rate (eGFR) at 12 months was similar (58.8 ± 17 versus 59.2 ± 18 mL/min/1.73 m(2), P = 0.307). There was no difference in new-onset diabetes (17 versus 20%, P = 0.581), BK viremia (10 versus 7%, P = 0.450), acute rejection (7 versus 16%, P = 0.067) or graft survival (97 versus 95%, P = 0.301). Time-to-steady state was similar (9.2 ± 1.1 versus 8.1 ± 4.7 days, P = 0.490) although extended-release patients required fewer adjustments to attain steady state (1.2 ± 1.7 [0-8] versus 1.7 ± 1.5 [0-7], P = 0.030) but a similar dose (7.2 ± 2.4 [2-17] versus 7 ± 2.7 [2-16] mg/day, P = 0.697). CONCLUSION: De novo KTRs prescribed extended-release or standard-release tacrolimus demonstrate similar 12-month outcomes.

Preparation and Characterization of Hydroxyapatite-Silica Composite Nanopowders

NASA Astrophysics Data System (ADS)

Latifi, S. M.; Fathi, M. H.; Golozar, M. A.

One of the most important objectives in the field of biomaterials science and engineering is development of new materials as bone substitutes. Silica (SiO2) has an important role in the biomineralization and biological responses. The aim of this research was to prepare and characterize hydroxyapatite-silica (HA-SiO2) composite nanopowder with different content of silica. Hydroxyapatite-silica composite nanopowders with 20 and 40 wt% silica were prepared using a sol-gel method at 600°C with phosphoric pentoxide and calcium nitrate tetrahydrate as a source of hydroxyapatite; also, tetraethylorthosilicate and methyltriethoxisilane as a source of silica. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) techniques were used for characterization and evaluation of the products. The results indicated the presence of nanocrystalline hydroxyapatite phase beside amorphous silica phase in prepared composite nanopowders. Moreover, by increasing the content of silica in composite nanopowders, the crystallinity will be decreased,and the ability of the product as a bone substitute material might be controlled by changing the content of the ingredients and subsequently its structure.

[Application of Fourier amplitude sensitivity test in Chinese healthy volunteer population pharmacokinetic model of tacrolimus].

PubMed

Guan, Zheng; Zhang, Guan-min; Ma, Ping; Liu, Li-hong; Zhou, Tian-yan; Lu, Wei

2010-07-01

In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.

Preparation of surface enhanced Raman substrate and its characterization

NASA Astrophysics Data System (ADS)

Liu, Y.; Wang, J. Y.; Wang, J. Q.

2017-10-01

Surface enhanced Raman spectroscopy (SERS) is a fast, convenient and highly sensitive detection technique, and preparing the good effect and repeatable substrate is the key to realize the trace amount and quantitative detection in the field of food safety detection. In this paper, a surface enhanced Raman substrate based on submicrometer silver particles structure was prepared by chemical deposition method, and characterized its structure and optical properties.

Chromatography in the detection and characterization of illegal pharmaceutical preparations.

PubMed

Deconinck, Eric; Sacré, Pierre-Yves; Courselle, Patricia; De Beer, Jacques O

2013-09-01

Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques such as infrared spectroscopy and Raman spectroscopy have always been the first methods of choice to detect counterfeits and illegal preparations, but due to the evolution in the seized products and the necessity of risk assessment, chromatographic methods are becoming more important in this domain. This review intends to give a general overview of the techniques described in literature to characterize counterfeit and illegal pharmaceutical preparations, focusing on the role of chromatographic techniques with different detection tools.

Granulosis rubra nasi: a rare condition treated successfully with topical tacrolimus.

PubMed

Kumar, Piyush; Gosai, Anubhav; Mondal, Ashim Kumar; Lal, Niharika Ranjan; Gharami, Ramesh Chandra

2012-01-02

A 20 years-old girl presented with multiple asymptomatic reddish vesicles on face for four years. It used to get worse in summer and was associated with localized hyperhidrosis. The lesions were notable for disappearance on diascopy. Histopathology from the vesicle showed mononuclear cell infiltration in the upper dermis, especially around eccrine sweat apparatus, along with dilatation of superficial capillaries and lymphatics. Based on clinical presentation and histopathology, diagnosis of Granulosis rubra nasi (GRN) was made. GRN usually resolves at puberty; however, rarely it may persist in adulthood. We here report a case of GRN having lesions persisting in adulthood. Moreover, she showed excellent response to topical tacrolimus, a finding not observed in literature.

Advanced Research Projects Agency on Materials Preparation and Characterization Research

DTIC Science & Technology

Briefly summarized is research concerned with such topics as: Preparation of silica glass from amorphous silica; Glass structure by Raman ...ferroelectrics; Silver iodide crystals; Vapor phase growth; Refractory optical host materials; Hydroxyapatite ; Calcite; Characterization of single crystals with a double crystal spectrometer; Characterization of residual strain.

Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy.

PubMed

Campbell, John N; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B

2014-01-01

Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later.

Advantage of Rapamycin Over Mycophenolate Mofetil When Used With Tacrolimus for Simultaneous Pancreas Kidney Transplants: Randomized, Single-Center Trial at 10 Years

PubMed Central

Ciancio, G.; Sageshima, J.; Chen, L.; Gaynor, J. J.; Hanson, L.; Tueros, L.; Montenora-Velarde, E.; Gomez, C.; Kupin, W.; Guerra, G.; Mattiazzi, A.; Fornoni, A.; Pugliese, A.; Roth, D.; Wolf, M.; Burke, G. W.

2015-01-01

Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent. PMID:22946986

Erosive pustular dermatosis of the scalp successfully treated with oral prednisone and topical tacrolimus*

PubMed Central

Zahdi, Mariana Ribas; Seidel, Gabriela Bestani; Soares, Vanessa Cristina; de Freitas, Camila Fernanda Novak Pinheiro; Mulinari-Brenner, Fabiane Andrade

2013-01-01

Erosive pustular dermatosis of the scalp is a rare inflammatory disorder of the scalp, affecting elderly patients after local trauma and leading to scarring or cicatricial alopecia. Case Report: An elderly female patient complained of painful pustules on the parietal region bilaterally with progressive enlargement and ulceration. A biopsy suggested erosive pustular dermatosis of the scalp and the patient was treated with prednisone 40 mg/day and 0.1% topical tacrolimus. After 10 weeks complete closure of the eroded areas was observed and a stable scarring alopecia developed. PMID:24173187

Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy

PubMed Central

Campbell, John N.; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B.

2014-01-01

Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later. PMID:25580467

Tacrolimus has immunosuppressive effects on heavy/light chain pairs and free light chains in patients after heart transplantation: A relationship with infection.

PubMed

Lavríková, Petra; Sečník, Peter; Kubíček, Zdenek; Jabor, Antonín; Hošková, Lenka; Franeková, Janka

2018-06-15

The aim of the study was to investigate the relationship between tacrolimus (TAC) immunosuppressive treatment and serum concentrations of immunoglobulin heavy/light chain pairs (sHLC) and free light chains (sFLC) in patients after heart transplantation (HTX) and to use these biomarkers to predict the risk of infection in these patients. A total of 88 patients with an immunosuppressive regimen involving tacrolimus who underwent HTX were analyzed over 24 months of follow-up. sFLC and sHLC levels were determined before and at three time points after HTX. TAC concentrations were determined at several time points after HTX, and mean TAC concentrations and areas under the curve (AUCs) of TAC concentration were calculated. Relevant clinical data were obtained from patients' medical records. A larger AUC of TAC was associated with decreases in the concentrations of IgG total (p < 0.05); similarly, cumulative AUC of TAC during 18 post-transplant months correlated inversely with sHLC IgG kappa (r = -0.228, p < 0.05) and IgG total (r = -0.352, p < 0.05). Concentrations of sFLC kappa, sFLC lambda, sHLC IgG kappa, and sHLC IgG total were significantly lower in infected patients (in the 9th month after HTX, all p < 0.05). Combined criteria for increased AUC (greater than the median of 12.9 mg·d/l) and decreased sFLC kappa (less than the median of 12.5 mg/l) correlated with the presence of infection (p < 0.03) in the 9th month after HTX. Ratio of concentration of TAC to sFLC kappa or lambda was significantly higher in infected patients (both p < 0.05). Intensive treatment with tacrolimus after HTX is possibly reflected by decreases in sFLC and sHLC (mainly sHLC IgG). Patients with decreased concentrations of these biomarkers are at increased risk for infection, primarily in the 9th month after HTX, when the concentrations of tacrolimus were the highest. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation and Characterization of New Geopolymer-Epoxy Resin Hybrid Mortars

PubMed Central

Colangelo, Francesco; Roviello, Giuseppina; Ricciotti, Laura; Ferone, Claudio; Cioffi, Raffaele

2013-01-01

The preparation and characterization of metakaolin-based geopolymer mortars containing an organic epoxy resin are presented here for the first time. The specimens have been prepared by means of an innovative in situ co-reticulation process, in mild conditions, of commercial epoxy based organic resins and geopolymeric slurry. In this way, geopolymer based hybrid mortars characterized by a different content of normalized sand (up to 66% in weight) and by a homogeneous dispersion of the organic resin have been obtained. Once hardened, these new materials show improved compressive strength and toughness in respect to both the neat geopolymer and the hybrid pastes since the organic polymer provides a more cohesive microstructure, with a reduced amount of microcracks. The microstructural characterization allows to point out the presence of an Interfacial Transition Zone similar to that observed in cement based mortars and concretes. A correlation between microstructural features and mechanical properties has been studied too. PMID:28811418

Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

PubMed

Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

2016-02-01

A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP-12.

PubMed

Hirsch, H H; Yakhontova, K; Lu, M; Manzetti, J

2016-03-01

BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV-specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)- and calcineurin-inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR-SP6-kinase activation. Sirolimus inhibition was rapid and effective up to 24 h postinfection during viral early gene expression, but not thereafter, during viral late gene expression. The mTORC-1 kinase inhibitor torin-1 showed a similar inhibition profile, supporting the notion that early steps of BKPyV replication depend on mTOR activity. Cyclosporine A also inhibited BKPyV replication, while tacrolimus activated BKPyV replication and reversed sirolimus inhibition. FK binding protein 12kda (FKBP-12) siRNA knockdown abrogated sirolimus inhibition and increased BKPyV replication similar to adding tacrolimus. Thus, sirolimus and tacrolimus exert opposite effects on BKPyV replication in renal tubular epithelial cells by a mechanism involving FKBP-12 as common target. Immunosuppressive drugs may therefore contribute directly to the risk of BKPyV replication and nephropathy besides suppressing T cell functions. The data provide rationales for clinical trials aiming at reducing the risk of BKPyV replication and disease in kidney transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Investigating the Impact of Drug Crystallinity in Amorphous Tacrolimus Capsules on Pharmacokinetics and Bioequivalence Using Discriminatory In Vitro Dissolution Testing and Physiologically Based Pharmacokinetic Modeling and Simulation.

PubMed

Purohit, Hitesh S; Trasi, Niraj S; Sun, Dajun D; Chow, Edwin C Y; Wen, Hong; Zhang, Xinyuan; Gao, Yi; Taylor, Lynne S

2018-05-01

Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or on storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both United States Pharmacopeia and noncompendial dissolution tests with different dissolution media and volumes. A physiologically based pharmacokinetic (PBPK) absorption model was developed to predict the impact of crystallinity extent on the oral absorption of the products and to evaluate the discriminatory ability of the different dissolution methods. Virtual bioequivalence simulations between partially crystallized tacrolimus capsules versus fresh Prograf or generic tacrolimus capsules were performed using the PBPK model and in vitro dissolution data of the various fresh and partially crystallized capsules under United States Pharmacopeia and noncompendial dissolution conditions. The results suggest that compendial dissolution tests may not be sufficiently discriminatory with respect to the presence of crystallinity in an amorphous formulation. Nonsink dissolution tests using lower dissolution volumes generate more discriminatory profiles that predict different pharmacokinetics of tacrolimus capsules containing different extents of drug crystallinity. In conclusion, the PBPK modeling approach can be used to assess the impact of partial drug crystallinity in the formulated product and to guide the development of appropriate dissolution methods. Copyright © 2018 American Pharmacists Association®. All rights

Clinical study of double dose of valsartan combined with tacrolimus in treatment of diabetic nephropathy.

PubMed

Jin, H; Zhang, H-N; Hou, X-L; Zhang, B; Wu, J; Zhang, H-B

2016-01-01

To investigate the clinical effect of double dose of valsartan combined with tacrolimus in the treatment of diabetic nephropathy (DN). HA total of 86 cases diagnosed with DN were selected from October 2013 to October 2014 in Zaozhuang Municipal Hospital, China. The study was approved by our hospital Ethics Committee and written consent was obtained from patients and their family members. Patients were randomly divided into three groups according to the sequence of admission, group A (conventional dose of valsartan group, n = 28 cases), group B (double dose of valsartan group, n = 29 cases) and group C (double dose of valsartan combined with tacrolimus group, n = 29). Clinical effects were compared by analyzing the renal function tests after 8 weeks. 24h urine protein, serum creatinine level of patients in group B and group C were significantly lower than that of group A. Those in group C was much lower. The glomerular filtration rates were significantly higher for group B and C than that of group A, and those in group C were much higher. The difference is statistically significant (p < 0.05). High-sensitivity C-reactive protein (hs CRP) and adiponectin levels of patients in group B and C of were significantly lower than that of group A and those in group C were much lower. The difference is statistically significant (p < 0.05). The high mobility group protein 1 (HMGB1) and renal tubular and interstitial damage index (TDI) of patients in B and C groups were significantly lower than those in the A group, and those in C group were significantly lower. The difference was statistically significant p < 0.05). The clinical effective rates of patients in group B and C were significantly higher than that in group A, and those of group C were much higher. The difference is statistically significant (p < 0.05). The recurrence rates of patients in group B and group C were significantly lower than those of group A and those in group C were much lower. The difference is

Correlation between viral load of cytomegalovirus and tacrolimus and sirolimus levels in transplanted pediatric patients.

PubMed

Reyes-Pérez, Herlinda; Sánchez-Huerta, José Luis; Varela-Fascinetto, Gustavo; Romo-Vázquez, José Carlos; Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M; Parra-Ortega, Israel; Ramírez-Ramírez, Graciela; López-Martínez, Briceida

Survival of transplant patients and grafts depends largely on the use of immunosuppressive drugs. However, a balance remains to be established among immunosuppression, transplant rejection and cytomegalovirus (CMV) infection, which results in a high rate of morbidity and mortality. The aim of this study was to define a better strategy for monitoring transplanted patients based on the analysis of the blood concentration of sirolimus and tacrolimus and the burden of CMV. Fifty five post-transplant (kidney and liver) pediatric patients, nine treated with sirolimus and 46 treated with tacrolimus, were included. A total of 541 measurements were obtained. In each measurement the concentration of immunosuppressant in whole blood and CMV viral load in plasma and whole blood was quantified by real-time PCR. Pearson correlation coefficient (r) was estimated. Values of r ≤0.0747 were found for the relationship between dose and concentration of immunosuppressant; r = 0.9406 for the relationship between viral load in whole blood and plasma, and r ≤0.4616 for the relationship between concentration of immunosuppressant and viral load. These data support that the doses of immunosuppressive drugs do not correlate with the levels of the same in whole blood. Therefore, systemic levels of immunosuppressant should be constantly monitored together with CMV load. Meanwhile, a high correlation between viral load measured in whole blood and plasma was found. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Preparation and Characterization of Polymeric Nanoparticles: An Interdisciplinary Experiment

ERIC Educational Resources Information Center

Ramalho, Maria J.; Pereira, M. Carmo

2016-01-01

In this work, a laboratory experiment to introduce graduate students to nanotechnology is described. Students prepared poly(lactic-"co"-glycolic acid) (PLGA) nanoparticles using two different synthesis procedures, a single and a double emulsion-solvent evaporation method. The students also performed a physicochemical characterization of…

Preparation and characterization of antimony barium composite oxide photocatalysts

NASA Astrophysics Data System (ADS)

Han, X. P.; Yao, B. H.; Pan, Q. H.; Pen, C.; Zhang, C. L.

2018-01-01

In this paper, two kinds of antimony barium composite oxide photocatalysts have been prepared by two methods and characterized by XRD and SEM. The photocatalytic activity was evaluated by a photocatalytic reactor and an ultraviolet spectrophotometer. The results showed that-BaSb2O5•4H2O, BaSb2O6 two kinds of antimony barium composite oxide photocatalysts were successfully prepared in this experiment and they showed good photocatalytic properties. In addition, BaSb2O6 morphology showed more regular, microstructure and better catalytic performance.

Preparation and characterization of supported magnetic nanoparticles prepared by reverse micelles

PubMed Central

Han, Luyang; Biskupek, Johannes; Kaiser, Ute; Ziemann, Paul

2010-01-01

Summary Monatomic (Fe, Co) and bimetallic (FePt and CoPt) nanoparticles were prepared by exploiting the self-organization of precursor loaded reverse micelles. Achievements and limitations of the preparation approach are critically discussed. We show that self-assembled metallic nanoparticles can be prepared with diameters d = 2–12 nm and interparticle distances D = 20–140 nm on various substrates. Structural, electronic and magnetic properties of the particle arrays were characterized by several techniques to give a comprehensive view of the high quality of the method. For Co nanoparticles, it is demonstrated that magnetostatic interactions can be neglected for distances which are at least 6 times larger than the particle diameter. Focus is placed on FePt alloy nanoparticles which show a huge magnetic anisotropy in the L10 phase, however, this is still less by a factor of 3–4 when compared to the anisotropy of the bulk counterpart. A similar observation was also found for CoPt nanoparticles (NPs). These results are related to imperfect crystal structures as revealed by HRTEM as well as to compositional distributions of the prepared particles. Interestingly, the results demonstrate that the averaged effective magnetic anisotropy of FePt nanoparticles does not strongly depend on size. Consequently, magnetization stability should scale linearly with the volume of the NPs and give rise to a critical value for stability at ambient temperature. Indeed, for diameters above 6 nm such stability is observed for the current FePt and CoPt NPs. Finally, the long-term conservation of nanoparticles by Au photoseeding is presented. PMID:21977392

Preparation and Characterization of Fluorescent SiO2 Microspheres

NASA Astrophysics Data System (ADS)

Xu, Cui; Zhang, Hao; Guan, Ruifang

2018-01-01

Fluorescent compound without typical fluorophores was synthesized with citric acid (CA) and aminopropyltriethoxysilane (APTS) firstly, and then it was grafted to the surface of the prepared SiO2 microspheres by chemical reaction. The fluorescent SiO2 microspheres with good fluorescent properties were obtained by optimizing the reaction conditions. And the morphology and structure of the fluorescent SiO2 microspheres have been characterized by scanning electron microscopy (SEM) and fourier transform infrared (FTIR) spectroscopy. The results showed that the preparation of fluorescent SiO2 microspheres have good monodispersity and narrow particle size distribution. Moreover, the fluorescent SiO2 microspheres can be applied to detect Fe3+ in aqueous solution, prepare fluorescent SiO2 rubber, and have potential to be applied in the fluorescent labeling and fingerprint appearing technique fields.

Tamoxifen citrate loaded ethosomes for transdermal drug delivery system: preparation and characterization.

PubMed

Sarwa, Khomendra Kumar; Suresh, Preeti K; Debnath, Manabendra; Ahmad, Mohammad Zaki

2013-08-01

Long term tamoxifen citrate therapy is imperative to treat several dermatological and hormonal sensitive disorders. Successful oral and parenteral administration of tamoxifen citrate has been challenging since it undergoes enzymatic degradation and has poor aqueous solubility issues. In the present work, tamoxifen citrate loaded ethosomes were prepared and characterized for transdermal applications. The prepared formulations were characterized for morphological features, particle size distribution, calorimetric attributes, zeta potential and drug entrapment. Permeation profile of prepared ethosomes was compared with liposomes and hydroethonalic solution across cellophane membrane and human cadaver skin. Results of the permeation studies indicate that ethosomes were able to deliver >90% drug within 24 hours of application, while liposomes and hydroethanolic solution delivered only 39.04% and 36.55% respectively. Skin deposition and stability studies are also reported.

Medium-Term Renal Function in a Large Cohort of Stable Kidney Transplant Recipients Converted From Twice-Daily to Once-Daily Tacrolimus.

PubMed

Guirado, Lluís; Burgos, Dolores; Cantarell, Carme; Fernández, Ana; Franco, Antonio; Gentil, Miguel Ángel; Mazuecos, Auxiliadora; Torregrosa, Josep Vicenç; Huertas, Ernesto Gómez; Ruiz, Juan Carlos; Plumed, Jaime Sánchez; Paul, Javier; Lauzurica, Ricardo; Zárraga, Sofía; Osuna, Antonio; Jiménez, Carlos; Alonso, Ángel; Rodríguez, Alberto; Bardají, Beatriz; Hernández, Domingo

2015-08-01

There is some evidence pointing toward better renal function in kidney transplant recipients (KTR) treated with once-daily tacrolimus (QD-TAC) vs. twice-daily tacrolimus (BID-TAC). This is an extension study of a 1-year, single arm prospective study of stable KTR who were converted from BID-TAC to QD-TAC (4.9 ± 4.0 years after transplantation) in Spanish routine clinical practice. Patient and graft survival, renal function, acute rejection episodes, and other analytic parameters were assessed at 24 and 36 months after conversion. A total of 1798 KTR were included in the extension study. Tacrolimus doses at 36 months were significantly lower compared to those at time of conversion (-0.2 mg/day; P = 0.023). Blood levels were lower than baseline during all the study (P < 0.001). Graft and patient survival at 3 years after conversion were 93.9% and 95.1%, respectively. Compared with baseline, the mean estimated glomerular filtration rate (eGFR) remained very stable at all timepoints (56.7 ± 19.8 vs 58.1 ± 24.6 mL/min per 1.73 m(2) at month 36; P = 0.623). Even when patients reinitiating dialysis were counted as eGFR = 0, the mean eGFR was very stable. In fact, a small but significant increase was observed at 36 months versus baseline (+0.1 mL/min per 1.73 m(2); P = 0.025). An increase in proteinuria was observed at 36 months versus baseline (+0.11 g/24 h; P < 0.001). Acute rejection rates were low during the study. Conversion from BID-TAC to QD-TAC in a large cohort of stable KTR was safe and associated with a very stable renal function after 3 years. Comparative studies are warranted to assess the feasibility of such conversion.

Medium-Term Renal Function in a Large Cohort of Stable Kidney Transplant Recipients Converted From Twice-Daily to Once-Daily Tacrolimus

PubMed Central

Guirado, Lluís; Burgos, Dolores; Cantarell, Carme; Fernández, Ana; Franco, Antonio; Gentil, Miguel Ángel; Mazuecos, Auxiliadora; Torregrosa, Josep Vicenç; Huertas, Ernesto Gómez; Ruiz, Juan Carlos; Plumed, Jaime Sánchez; Paul, Javier; Lauzurica, Ricardo; Zárraga, Sofía; Osuna, Antonio; Jiménez, Carlos; Alonso, Ángel; Rodríguez, Alberto; Bardají, Beatriz; Hernández, Domingo

2015-01-01

Background There is some evidence pointing toward better renal function in kidney transplant recipients (KTR) treated with once-daily tacrolimus (QD-TAC) vs. twice-daily tacrolimus (BID-TAC). Methods This is an extension study of a 1-year, single arm prospective study of stable KTR who were converted from BID-TAC to QD-TAC (4.9 ± 4.0 years after transplantation) in Spanish routine clinical practice. Patient and graft survival, renal function, acute rejection episodes, and other analytic parameters were assessed at 24 and 36 months after conversion. Results A total of 1798 KTR were included in the extension study. Tacrolimus doses at 36 months were significantly lower compared to those at time of conversion (−0.2 mg/day; P = 0.023). Blood levels were lower than baseline during all the study (P < 0.001). Graft and patient survival at 3 years after conversion were 93.9% and 95.1%, respectively. Compared with baseline, the mean estimated glomerular filtration rate (eGFR) remained very stable at all timepoints (56.7 ± 19.8 vs 58.1 ± 24.6 mL/min per 1.73 m2 at month 36; P = 0.623). Even when patients reinitiating dialysis were counted as eGFR = 0, the mean eGFR was very stable. In fact, a small but significant increase was observed at 36 months versus baseline (+0.1 mL/min per 1.73 m2; P = 0.025). An increase in proteinuria was observed at 36 months versus baseline (+0.11 g/24 h; P < 0.001). Acute rejection rates were low during the study. Conclusions Conversion from BID-TAC to QD-TAC in a large cohort of stable KTR was safe and associated with a very stable renal function after 3 years. Comparative studies are warranted to assess the feasibility of such conversion. PMID:27500226

Evaluation of the Crystallization Tendency of Commercially Available Amorphous Tacrolimus Formulations Exposed to Different Stress Conditions.

PubMed

Trasi, Niraj S; Purohit, Hitesh S; Taylor, Lynne S

2017-10-01

Tacrolimus, an immunosuppressant, is a poorly water soluble compound whereby the commercially available capsule formulations contain the drug in amorphous form. The goal of this study was to evaluate the robustness of the innovator product and five generic formulations to crystallization following storage at stress conditions. Products were purchased from a pharmacy and stored at 40°C/75% relative humidity (RH), open dish conditions. Crystallinity was determined using X-ray diffraction. The quantity of the ingredients in the formulations were determined using different approaches and the various factors that might cause instability in the formulations were studied. After 4 weeks of open dish storage at 40°C/75% RH, one of the generic formulations showed evidence of tacrolimus crystallization. Further investigations revealed batch-to-batch variations in crystallization tendency with the extent of crystallinity varying between 50 and 100% for different batches. Crystallization was also observed at lower storage temperatures (30°C) when the RH was maintained at 75%. It was found that crystallization could be induced in a model formulation by wet granulating an ethanolic solution of the drug with lactose and drying at 60-70°C followed by exposure to stress conditions. It seems probable that the generic that was susceptible to crystallization contains amorphous drug physically mixed with polymeric excipients, rather than as an amorphous solid dispersion. This study highlights the importance of considering the manufacturing process on the stability of the resultant amorphous product.

Preparation, characterization and thermolysis of phenylenediammonium dinitrate salts.

PubMed

Kapoor, Inder Pal Singh; Srivastava, Pratibha; Singh, Gurdip

2008-02-11

Four phenylenediammonium dinitrate salts were prepared and characterized by elemental, Infrared spectroscopy (IR), Ultraviolet spectroscopy (UV) and gravimetric methods. These dinitrates find application in propellant, explosives and pyrotechnics. Their thermal decomposition has been studied using thermogravimetry (TG) and simultaneous thermogravimetry-differential scanning calorimetry (TG-DSC). Kinetics parameters were evaluated by model fitting and isoconversional methods. Their thermolytic pathways have also been suggested, which involves decomposition followed by ignition.

Focal metatarsal fistulae syndrome affecting a greyhound dog successfully treated with topical 0.1% tacrolimus ointment.

PubMed

Scholz, Fiona M; Muse, Russell; Burrows, Amanda K

2015-12-01

Metatarsal fistulation is an uncommon cutaneous condition reported almost exclusively in German shepherd dogs and their cross-breeds. To the best of the authors' knowledge this is the first reported case of focal metatarsal fistulae syndrome affecting a greyhound. Remission was obtained within 6 weeks of commencing treatment using compounded 0.1% tacrolimus ointment twice daily and the dog remained stable for another 6 months with twice weekly application before treatment was discontinued. The dog remained in remission at the time of writing, which is 1 year after treatment withdrawal. © 2015 ESVD and ACVD.

Preparation and Characterization of Activated Alumina

NASA Astrophysics Data System (ADS)

Rabia, A. R.; Ibrahim, A. H.; Zulkepli, N. N.

2018-03-01

Activated alumina is a high surface area and highly porous form of aluminum oxide that can be employed for contaminant species adsorb from ether gases or liquids without changing its form. The research in getting this material has generated huge interested. Thus, this paper presented preparation of activated alumina from chemical process. Pure aluminum (99.9% pure) reacted at room temperature with an aqueous NaOH in a reactor to produce a solution of sodium aluminate (NaAlO2). This solution was passed through filter paper and the clear filtrate was neutralized with H2SO4, to pH 6, 7 or 8, resulting in the precipitation of a white gel, Al(OH)3·XH2O. The washed gel for sulfate ions were dried at 80 °C for 6 h, a 60 mesh sieve was to separate and sort them into different sizes. The samples were then calcined (burn) for 3h in a muffle furnace, in air, at a heating rate of 2 °C min-1. The prepared activated alumina was further characterized for better understanding of its physical properties in order to predict its chemical mechanism.

Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study.

PubMed

Jeng, Long-Bin; Lee, Sung Gyu; Soin, Arvinder Singh; Lee, Wei-Chen; Suh, Kyung-Suk; Joo, Dong Jin; Uemoto, Shinji; Joh, Jaewon; Yoshizumi, Tomoharu; Yang, Horng-Ren; Song, Gi-Won; Lopez, Patricia; Kochuparampil, Jossy; Sips, Carole; Kaneko, Shuhei; Levy, Gary

2018-06-01

In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m 2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m 2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Characterization and morphology of prepared titanium dioxide nanofibers by electrospinning.

PubMed

Park, Ju-Young; Lee, In-Hwa

2010-05-01

Dispersed titanium dioxide in polymer nanofibers were prepared by sol-gel processing and electrospinning techniques using titanium isopropoxide (TiP)/polyvinylpyrrolidone (PVP) solution. The prepared titanium dioxide nanofibers were characterized by FE-SEM, TEM, XRD, and FT-IR. Pure titanium dioxide nanofibers were obtained from calcination of inorganic-organic composite fiber. The diameter of titanium oxide nanofibers were in the range of 70 nm to 150 nm. Prepared titanium dioxide nanofibers show rough surface and rather small diameter compare with TiP/PVP composite nanofibers. After calcined at 500 degrees C, TiO2 nanofibers convert into anatase and rutile mixed phased from amorphous structure. Calcination of these composite fibers above 600 degrees C resulted in pure rutile TiO2 nanofibers.

Preparation and Characterization of Colloidal Silica Particles under Mild Conditions

ERIC Educational Resources Information Center

Neville, Frances; Zin, Azrinawati Mohd.; Jameson, Graeme J.; Wanless, Erica J.

2012-01-01

A microscale laboratory experiment for the preparation and characterization of silica particles at neutral pH and ambient temperature conditions is described. Students first employ experimental fabrication methods to make spherical submicrometer silica particles via the condensation of an alkoxysilane and polyethyleneimine, which act to catalyze…

A pilot comparative study of topical latanoprost and tacrolimus in combination with narrow-band ultraviolet B phototherapy and microneedling for the treatment of nonsegmental vitiligo.

PubMed

Korobko, Igor V; Lomonosov, Konstantin M

2016-11-01

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management. © 2016 Wiley Periodicals, Inc.

Preparation, characterization and antimicrobial efficiency of Ag/PDDA-diatomite nanocomposite.

PubMed

Panáček, Aleš; Balzerová, Anna; Prucek, Robert; Ranc, Václav; Večeřová, Renata; Husičková, Vendula; Pechoušek, Jiří; Filip, Jan; Zbořil, Radek; Kvítek, Libor

2013-10-01

Nanocomposites consisting of diatomaceous earth particles and silver nanoparticles (silver NPs) with high antimicrobial activity were prepared and characterized. For the purpose of nanocomposite preparation, silver NPs with an average size of 28nm prepared by modified Tollens process were used. Nanocomposites were prepared using poly(diallyldimethylammonium) chloride (PDDA) as an interlayer substance between diatomite and silver NPs which enables to change diatomite original negative surface charge to positive one. Due to strong electrostatic interactions between negatively charged silver NPs and positively charged PDDA-modified diatomite, Ag/PDDA-diatomite nanocomposites with a high content of silver (as high as 46.6mgAg/1g of diatomite) were prepared. Because of minimal release of silver NPs from prepared nanocomposites to aqueous media (<0.3mg Ag/1g of nanocomposite), the developed nanocomposites are regarded as a potential useful antimicrobial material with a long-term efficiency showing no risk to human health or environment. All the prepared nanocomposites exhibit a high bactericidal activity against Gram-negative and Gram-positive bacteria and fungicidal activity against yeasts at very low concentrations as low as 0.11g/L, corresponding to silver concentration of 5mg/L. Hence, the prepared nanocomposites constitute a promising candidate suitable for the microbial water treatment in environmental applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Pharmacogenetics of tacrolimus and sirolimus in renal transplant patients: from retrospective analyses to prospective studies.

PubMed

Anglicheau, D; Legendre, C; Thervet, E

2007-09-01

The promises of pharmacogenetics are to elucidate the inherited basis of differences between individual responses to drugs in order to identify the right drug and dose for each patient. The recent identification of genetic polymorphisms in drug-metabolizing enzymes and drug transporters led to the hypothesis that genetic factors may be implicated in the interindividual variability of the pharmacokinetic or pharmacodynamic characteristics of immunosuppressive drugs, major side effects, and efficacy. The purpose of this study was to provide a short overview of recent results obtained in the field of pharmacogenetics of tacrolimus and sirolimus, both substrates of the cytochrome P450 3A (CYP3A) enzymes and of the efflux pump P-glycoprotein, the product of the Multidrug Resistance-1 (MDR1) genes. A number of retrospective studies that demonstrated a link between the polymorphisms governing the CYP3A5 protein expression, with more conflicting results with the MDR1 gene polymorphisms, related to the daily dose necessary to achieve adequate blood tacrolimus levels. The CYP3A5 polymorphisms have also been associated with sirolimus pharmacokinetics. One challenge is to investigate the combined effect of a number of different polymorphisms in various genes to define genetic backgrounds with different pharmacokinetic profiles using high throughput technologies. Another challenge is to move toward prospective randomized studies to explore whether a pharmacogenetic approach, taking into account a limited number of polymorphisms prior to drug treatment, could be used on an individual basis to guide initial dosing of a given drug. The last challenge is based on "target" pharmacogenetics to investigate the role of the polymorphisms of other genes implicated in the efficacy and/or safety of the drug.

Sample preparation for thermo-gravimetric determination and thermo-gravimetric characterization of refuse derived fuel.

PubMed

Robinson, T; Bronson, B; Gogolek, P; Mehrani, P

2016-02-01

Thermo-gravimetric analysis (TGA) is a useful method for characterizing fuels. In the past it has been applied to the study of refuse derived fuel (RDF) and related materials. However, the heterogeneity of RDF makes the preparation of small representative samples very difficult and this difficulty has limited the effectiveness of TGA for characterization of RDF. A TGA method was applied to a variety of materials prepared from a commercially available RDF using a variety of procedures. Applicability of TGA method to the determination of the renewable content of RDF was considered. Cryogenic ball milling was found to be an effective means of preparing RDF samples for TGA. When combined with an effective sample preparation, TGA could be used as an alternative method for assessing the renewable content of RDF. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Hydroxyapatite nanocrystals: simple preparation, characterization and formation mechanism.

PubMed

Mohandes, Fatemeh; Salavati-Niasari, Masoud; Fathi, Mohammadhossein; Fereshteh, Zeinab

2014-12-01

Crystalline hydroxyapatite (HAP) nanoparticles and nanorods have been successfully synthesized via a simple precipitation method. To control the shape and particle size of HAP nanocrystals, coordination ligands derived from 2-hydroxy-1-naphthaldehyde were first prepared, characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance ((1)H-NMR) spectroscopies, and finally applied in the synthesis process of HAP. On the other hand, the HAP nanocrystals were also characterized by several techniques including powder X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). According to the FE-SEM and TEM micrographs, it was found that the morphology and crystallinity of the HAP powders depended on the coordination mode of the ligands. Copyright © 2014 Elsevier B.V. All rights reserved.

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

PubMed Central

Shirazi, F.

2013-01-01

The calcineurin pathway regulates antifungal drug resistance and the virulence of several major human-pathogenic fungi, including the recalcitrant Mucorales. We hypothesized that the fungistatic triazoles posaconazole (PCZ) and itraconazole (ICZ) become fungicidal in the setting of the calcineurin inhibitor tacrolimus (TCR) and that such an effect is mediated through apoptosis. Fungicidal activity and apoptosis were studied using standard microbiological techniques and hyphal metabolic and vital dye reduction assays at 37°C in RPMI 1640. Apoptosis was characterized by detecting intracellular Ca2+, phosphatidylserine (PS) externalization, DNA fragmentation, plasma membrane integrity, chromatin condensation, reactive oxygen species (ROS) generation, caspase-like activity, ATP, and cytochrome c release. MICs for PCZ and ICZ alone were significantly higher (8 to 128 μg/ml) than those of PCZ or ICZ plus TCR (0.25 to 4 μg/ml) for Rhizopus oryzae, Cunninghamella bertholletiae, and Mucor circinelloides. Both PCZ and ICZ in combination with TCR became fungicidal, and their activity was mediated through increased apoptotic cell death of R. oryzae (10 to 50%), C. bertholletiae (5 to 50%), and M. circinelloides (5 to 55%) germlings, with morphological apoptotic changes characterized by externalization of PS, nuclear condensation, and DNA fragmentation. Moreover, activation of the caspase-like activity was correlated with cell death induced by TCR plus PCZ or ICZ. These changes correlated with elevated intracellular Ca2+ and ROS levels and disturbance of mitochondrial potential. We found that PCZ or ICZ in combination with TCR renders Mucorales sensitive to triazoles via apoptotic death. These observations could serve as a new paradigm for the development of new therapeutic strategies. PMID:23851337

The calcineurin pathway inhibitor tacrolimus enhances the in vitro activity of azoles against Mucorales via apoptosis.

PubMed

Shirazi, F; Kontoyiannis, D P

2013-09-01

The calcineurin pathway regulates antifungal drug resistance and the virulence of several major human-pathogenic fungi, including the recalcitrant Mucorales. We hypothesized that the fungistatic triazoles posaconazole (PCZ) and itraconazole (ICZ) become fungicidal in the setting of the calcineurin inhibitor tacrolimus (TCR) and that such an effect is mediated through apoptosis. Fungicidal activity and apoptosis were studied using standard microbiological techniques and hyphal metabolic and vital dye reduction assays at 37°C in RPMI 1640. Apoptosis was characterized by detecting intracellular Ca(2+), phosphatidylserine (PS) externalization, DNA fragmentation, plasma membrane integrity, chromatin condensation, reactive oxygen species (ROS) generation, caspase-like activity, ATP, and cytochrome c release. MICs for PCZ and ICZ alone were significantly higher (8 to 128 μg/ml) than those of PCZ or ICZ plus TCR (0.25 to 4 μg/ml) for Rhizopus oryzae, Cunninghamella bertholletiae, and Mucor circinelloides. Both PCZ and ICZ in combination with TCR became fungicidal, and their activity was mediated through increased apoptotic cell death of R. oryzae (10 to 50%), C. bertholletiae (5 to 50%), and M. circinelloides (5 to 55%) germlings, with morphological apoptotic changes characterized by externalization of PS, nuclear condensation, and DNA fragmentation. Moreover, activation of the caspase-like activity was correlated with cell death induced by TCR plus PCZ or ICZ. These changes correlated with elevated intracellular Ca(2+) and ROS levels and disturbance of mitochondrial potential. We found that PCZ or ICZ in combination with TCR renders Mucorales sensitive to triazoles via apoptotic death. These observations could serve as a new paradigm for the development of new therapeutic strategies.

Preparation and characterization of Sb2Se3 devices for memory applications

NASA Astrophysics Data System (ADS)

Shylashree, N.; Uma B., V.; Dhanush, S.; Abachi, Sagar; Nisarga, A.; Aashith, K.; Sangeetha B., G.

2018-05-01

In this paper, A phase change material of Sb2Se3 was proposed for non volatile memory application. The thin film device preparation and characterization were carried out. The deposition method used was vapor evaporation technique and a thickness of 180nm was deposited. The switching between the SET and RESET state is shown by the I-V characterization. The change of phase was studied using R-V characterization. Different fundamental modes were also identified using Raman spectroscopy.

Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

PubMed

Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H L; Brown, Malcolm W; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R J

2017-08-01

ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10

Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial

PubMed Central

Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H. L.; Brown, Malcolm W.; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R. J.

2017-01-01

Background ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. Methods All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m2), acute rejection and graft and patient survival. Results The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan–Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. Conclusions A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients

Preparation and characterization of (St-DVB-MAA) ion exchange resins

NASA Astrophysics Data System (ADS)

Jiang, Shanquan; Sun, Xiangwei; Ling, Lixing; Wang, Shumin; Wu, Wufeng; Cheng, Shihong; Hu, Yue; Zhong, Chunyan

2017-08-01

In this paper, used polyvinyl alcohol as dispersing agent, Benzoyl peroxide as initiator of polymerization, Divinyl benzene as cross-linking agent, Styrene and 2-Methylpropenoic acid as monomer, ion exchange resin (copolymer of St-DVB-MAA)were prepared by suspension polymerization on 80°C. The structures, components and properties of the prepared composite micro gels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA). The experiment of ion exchange was conducted by resin to deal with copper ions in the solution. The result showed that performance of the ion exchange capacity was excellent, which impacted by pH.

Artemisinin nanoformulation suitable for intravenous injection: Preparation, characterization and antimalarial activities.

PubMed

Ibrahim, Nehal; Ibrahim, Hany; Sabater, Alicia Moreno; Mazier, Dominique; Valentin, Alexis; Nepveu, Françoise

2015-11-30

More than 40 years after its discovery, artemisinin has become the most promising antimalarial agent. However, no intravenous formulation is available due to its poor aqueous solubility. Here, we report the preparation, characterization, and in vitro and in vivo biological evaluation of biodegradable albumin-bound artemisinin nanoparticles. The nanoparticles were prepared by a combination of a bottom-up and a top-down processes and characterized by different spectroscopic techniques. The preparation process was optimized to develop a nanoformulation with the smallest possible diameter and good homogeneity suitable for intravenous injection enabling direct contact of artemisinin with infected erythrocytes. Chemically and physically stable artemisinin nanoparticles were obtained with excellent entrapment efficiency. In in vitro experiments, the artemisinin nanoformulation was interestingly more effective than non-formulated artemisinin. In Plasmodiumm falciparum-infected 'humanized' mice, the nanoparticles proved to be highly effective with 96% parasitemia inhibition at 10mg/kg/day, prolonging mean survival time without recrudescence. This nanoparticulate albumin-bound system allows the intravenous administration of artemisinin for the first time without harsh organic solvents or cosolvents with 100% bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

Age-dependent metabolic and immunosuppressive effects of Tacrolimus

PubMed Central

Krenzien, Felix; Quante, Markus; Heinbokel, Timm; Seyda, Midas; Minami, Koichiro; Uehara, Hirohito; Biefer, Hector Rodriguez Cetina; Schuitenmaker, Jeroen M.; Gabardi, Steven; Splith, Katrin; Schmelzle, Moritz; Petrides, Athena K.; Azuma, Haruhito; Pratschke, Johann; Li, Xian C.; ElKhal, Abdallah; Tullius, Stefan G.

2016-01-01

Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor Tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T-cells. Old recipient mice exhibited prolonged skin graft survival when compared to young animals following TAC administration. More importantly, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce pro-inflammatory IFN-γ cytokine production and promote IL-10 production in old CD4+ T-cells. In addition, TAC administration decreased IL-2 secretion in old CD4+ T-cells more effectively while inhibiting the proliferation of CD4+ T-cells in old mice. Both, TAC treated murine and human CD4+ T-cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca2+-influx, two critical pathways in T-cell activation. Of note, depletion of CD8+ T-cells did not alter allograft survival outcome in old TAC treated mice, suggesting that TAC age-specific effects were mainly CD4+ T-cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4+ T-cell mediated. The suppression of calcineurin levels and Ca2+-influx in both, old murine and human T-cells emphasizes on the clinical relevance of age-specific effects when utilizing TAC. PMID:27754593

Preparation and characterization of triclosan nanoparticles for periodontal treatment.

PubMed

Piñón-Segundo, E; Ganem-Quintanar, A; Alonso-Pérez, V; Quintanar-Guerrero, D

2005-04-27

The aim of this work was to produce and characterize triclosan-loaded nanoparticles (NPs) by the emulsification-diffusion process, in an attempt to obtain a novel delivery system adequate for the treatment of periodontal disease. The NPs were prepared using poly(D,L-lactide-co-glycolide) (PLGA), poly(D,L-lactide) (PLA) and cellulose acetate phthalate (CAP). Poly(vinyl alcohol) (PVAL) was used as stabilizer. Batches were prepared with different amounts of triclosan (TCS) in order to evaluate the influence of drug on NP properties. Solid NPs of less than 500 nm in diameter were obtained. Entrapment efficiencies were higher than 63.8%. The characterization by scanning electron microscopy and light scattering indicated that high concentrations of TCS seemingly caused the increase of NP mean size. A decrease in the PLGA glass transition temperature was observed by differential scanning calorimetry. This could indicate that TCS in PLGA-NPs behaves as a non-conventional plasticizer. Subsequently, in vitro release studies were carried out under sink conditions using a device designed in our laboratory to allow a direct contact between the particles and the dissolution medium. A fast release of TCS from NPs was detected. A preliminary in vivo study in dogs with induced periodontal defects suggested that TCS-loaded NPs penetrate through the junctional epithelium.

Preparation and characterization of triple shape memory composite foams.

PubMed

Nejad, Hossein Birjandi; Baker, Richard M; Mather, Patrick T

2014-10-28

Foams prepared from shape memory polymers (SMPs) offer the potential for low density materials that can be triggered to deploy with a large volume change, unlike their solid counterparts that do so at near-constant volume. While examples of shape memory foams have been reported in the past, they have been limited to dual SMPs: those polymers featuring one switching transition between an arbitrarily programmed shape and a single permanent shape established by constituent crosslinks. Meanwhile, advances by SMP researchers have led to several approaches toward triple- or multi-shape polymers that feature more than one switching phase and thus a multitude of temporary shapes allowing for a complex sequence of shape deployments. Here, we report the design, preparation, and characterization of a triple shape memory polymeric foam that is open cell in nature and features a two phase, crosslinked SMP with a glass transition temperature of one phase at a temperature lower than a melting transition of the second phase. The soft materials were observed to feature high fidelity, repeatable triple shape behavior, characterized in compression and demonstrated for complex deployment by fixing a combination of foam compression and bending. We further explored the wettability of the foams, revealing composition-dependent behavior favorable for future work in biomedical investigations.

High-performance liquid chromatography-tandem mass spectrometry as a reference for analysis of tacrolimus to assess two immunoassays in patients with liver and renal transplants.

PubMed

Salm, P; Taylor, P J; Clark, A; Balderson, G A; Grygotis, A; Norris, R L; Lynch, S V; Shaw, L M; Pond, S M

1997-12-01

The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (< 10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation < 10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD > 13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD > 23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some

Preparation and biophysical characterization of recombinant Pseudomonas aeruginosa phosphorylcholine phosphatase.

PubMed

Beassoni, Paola R; Berti, Federico Pérez de; Otero, Lisandro H; Risso, Valeria A; Ferreyra, Raul G; Lisa, Angela T; Domenech, Carlos E; Ermácora, Mario R

2010-06-01

Pseudomonas aeruginosa infections constitute a widespread health problem with high economical and social impact, and the phosphorylcholine phosphatase (PchP) of this bacterium is a potential target for antimicrobial treatment. However, drug design requires high-resolution structural information and detailed biophysical knowledge not available for PchP. An obstacle in the study of PchP is that current methods for its expression and purification are suboptimal and allowed only a preliminary kinetic characterization of the enzyme. Herein, we describe a new procedure for the efficient preparation of recombinant PchP overexpressed in Escherichia coli. The enzyme is purified from urea solubilized inclusion bodies and refolded by dialysis. The product of PchP refolding is a mixture of native PchP and a kinetically-trapped, alternatively-folded aggregate that is very slowly converted into the native state. The properly folded and fully active enzyme is isolated from the refolding mixture by size-exclusion chromatography. PchP prepared by the new procedure was subjected to chemical and biophysical characterization, and its basic optical, hydrodynamic, metal-binding, and catalytic properties are reported. The unfolding of the enzyme was also investigated, and its thermal stability was determined. The obtained information should help to compare PchP with other phosphatases and to obtain a better understanding of its catalytic mechanism. In addition, preliminary trials showed that PchP prepared by the new protocol is suitable for crystallization, opening the way for high-resolution studies of the enzyme structure.

Characterization of factor VIII pharmaceutical preparations by means of MudPIT proteomic approach.

PubMed

Basilico, Fabrizio; Nardini, Ilaria; Mori, Filippo; Brambilla, Elena; Benazzi, Louise; De Palma, Antonella; Rosti, Enrico; Farina, Claudio; Mauri, PierLuigi

2010-09-21

For a good clinical outcome of Haemophilia A substitutive therapy a detailed characterization of factor VIII (FVIII) concentrates is required, in order to disclose the eventual relations between differently composed concentrates and their biological effects. This preliminary work could be a first step towards a deep structural characterization of FVIII concentrates, using the fast and simply manageable MudPIT technology, which enables the identification and characterization of protein mixtures taking advantage of both the high separation capacity of two-dimensional chromatography and the powerful peptide characterization ability of tandem mass spectrometry. The aim of this study was to evaluate the suitability of for the characterization of FVIII molecule in complex mixtures such its commercial concentrates, both plasma-derived and recombinant, and for the determination of the protein composition of different FVIII preparations. By means of Multidimensional Protein Identification Technology (MudPIT) it was possible to assess the presence of factor VIII in its preparations and to identify most of the contaminant proteins without gel separation. In particular, 125 and 42 proteins were identified in plasma-derived and recombinant concentrates, respectively. Concerning investigation of FVIII, 24 different peptides were identified in plasma-derived corresponding to 7, 29, 27, 19 and 67 of percentage coverage for A1, A2, A3, C1 and C2 domains, respectively. About its multimeric carrier von Willebrand factor (VWF), we have sequenced 42% of domain interacting with A3 and C2 domains of FVIII. Finally, it has been observed that normalized parameters, such as total peptide hits obtained by SEQUEST may be used for evaluation of the relative abundance of FVIII in different preparations. Copyright 2010 Elsevier B.V. All rights reserved.

Supercritical antisolvent versus coevaporation: preparation and characterization of solid dispersions.

PubMed

Majerik, Viktor; Horváth, Géza; Szokonya, László; Charbit, Gérard; Badens, Elisabeth; Bosc, Nathalie; Teillaud, Eric

2007-09-01

The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual dichloromethane (DCM) than poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.

Preparation and Characterization of Nano-CL-20 Explosive

NASA Astrophysics Data System (ADS)

Bayat, Yadollah; Zeynali, Vida

2011-10-01

Nano-CL-20 was prepared via precipitative crystallization by spraying a solution of CL-20 in a solvent (ethyl acetate) into a nonsolvent (isooctane). Scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) were used to characterize the appearance and the size of the particles. The results revealed that nano-CL-20 particles have the shape of spheres or ellipsoids with an average size of 95 nm. Due to their small diameter and high surface energy, the particles tended to agglomerate. Impact sensitivity of nanosize CL-20 was decreased in comparison to micrometer-size CL-20.

Preparation, characterization and properties of ZnO nanomaterials

NASA Astrophysics Data System (ADS)

Luo, Jiaolian; Zhang, Xiaoming; Chen, Ruxue; Wang, Xiaohui; Zhu, Ji; Wang, Xiaomin

2017-06-01

In this paper, using the hydrothermal synthesis method, NaOH, Zn(NO3)2, anhydrous ethanol, deionized water as raw material to prepare ZnO nanomaterial, and by X ray diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence spectroscopy (PL) on the synthesis of nano materials, surface morphology and phase luminescence characterization. The results show that the nano materials synthesized for single-phase ZnO, belonging to the six wurtzite structure; material surface shaped, arranged evenly distributed, and were the top six party structure; ZnO nano materials synthesized with strong emission spectra, emission peak is located at 394nm.

Preparation and characterization of conjugated polymers made by postpolymerization reactions of alternating polyketones.

PubMed

Cheng, Chen; Guironnet, Damien; Barborak, James; Brookhart, Maurice

2011-06-29

Conjugated polymers possessing a poly(2,5-dimethylene-2,5-dihydrofuran) backbone were prepared through postpolymerization reaction of styrenic polyketones with bromine in one-pot reactions. The modification is proposed to proceed via condensation of two repeating units to form a fully characterized polymer with a poly(2,5-dimethylenetetrahydrofuran) backbone. Subsequent bromination and elimination of HBr yield a polymer with a fully conjugated carbon backbone. The new conjugated polymers were characterized by NMR, IR, and UV-vis spectroscopies and by CV. These polymers have strong absorption in the visible region, with the absorption peaks shifted to the NIR region upon doping with acids. The ease of the synthesis of the starting polyketone and of the modifications allows large-scale preparation of those conjugated polymers.

Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus.

PubMed

Krenzien, F; Quante, M; Heinbokel, T; Seyda, M; Minami, K; Uehara, H; Biefer, H R C; Schuitenmaker, J M; Gabardi, S; Splith, K; Schmelzle, M; Petrides, A K; Azuma, H; Pratschke, J; Li, X C; ElKhal, A; Tullius, S G

2017-05-01

Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T cells. Old recipient mice exhibited prolonged skin graft survival compared with young animals after TAC administration. More important, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce proinflammatory interferon-γ cytokine production and promote interleukin-10 production in old CD4 + T cells. In addition, TAC administration decreased interleukin-2 secretion in old CD4 + T cells more effectively while inhibiting the proliferation of CD4 + T cells in old mice. Both TAC-treated murine and human CD4 + T cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca 2+ influx, two critical pathways in T cell activation. Of note, depletion of CD8 + T cells did not alter allograft survival outcome in old TAC-treated mice, suggesting that TAC age-specific effects were mainly CD4 + T cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4 + T cell mediated. The suppression of calcineurin levels and Ca 2+ influx in both old murine and human T cells emphasizes the clinical relevance of age-specific effects when using TAC. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Polymeric nanoparticles: A study on the preparation variables and characterization methods.

PubMed

Crucho, Carina I C; Barros, Maria Teresa

2017-11-01

Since the emergence of Nanotechnology in the past decades, the development and design of nanomaterials has become an important field of research. An emerging component in this field is nanomedicine, wherein nanoscale materials are being developed for use as imaging agents or for drug delivery applications. Much work is currently focused in the preparation of well-defined nanomaterials in terms of size and shape. These factors play a significantly role in the nanomaterial behavior in vivo. In this context, this review focuses on the toolbox of available methods for the preparation of polymeric nanoparticles. We highlight some recent examples from the literature that demonstrate the influence of the preparation method on the physicochemical characteristics of the nanoparticles. Additionally, in the second part, the characterization methods for this type of nanoparticles are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and characterization of bio-composite PEEK/nHA

NASA Astrophysics Data System (ADS)

Jin, Y. S.; Bian, C. C.; Zhang, Z. Q.; Zhao, Y.; Yang, L.

2017-01-01

PEEK/nHA composite material, with excellent mechanical property as polyetheretherketone (PEEK) and biological activity as hydroxyapatite (HA), has attracted wide attention of medical experts and materials science experts. The addition of hydroxyapatite was the decisive factor for biological activity in PEEK/nHA composite. In this paper, acicular nanohydroxyapatite was prepared by chemical precipitation method with Ca(NO3)2, (NH4)2HPO4 as raw material; PEEK/nHA composite was prepared by solution blending and vacuum sintering method. The composite was characterized with FT-IR, XRD, DSC, TG and mechanical property test. Results showed that the composite has good thermal stability and compressive property when the mass ratio of PEEK to nHA is 10:3; and high nHA content can improve the biological activity of the composite, which can meet the basic requirements for bone tissue engineering scaffold.

Preparation and characterization of progesterone dispersions using supercritical carbon dioxide.

PubMed

Falconer, James R; Wen, Jingyuan; Zargar-Shoshtari, Sara; Chen, John J; Farid, Mohammed; Tallon, Stephen J; Alany, Raid G

2014-04-01

Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable. To design, develop and construct a unit for the particles from a gas-saturated suspension/solution (PGSS) method and form endogenous progesterone (PGN) dispersion systems using SC-CO2. The PGN dispersions were manufactured using three selected excipients: polyethylene glycol (PEG) 400/4000 (50:50), Gelucire 44/14 and D-α-tocopheryl PEG 1000 succinate (TPGS). Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting (CM), cosolvent (CS) and physical mixing (PM). The dispersion systems made were characterized by Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), PGN recovery, uniformity and in vitro dissolution, analyzed by high-performance liquid chromatography (HPLC). Raman spectra revealed no changes in the crystalline structure of PGN treated with SC-CO2 compared to that of untreated PGN. XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient. All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min (p value < 0.05). The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.

In Vitro Interactions between Tacrolimus and Azoles against Candida albicans Determined by Different Methods▿

PubMed Central

Sun, Shujuan; Li, Yan; Guo, Qiongjie; Shi, Changwen; Yu, Jinlong; Ma, Lin

2008-01-01

Combination therapy could be of use for the treatment of fungal infections, especially those caused by drug-resistant fungi. However, the methods and approaches used for data generation and result interpretation need further optimizing. The fractional inhibitory concentration index (FICI) is the most commonly used method, but it has several drawbacks in characterizing antifungal drug interaction. Alternatively, some new methods can be used such as the ΔE model (difference between the predicted and measured fungal growth percentages) and the response surface approach, which uses the concentration-effect relationship over the whole concentration range instead of just the MIC. In the present study, in vitro interactions between tacrolimus (FK506) and three azoles—fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against Candida albicans were evaluated by the checkerboard microdilution method and time-killing test. The intensity of the interactions was determined by visual reading and the spectrophotometric method in a checkerboard assay, and the nature of the interactions was assessed by nonparametric models of FICI and ΔE. Colony counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were used for evaluating the combination antifungal effects over time. Synergistic and indifferent effects were found for the combination of FK506 and azoles against azole-sensitive strains, while strong synergy was found against azole-resistant strains analyzed by FICI. The ΔE model gave more consistent results with FICI. The positive interactions were also confirmed by the time-killing test. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and azoles to augment activity against resistant C. albicans. PMID:18056277

High Intrapatient Variability of Tacrolimus Exposure in the Early Period After Liver Transplantation Is Associated With Poorer Outcomes.

PubMed

Rayar, Michel; Tron, Camille; Jézéquel, Caroline; Beaurepaire, Jean Marie; Petitcollin, Antoine; Houssel-Debry, Pauline; Camus, Christophe; Verdier, Marie Clémence; Dehlawi, Ammar; Lakéhal, Mohamed; Desfourneaux, Véronique; Meunier, Bernard; Sulpice, Laurent; Bellissant, Eric; Boudjema, Karim; Lemaitre, Florian

2018-03-01

Tacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high interpatient and intrapatient variability (IPV) leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC IPV (IPV) on graft and patient outcomes after LT. We retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations. Patients were categorized in 2 groups: low IPV (CV < 40%) and high IPV (CV ≥ 40%). There were significantly more neurologic complications (31.2% vs 16.6%, P < 0.001), cardiovascular complications (19.7% vs 9.7%, P < 0.001), and acute renal failure requiring dialysis (8.5% vs 2.2%, P < 0.001) in the high CV group than in the low CV group. Moreover, graft survival was significantly poorer in the high CV group (hazard ratio, 1.42; 95% confidence interval, 1.04-1.95; P = 0.03). A pretransplantation elevated Model for End-Stage Liver Disease score (P < 0.001) and Child-Pugh grade (P < 0.001) were identified as risk factors for presenting a high CV. A high CV of TAC concentrations was found to be predictive of TAC-related toxicity and poorer survival.

Piroxicam cocrystals with phenolic coformers: preparation, characterization, and dissolution properties.

PubMed

Emami, Shahram; Adibkia, Khosro; Barzegar-Jalali, Mohammad; Siahi-Shadbad, Mohammadreza

2018-04-04

This study explores the preparation and investigation of dissolution properties of piroxicam cocrystals. Differential scanning calorimetry (DSC) was used to determine the capability of resorcinol (RES), methylparaben (MPB), and vanillin (VAN) to form cocrystals with piroxicam (PRX). Generation of cocrystals was attempted by liquid assisted grinding and slurry methods. Cocrystals were characterized by thermal methods, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. Apparent solubility, intrinsic dissolution rate (IDR), and powder dissolution profile of cocrystals were compared with anhydrous piroxicam, piroxicam monohydrate (PRXMH), and previously reported piroxicam-succinic acid cocrystal. Contact angles and particle sizes of the studied solids were also measured. Based on the DSC screening results, we prepared and characterized PRX-RES and PRX-MPB cocrystals. Interestingly, the cocrystals not only failed to improve apparent solubility and IDR of PRX but also showed lower values than PRX that were attributed to induction of phase transformation of PRX to PRXMH. In contrary, cocrystals performed better than PRX in powder dissolution studies. The higher dissolution rates of cocrystals were explained by improved wettability and reduced sizes. This study has highlighted the complexity of solid state properties of cocrystals and has provided new evidence for the in-solution stability issues of cocrystals.

Metal oxide nanostructures: preparation, characterization and functional applications as chemical sensors.

PubMed

Zappa, Dario; Bertuna, Angela; Comini, Elisabetta; Kaur, Navpreet; Poli, Nicola; Sberveglieri, Veronica; Sberveglieri, Giorgio

2017-01-01

Preparation and characterization of different metal oxide (NiO, WO 3 , ZnO, SnO 2 and Nb 2 O 5 ) nanostructures for chemical sensing are presented. p-Type (NiO) and n-type (WO 3 , SnO 2 , ZnO and Nb 2 O 5 ) metal oxide nanostructures were grown on alumina substrates using evaporation-condensation, thermal oxidation and hydrothermal techniques. Surface morphologies and crystal structures were investigated through scanning electron microscopy and Raman spectroscopy. Furthermore, different batches of sensors have been prepared, and their sensing performances towards carbon monoxide and nitrogen dioxide have been explored. Moreover, metal oxide nanowires have been integrated into an electronic nose and successfully applied to discriminate between drinking and contaminated water.

Preparation and characterization of biodegradable magnetic carriers by single emulsion-solvent evaporation

NASA Astrophysics Data System (ADS)

Liu, Xianqiao; Kaminski, Michael D.; Riffle, Judy S.; Chen, Haitao; Torno, Michael; Finck, Martha R.; Taylor, LaToyia; Rosengart, Axel J.

2007-04-01

This paper describes a single emulsion-solvent evaporation protocol to prepare PEGylated biodegradable/biocompatible magnetic carriers by utilizing hydrophobic magnetite and a mixture of poly( D,L lactide-co-glycolide) (PLGA) and poly(lactic acid-block-polyethylene glycol) (PLA-PEG) (26:1 by mass) polymers. We characterized the magnetic microspheres in terms of morphology, composite microstructure, size and size distribution, and magnetic properties. Results show that the preparation produces magnetic microspheres with a good spherical morphology, small size (mean diameter of 1.2-1.5 μm) by means of large size distributions, and magnetizations up to 20-30 emu/g of microspheres.

Preparation and characterization of PEGylated chitosan nanocapsules as a carrier for pharmaceutical application

NASA Astrophysics Data System (ADS)

Najafabadi, Alireza Hassani; Abdouss, Majid; Faghihi, Shahab

2014-03-01

A new method to conjugate methoxy polyethylene glycol (mPEG) to C6 position of chitosan under the mild condition is introduced that improves the biocompatibility and water solubility of chitosan. Harsh deprotecting step and several purification cycles are two major disadvantages of the current methods for preparing PEGylated chitosan. In this study, the amine groups at C2 position of chitosan are protected using SDS followed by grafting the PEG. The protecting group of chitosan is simply removed by dialyzing against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and 1H NMR spectroscopy. Fourier transformed-infrared (FT-IR) and 1H NMR spectra confirmed that the mPEG is successfully grafted to C6 position of chitosan. Prepared methoxy polyethylene glycol (mPEG) is then employed to prepare the nanocapsules for the encapsulation of poor water-soluble drug, propofol. The TEM, AFM, and DLS techniques are used to characterize the prepared nanocapsules size and morphology. The results show a size of about 80 nm with spherical shape for nanocapsules. In vitro drug release is carried out to evaluate the potential of nanocarriers for the intravenous delivery of drugs. The profile of release from formulated nanocapsules is similar to those of commercial lipid emulsion (CLE). In vivo animal sleep-recovery test on rats shows a close similarity between the time of unconsciousness and recovery of righting reflex between nanoparticles and CLE. This study provides an efficient, novel, and easy method for preparing a carrier system that requires less intensive reaction conditions, fewer reaction steps, and less purification steps. In addition, the nanocapsules introduced here could be a promising nano carrier for the delivery of poor water-soluble drugs.

Preparation and characterization of ultraflat Pt facets by atom-height-resolved differential optical microscopy

NASA Astrophysics Data System (ADS)

Azhagurajan, M.; Wen, R.; Kim, Y. G.; Itoh, T.; Sashikata, K.; Itaya, K.

2015-01-01

We recently demonstrated that improvements to our technique, laser confocal microscopy with differential interference microscopy (LCM-DIM), has rendered it fully capable of resolving monatomic steps with heights of ca. 0.25 nm on Au(111) and Pd(111) surfaces, even as low as 0.14 nm on Si(100), in aqueous solution. In this paper, we describe in detail a method to prepare and characterize, via atomic-layer-resolved LCM-DIM, ultraflat Pt(111) and Pt(100) facets over a wide surface area. The preparation of ultraflat surfaces is important in the characterization at the atomic scale of electrochemical processes under reaction conditions. To showcase the elegance of LCM-DIM, the anodic dissolution of Pt in aqueous HCl is briefly recounted.

Preparation, characterization, and activity of a peptide-cellulosic aerogel protease sensor from cotton

USDA-ARS?s Scientific Manuscript database

Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties of both high porosity and specific surface area for biosensor design. We report here the preparation, characterization, and activity of a peptide-nanocellulose aerogel (PA) made from unprocessed cot...

Preparation and Characterization of an Amphipathic Magnetic Nanosphere

PubMed Central

Ji, Yongsheng; Lv, Ruihong; Xu, Zhigang; Zhao, Chuande; Zhang, Haixia

2014-01-01

The amphipathic magnetic nanospheres were synthesized using C8 and polyethylene glycol as ligands. Their morphology, structure, and composition were characterized by transmission electron microscope, Fourier transform infrared, and elementary analysis. The prepared materials presented uniform sphere with size distribution about 200 nm. The magnetic characteristics of magnetic nanomaterials were measured by vibrating sample magnetometer. The target products had a saturation magnetization value of 50 emu g−1 and superparamagnetism. The adsorption capability was also studied by static tests, and the material was applied to enrich benzenesulfonamide from calf serum. The results exhibited that the C8-PEG phase owned better adsorption capability, biocompatible property, and dispersivity in aqueous samples. PMID:24729917

Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing.

PubMed

Overhoff, Kirk A; McConville, Jason T; Yang, Wei; Johnston, Keith P; Peters, Jay I; Williams, Robert O

2008-01-01

Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes. The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit. The rank order of C/Ceq(max) in the dissolution studies at acidic conditions was URF-P407 > URF-SDS > Prograf (PRO) > URF-PVA:P407. For C/Ceq(max) under enteric conditions, the order was URF-SDS > PRO > URF-PVA:P407 > URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS>PRO>URF-PVA:P407>URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C (max) with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T (max) compared to PRO. The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.

Preparation and Characterization of Nano Gold Supported over Montmorillonite Clays

NASA Astrophysics Data System (ADS)

Suraja, P. V.; Binitha, N. N.; Yaakob, Z.; Silija, P. P.

2011-02-01

The use of montmorillonite clays as a matrix, or as a host, for obtaining intercalated/supported metal particles has potential applications in catalysis and other areas. The gold nanoparticles were obtained from the most common anionic gold precursor HAuCl4·3H2O by deposition-precipitation (DP) methods. However, it is difficult to prepare nanoscale gold catalysts supported on silica surfaces with lower isoelectric point (IEP). Homogeneous precipitation method using urea also fails on silica surfaces. Reasons for the inefficiency of these methods are the negative charge of the metal precursor as well as the support surface and the high pH required for depositing gold nanoparticles. In the present work, we use glucose as the reductant in the presence of stabilizer for preparation of nano gold supported on montmorillonite clay. There is no need of increasing the pH of the solution to reduce the Au3+ ions. The prepared systems are characterized using various techniques such as using X-ray fluorescence (XRF), UV-VIS Diffuse reflectance spectra (DRS) and Fourier Transform infra red spectra (FTIR) to prove the efficiency of the present method.

Characterization and preparation of Aspergillus niger naringinase for debittering citrus juice.

PubMed

Ni, Hui; Chen, Feng; Cai, Huinong; Xiao, Anfeng; You, Qi; Lu, Yunzhen

2012-01-01

Naringinase from Aspergillus niger was prepared and characterized to evaluate its effectiveness in debittering citrus juice. The enzyme was purified to homogeneity by sulfate fractionation and chromatographies on Q-Sepharose, Sephacryl S-200, and S-100 HR columns, and estimated by gel filtration chromatography (GFC) to have a molecular weight (MW) of 131 kDa, of which its subunit was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be around 65.5 kDa. The enzyme showed active and stable pH ranges both within 4.5 to 5.0. Its optimal temperature was in the range of 45 to 55 °C. Freeze drying provided an estimated enzymatic recovery of 95.9%, greater than spray drying with the recovery at 55.6%. The freeze-drying powder could retain its enzymatic activity stably at 4 °C for 6 mo. Also, the enzyme in 0.220 U/mL citrus juice could sufficiently remove the naringin for the bitterness. Oral acute toxicity study revealed the maximum tolerated dose (MTD) of the naringinase powder was >10 g/kg in mice. The contents of arsenic (As), lead (Pb), mercury (Hg), the aerobic plate count, and coliform number in the enzyme powder all met the criteria for food use. These characteristics suggest that the naringinase from A. niger is efficient and suitable for debittering the citrus juice, and the process consisting of fermentation, salt precipitation, ion exchange, ultrafiltration, and freeze drying is a promising means to prepare the naringinase for food industry, setting up a strong base to enzymatically debitter citrus juice. This study focused on characterization, preparation, and validation of naringinase from A. niger, which provided useful information on how to prepare, store, and use the naringinase. In addition, this naringinase met the safety standards for food use and showed strong ability to remove the bitter taste from citrus juice, which provided useful information for interested readers, and the food industry. © 2011 Institute of Food

Gravimetric preparation and characterization of primary reference solutions of molybdenum and rhodium.

PubMed

Kaltenbach, Angela; Noordmann, Janine; Görlitz, Volker; Pape, Carola; Richter, Silke; Kipphardt, Heinrich; Kopp, Gernot; Jährling, Reinhard; Rienitz, Olaf; Güttler, Bernd

2015-04-01

Gravimetrically prepared mono-elemental reference solutions having a well-known mass fraction of approximately 1 g/kg (or a mass concentration of 1 g/L) define the very basis of virtually all measurements in inorganic analysis. Serving as the starting materials of all standard/calibration solutions, they link virtually all measurements of inorganic analytes (regardless of the method applied) to the purity of the solid materials (high-purity metals or salts) they were prepared from. In case these solid materials are characterized comprehensively with respect to their purity, this link also establishes direct metrological traceability to The International System of Units (SI). This, in turn, ensures the comparability of all results on the highest level achievable. Several national metrology institutes (NMIs) and designated institutes (DIs) have been working for nearly two decades in close cooperation with commercial producers on making an increasing number of traceable reference solutions available. Besides the comprehensive characterization of the solid starting materials, dissolving them both loss-free and completely under strict gravimetric control is a challenging problem in the case of several elements like molybdenum and rhodium. Within the framework of the European Metrology Research Programme (EMRP), in the Joint Research Project (JRP) called SIB09 Primary standards for challenging elements, reference solutions of molybdenum and rhodium were prepared directly from the respective metals with a relative expanded uncertainty associated with the mass fraction of U rel(w) < 0.05 %. To achieve this, a microwave-assisted digestion procedure for Rh and a hotplate digestion procedure for Mo were developed along with highly accurate and precise inductively coupled plasma optical emission spectrometry (ICP OES) and multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) methods required to assist with the preparation and as dissemination tools.

Submicron magnetic core conducting polypyrrole polymer shell: Preparation and characterization.

PubMed

Tenório-Neto, Ernandes Taveira; Baraket, Abdoullatif; Kabbaj, Dounia; Zine, Nadia; Errachid, Abdelhamid; Fessi, Hatem; Kunita, Marcos Hiroiuqui; Elaissari, Abdelhamid

2016-04-01

Magnetic particles are of great interest in various biomedical applications, such as, sample preparation, in vitro biomedical diagnosis, and both in vivo diagnosis and therapy. For in vitro applications and especially in labs-on-a-chip, microfluidics, microsystems, or biosensors, the needed magnetic dispersion should answer various criteria, for instance, submicron size in order to avoid a rapid sedimentation rate, fast separations under an applied magnetic field, and appreciable colloidal stability (stable dispersion under shearing process). Then, the aim of this work was to prepare highly magnetic particles with a magnetic core and conducting polymer shell particles in order to be used not only as a carrier, but also for the in vitro detection step. The prepared magnetic seed dispersions were functionalized using pyrrole and pyrrole-2-carboxylic acid. The obtained core-shell particles were characterized in terms of particle size, size distribution, magnetization properties, FTIR analysis, surface morphology, chemical composition, and finally, the conducting property of those particles were evaluated by cyclic voltammetry. The obtained functional submicron highly magnetic particles are found to be conducting material bearing function carboxylic group on the surface. These promising conducting magnetic particles can be used for both transport and lab-on-a-chip detection. Copyright © 2015. Published by Elsevier B.V.

TiO2 nanocomposites: Preparation, characterization, mechanical and biological properties

NASA Astrophysics Data System (ADS)

Koşarsoy, Gözde; Şen, Elif Hilal; Aksöz, Nilüfer; İde, Semra; Aksoy, Hüsnü

2014-11-01

Some novel nanocomposites, which contain different concentrations of TiO2 nanopowders, were firstly prepared by using marble dust with convenient chemical components. Their nano structures characterized and distributions of the nano-aggregations related with internal structural content of the samples have been determined by X-ray Scattering Methods (SAXS and WAXS) and mechanical properties were determined by using strain-stress measurements to increase their potential usage possibility as building materials in health and research centers. In the last and important part of the study, Candida albicans and Aspergillus niger which are a significant risk to medical patients were used to investigate originally prepared nanostructured samples' photocatalyst effect. During the last part of the study, effect of UV and visible light on photocatalyst nanocomposites were also researched. Heterogeneous photocatalysts can carry out advanced oxidation processes used for an antimicrobial effect on microorganisms. TiO2 nanoparticles as one of heterogeneous photocatalysts have been shown to exhibit strong cytotoxicity when exposed to UV and visible light.

Characterization of nanodimensional Ni-Zn ferrite prepared by mechanochemical and thermal methods

NASA Astrophysics Data System (ADS)

Manova, E.; Paneva, D.; Kunev, B.; Rivière, E.; Estournès, C.; Mitov, I.

2010-03-01

Nickel zinc ferrite nanoparticles, Ni1-xZnxFe2O4 (x = 0, 0.2, 0.5, 0.8, 1.0), with dimensions below 10 nm have been prepared by combining chemical precipitation with high-energy ball milling. For comparison, their analogues obtained by thermal synthesis have also been studied. Mössbauer spectroscopy, X-ray diffraction, and magnetic measurements are used for the characterization of the obtained materials. X-ray diffraction shows that after 3h of mechanical treatment ferrites containing zinc are formed, while 6h of treatment is needed to obtain NiFe2O4. The magnetic properties of the samples exhibit a strong dependence on the phase composition, particle size and preparation method.

[A new method for the preparation of potassium ferrate and spectroscopic characterization].

PubMed

Zheng, Huai-li; Deng, Lin-li; Ji, Fang-ying; Jiang, Shao-jie; Zhang, Peng

2010-10-01

Calcium hypochlorite was used as the raw material for preparation of the high purity potassium ferrate. The study includes the effects of reaction temperature, recrystallization temperature, reaction time, Ca(ClO)2 dosage, and the amount of calcium hypochlorite on the yield. It was determined that when the reaction temperature was 25 degrees C, recrystallization temperature 0 degree C and reaction time 40 min, the yield was more than 75%. The purity was detected by direct spectrophotometric method to be more than 92%. The product was characterized by infrated spectrum(IR), X-ray diffraction (XRD) and ultraviolet spectrum (UV) methods and proved to be potassium ferrate that was prepared by calcium hypochlorite as the raw material.

Preparation and characterizations of activated carbon monolith from rubber wood and its effect on supercapacitor performances

NASA Astrophysics Data System (ADS)

Taer, E.; Taslim, R.; Deraman, M.

2016-02-01

Preparation of activated carbon monolith (ACM) from rubber wood was investigated. Two kind of preparation method were carried out by pre-carbonized of rubber wood saw dust and rubber wood material as it is naturally. The samples were prepared with pelletizing method and small cutting of rubber wood in cross sectional method. Both of samples were characterized by physical and electrochemical technique. The physical properties such as morphology and porosity were investigated. The electrochemical properties of both samples such as equivalent series resistances (ESR) and specific capacitances were also compared. In conclusion, this study showed that both of different preparation method would propose a simple method of ACM electrode preparation technique for supercapacitor applications.

Preparation and characterization of the silicon clathrate NaxSi{136} (x -> 0)

NASA Astrophysics Data System (ADS)

Ammar, A.; Cros, C.; Pouchard, M.; Jaussaud, N.; Bassat, J.-M.; Villeneuve, G.; Reny, E.

2005-03-01

The type-II silicon clathrate, NaxSi{136}, having a residual sodium content as low as 37 ppm (x = 0.0062) has been prepared by thermal decomposition of NaSi under high vacuum in the temperature range 340-420 ° C followed by subsequent treatments under high vacuum, and completed by several treaments with iodine at 300-350 ° C. The final sample was characterized by XRD, chemical analysis and EPR spectroscopy. This latter technique proved to be particularly suitable to the characterization of highly diluted sodium atoms in the open host lattice of a type II clathrate of silicon and the quantitaive determination of the residual sodium content

Preparation and Characterization of Novel Montmorillonite Nanocomposites

NASA Astrophysics Data System (ADS)

Mansa, Rola

Clay minerals have historically played a consequential role in human health. While the beginnings were rooted in geophagy, a primitive act of consuming earth, the health-related uses of clay minerals have evolved and diversified over time.. As excipients in pharmaceutical formulations, clay minerals can attribute novel properties onto intercalated compounds. Intercalating oxybenzone, a UV filter, within the interlamellar space of montmorillonite is desirable in order to minimize direct contact with skin. Intercalating resveratrol, a compound known for attributing beneficial effects onto human health, may be advantageous since this compound is susceptible to cis-trans isomerisation. The strategy of using alkylammonium--modified clay was undertaken and proved successful for the intercalation of oxybenzone. The field of biopolymer/layered silicate nanocomposites is heavily researched for use in a multitude of applications. Novel montmorillonite nanocomposites were prepared with neutral guar gum and cationic guar gum, using an environmentally friendly process and are fully characterized.

Preparation, Modification, Characterization, and Biosensing Application of Nanoporous Gold Using Electrochemical Techniques.

PubMed

Bhattarai, Jay K; Neupane, Dharmendra; Nepal, Bishal; Mikhaylov, Vasilii; Demchenko, Alexei V; Stine, Keith J

2018-03-16

Nanoporous gold (np-Au), because of its high surface area-to-volume ratio, excellent conductivity, chemical inertness, physical stability, biocompatibility, easily tunable pores, and plasmonic properties, has attracted much interested in the field of nanotechnology. It has promising applications in the fields of catalysis, bio/chemical sensing, drug delivery, biomolecules separation and purification, fuel cell development, surface-chemistry-driven actuation, and supercapacitor design. Many chemical and electrochemical procedures are known for the preparation of np-Au. Recently, researchers are focusing on easier and controlled ways to tune the pores and ligaments size of np-Au for its use in different applications. Electrochemical methods have good control over fine-tuning pore and ligament sizes. The np-Au electrodes that are prepared using electrochemical techniques are robust and are easier to handle for their use in electrochemical biosensing. Here, we review different electrochemical strategies for the preparation, post-modification, and characterization of np-Au along with the synergistic use of both electrochemistry and np-Au for applications in biosensing.

Experimental preparation and characterization of four-dimensional quantum states using polarization and time-bin modes of a single photon

NASA Astrophysics Data System (ADS)

Yoo, Jinwon; Choi, Yujun; Cho, Young-Wook; Han, Sang-Wook; Lee, Sang-Yun; Moon, Sung; Oh, Kyunghwan; Kim, Yong-Su

2018-07-01

We present a detailed method to prepare and characterize four-dimensional pure quantum states or ququarts using polarization and time-bin modes of a single-photon. In particular, we provide a simple method to generate an arbitrary pure ququart and fully characterize the state with quantum state tomography. We also verify the reliability of the recipe by showing experimental preparation and characterization of 20 ququart states in mutually unbiased bases. As qudits provide superior properties over qubits in many fundamental tests of quantum physics and applications in quantum information processing, the presented method will be useful for photonic quantum information science.

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol

PubMed Central

Goldsmith, Petra M; Bottomley, Matthew J; Okechukwu, Okidi; Ross, Victoria C; Ghita, Ryan; Wandless, David; Falconer, Stuart J; Papachristos, Stavros; Nash, Philip; Androshchuk, Vitaliy; Clancy, Marc

2017-01-01

Introduction High intrapatient variability (IPV) in tacrolimus trough levels has been shown to be associated with higher rates of renal transplant failure. There is no consensus on what level of IPV constitutes a risk of graft loss. The establishment of such a threshold could help to guide clinicians in identifying at-risk patients to receive targeted interventions to improve IPV and thus outcomes. Methods and analysis A multicentre Transplant Audit Collaborative has been established to conduct a retrospective study examining tacrolimus IPV and renal transplant outcomes. Patients in receipt of a renal transplant at participating centres between 2009 and 2014 and fulfilling the inclusion criteria will be included in the study. The aim is to recruit a minimum of 1600 patients with follow-up spanning at least 2 years in order to determine a threshold IPV above which a renal transplant recipient would be considered at increased risk of graft loss. The study also aims to determine any national or regional trends in IPV and any demographic associations. Ethics and dissemination Consent will not be sought from patients whose data are used in this study as no additional procedures or information will be required from participants beyond that which would normally take place as part of clinical care. The study will be registered locally in each participating centre in line with local research and development protocols. It is anticipated that the results of this audit will be disseminated locally, in participating NHS Trusts, through national and international meetings and publications in peer-reviewed journals. PMID:28756385

Incidence and risk factors for the metabolic syndrome and posttransplant diabetes in renal transplant recipients taking tacrolimus.

PubMed

Pérez-Flores, I; Sánchez-Fructuoso, A; Calvo, N; Valga, E F; Barrientos, A

2010-10-01

We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year. We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index. Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P=.004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P=.035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation. There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of

Preparation and characterization of strontium-fluorapatite nanopowders by sol-gel method

NASA Astrophysics Data System (ADS)

Kamaei, Maryam; Fathi, Mohammad Hossein

2018-01-01

Biomaterials based on calcium orthophosphate are especially attractive for use in medicine, for bone and teeth implants due to their biological properties, such as biocompatibility and bioactivity. Among them, hydroxyapatite (HAP; Ca10(PO4)6(OH)2) is used particularly because of its similarities to the inorganic component of bone. Hydroxyapatite has been widely used for biomedical applications. Despite desirable properties such as bioactivity, biocompatibility, solubility and adsorption, synthetic HA is limited in application due to poor thermostability and poor mechanical properties. Properties of HA can be tailored over a wide range by incorporating different ions into HA lattice. Use of the sol-gel technique is technically simple, cost effective and beneficial for fabrication biomaterials. This research aimed to prepare and characterize Sr-doped FA nanopowders (Sr-FA). Sr-FA with different Sr contents was prepared by sol-gel method. The designated degree of substitution of Ca by Sr in the mixture was determined by the x value in the general formula of (Ca10-x Srx(PO4)6F2), where x=0,0.5,1. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) techniques were utilized to characterize the obtained nano powders. Results showed that Sr ions entered into the fluorapatite lattice and occupied Ca sites. The incorporation of Sr ions into the fluorapatite resulted in the increase of the lattice parameters.

Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates.

PubMed

Denardi, Laura Bedin; Mario, Débora Alves Nunes; Loreto, Érico Silva; Santurio, Janio Morais; Alves, Sydney Hartz

2015-03-01

In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata , a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro , notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

Preparation and characterization of polystyrene/neodymium hydroxide (PS/Nd(OH)3) nano-composites

NASA Astrophysics Data System (ADS)

Alsewailem, Fares D.; Bagabas, Abdulaziz A.; Binkhodor, Yazeed A.

2018-03-01

Composites of polystyrene and Neodymium hydroxide nanrods (PS/Nd(OH)3) were formulated and characterized in this study. Cetyl (1-hexadccyl) trimethyl ammonium bromide (CTAB) was used as dispersion agent for the Nd(OH)3 rods in the PS matrix. PS/Nd(OH)3 composites were prepared by solution and melt compounding. Morphological, thermal, and mechanical properties of the prepared composites were investigated. CTAB was found to be more effective as dispersion agent in composites prepared by solution compounding in comparison with those prepared by melt compounding, and that was due to the mild conditions used in solution compounding. Nonetheless, impact strength of the composite at 0.5 wt% Nd(OH)3 was drastically reduced in the absence of CTAB. Both tensile and impact strengths were found to greatly decreased at higher loading of Nd(OH)3, e.g. 5 wt%, even with the use of CTAB. Thermal stability of the PS/Nd(OH)3 composites was noticeably increased at relatively low loading of Nd(OH)3, e.g. 0.5 wt%.

Preparation and characterization of Fe50Co50 nanostructured alloy

NASA Astrophysics Data System (ADS)

Yepes, N.; Orozco, J.; Caamaño, Z.; Mass, J.; Pérez, G.

2014-04-01

Nanostructured Fe50Co50 alloy was prepared by mechanical alloying of Fe and Co powders in a planetary high energy ball milling. The microstructure and structural evolution of the alloy have been investigated as a function of milling time (0 h, 8 h, 20 h and 35 h) by scanning electron microscopy (SEM) and X-Ray diffraction (XRD) characterization techniques. SEM micrographs showed different powder particles morphologies during the mechanical alloying stages. By XRD analysis it could be identified the structural phases of the alloy and the crystallite size was calculated as a function of the milling time.

Preparation and characterization of a siloxane containing bismaleimide

NASA Technical Reports Server (NTRS)

Maudgal, S.; St. Clair, T. L.

1984-01-01

A novel siloxane containing bismaleimide has been prepared by reacting maleic anhydride, benzophenonetetracarboxylic dianhydride and bis(gamma-aminopropyl)tetramethyldisiloxane. Characterization of this monomer was done by comparing its nuclear magnetic resonance spectrum (NMR) to those of model compounds. Solubility of the prepolymer was tested in amide, chlorinated and ether solvents. Films were cast from solution as well as by melt processing and a cure cycle was determined. Infrared spectrum (IR) of the resulting film was obtained. Thermal polymerization was investigated by differential scanning calorimetry (DSC). Thermal properties of the cured resin were followed by means of thermogravimetric analysis (TGA), torsional braid analysis (TBA) and dynamic mechanical analysis (DMA). Thermomechanical analysis (TMA) was used to study the effect of postcure on the glass transition temperature (Tg) of the resin. Adhesive strength of the resin was obtained at ambient temperature.

Preparation and Characterization of Polyimide/Organoclay Nanocomposites

NASA Technical Reports Server (NTRS)

Delozier, D. M.; Orwoll, R. A.; Cahoon, J. F.; Johnston, N. J.; Smith, J. G., Jr.; Connell, J. W.

2002-01-01

Organically modified montmorrrillonite clay, containing a long chain aliphatic quarternary ammonium cation, was used to prepare polyimide/organoclay hybrids. Several approaches were examined in an attempt to achieve fully exfoliated nanocomposites. These included simple mixing of the clay in a pre-made high molecular weight poly(amide acid) solution; simple mixing followed by sonication of the organoclay/poly(amide acid) solutions; and the preparation of high molecular weight poly(amide acid)s in the presence of the organoclay dispersed in N-methyl-2-pyrrolidinone (NMP). The best results were obtained using the in-situ polymerization approach. The resulting nanocomposite films (both amide acid and imide), containing 3-8% by weight of organoclay, were characterized by differential scanning calorimetry (DSC), dynamic thermogravimetric analysis (TGA), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thin film tensile properties. A significant degree of dispersion was observed in the nanocomposite films of the amide acid and the imide. After thermal treatment of amide acid films to effect imidization, in both air and nitrogen, the films were visually darker than control films without clay and the level of clay dispersion appeared to have decreased. In the latter case, the separation between the layers of the clay decreased to a spacing less than that present in the original organoclay. These observations suggest that thermal degradation of the aliphatic quarternary ammonium cation occurred likely during thermal treatment to effect imidization and solvent removal. These thermal degradation effects were less pronounced when thermal treatment was performed under nitrogen. The polyimide/organoclay hybrid films exhibited higher room temperature tensile moduli and lower strength and elongation to break than the control films.

Characterization of silver/polystyrene nanocomposites prepared by in situ bulk radical polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vukoje, Ivana D., E-mail: ivanav@vinca.rs; Vodnik, Vesna V., E-mail: vodves@vinca.rs; Džunuzović, Jasna V., E-mail: jasnav2002@googlemail.com

2014-01-01

Graphical abstract: - Highlights: • Synthesis and characterization of polystyrene nanocomposites based on Ag nanoparticles. • The glass transition temperature decreased in nanocomposites with respect to the pure polymer. • Resistance of the polymer to thermal degradation enhanced with Ag nanoparticles content. - Abstract: Nanocomposites (NCs) with different content of silver nanoparticles (Ag NPs) embeded in polystyrene (PS) matrix were prepared by in situ bulk radical polymerization. The nearly monodisperse Ag NPs protected with oleylamine were synthesized via organic solvo-thermal method and further used as a filler. The as-prepared spherical Ag NPs with diameter of 7.0 ± 1.5 nm weremore » well dispersed in the PS matrix. The structural properties of the resulting Ag/PS NCs were characterized by transmission electron microscope (TEM) and Fourier transform infrared (FTIR) spectroscopy, while optical properties were characterized using optical absorption measurements. The gel permeation chromatography (GPC) measurements showed that the presence of Ag NPs stabilized with oleylamine has no influence on the molecular weight and polydispersity of the PS matrix. The influence of silver content on the thermal properties of Ag/PS NCs was investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results indicated that resistance of PS to thermal degradation was improved upon incorporation of Ag NPs. The Ag/PS NCs have lower glass transition temperatures than neat PS because loosely packed oleylamine molecules at the interface caused the increase of free volume and chain segments mobility near the surface of Ag NPs.« less

Preparation and characterization of Fe3O4-Pt nanoparticles

NASA Astrophysics Data System (ADS)

Andrade, Ângela Leão; Cavalcante, Luis Carlos Duarte; Fabris, José Domingos; Pereira, Márcio César; Ardisson, José Domingos; Domingues, Rosana Zacarias

2017-11-01

Pt and Pt-based nanomaterials are active anticancer drugs for their ability to inhibit the division of living cells. Nanoparticles of magnetite containing variable proportions of platinum were prepared in the laboratory. The magnetite nanoparticles with platinum (Pt-Fe3O4) were obtained by reducing the Fe3+ of the maghemite ( γ Fe2O3) mixed with platinum (II) acetylacetonate and sucrose in two inversely coupled ceramic crucibles and heated in a furnace at 400 °C for 20 min. The formed carbon during this preparation acts to chemically reduce the ferric iron in maghemite. Moreover, its residual layer on the particle surface prevents the forming magnetite from oxidizing in air and helps retain the platinum in the solid mixture. The produced Pt-magnetite samples were characterized by 57Fe-Mössbauer spectroscopy, powder X-ray diffraction, scanning electron microscopy, and magnetization measurements. Measurements of AC magnetic-field-induced heating properties of the obtained nanocomposites, in aqueous solution, showed that they are suitable as a hyperthermia agent for biological applications.

Preparation and characterization of bagasse/HDPE composites using multi-walled carbon nanotubes.

PubMed

Ashori, Alireza; Sheshmani, Shabnam; Farhani, Foad

2013-01-30

This article presents the preparation and characterization of bagasse/high density polyethylene (HDPE) composites. The effects of multi-walled carbon nanotubes (MWCNTs), as reinforcing agent, on the mechanical and physical properties were also investigated. In order to increase the interphase adhesion, maleic anhydride grafted polyethylene (MAPE) was added as a coupling agent to all the composites studied. In the sample preparation, MWCNTs and MAPE contents were used as variable factors. The morphology of the specimens was characterized using scanning electron microscopy (SEM) technique. The results of strength measurement indicated that when 1.5 wt% MWCNTs were added, tensile and flexural properties reached their maximum values. At high level of MWCNTs loading (3 or 4 wt%), increased population of MWCNTs lead to agglomeration and stress transfer gets blocked. The addition of MWCNTs filler slightly decreased the impact strength of composites. Both mechanical and physical properties were improved when 4 wt% MAPE was applied. SEM micrographs also showed that the surface roughness improved with increasing MAPE loading from 0 to 4 wt%. The improvement of physicomechanical properties of composites confirmed that MWCNTs have good reinforcement and the optimum synergistic effect of MWCNTs and MAPE was achieved at the combination of 1.5 and 4 wt%, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preparation, Modification, Characterization, and Biosensing Application of Nanoporous Gold Using Electrochemical Techniques

PubMed Central

Neupane, Dharmendra; Nepal, Bishal; Mikhaylov, Vasilii; Stine, Keith J.

2018-01-01

Nanoporous gold (np-Au), because of its high surface area-to-volume ratio, excellent conductivity, chemical inertness, physical stability, biocompatibility, easily tunable pores, and plasmonic properties, has attracted much interested in the field of nanotechnology. It has promising applications in the fields of catalysis, bio/chemical sensing, drug delivery, biomolecules separation and purification, fuel cell development, surface-chemistry-driven actuation, and supercapacitor design. Many chemical and electrochemical procedures are known for the preparation of np-Au. Recently, researchers are focusing on easier and controlled ways to tune the pores and ligaments size of np-Au for its use in different applications. Electrochemical methods have good control over fine-tuning pore and ligament sizes. The np-Au electrodes that are prepared using electrochemical techniques are robust and are easier to handle for their use in electrochemical biosensing. Here, we review different electrochemical strategies for the preparation, post-modification, and characterization of np-Au along with the synergistic use of both electrochemistry and np-Au for applications in biosensing. PMID:29547580

Preparation and characterization of kefiran electrospun nanofibers.

PubMed

Esnaashari, Seyedeh Sara; Rezaei, Sasan; Mirzaei, Esmaeil; Afshari, Hamed; Rezayat, Seyed Mahdi; Faridi-Majidi, Reza

2014-09-01

In this study, we report the first successful production of kefiran nanofibers through electrospinning process using distilled water as solvent. For this purpose, kefiran was extracted from cultured kefir grains, and homogenous kefiran solutions with different concentrations were prepared and then electrospun to obtain uniform nanofibers. The effect of main process parameters, including applied voltage, tip-to-collector distance, and feeding rate, on diameter and morphology of produced nanofibers, was studied. Scanning electron microscopy (SEM) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were used to characterize electrospun mats. Rheological behavior of the kefiran solution was evaluated via a cone and plate rheometer too. The results exhibited that diameter of kefiran nanofibers increased with increasing polymer concentration, applied voltage, and polymer feeding rate, while tip-to-collector distance did not have significant effect on nanofiber diameter. ATR-FTIR spectra showed that kefiran has maintained its molecular structure during electrospinning process. Flow curves also demonstrated shear thinning behavior for kefiran solutions. Copyright © 2014 Elsevier B.V. All rights reserved.

Distinct deleterious effects of cyclosporine and tacrolimus and combined tacrolimus-sirolimus on endothelial cells: protective effect of defibrotide.

PubMed

Carmona, Alba; Díaz-Ricart, Maribel; Palomo, Marta; Molina, Patricia; Pino, Marc; Rovira, Montserrat; Escolar, Ginés; Carreras, Enric

2013-10-01

Endothelial dysfunction seems to be a key factor in the development of several complications observed early after hematopoietic stem cell transplantation (HSCT). The conditioning regimen and many other factors associated with the procedure are responsible for this endothelial damage. The effects of immunosuppressive agents on endothelial function have not been explored in detail. We evaluated the effects of 3 drugs commonly used in HSCT: 2 calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus (TAC), and an inhibitor of mTOR, sirolimus (SIR). We also evaluated the effect of the combination of TAC and SIR (TAC+SIR), which is used increasingly in clinical practice. Microvascular endothelial cells (HMEC-1) were exposed to these drugs to evaluate changes in (1) intercellular adhesion molecule (ICAM)-1 expression on the cell surface, assessed by immunofluorescence labeling and expressed as the mean gray value (MGV); (2) reactivity of the extracellular matrix (ECM) toward platelets, upon exposure of the ECM to circulating blood; and (3) whole-blood clot formation, assessed by thromboelastometry. Studies were conducted in the absence and presence of defibrotide (DF) to assess its possible protective effect. The exposure of HMEC-1 to CSA and TAC+SIR significantly increased the expression of ICAM-1 (157.5 ± 11.6 and 153.4 ± 9.5 MGV, respectively, versus 105.7 ± 6.5 MGV in controls [both P < .05]). TAC applied alone increased ICAM-1 slightly (120.3 ± 8.2 MGV), and SIR had no effect (108.9 ± 7.4 MGV). ECM reactivity increased significantly only in response to CSA (surface covered by platelets of 41.2% ± 5.4% versus 30.1% ± 2.0%, P < .05). DF attenuated all these changes. No significant changes in the viscoelastic properties of clot formation were observed in any condition with blood samples incubated in vitro. In conclusion, CSA and TAC+SIR had a proinflammatory effect, but only CSA exhibited an additional prothrombotic effect. Interestingly, DF exerted clear

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

PubMed

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

Preparation and characterizations of EGDE crosslinked chitosan electrospun membranes.

PubMed

Aqil, A; Tchemtchoua, V T; Colige, A; Atanasova, G; Poumay, Y; Jérôme, C

2015-01-01

Composite Crosslinked nanofibrous membranes of chitosan, ethylene glycol diglycidyl ether (EGDE) and polyethylene oxide was successfully prepared with bead free morphology via electrospinning technique followed by heat mediated chemical crosslinking. Architectural stability of nanofiber mat in aqueous medium was achieved by chemical crosslinking of only 1% EGDE, and tensile strength tests revealed that increasing EGDE content has considerably enhance the elastic modulus of nanofibers. The structure, morphology and mechanical properties of nanofibers were characterized by Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM) and Instron machine, respectively. Skin fibroblasts and endothelial cells showed good attachment, proliferation and viability on crosslinked electrospun membranes. The results indicate a good biocompatibility and non-toxic nature of the resulted membrane.

Automated processing of whole blood samples for the determination of immunosuppressants by liquid chromatography tandem-mass spectrometry.

PubMed

Vogeser, Michael; Spöhrer, Ute

2006-01-01

Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is an efficient technology for routine determination of immunosuppressants in whole blood; however, time-consuming manual sample preparation remains a significant limitation of this technique. Using a commercially available robotic pipetting system (Tecan Freedom EVO), we developed an automated sample-preparation protocol for quantification of tacrolimus in whole blood by LC-MS/MS. Barcode reading, sample resuspension, transfer of whole blood aliquots into a deep-well plate, addition of internal standard solution, mixing, and protein precipitation by addition of an organic solvent is performed by the robotic system. After centrifugation of the plate, the deproteinized supernatants are submitted to on-line solid phase extraction, using column switching prior to LC-MS/MS analysis. The only manual actions within the entire process are decapping of the tubes, and transfer of the deep-well plate from the robotic system to a centrifuge and finally to the HPLC autosampler. Whole blood pools were used to assess the reproducibility of the entire analytical system for measuring tacrolimus concentrations. A total coefficient of variation of 1.7% was found for the entire automated analytical process (n=40; mean tacrolimus concentration, 5.3 microg/L). Close agreement between tacrolimus results obtained after manual and automated sample preparation was observed. The analytical system described here, comprising automated protein precipitation, on-line solid phase extraction and LC-MS/MS analysis, is convenient and precise, and minimizes hands-on time and the risk of mistakes in the quantification of whole blood immunosuppressant concentrations compared to conventional methods.

Characterization of Polysulfone Membranes Prepared with Thermally Induced Phase Separation Technique

NASA Astrophysics Data System (ADS)

Tiron, L. G.; Pintilie, Ș C.; Vlad, M.; Birsan, I. G.; Baltă, Ș

2017-06-01

Abstract Membrane technology is one of the most used water treatment technology because of its high removal efficiency and cost effectiveness. Preparation techniques for polymer membranes show an important aspect of membrane properties. Generally, polysulfone (PSf) and polyethersulfone (PES) are used for the preparation of ultrafiltration (UF) membranes. Polysulfone (PSf) membranes have been widely used for separation and purification of different solutions because of their excellent chemical and thermal stability. Polymeric membranes were obtained by phase inversion method. The polymer solution introduced in the nonsolvent bath (distilled water) initiate the evaporation of the solvent from the solution, this phenomenon has a strong influence on the transport properties. The effect of the coagulation bath temperature on the membrane properties is of interest for this study. Membranes are characterized by pure water flux, permeability, porosity and retention of methylene blue. The low temperature of coagulation bath improve the membrane’s rejection and its influence was most notable.

Preparation and Characterization of Fluorescent Derivatives of Lysozyme

NASA Technical Reports Server (NTRS)

Smith, Lori; Pusey, Marc

1998-01-01

Fluorescence is one of the most versatile and powerful tools for the study of macromolecules. However, its use in macromolecular crystal growth studies is hampered by the necessity of preparing fluorescent derivatives where the probe does not markedly affect the crystal packing. Alternatively, one can prepare derivatives of limited utility if it is known that they will not affect the specific goals of a given study. We have prepared a number of fluorescent derivatives of chicken egg white lysozyme, covalently attaching fluorescent probes to two different sites on the protein molecule. The first site is the side chain carboxyl group of ASP 101. Amine containing probes such as lucifer yellow, cascade blue, and 5- (2-aminoethyl) aminonapthalene-l-sulfonic acid (EDANS) have been attached using a carbodiimide coupling procedure. ASP 101 lies within the active site cleft, and it is believed that the probes are "buried" within that cleft. This is supported by the fact that all such derivatives have been found to crystallize, with the crystals being fluorescent. Tetragonal crystals of the lucifer yellow derivative have been found to diffract to at least 1.9 A resolution. X-ray diffraction data has been acquired and we are now working on the structure of this derivative. The second group of derivatives is to the N-terminal amine group. The derivatization reaction is performed by using a succinimidyl ester of the probe to be attached. Fluorescent probes such as pyrene acetic acid, 5-carboxyfluorescein, and Oregon green have been attached to this site. We have had little success in crystallizing these derivatives, probably because this site is part of the contact region between the 43 helix chains. However, these sites do not interfere with formation of the 43 helices and the derivatives are suitable for study of their formation in solution. The derivatives are being characterized by steady state and lifetime fluorescence methods, and the presentation will discuss these

Preparation and characterization of graphene/turbostratic carbon derived from chitosan film for supercapacitor electrodes

NASA Astrophysics Data System (ADS)

Hanappi, M. F. Y. M.; Deraman, M.; Suleman, M.; Othman, M. A. R.; Basri, N. H.; Nor, N. S. M.; Hamdan, E.; Sazali, N. E. S.; Tajuddin, N. S. M.

2018-04-01

Electrochemical capacitors or supercapacitors are the potential energy storage devices which are known for having higher specific capacitance and specific energy than electrolytic capacitors. Electric double-layer capacitors (EDLCs) also referred as ultracapacitors is a class of supercapacitors that employ different forms of carbon like activated carbon, CNT, graphene etc., as electrodes. The performance of the supercapacitors is determined by its components namely electrolyte, electrode, etc. Carbon electrodes with high surface area and desired pore size distribution are always preferred and which can be tailored by varying the precursor and method of preparation. In recent years, owing to their low cost, ease of synthesis, high stability and conductivity, the activated carbons derived from biomass precursors have been investigated as potential electrode material for the EDLCs. In this report, we present the preparation and characterization of graphene/turbostratic carbon monolith (CM) electrodes from the carbon grains (CGs) obtained by carbonization (under the flow of nitrogen, N2 gas and over a temperature range from 600 °C to 1000 °C) of biomass precursor chitosan film. The procedure to prepare the chitosan film is described elsewhere. The carbon grains are characterized using Raman spectroscopy (RS) and X-ray diffraction (XRD). We expect that the CGs would have the similar characteristics as graphene and would be a potential electrode material for EDLCs application.

Preparation and characterization of nanosilica from oil shale ash.

PubMed

Li, Jinhong; Qian, Tingting; Tong, Lingxin; Shen, Jie

2014-05-01

Nano-sized silica powders was prepared using oil shale ash (OSA) as starting materials. A combined process was proposed for the utilization of OSA in the production of the nanosilica, including three stages: calcination, alkaline leaching and carbon dioxide separation. Effects of the calcining temperature, sodium hydroxide concentration and holding time on the desilication ratio were investigated. The microstructure and morphologies of the nano-sized silica were characterized by X-ray diffraction, transmission electron microscopy, and Brunauer-Emmett-Teller nitrogen-gas adsorption method. The results indicated that the obtained powders with particle size of about 40 nm are homegeneously dispersed and its specific surface area is 387 m2/g. The properties of the nano-sized silica powder meet the requirements of the Chinese Chemical Industry Standard HG/T 3061-1999.

Preparation and characterization of graphene/CdS nanocomposites

NASA Astrophysics Data System (ADS)

Wu, Jili; Bai, Song; Shen, Xiaoping; Jiang, Lei

2010-11-01

Graphene-based nanocomposites are emerging as a new class of materials that hold promise for many applications. In this paper, we present a facile approach for the preparation of graphene/CdS nanocomposites through simple reflux processes, in which thiourea (CS(NH 2) 2) and thioacetamide (C 2H 5NS) act as a sulphide source, respectively. The samples were characterized by the X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectrum (FT-IR), ultraviolet-visible (UV-vis) spectroscopy and thermogravimetry analysis. It was shown that in the nanocomposites, the CdS nanoparticles were densely and uniformly deposited on the graphene sheets, and the sulphide source used has a great influence on the morphology, structure and property of the graphene/CdS nanocomposites. The good distribution of CdS nanoparticles on graphene sheets guarantees the efficient optoelectronic properties of graphene/CdS and would be promising for practical applications in future nanotechnology.

Preparation and characterization of biocompatible magnetic carbon nanotubes

NASA Astrophysics Data System (ADS)

Shan, Yan; Chen, Kezheng; Yu, Xuegang; Gao, Lian

2010-11-01

Magnetic carbon nanotubes consisting of multi-wall carbon nanotubes (MWNTs) core and Fe3O4 shell were successfully prepared by in situ thermal decomposition of Fe(acac)3 or FeCl3 or Fe(CO)5 in 2-pyrrolidone containing acid treated MWNTs at 240 °C with the protection of nitrogen gas. The samples were characterized by TEM, XRD, SEAD, XPS and superconducting quantum interference device. Also, their biocompatibility was compared with naked carbon nanotubes. The results showed that after coated with Fe3O4 nanoparticles, the obtained magnetic carbon nanotubes show superparamagnetic characteristic at room temperature, and their blocking temperature is about 80 K. The magnetic properties of the nanotubes are relevant to the content of magnetic particles, increasing content of magnetic nanoparticles leads to higher blocking temperature and saturation magnetization. The results of antimicrobial activities to bacterial cells (Escherichia coli) showed that the MWNTs have antimicrobial activity, while the magnetic nanotubes are biocompatible even with a higher concentration than that of MWNTs.

Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

PubMed Central

Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

2010-01-01

The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

Kombucha-synthesized bacterial cellulose: preparation, characterization, and biocompatibility evaluation.

PubMed

Zhu, Changlai; Li, Feng; Zhou, Xinyang; Lin, Lin; Zhang, Tianyi

2014-05-01

Bacterial cellulose (BC) is a natural biomaterial with unique properties suitable for tissue engineering applications, but it has not yet been used for preparing nerve conduits to repair peripheral nerve injuries. The objectives of this study were to prepare and characterize the Kampuchea-synthesized bacterial cellulose (KBC) and further evaluate the biocompatibility of KBC with peripheral nerve cells and tissues in vitro and in vivo. KBC membranes were composed of interwoven ribbons of about 20-100 nm in width, and had a high purity and the same crystallinity as that of cellulose Iα. The results from light and scanning electron microscopy, MTT assay, flow cytometry, and RT-PCR indicated that no significant differences in the morphology and cell function were observed between Schwann cells (SCs) cultured on KBC membranes and glass slips. We also fabricated a nerve conduit using KBC, which was implanted into the spatium intermusculare of rats. At 1, 3, and 6 weeks post-implantation, clinical chemistry and histochemistry showed that there were no significant differences in blood counts, serum biochemical parameters, and tissue reactions between implanted rats and sham-operated rats. Collectively, our data indicated that KBC possessed good biocompatibility with primary cultured SCs and KBC did not exert hematological and histological toxic effects on nerve tissues in vivo. Copyright © 2013 Wiley Periodicals, Inc.

Cholesterol-imprinted macroporous monoliths: Preparation and characterization.

PubMed

Stepanova, Mariia А; Kinziabulatova, Lilia R; Nikitina, Anna A; Korzhikova-Vlakh, Evgenia G; Tennikova, Tatiana B

2017-11-01

The development of sorbents for selective binding of cholesterol, which is a risk factor for cardiovascular disease, has a great importance for analytical science and medicine. In this work, two series of macroporous cholesterol-imprinted monolithic sorbents differing in the composition of functional monomers (methacrylic acid, butyl methacrylate, 2-hydroxyethyl methacrylate and ethylene dimethacrylate), amount of a template (4, 6 and 8 mol%) used for molecular imprinting, as well as mean pore size were synthesized by in situ free-radical process in stainless steel housing of 50 mm × 4.6 mm i.d. All prepared materials were characterized regarding to their hydrodynamic permeability and porous properties, as well as examined by BET and SEM methods. Imprinting factors, apparent dynamic dissociation constants, the maximum binding capacity, the number of theoretical plates and the height equivalent to a theoretical palate of MIP monoliths at different mobile phase flow rates were determined. The separation of a mixture of structural analogues, namely, cholesterol and prednisolone, was demonstrated. Additionally, the possibility of using the developed monoliths for cholesterol solid-phase extraction from simulated biological solution was shown. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A review of tin oxide-based catalytic systems: Preparation, characterization and catalytic behavior

NASA Technical Reports Server (NTRS)

Hoflund, Gar B.

1987-01-01

This paper reviews the important aspects of the preparation, characterization and catalytic behavior of tin oxide-based catalytic systems including doped tin oxide, mixed oxides which contain tin oxide, Pt supported on tin oxide and Pt/Sn supported on alumina. These systems have a broad range of applications and are continually increasing in importance. However, due to their complex nature, much remains to be understood concerning how they function catalytically.

Duloxetine HCl lipid nanoparticles: preparation, characterization, and dosage form design.

PubMed

Patel, Ketan; Padhye, Sameer; Nagarsenker, Mangal

2012-03-01

Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and high-dosing frequency. The DLX-SLNs were prepared by using two different techniques, viz. solvent diffusion method and ultrasound dispersion method, and evaluated for particle size, zeta potential, entrapment efficiency, physical characteristics, and chemical stability. Best results were obtained when SLNs were prepared by ultrasound dispersion method using glyceryl mono stearate as solid lipid and DLX in ratio of 1:20 and mixture of polysorbate 80 and poloxamer 188 as surfactant in concentration of 3%. The mean particle size of formulation and entrapment efficiency was 91.7 nm and 87%, respectively, and had excellent stability in acidic medium. Differential scanning calorimetry and X-ray diffraction data showed complete amorphization of DLX in lipid. In vitro drug release from SLNs was observed for 48 h and was in accordance with Higuchi kinetics. In vivo antidepressant activity was evaluated in mice by forced swim test. DLX-SLNs showed significant enhancement in antidepressant activity at 24 h when administered orally in comparison to drug solution. These results confirm the potential of SLNs in enhancing chemical stability and improving the efficacy of DLX via oral route. The SLN dispersion was converted into solid granules by adsorbing on colloidal silicon dioxide and characterized for particle size after redispersion, morphology, and flow properties. Results indicated that nanoparticles were successfully adsorbed on the carrier and released SLNs when dispersed in water.

Multiple-step preparation and physicochemical characterization of crystalline α-germanium hydrogenphosphate

NASA Astrophysics Data System (ADS)

Romano, Ricardo; Ruiz, Ana I.; Alves, Oswaldo L.

2004-04-01

The reaction between germanium oxide and phosphoric acid has previously been described and led to impure germanium hydrogenphosphate samples with low crystallinity. A new multiple-step route involving the same reaction under refluxing and soft hydrothermal conditions is described for the preparation of pure and crystalline α-GeP. The physicochemical characterization of the samples allows accompaniment of the reaction evolution as well as determining short- and long-range structural organization. The phase purity of the α-GeP sample was confirmed by applying Rietveld's profile analysis, which also determined the cell parameters of its crystals.

Effort versus reward: preparing samples for fungal community characterization in high-throughput sequencing surveys of soils

USDA-ARS?s Scientific Manuscript database

Next generation fungal amplicon sequencing is being used with increasing frequency to study fungal diversity in various ecosystems; however, the influence of sample preparation on the characterization of fungal community is poorly understood. We investigated the effects of four procedural modificati...

Preparation, characterization and dynamical mechanical properties of dextran-coated iron oxide nanoparticles (DIONPs).

PubMed

Can, Hatice Kaplan; Kavlak, Serap; ParviziKhosroshahi, Shahed; Güner, Ali

2018-03-01

Dextran-coated iron oxide nanoparticles (DIONPs) with appropriate surface chemistry exhibit many interesting properties that can be exploited in a variety of biomedical applications such as magnetic resonance imaging (MRI) contrast enhancement, tissue repair, hyperthermia, drug delivery and in cell separation. This paper reports the experimental detail for preparation, characterization and investigation of thermal and dynamical mechanical characteristics of the dextran-coated Fe 3 O 4 magnetic nanoparticles. In our work, DIONPs were prepared in a 1:2 ratio of Fe(II) and Fe(III) salt in the HCl solution with NaOH at given temperature. The obtained dextran-coated iron-oxide nanoparticles structure-property correlation was characterized by spectroscopic methods; attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and XRD. Coating dextran on the iron-oxide proof of important peaks can be seen from the ATR-FTIR. Dramatic crystallinity increment can be observed from the XRD pattern of the iron-oxide dextran nanoparticles. The thermal analysis was examined by differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). Dynamical mechanical properties of dextran nanoparticles were analysed by dynamic mechanical analysis (DMA). Thermal stability of the iron oxide dextran nanoparticles is higher than that of the dextran.

Preparation and characterization of a thermoresponsive gigaporous medium for high-speed protein chromatography.

PubMed

Qu, Jian-Bo; Chen, Yan-Li; Huan, Guan-Sheng; Zhou, Wei-Qing; Liu, Jian-Guo; Zhu, Hu; Zhang, Xiao-Yun

2015-01-01

A high-speed thermoresponsive medium was developed by grafting poly(N-isopropylacrylamide-co-butyl methacrylate) (P(NIPAM-co-BMA)) brushes onto gigaporous polystyrene (PS) microspheres via surface-initiated atom transfer radical polymerization (ATRP) technique, which has strong mechanical strength, good chemical stability and high mass transfer rate for biomacromolecules. The gigaporous structure, surface chemical composition, static protein adsorption, and thermoresponsive chromatographic properties of prepared medium (PS-P(NIPAM-co-BMA)) were characterized in detail. Results showed that the PS microspheres were successfully grafted with P(NIPAM-co-BMA) brushes and that the gigaporous structure was robustly maintained. After grafting, the nonspecific adsorption of proteins on PS microspheres was greatly reduced. A column packed with PS-P(NIPAM-co-BMA) exhibited low backpressure and significant thermo-responsibility. By simply changing the column temperature, it was able to separate three model proteins at the mobile phase velocity up to 2167 cm h(-1). In conclusion, the thermoresponsive polymer brushes grafted gigaporous PS microspheres prepared by ATRP are very promising in 'green' high-speed preparative protein chromatography. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparative isolation and characterization of some minor impurities of astaxanthin by high-performance liquid chromatography.

PubMed

Rao, R Nageswara; Alvi, S Naseeruddin; Rao, B Nageswara

2005-05-27

A simple and rapid preparative high-performance liquid chromatography (HPLC) method has been developed to isolate and characterize some minor impurities of astaxanthin using a normal-phase Lichrosorb silica column with n-hexane-acetone-tetrahydrofuran (90:2:8, v/v/v) as mobile-phase and detection at 475 nm. The isolated impurities were characterized as astacene, dehydro astacene and apoastaxanthinal by UV-vis, ESI-MS, 1H and 13C NMR spectroscopy and the molecular structures were assigned. The impurities collected using the developed conditions were over 98% pure.

Crosslinked type II collagen matrices: preparation, characterization, and potential for cartilage engineering.

PubMed

Pieper, J S; van der Kraan, P M; Hafmans, T; Kamp, J; Buma, P; van Susante, J L C; van den Berg, W B; Veerkamp, J H; van Kuppevelt, T H

2002-08-01

The limited intrinsic repair capacity of articular cartilage has stimulated continuing efforts to develop tissue engineered analogues. Matrices composed of type II collagen and chondroitin sulfate (CS), the major constituents of hyaline cartilage, may create an appropriate environment for the generation of cartilage-like tissue. In this study, we prepared, characterized, and evaluated type 11 collagen matrices with and without CS. Type II collagen matrices were prepared using purified, pepsin-treated, type II collagen. Techniques applied to prepare type I collagen matrices were found unsuitable for type II collagen. Crosslinking of collagen and covalent attachment of CS was performed using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. Porous matrices were prepared by freezing and lyophilization, and their physico-chemical characteristics (degree of crosslinking, denaturing temperature, collagenase-resistance, amount of CS incorporated) established. Matrices were evaluated for their capacity to sustain chondrocyte proliferation and differentiation in vitro. After 7 d of culture, chondrocytes were mainly located at the periphery of the matrices. In contrast to type I collagen, type II collagen supported the distribution of cells throughout the matrix. After 14 d of culture, matrices were surfaced with a cartilagenous-like layer, and occasionally clusters of chondrocytes were present inside the matrix. Chondrocytes proliferated and differentiated as indicated by biochemical analyses, ultrastructural observations, and reverse transcriptase PCR for collagen types I, II and X. No major differences were observed with respect to the presence or absence of CS in the matrices.

Preparation, characterization and gas sensing performance of BaTiO3 nanostructured thin films

NASA Astrophysics Data System (ADS)

Suryawanshi, Dinesh N.; Pathan, Idris G.; Bari, Anil. R.; Patil, Lalchand A.

2018-05-01

Spray pyrolysis techniques was employed to prepare BaTiO3 thin films. AR grade solutions of Barium chloride (0.05 M) and Titanium chloride (0.05 M) were mixed in the proportion of 30:70, 50:50 and 70:30. The solutions were sprayed on quartz substrate heated at 350°C temperature to obtain the films. These thin films were annealed for a two hours at 600°C in air medium respectively. The prepared thin films were characterized using XRD, FESEM, EDAX, TEM. The electrical and gas sensing properties of these films were investigated. 50:50 film showed better response to Liquid Petroleum Gas (LPG) as compare 30:70 and 70:30 films.

PREPARATION AND CHARACTERIZATION OF ORALLY DISINTEGRATING LORATADINE TABLETS MANUFACTURED WITH CO-PROCESSED MIXTURES.

PubMed

Amelian, Aleksandra; Szekalska, Marta; Wilczewska, Agnieszka Zofia; Basa, Anna; Winnicka, Katarzyna

2016-01-01

The aim of this study was to develop orally disintegrated tablets (ODT) with loratadine using Parteck ODT and Ludiflash--new commercially available tableting excipients based on co-processed mannitol. ODT containing loratadine were prepared with 3% addition of various superdisintegrants (AcDiSol, Kollidon CL-F and Kollidon CL-SF) by direct compression method. Obtained tablets were characterized for friability, pore structure, and wetting and disintegration time measured by four independents methods. In order to identify possible interactions between loratadine and the excipients, differential scanning calorimetry was used. The results showed that all formulated ODT were characterized by appropriate mechanical properties (friability < 1%), the uniform content of the drug substance and pleasant mouth feeling. Disintegration time below 30 s was observed in formulations with crospovidones as disintegrant.

Preparation and characterization of solid dispersion freeze-dried efavirenz - polyvinylpyrrolidone K-30.

PubMed

Fitriani, Lili; Haqi, Alianshar; Zaini, Erizal

2016-01-01

The aim of this research is to prepare and characterize solid dispersion of efavirenz - polyvinylpyrrolidone (PVP) K-30 by freeze drying to increase its solubility. Solid dispersion of efavirenz - PVP K-30 was prepared by solvent evaporation method with ratio 2:1, 1:1, and 1:2 and dried using a freeze dryer. Characterizations were done by scanning electron microscopy (SEM), powder X-ray diffraction analysis, differential thermal analysis (DTA), and Fourier transform infrared (FT-IR) spectroscopy. Solubility test was carried out in CO2-free distilled water, and efavirenz assay was conducted using high-performance liquid chromatography with acetonitrile:acetic acid (80:20) as the mobile phases. Powder X-ray diffractogram showed a decrease in the peak intensity, which indicated the crystalline altered to amorphous phase. DTA thermal analysis showed a decrease in the melting point of the solid dispersion compared to intact efavirenz. SEM results indicated the changes in the morphology of the crystal into an amorphous form compared to pure components. FT-IR spectroscopy analysis showed a shift wavenumber of the spectrum efavirenz and PVP K-30. The solubility of solid dispersion at ratio 2:1, 1:1, and 1:2 was 6.777 μg/mL, 6.936 μg/mL, and 14,672 μg/mL, respectively, whereas the solubility of intact efavirenz was 0.250 μg/mL. In conclusion, the solubility of solid dispersion increased significantly (P < 0.05).

Characterization of fermented seaweed sauce prepared from nori (Pyropia yezoensis).

PubMed

Uchida, Motoharu; Kurushima, Hirotaka; Ishihara, Kenji; Murata, Yuko; Touhata, Ken; Ishida, Noriko; Niwa, Kentaro; Araki, Toshiyoshi

2017-03-01

High-salt content seaweed sauces were prepared for the first time using nori (Pyropia yezoensis) by fermentation and characterized. Components and taste of the two nori sauces (NSs) prepared separately were compared with those of soy and fish sauces. The NSs were rich in total nitrogen compounds (1.5 g N/100 ml on average) and potassium (880 mg/100 g), and had a unique free amino acid composition (e.g., taurine 617 mg/100 g), explaining their unique taste as evaluated by a taste sensing system. As for their food function, inhibitory activity of angiotensin-converting enzyme was observed. As for their food safety, arsenic was detected at a 0.8 mg/100 g level in total, but inorganic arsenic was not detected (<0.05 mg/100 g) and not regarded as a problem. Allergy-causing substances contained in wheat, soy beans, and crustaceans were not detected (<0.1 mg/100 g) with NSs. These results suggest that the nori sauce has a high potential as a novel nutritional source for humans. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Optical characterization of pure and Al-doped ZnO prepared by sol-gel method

NASA Astrophysics Data System (ADS)

Belka, Radosław; Keczkowska, Justyna; Kasińska, Justyna

2016-09-01

In this paper the preparation process and optical characterization of pure and Al3+ doped zinc oxide (Al:ZnO) coatings will be presented. ZnO based materials have been studied extensively due to their potential applications in optoelectronic devices as conductive gas sensors, transparent conductive, electrodes, solar cell windows, varistors, UVfilters or photovoltaic cells. It is II-VI semiconductor with wide-band gap of 3.37 eV and large exciton binding energy of 60meV. It is possible to improve the conductivity of ZnO coating by intentionally doping ZnO with aluminium ions during preparation process. Such transparent and conducting thin films, known as AZO (Aluminium Zinc Oxide) films, are very good candidate for application as transparent conducting materials in many optoelectronic devices. The well-known sol-gel method is used for preparation of solution, coated on glass substrates by dip coating process. Prepared samples were investigated by Raman and UV-VIS spectroscopy. Transmittance as well as specular and diffuse reflectance spectroscopy methods were used for studies of optical parameters. We found that Al admixture influences on optical bandgap of ZnO.

Characterization of amylose nanoparticles prepared via nanoprecipitation: Influence of chain length distribution.

PubMed

Chang, Yanjiao; Yang, Jingde; Ren, Lili; Zhou, Jiang

2018-08-15

The influence of chain length distribution of amylose on size and structure of the amylose nanoparticles (ANPs) prepared through nanoprecipitation was investigated. Amylose with different chain length distributions was obtained by β-amylase treating amylose paste for different times and measured by size exclusion chromatography (SEC) and fluorophore-assisted carbohydrate electrophoresis (FACE). ANPs prepared via precipitation were characterized by using dynamic light scattering (DLS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Results showed that the β-amylase treatments led to decrease in chain length of amylose, and it was the most important factor affecting size of ANPs. When hydrolysis degree of amylose was 52.8%, mean size of ANPs decreased from 206.4 nm to 102.7 nm. All the ANPs displayed a V-type crystalline structure and the effect of amylose chain length on crystallinity of the precipitated ANPs was negligible in the investigated range. Copyright © 2018 Elsevier Ltd. All rights reserved.

Proniosome-derived niosomes for tacrolimus topical ocular delivery: in vitro cornea permeation, ocular irritation, and in vivo anti-allograft rejection.

PubMed

Li, Qi; Li, Zhanrong; Zeng, Weidong; Ge, Shumin; Lu, Haoyang; Wu, Chuanbin; Ge, Li; Liang, Dan; Xu, Yuehong

2014-10-01

The objective of this study was to develop proniosome-derived niosomes for topical ophthalmic delivery of Tacrolimus (FK506). The FK506 loaded proniosomes containing poloxamer 188 and lecithin as surfactants, cholesterol as a stabilizer, and minimal amount of ethanol and trace water reconstituted to niosomes prior to use. The stability of FK506 loaded proniosomes was assessed, and the morphology, size, zeta potential, surface tension, and entrapment efficiency of the derived niosomes were characterized, indicating they were feasible for instillation in the eyes. The in vitro permeation of FK506 through the freshly excised rabbit cornea, the cumulative permeation amount of FK506 from niosomes, and the drug retention in the cornea all exhibited significant increase as compared to 0.1% FK506 commercial ointments. The in vivo ocular irritation test of 0.1% FK506 loaded niosomes instilled 4 times per day in rat eyes for 21 consecutive days showed no irritation and good biocompatibility with cornea. The in vivo anti-allograft rejection assessment was performed in a Sprague-Dawley (SD) rat corneal xenotransplantation model. The results showed treatment with 0.1% FK506 loaded niosomes delayed the occurrence of corneal allograft rejection and significantly prolonged the median survival time of corneal allografts to13.86±0.80days as compared with those treated with 1% Cyclosporine (CsA) eye drops, drug-free niosomes, or untreated. In conclusion, the proniosome-derived niosomes may be a promising vehicle for effective ocular drug delivery of FK506. Copyright © 2014 Elsevier B.V. All rights reserved.

[Preparation and spectral characterization of CdS(y)Te(1-y) thin films].

PubMed

Li, Wei; Feng, Liang-Huan; Wu, Li-Li; Zhang, Jing-Quan; Li, Bing; Lei, Zhi; Cai, Ya-Ping; Zheng, Jia-Gui; Cai, Wei; Zhang, Dong-Min

2008-03-01

CdS(y)Te(1-y) (0 < or = y < or = 1) polycrystalline thin films were prepared on glass substrates by co-evaporation of powders of CdTe and CdS. For the characterization of the structure and composition of the CdS(y)Te(1-y) thin films the X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) were used. The results indicate that the values of sulfur content y detected and controlled by the quartz wafer detector show good agreement with the EDS results. The films were found to be cubic for x < 0. 3, and hexagonal for x > or = 0.3. The 20-50 nm of grain sizes for CdS(y)Te(1-y) thin films were calculated using a method of XRD analysis. Finally, the optical properties of CdS(y)Te(1-y) thin films were characterized by UV-Vis-NIR spectroscopy alone. According to a method from Swanepoel, together with the first-order Sellmeier model, the thickness, of d-535 nm, energy gap of E(g)-1.41 eV, absorption coefficient, alpha(lambda) and refractive index, n(lambda) of CdS(0.22) Te(0.78) thin films were determined from the transmittance at normal incidence of light in the wavelength range 300-2 500 nm. The results also indicate that the CdS(y)Te(1-y) thin films with any composition (0 < or = y < or = 1) can be prepared by co-evaporation, and the method to characterize the optical properties of CdS(y)Te(1-y) thin films can be implemented for other semiconductor thin films.

Niosomes encapsulating Ibuprofen-cyclodextrin complexes: preparation and characterization.

PubMed

Marianecci, Carlotta; Rinaldi, Federica; Esposito, Sara; Di Marzio, Luisa; Carafa, Maria

2013-08-01

A new delivery system based on ibuprofen-β-cyclodextrin (βCd) complexation and its loading into non-ionic surfactant vesicles (NSVs) was developed to improve ibuprofen therapeutic efficacy in topical formulations. The proposed strategy exploits the well known solubilizing and stabilizing properties of cyclodextrins together with the high tolerability and percutaneous absorption enhancing properties of NSVs. The complexing capacity of Cds in the presence of Ibuprofen in aqueous solution was evaluated by means of phase solubility studies. The technique used to obtain solid ibuprofen-βCd complexes was the co-lyophilization method. The influence of the preparation method on the physicochemical properties of the final product was evaluated by means of Fourier Transform Infrared Spectroscopy and Differential scanning calorimetry studies. Ibuprofen-βCd complexes were included in Tween 20/Cholesterol vesicles and characterized in terms of size, zeta (ζ)-potential, stability, drug entrapment efficiency and drug release. The best ibuprofen-βCd-NSV system exhibited in vitro drug permeation properties significantly improved with respect to those of the plain drug suspension.

Preparation and Characterization of Graphene Oxide Paper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dikin,D.; Stankovich, S.; Zimney, E.

2007-01-01

Free-standing paper-like or foil-like materials are an integral part of our technological society. Their uses include protective layers, chemical filters, components of electrical batteries or supercapacitors, adhesive layers, electronic or optoelectronic components, and molecular storage. Inorganic 'paper-like' materials based on nanoscale components such as exfoliated vermiculite or mica platelets have been intensively studied and commercialized as protective coatings, high-temperature binders, dielectric barriers and gas-impermeable membranes. Carbon-based flexible graphite foils composed of stacked platelets of expanded graphite have long been used in packing and gasketing applications because of their chemical resistivity against most media, superior sealability over a wide temperature range,more » and impermeability to fluids. The discovery of carbon nanotubes brought about bucky paper, which displays excellent mechanical and electrical properties that make it potentially suitable for fuel cell and structural composite applications. Here we report the preparation and characterization of graphene oxide paper, a free-standing carbon-based membrane material made by flow-directed assembly of individual graphene oxide sheets. This new material outperforms many other paper-like materials in stiffness and strength. Its combination of macroscopic flexibility and stiffness is a result of a unique interlocking-tile arrangement of the nanoscale graphene oxide sheets.« less

Preparation and characterization of graphene oxide paper.

PubMed

Dikin, Dmitriy A; Stankovich, Sasha; Zimney, Eric J; Piner, Richard D; Dommett, Geoffrey H B; Evmenenko, Guennadi; Nguyen, SonBinh T; Ruoff, Rodney S

2007-07-26

Free-standing paper-like or foil-like materials are an integral part of our technological society. Their uses include protective layers, chemical filters, components of electrical batteries or supercapacitors, adhesive layers, electronic or optoelectronic components, and molecular storage. Inorganic 'paper-like' materials based on nanoscale components such as exfoliated vermiculite or mica platelets have been intensively studied and commercialized as protective coatings, high-temperature binders, dielectric barriers and gas-impermeable membranes. Carbon-based flexible graphite foils composed of stacked platelets of expanded graphite have long been used in packing and gasketing applications because of their chemical resistivity against most media, superior sealability over a wide temperature range, and impermeability to fluids. The discovery of carbon nanotubes brought about bucky paper, which displays excellent mechanical and electrical properties that make it potentially suitable for fuel cell and structural composite applications. Here we report the preparation and characterization of graphene oxide paper, a free-standing carbon-based membrane material made by flow-directed assembly of individual graphene oxide sheets. This new material outperforms many other paper-like materials in stiffness and strength. Its combination of macroscopic flexibility and stiffness is a result of a unique interlocking-tile arrangement of the nanoscale graphene oxide sheets.

A protocol for preparing, characterizing and using three RNA-specific, live cell imaging probes: E36, E144 and F22.

PubMed

Li, Qian; Chang, Young-Tae

2006-01-01

This protocol outlines a methodology for the preparation and characterization of three RNA-specific fluorescent probes (E36, E144 and F22) and their use in live cell imaging. It describes a detailed procedure for their chemical synthesis and purification; serial product characterization and quality control tests, including measurements of their fluorescence properties in solution, measurement of RNA specificity and analysis of cellular toxicity; and live cell staining and counterstaining with Hoechst or DAPI. Preparation and application of these RNA imaging probes takes 1 week.

Preparation, Characterization, and Catalytic Activity of MoCo/USY Catalyst on Hydrodeoxygenation Reaction of Anisole

NASA Astrophysics Data System (ADS)

Nugrahaningtyas, K. D.; Suharbiansah, R. S. R.; Rahmawati, F.

2018-03-01

This research aims to prepare, characterize, and study the catalytic activity of Molybdenum (Mo) and Cobalt (Co) metal with supporting material Ultra Stable Y-Zeolite (USY), to produce catalysts with activity in hydrotreatment reaction and in order to eliminate impurities compounds that containing unwanted groups heteroatoms. The bimetallic catalysts MoCo/USY were prepared by wet impregnation method with weight variation of Co metal 0%, 2%, 4%, 6%, 8%, and Mo metal 8% (w/w), respectively. Activation method of the catalyst included calcination, oxidation, reduction and the crystallinity was characterized using X-ray diffraction (XRD), the acidity of the catalyst was analyzed using Fourier Transform Infrared Spectroscopy (FT-IR) and gravimetry method, minerals present in the catalyst was analyzed using X-Ray Fluorescence (XRF), and surface of the catalyst was analyzed using Surface Area Analyzer (SAA). Catalytic activity test (benzene yield product) of MoCo/USY on hydrodeoxigenation reaction of anisole aimed to determine the effect of Mo-Co/USY for catalytic activity in the reaction hydrodeoxigenation (HDO) anisole. Based on characterization and test of catalytic activity, it is known that catalytic of MoCo/USY 2% (catalyst B) shows best activities with acidity of 10.209 mmol/g, specific area of catalyst of 426.295 m2/g, pore average of 14.135 Å, total pore volume 0.318 cc/g, and total yield of HDO products 6.06%.

[Preparation and performance characterization of gold nanoparticles modified chiral capillary electrochromatography stationary phase].

PubMed

Xiong, Lele; Li, Ruijun; Ji, Yibing

2017-07-08

Gold nanoparticles (GNPs, 15 nm) were prepared and introduced to amino groups derived silica monolithic column. Bovine serum albumin (BSA) was immobilized via covalent modification method onto the carboxylic functionalized GNPs to afford chiral stationary phase (CSP) for enantioseparation. GNPs were well dispersed and successfully incorporated onto the columns with the contents as high as 17.18% by characterization method such as transmission electron microscopy (TEM), ultraviolet (UV)-visible absorption spectra and scanning electron microscopy (SEM). The preparation conditions of the BSA modified CSP were optimized and 10% (v/v) 3-aminopropyltriethoxysilane (APTES) and 15 g/L BSA were selected as appropriate reaction conditions. The enantioseparation performance of the BSA modified CSP has been investigated by capillary electrochromatography (CEC). Enantiomers of tryptophan, ephedrine and atenolol were resolved, and the baseline separation of tryptophan was achieved. Meanwhile, the influences of pH value, buffer concentrations and applied voltages used on the chiral separation were studied, and the optimal separation conditions were 10 mmol/L phosphate buffer at pH 7.4 and 15 kV applied voltages. In comparison with the BSA modified CSP prepared by physical adsorption, the CSP prepared by covalent modification method had better separation results, and the analytes could be separated directly without pre-column derivatization. In addition, the prepared BSA modified CSP exhibited good run to run repeatability with relative standard deviations (RSDs) of the migration times and selectivity factors not more than 2.3% and 0.96%, respectively. This work offers a good thinking for modification with other proteins or other types of chiral selectors.

Magnetic hyaluronate hydrogels: preparation and characterization

NASA Astrophysics Data System (ADS)

Tóth, Ildikó Y.; Veress, Gábor; Szekeres, Márta; Illés, Erzsébet; Tombácz, Etelka

2015-04-01

A novel soft way of hyaluronate (HyA) based magnetic hydrogel preparation was revealed. Magnetite nanoparticles (MNPs) were prepared by co-precipitation. Since the naked MNPs cannot be dispersed homogenously in HyA-gel, their surface was modified with natural and biocompatible chondroitin-sulfate-A (CSA) to obtain CSA-coated MNPs (CSA@MNPs). The aggregation state of MNPs and that loaded with increasing amount of CSA up to 1 mmol/g was measured by dynamic light scattering at pH~6. Only CSA@MNP with ≥0.2 mmol/g CSA content was suitable for magnetic HyA-gel preparation. Rheological studies showed that the presence of CSA@MNP with up to 2 g/L did not affect the hydrogel's rheological behavior significantly. The results suggest that the HyA-based magnetic hydrogels may be promising formulations for future biomedical applications, e.g. as intra-articular injections in the treatment of osteoarthritis.

Preparation and characterization of glass hollow fiber membrane for water purification applications.

PubMed

Makhtar, Siti Nurfatin Nadhirah Mohd; Rahman, Mukhlis A; Ismail, Ahmad Fauzi; Othman, Mohd Hafiz Dzarfan; Jaafar, Juhana

2017-07-01

This work discusses the preparation and characterizations of glass hollow fiber membranes prepared using zeolite-5A as a starting material. Zeolite was formed into a hollow fiber configuration using the phase inversion technique. It was later sintered at high temperatures to burn off organic materials and change the zeolite into glass membrane. A preliminary study, that used thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Fourier transform infrared (FTIR), confirmed that zeolite used in this study changed to glass at temperatures above 1000 °C. The glass hollow fiber membranes prepared using the phase inversion technique has three different microstructures, namely (i) sandwich-like structure that originates from inner layer, (ii) sandwich-like that originates from outer layer, and (iii) symmetric sponge like. These variations were influenced by zeolite weight loading and the flow rate of water used to form the lumen. The separation performances of the glass hollow fiber membrane were studied using the pure water permeability and the rejection test of bovine serum albumin (BSA). The glass hollow fiber membrane prepared from using 48 wt% zeolite loading and bore fluid with 9 mL min -1 flow rate has the highest BSA rejection of 85% with the water permeability of 0.7 L m -2  h -1  bar -1 . The results showed that the separation performance of glass hollow fiber membranes was in the ultrafiltration range, enabled the retention of solutes with molecular sizes larger than 67 kDa such as milk proteins, endotoxin pyrogen, virus, and colloidal silica.

Preparation for implementation of the mechanistic-empirical pavement design guide in Michigan : part 1 - HMA mixture characterization.

DOT National Transportation Integrated Search

2013-03-01

This is the final report of the Part 1 (HMA Mixture Characterization) of the Preparation for Implementation of the Mechanistic-Empirical Pavement Design Guide in Michigan project. The main objectives of the Part 1 were (i) to conduct a literatu...

Preparation, characterization and in vitro evaluation of solid dispersions containing docetaxel.

PubMed

Chen, Jie; Qiu, Liyan; Hu, Minxin; Jin, Yi; Han, Jieru

2008-06-01

Solid dispersions using water-soluble carriers were studied for improving the dissolution of docetaxel, a poorly soluble compound. In order to obtain the most optimized formulation, we prepared many solid dispersions with different carriers, different solvents, or at a series of drug-to-carrier ratios, and compared their dissolution. The accumulative dissolution of docetaxel from poloxamer 188 was more excellent than that from PVP(k30) and glyceryl monostearate, and the dissolution of docetaxel from solid dispersion was markedly higher than that of pure docetaxel; meanwhile the increased dissolution was partly dependent on the ratios of docetaxel and poloxamer 188. The ethanol used to prepare solid dispersion is of more significant effect on the dissolution of docetaxel than that of acetone. The docetaxel/poloxamer 188 system was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and environmental scanning electron microscope (ESEM). The results of DSC, XRD, and ESEM analyses of docetaxel/poloxamer 188 system showed that there are intermolecular interactions between docetaxel and poloxamer, and the crystallinity of docetaxel disappeared. These results show that solid dispersion is a promising approach of developing docetaxel drug formulates.

Preparation and characterization of chitosan-clay nanocomposites for the removal of Cu(II) from aqueous solution.

PubMed

Azzam, Eid M S; Eshaq, Gh; Rabie, A M; Bakr, A A; Abd-Elaal, Ali A; El Metwally, A E; Tawfik, Salah M

2016-08-01

In the present study, chitosan assembled on gold and silver nanoparticles were prepared and characterized by UV-vis, TEM, EDX and DLS techniques. The nanocomposites chitosan (Ch)/clay, chitosan (Ch)/AgNPs/clay and chitosan (Ch)/AuNPs/clay were prepared by solution mixing method and characterized by FTIR, XRD, and SEM techniques. The adsorption of copper(II) ions onto the prepared hybrid composites from an aqueous solution using batch adsorption was examined. The results showed that benefiting from the surface property of clay, the abundant amino and hydroxyl functional groups of chitosan, the adsorbent provides adequate and versatile adsorption for the Cu(II) ions under investigation. The batch adsorption experiments showed that the adsorption of the Cu(II) is considerably dependent on pH of milieu, the amount of adsorbent, and contact time. Batch adsorption studies revealed that the adsorption capacity of Cu(II) increased with increase in initial concentration and contact time with optimum pH in the range around neutral. The maximum uptake of Cu(II) ions by (Ch)/AgNPs/clay composite was found to be 181.5mg/g. The adsorption efficiency of Cu(II) ions by prepared (Ch)/AgNPs/clay and (Ch)/AuNPs/clay is bigger than that the individual chitosan (Ch)/clay composite which clarifies the role of metal nanoparticles in enhancement the adsorption characters. The study suggests that the (Ch)/AgNPs/clay hybrid composite is a promising nano-adsorbent for the removal of Cu(II) ions from aqueous solution. Copyright © 2016 Elsevier B.V. All rights reserved.

Spray Dried Chitosan Microparticles for Intravesical Delivery of Celecoxib: Preparation and Characterization.

PubMed

Lopedota, Angela; Cutrignelli, Annalisa; Laquintana, Valentino; Denora, Nunzio; Iacobazzi, Rosa Maria; Perrone, Mara; Fanizza, Elisabetta; Mastrodonato, Maria; Mentino, Donatella; Lopalco, Antonio; Depalo, Nicoletta; Franco, Massimo

2016-09-01

Chitosan microparticles containing celecoxib (CB), were developed as chemoprevention of bladder cancer. Furthermore two inclusion complexes of CB with methyl-β-cyclodextrin (C1 and C2) were prepared to improve the solubility of the drug. C1 and C2 were obtained by freeze-drying and characterized in the solid state and in solution. Microparticles loaded with CB or C1 or C2 were prepared by spray drying and fully characterized. The yield and encapsulation efficiencies of microparticles depended by both the viscosity and the presence of the inclusion complex in the feed medium nebulised. Generally, the microparticles exhibited a spherical shape with mean diameter of approximately 2 μm which was compatible with local intravesical administration using a catheter. The CB release studies from the microparticles allowed us to identify both immediate release systems (microparticles including the complexes) and prolonged release systems (microparticles including CB alone). The latter exhibited good adhesion to the bladder mucosa, as highlighted by a mucoadhesion study. Histological studies revealed a desquamation of the superficial cells when the bladder mucosa was treated with microparticles loaded with CB, while the morphology of the urothelium did not change when it was treated with microparticles loaded with the inclusion complex. A new CB intravesical formulation than can easily be administered with a catheter and is able to release the drug at the target site for several hours was realized. This new delivery system could be a good alternative to classic oral CB administration.

Preparation and characterization of fusion processed solid dispersions containing a viscous thermally labile polymeric carrier.

PubMed

Hughey, Justin R; Keen, Justin M; Miller, Dave A; Brough, Chris; McGinity, James W

2012-11-15

The primary aim of the present study was to investigate the ability of hydroxypropyl and methoxyl substituted cellulose ethers to stabilize supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak base, after an acid-to-neutral pH transition. A secondary aim of the study was to evaluate the effect of fusion processes on polymer stability and molecular weight. Polymer screening studies showed that stabilization of ITZ supersaturation was related to the molecular weight of the polymer and levels of hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is characterized as having a high melt viscosity, was selected for solid dispersion formulation studies. Hot-melt extrusion processing of E50LV based compositions resulted in high torque loads, low material throughput and polymer degradation. KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as a method to prepare the solid dispersions with reduced levels of polymer degradation. An experimental design revealed that polymer molecular weight was sensitive to shearing forces and high temperatures. However, optimal processing conditions resulted in significantly reduced E50LV degradation relative to HME processing. The technique was effectively utilized to prepare homogenous solid solutions of E50LV and ITZ, characterized as having a single glass transition temperature over a wide range of drug loadings. All prepared compositions provided for a high degree of ITZ supersaturation stabilization. Copyright © 2012 Elsevier B.V. All rights reserved.

Preparation, characterization, physical properties, and photoconducting behaviour of anthracene derivative nanowires

NASA Astrophysics Data System (ADS)

Xiao, Jinchong; Yin, Zongyou; Yang, Bo; Liu, Yi; Ji, Li; Guo, Jun; Huang, Ling; Liu, Xuewei; Yan, Qingyu; Zhang, Hua; Zhang, Qichun

2011-11-01

Organic nanowires of 9,10-dibromoanthracene (DBA) and 9,10-dicyanoanthracene (DCNA) were obtained by adding the THF solution of DBA/DCNA into water containing P123 surfactants. The as-prepared nanowires were characterized by UV-vis, fluorescence spectra, Field Emission Scanning Electron Microscopy (FESEM), and Transmission Electron Microscopy (TEM). We found that DBA and DCNA nanowires emitted green light rather than blue light for molecules in THF solution. The red-shift UV and fluorescent spectra of DBA and DCNA nanowires implied that these nanowires were formed through J-aggregation. The photoconducting study of DBA/DCNA nanowire-based network on rGO/SiO2/Si shows different photocurrent behaviors upon irradiation, which displayed that electron transfer from DCNA nanowire to rGO was stronger than that of DBA nanowires to rGO.Organic nanowires of 9,10-dibromoanthracene (DBA) and 9,10-dicyanoanthracene (DCNA) were obtained by adding the THF solution of DBA/DCNA into water containing P123 surfactants. The as-prepared nanowires were characterized by UV-vis, fluorescence spectra, Field Emission Scanning Electron Microscopy (FESEM), and Transmission Electron Microscopy (TEM). We found that DBA and DCNA nanowires emitted green light rather than blue light for molecules in THF solution. The red-shift UV and fluorescent spectra of DBA and DCNA nanowires implied that these nanowires were formed through J-aggregation. The photoconducting study of DBA/DCNA nanowire-based network on rGO/SiO2/Si shows different photocurrent behaviors upon irradiation, which displayed that electron transfer from DCNA nanowire to rGO was stronger than that of DBA nanowires to rGO. Electronic supplementary information (ESI) available: XRD patterns and simulations, and FT-IR spectra. CCDC reference numbers 840471. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c1nr10655d

Spindly cobalt ferrite nanocrystals: preparation, characterization and magnetic properties.

PubMed

Cao, Xuebo; Gu, Li

2005-02-01

In this paper we describe the preparation of homogeneously needle-shaped cobalt ferrite (CoFe(2)O(4)) nanocrystals on a large scale through the smooth decomposition of urea and the resulting co-precipitation of Co(2+) and Fe(3+) in oleic acid micelles. Furthermore, we found that other ferrite nanocrystals with a needle-like shape, such as zinc ferrite (ZnFe(2)O(4)) and nickel ferrite (NiFe(2)O(4)), can be prepared by the same process. Needle-shaped CoFe(2)O(4) nanocrystals dispersed in an aqueous solution containing oleic acid exhibit excellent stability and the formed colloid does not produce any precipitations after two months, which is of prime importance if these materials are applied in magnetic fluids. X-ray diffraction (XRD) measurements were used to characterize the phase and component of the co-precipitation products, and demonstrate that they are spinel ferrite with a cubic symmetry. Transmission electron microscopy (TEM) observation showed that all the nanocrystals present a needle-like shape with a 22 nm short axis and an aspect ratio of around 6. Varying the concentration of oleic acid did not bring about any obvious influence on the size distribution and shapes of CoFe(2)O(4). The magnetic properties of the needle-shaped CoFe(2)O(4) nanocrystals were evaluated by using a vibrating sample magnetometer (VSM), electron paramagnetic resonance (EPR), and a Mössbauer spectrometer, and the results all demonstrated that CoFe(2)O(4) nanocrystals were superparamagnetic at room temperature.

Preparation and characterization of citral-loaded solid lipid nanoparticles.

PubMed

Tian, Huaixiang; Lu, Zhuoyan; Li, Danfeng; Hu, Jing

2018-05-15

Citral-loaded solid lipid nanoparticles (citral-SLNs) were prepared via a high-pressure homogenization method, using glyceryl monostearate (GMS) as the solid lipid and a mixture of Tween 80 (T-80) and Span 80 (S-80) at a weight ratio of 1:1 as the surfactant. The microstructure and properties of the citral-SLNs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermal gravimetric analysis (TGA). The chemical stability of citral in the citral-SLNs was analyzed by solid-phase microextraction gas chromatography (SPME-GC). The GC results showed that 67.0% of the citral remained in the citral-SLN suspensions after 12 days, while only 8.22% remained in the control. Therefore, the encapsulation of citral in the solid lipid can enhance its stability in acidic surroundings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and characterization of clove essential oil-loaded liposomes.

PubMed

Sebaaly, Carine; Jraij, Alia; Fessi, Hatem; Charcosset, Catherine; Greige-Gerges, Hélène

2015-07-01

In this study, suitable formulations of natural soybean phospholipid vesicles were developed to improve the stability of clove essential oil and its main component, eugenol. Using an ethanol injection method, saturated (Phospholipon 80H, Phospholipon 90H) and unsaturated soybean (Lipoid S100) phospholipids, in combination with cholesterol, were used to prepare liposomes at various eugenol and clove essential oil concentrations. Liposomal batches were characterized and compared for their size, polydispersity index, Zeta potential, loading rate, encapsulation efficiency and morphology. The liposomes were tested for their stability after storing them for 2 months at 4°C by monitoring changes in their mean size, polydispersity index and encapsulation efficiency (EE) values. It was found that liposomes exhibited nanometric oligolamellar and spherical shaped vesicles and protected eugenol from degradation induced by UV exposure; they also maintained the DPPH-scavenging activity of free eugenol. Liposomes constitute a suitable system for encapsulation of volatile unstable essential oil constituents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation and characterization of isoniazid-loaded crude soybean lecithin liposomes.

PubMed

Nkanga, Christian Isalomboto; Krause, Rui Werner; Noundou, Xavier Siwe; Walker, Roderick Bryan

2017-06-30

Tuberculosis (TB) is a poverty related infectious disease that is rapidly giving rise to public health concerns. Lengthy drug administration and frequent adverse side-effects associated with TB treatment make anti-tubercular drugs (ATDs) good candidates for drug delivery studies. This work aimed to formulate and prepare liposomes as a cost-effective option for ATD delivery. Liposomes were prepared by film hydration using crude soybean lecithin (CL) and not pure phospholipids as in the normal practice. Cholesterol was also used (up to 25% mass ratio), and isoniazid (INH) was encapsulated as model drug using a freeze-thaw loading technique. Purified soybean lecithin (PL) was also used for comparative purposes, under the same conditions. INH-loaded liposomes were characterized for particle size, Zeta Potential (ZP), encapsulation efficiency (EE) and drug release. Physicochemical properties were investigated using thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared. INH-loaded CL-based liposomes showed high EE (79±2.45%). The average particle size (813.00±9.21nm) and ZP (-42.80±4.31mV) of this formulation are promising for the treatment of TB by pulmonary delivery. These findings suggest the possibility of encapsulating ATDs in liposomes made of crude soybean lecithin that is cheap and readily available. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface Structure Spread Single Crystals (S4C): Preparation and characterization

NASA Astrophysics Data System (ADS)

de Alwis, A.; Holsclaw, B.; Pushkarev, V. V.; Reinicker, A.; Lawton, T. J.; Blecher, M. E.; Sykes, E. C. H.; Gellman, A. J.

2013-02-01

A set of six spherically curved Cu single crystals referred to as Surface Structure Spread Single Crystals (S4Cs) has been prepared in such a way that their exposed surfaces collectively span all possible crystallographic surface orientations that can be cleaved from the face centered cubic Cu lattice. The method for preparing these S4Cs and for finding the high symmetry pole point is described. Optical profilometry has been used to determine the true shapes of the S4Cs and show that over the majority of the surface, the shape is extremely close to that of a perfect sphere. The local orientations of the surfaces lie within ± 1° of the orientation expected on the basis of the spherical shape; their orientation is as good as that of many commercially prepared single crystals. STM imaging has been used to characterize the atomic level structure of the Cu(111) ± 11°-S4C. This has shown that the average step densities and the average step orientations match those expected based on the spherical shape. In other words, although there is some distribution of step-step spacing and step orientations, there is no evidence of large scale reconstruction or faceting. The Cu S4Cs have local structures based on the ideal termination of the face centered cubic Cu lattice in the direction of termination. The set of Cu S4Cs will serve as the basis for high throughput investigations of structure sensitive surface chemistry on Cu.

RapTOR: Automated Sequencing Library Preparation and Suppression for Rapid Pathogen Characterization (7th Annual SFAF Meeting, 2012)

ScienceCinema

Lane, Todd

2018-05-18

Todd Lane on "RapTOR: Automated sequencing library preparation and suppression for rapid pathogen characterization" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

RapTOR: Automated Sequencing Library Preparation and Suppression for Rapid Pathogen Characterization (7th Annual SFAF Meeting, 2012)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lane, Todd

2012-06-01

Todd Lane on "RapTOR: Automated sequencing library preparation and suppression for rapid pathogen characterization" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Preparation using pectinase and characterization of nanofibers from orange peel waste in juice factories.

PubMed

Hideno, Akihiro; Abe, Kentaro; Yano, Hiroyuki

2014-06-01

This study reports the preparation and characterization of nanofibers consisting mainly of cellulose microfibrils from orange peel (OP), which is a significant byproduct of orange juice production. Three treatments (boiling, alkaline, and pectinase) were investigated with and without subsequent grinding treatment. It was possible to prepare the cellulose nanofibers (CNFs) using these methods, except for the boiling treatment with grinding. Interestingly, only pectinase and a mild-physical blender treatment without grinding produced nanofibers. The width of the nanofibers from OP was approximately 10 to 50 nm. The microfibril bundles of OP were considered to be thinner than those of commercial CNFs. Our data indicated that the removal of pectic polysaccharides and hemicelluloses covering the cellulose microfibrils was important for the preparation of nanofibers from OP. These nanofibers from OP using pectinase are proposed to be applicable as food materials, pharmaceuticals, and filters for the tractive characteristics of the sheet. This study demonstrates: (1) it was possible to prepare the nanofibers from orange peel using pectinase and (2) the width of the nanofibers from orange peel was approximately 10 to 50 nm. (3) Removal of polysaccharides such as pectin and hemicelluloses covering cellulose microfibrils was very important for preparation of nanofibers from OP. Considering the tractive characteristics of the sheets from nanofibers and the origin of orange peel, they are suitable for application of food materials, pharmaceuticals, and filters. © 2014 Institute of Food Technologists®

TAC-TIC use of tacrolimus-based regimens in lupus nephritis

PubMed Central

Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

2016-01-01

Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

Preparation and characterization of Polyacrylonitrile/ Manganese Dioxides- based Carbon Nanofibers via electrospinning process

NASA Astrophysics Data System (ADS)

Che Othman, F. E.; Yusof, N.; Jaafar, J.; Ismail, A. F.; Hasbullah, H.; Abdullah, N.; Ismail, M. S.

2016-06-01

This research reports the production of precursor polyacrylonitrile (PAN)/ manganese dioxide (MnO2) nanofibers (NFs) via electrospinning method followed by stabilization and carbonization processes. Nowadays, electrospinning has become a suitable method in manufacturing continuous NFs, thus it is employed to fabricate NFs in this study. The microstructural properties and adsorption competencies of the produced NFs were also studied. The NFs were prepared by electrospinning the polymer solution of Polyacrylonitrile (PAN) and Manganese Dioxide (MnO2) in, N, N-Dimethylformamide (DMF) solvent. The factors considered in this study were various polymer PAN/MnO2 concentrations which will significantly affect the specific surface area, fiber morphology and the diameter of the NFs prepared. Subsequently, heat treatment is applied by setting up the stabilization temperature at 275 °C and carbonization temperature at 800 °C with constant dwelling time (30 min). Nitrogen gas at constant rate 0.2 L/min was used for stabilization and carbonization with the stabilization rate (2 °C/min) and carbonization rate (5 °C/min). The carbon nanofibers (CNFs) produced were characterized using Scanning Electron Microscopy (SEM), Brunauer Emmett and Teller (BET) surface area and Fourier Transmission Infrared Spectroscopy (FTIR). It was found that the PAN/MnO2 CNFs were successfully produced with the carbonization temperature of 800 °C. The prepared PAN/MnO2 CNFs prepared showed an enhanced in specific surface area about two times compared to it precursor NFs.

Binary Alkali-Metal Silicon Clathrates by Spark Plasma Sintering: Preparation and Characterization

PubMed Central

Veremchuk, Igor; Beekman, Matt; Antonyshyn, Iryna; Schnelle, Walter; Baitinger, Michael; Nolas, George S.; Grin, Yuri

2016-01-01

The binary intermetallic clathrates K8-xSi46 (x = 0.4; 1.2), Rb6.2Si46, Rb11.5Si136 and Cs7.8Si136 were prepared from M4Si4 (M = K, Rb, Cs) precursors by spark-plasma route (SPS) and structurally characterized by Rietveld refinement of PXRD data. The clathrate-II phase Rb11.5Si136 was synthesized for the first time. Partial crystallographic site occupancy of the alkali metals, particularly for the smaller Si20 dodecahedra, was found in all compounds. SPS preparation of Na24Si136 with different SPS current polarities and tooling were performed in order to investigate the role of the electric field on clathrate formation. The electrical and thermal transport properties of K7.6Si46 and K6.8Si46 in the temperature range 4–700 K were investigated. Our findings demonstrate that SPS is a novel tool for the synthesis of intermetallic clathrate phases that are not easily accessible by conventional synthesis techniques. PMID:28773710

Preparation and characterization of gamma irradiated Starch/PVA/ZnO nanocomposite films

NASA Astrophysics Data System (ADS)

Akhavan, Azam; Khoylou, Farah; Ataeivarjovi, Ebrahim

2017-09-01

In this study starch/PVA/ZnO nanocomposite films with antibacterial activity were prepared and modified using gamma irradiation for packaging applications. ZnO nanoparticles (NPs) were synthesized from Zn(OH)2 using hydrothermal process and characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The prepared ZnO NPs were incorporated into blend films of starch and poly (vinyl alcohol) (PVA) with different concentrations from 0.1 to 1 wt% using solution casting method. The results of SEM confirmed good dispersion of ZnO NPs into the films while FTIR spectroscopy showed interactions between ZnO particles and starch/PVA blend. The nanocomposite films were irradiated at the dose range of 1-5 kGy. It was found that gamma irradiation induces a significant reduction in water absorptions of the films at the dose of 3 kGy. Different trends were observed for the tensile and elongation properties of the irradiated films. Based on the results, the bacterial growth on the films was effectively inhibited when the dosage of ZnO NPs was only 0.5 wt%.

Protocols for the analytical characterization of therapeutic monoclonal antibodies. II - Enzymatic and chemical sample preparation.

PubMed

Bobaly, Balazs; D'Atri, Valentina; Goyon, Alexandre; Colas, Olivier; Beck, Alain; Fekete, Szabolcs; Guillarme, Davy

2017-08-15

The analytical characterization of therapeutic monoclonal antibodies and related proteins usually incorporates various sample preparation methodologies. Indeed, quantitative and qualitative information can be enhanced by simplifying the sample, thanks to the removal of sources of heterogeneity (e.g. N-glycans) and/or by decreasing the molecular size of the tested protein by enzymatic or chemical fragmentation. These approaches make the sample more suitable for chromatographic and mass spectrometric analysis. Structural elucidation and quality control (QC) analysis of biopharmaceutics are usually performed at intact, subunit and peptide levels. In this paper, general sample preparation approaches used to attain peptide, subunit and glycan level analysis are overviewed. Protocols are described to perform tryptic proteolysis, IdeS and papain digestion, reduction as well as deglycosylation by PNGase F and EndoS2 enzymes. Both historical and modern sample preparation methods were compared and evaluated using rituximab and trastuzumab, two reference therapeutic mAb products approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA). The described protocols may help analysts to develop sample preparation methods in the field of therapeutic protein analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and characterization of shape memory polymer scaffolds via solvent casting/particulate leaching.

PubMed

De Nardo, Luigi; Bertoldi, Serena; Cigada, Alberto; Tanzi, Maria Cristina; Haugen, Håvard Jostein; Farè, Silvia

2012-09-27

Porous Shape Memory Polymers (SMPs) are ideal candidates for the fabrication of defect fillers, able to support tissue regeneration via minimally invasive approaches. In this regard, control of pore size, shape and interconnection is required to achieve adequate nutrient transport and cell ingrowth. Here, we assessed the feasibility of the preparation of SMP porous structures and characterized their chemico-physical properties and in vitro cell response. SMP scaffolds were obtained via solvent casting/particulate leaching of gelatin microspheres, prepared via oil/water emulsion. A solution of commercial polyether-urethane (MM-4520, Mitsubishi Heavy Industries) was cast on compacted microspheres and leached-off after polymer solvent evaporation. The obtained structures were characterized in terms of morphology (SEM and micro-CT), thermo-mechanical properties (DMTA), shape recovery behavior in compression mode, and in vitro cytocompatibility (MG63 Osteoblast-like cell line). The fabrication process enabled easy control of scaffold morphology, pore size, and pore shape by varying the gelatin microsphere morphology. Homogeneous spherical and interconnected pores have been achieved together with the preservation of shape memory ability, with recovery rate up to 90%. Regardless of pore dimensions, MG63 cells were observed adhering and spreading onto the inner surface of the scaffolds obtained for up to seven days of static in vitro tests. A new class of SMP porous structures has been obtained and tested in vitro: according to these preliminary results reported, SMP scaffolds can be further exploited in the design of a new class of implantable devices.

Preparation and characterization of adefovir dipivoxil-stearic acid cocrystal with enhanced physicochemical properties.

PubMed

Seo, Jeong-Woong; Hwang, Kyu-Min; Lee, Sung-Hoon; Kim, Dong-Wook; Park, Eun-Seok

2017-06-11

The objectives of this study were to prepare cocrystal composed of adefovir dipivoxil (AD) and stearic acid (SA) and to investigate the enhanced properties of the cocrystal. The cocrystal was prepared by antisolvent precipitation and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). The enhanced properties were evaluated by dissolution testing, permeability studies, and powder rheology analysis. The AD raw material has a cuboid-like crystal and the cocrystal has a needle shape. In the FT-IR study, there were bathochromic shifts caused by the hydrogen bonding. The melting point of the cocrystal was 52.9 °C, which was lower than that of AD. The XRPD pattern also had distinct differences, supporting the formation of a new crystalline form. The cocrystal showed changes in the lattice energy and the solvation strength, which caused an enhanced dissolution. The permeability was increased due to the SA, which acts as a P-gp inhibitor. The tabletability was enhanced due to the altered crystal habit. In conclusion, cocrystal containing AD and SA was successfully prepared, presenting advantages such as enhanced solubility, tabletability, and permeability. The use of the cocrystal is a desirable approach for the improved physicochemical properties.

Preparation and characterization of dialdehyde starch by one-step acid hydrolysis and oxidation.

PubMed

Zuo, Yingfeng; Liu, Wenjie; Xiao, Junhua; Zhao, Xing; Zhu, Ying; Wu, Yiqiang

2017-10-01

Dialdehyde starch was prepared by one-step synthesis of acid hydrolysis and oxidation, using corn starch as the raw material, sodium periodate (NaIO 4 ) as the oxidant, and hydrochloric acid (HCl) as the acid solution. The prepared dialdehyde starch was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and gel permeation chromatography (GPC). The results confirmed that oxidation occurred between the starch and NaIO 4 . The acid hydrolysis reaction reduced the molecular weight of starch and effectively improved the aldehyde group contents (92.7%). Scanning electron microscope (SEM) analysis indicated that the average particle size decreased after acid hydrolysis and oxidation reaction. X-ray diffraction (XRD) and thermal gravimetric analyzer (TGA) analysis demonstrated that the crystallinity of the obtained dialdehyde starch showed a downward trend and a decelerated thermal decomposition rate. The starch after acid hydrolysis and oxidation exhibited lower hot paste viscosity and higher reactivity. Copyright © 2017. Published by Elsevier B.V.

Preparation and characterization of erythromycin molecularly imprinted polymers based on distillation-precipitation polymerization.

PubMed

Liu, Jiang; Li, Le; Tang, Hui; Zhao, Feilang; Ye, Bang-Ce; Li, Yingchun; Yao, Jun

2015-09-01

Erythromycin-imprinted polymers with excellent recognition properties were prepared by an innovative strategy called distillation-precipitation polymerization. The interaction between erythromycin and methacrylic acid was studied by ultraviolet absorption spectroscopy, and the as-prepared materials were characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Moreover, their binding performances were evaluated in detail by static, kinetic and selective sorption tests. It was found that the molecularly imprinted polymers afforded good morphology, monodispersity, and high adsorption capacity when the fraction of the monomers was 7 vol% in the whole reaction system, and the adsorption data for imprinted polymers correlated well with the Langmuir model. The maximum capacity of the imprinted and the non-imprinted polymers for adsorbing erythromycin is 44.03 and 19.95 mg/g, respectively. The kinetic studies revealed that the adsorption process fitted a pseudo-second-order kinetic model. Furthermore, the imprinted polymers display higher affinity toward erythromycin, compared with its analogue roxithromycin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hemostatic gauze based on chitosan and hydroquinone: preparation, characterization and blood coagulation evaluation.

PubMed

Cassano, Roberta; Di Gioia, Maria Luisa; Mellace, Silvia; Picci, Nevio; Trombino, Sonia

2017-11-07

This work concerns on the preparation and performance evaluation of a new chitosan hydroquinone based gauze for hemostatic use. Chitosan and hydroquinone were firstly connected by etherification and then linked to the pre-carboxylate gauze. The functionalized material and the chitosan-hydroquinone ether were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy and Differential Scanning Calorimetry (DSC). FT-IR results showed that an esterification occurred on carboxylic group of the gauze. The gauze functionalization degree was also evaluated by volumetric analysis. The ether hydroquinone content was obtained by the Folin test. Moreover, the linkage between hydroquinone and chitosan was confirmed by nuclear magnetic resonance (NMR). The hemostatic activity of functionalized gauze was evaluated by dynamic blood clotting assays. The obtained results showed that the prepared material can shorten the blood clotting time and induce the adhesion and activation of platelets. Finally, swelling characteristic of the new gauze was evaluated to confirm its high capacity to absorb the blood.

Preparation and Characterization of Rivastigmine Transdermal Patch Based on Chitosan Microparticles.

PubMed

Sadeghi, Mohsen; Ganji, Fariba; Taghizadeh, Seyyed Mojtaba; Daraei, Bahram

2016-01-01

Here we report a novel approach for preparation of a 6-day transdermal drug delivery system (TDDS) as treatment for mild to moderate Alzheimer's disease. The spray drying method was used to prepare microparticles containing the anti-Alzheimer drug, Rivastigmine, in combination with the natural polymer, chitosan, for transdermal drug delivery applications. The content of the drug was determined by High Performance Liquid Chromatography (HPLC) method which was validated as per FDA guidelines. The morphology and size range of the microparticles were determined; and the effect of drug concentration in the solution injected into the spray dryer on the particles characterizations was studied. The stability of Rivastigmine at high temperature was confirmed using FTIR analysis as well as a validate HPLC assay. The obtained results show that the drug was stable at high temperatures with 7 to 42% loading in the microparticles, and the higher drug concentrations of the solution injected into the spray dryer resulted in increase of the drug loading, surface drug and microparticles distortion. The TDDS containing the microparticles was also prepared with microparticle to dry adhesive ratios of 5, 10 and 15% using acrylic adhesive. Based on adhesion properties of the patches, gained from the probe tack and the peel adhesion 180° tests, and the 15% patch by having more drug content per unit area of the patch, and still having similar adhesion properties was compared to the microparticles-free patch of 5.1% Rivastigmine salt (equivalent to the drug content of the 15% patch) from the permeation point of view by using Franz cell diffusion over 6 days. The drug permeation rate from the microparticle-free patch was slower than the 15% microparticles patch, which is the result of crystallization of Rivastigmine salt in the acrylic adhesive. The 6-day-prepared TDDS can be considered as an alternative for one-week application of 6 Exelon patches.

[Preparation and characterization of nanoemulsion].

PubMed

Sun, Yu-Jing; Wu, Dao-Cheng; Cao, Yun-Xin; Sui, Yan-Fang

2005-01-01

To prepare nanoemulsion-encapsulated BSA-FITC (NEBSA-FITC), study its characteristics, and measure its uptake by dendritic cells (DCs) and peritoneal macrophages. NEBSA-FITC was prepared by a method of interfacial polymerization.The encapsulation rate, drug-carrying capacity and stability of the nanoemulsion were determined by Sephadex-G100 chromatography. The shape and size of NEBSA-FITC were observed under electron microscope. The uptake of NEBSA-FITC by DCs and macrophage cells was detected by FACS and laser confocal microscopy. The mean size of NEBSA-FITC was (25+/-10) nm. The encapsulation rate was 91%, the drug-carrying capacity was 0.091 g/L and NEBSA-FITC had a good stability. The FACS analysis showed that DCs and macrophage cells could take in more NEBSA-FITC than free BSA. The observation under laser confocal microscope found that NEBSA-FITC was located in the cytoplasm of DCs. Nanoemulsion can be efficiently taken by DCs and macrophage cells, and therefore may be promising efficient carrier of APCs-targeted antitumor vaccine.

Vaginal inserts based on chitosan and carboxymethylcellulose complexes for local delivery of chlorhexidine: preparation, characterization and antimicrobial activity.

PubMed

Bigucci, Federica; Abruzzo, Angela; Vitali, Beatrice; Saladini, Bruno; Cerchiara, Teresa; Gallucci, Maria Caterina; Luppi, Barbara

2015-01-30

The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose polyelectrolyte complexes for local delivery of chlorhexidine digluconate. Complexes were prepared with different chitosan/carboxymethylcellulose molar ratios at a pH value close to pKa interval of the polymers and were characterized in terms of physico-chemical properties, complexation yield and drug loading. Then complexes were used to prepare inserts as vaginal dosage forms and their physical handling, morphology, water-uptake ability and drug release properties as well as antimicrobial activity toward Candida albicans and Escherichia coli were evaluated. Results confirmed the ionic interaction between chitosan and carboxymethylcellulose and the influence of the charge amount on the complexation yield. Complexes were characterized by high values of drug loading and showed increasing water-uptake ability with the increase of carboxymethylcellulose amount. The selection of appropriate chitosan/carboxymethylcellulose molar ratios allowed to obtain cone-like shaped solid inserts, easy to handle and able to hydrate releasing the drug over time. Finally, the formulated inserts showed antimicrobial activity against common pathogens responsible for vaginal infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation of chitosan-ferulic acid conjugate: Structure characterization and in the application of pharmaceuticals.

PubMed

Li, Chen; Li, Jian-Bin

2017-12-01

A novel drug delivery system based on chitosan derivatives was prepared by introducting ferulic acid to chitosan adopting a free radical-induced grafting procedure. This paper used an ascorbic acid/hydrogen peroxide redox pair as radical initiator. The chitosan derivative was characterized by Fourier transformed infrared (FTIR), Ultraviolet-visible spectrum (UV), Differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Electron microscopic scanning (SEM). What is more, preparing microcapsules with the chitosan conjugate as wall material, the drug release propertie of chitosan conjugates were compared with that of a blank chitosan, which treated in the same conditions but in the absence of ferulic acid. The study clearly demonstrates that free radical-induced grafting procedure was an effective reaction methods and chitosan-ferulic acid is a potential functionalized carrier material for drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

PubMed

Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

2016-02-01

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation.

PubMed

Shanmugam, Srinivasan; Kim, Young-Hun; Park, Jeong-Hee; Im, Ho Taek; Sohn, Young Taek; Kim, Kyeong Soo; Kim, Yong-Il; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon; Woo, Jong Soo

2014-06-01

The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS). Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated. The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 ± 0.020 g, 98.25 ± 2.50%, 2.5 ± 0.08 kg and 9 ± 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0-24 h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0-24 h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution. This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.

Preparation and characterization of mono-sheet bipolar membranes by pre-irradiation grafting method for fuel cell applications

NASA Astrophysics Data System (ADS)

Guan, Yingjie; Fang, Jun; Fu, Tao; Zhou, Huili; Wang, Xin; Deng, Zixiang; Zhao, Jinbao

2016-09-01

A new method for the preparation of the mono-sheet bipolar membrane applied to fuel cells was developed based on the pre-irradiation grafting technology. A series of bipolar membranes were successfully prepared by simultaneously grafting of styrene onto one side of the poly(ethylene-co-tetrafluoroethylene) base film and 1-vinylimidazole onto the opposite side, followed by the sulfonation and alkylation, respectively. The chemical structures and microstructures of the prepared membranes were investigated by ATR-FTIR and SEM-EDS. The TGA measurements demonstrated the prepared bipolar membranes have reasonable thermal stability. The ion exchange capacity, water uptake and ionic conductivity of the membranes were also characterized. The H2/O2 single fuel cells using these membranes were evaluated and revealed a maximum power density of 107 mW cm-2 at 35 °C with unhumidified hydrogen and oxygen. The preliminary performances suggested the great prospect of these membranes in application of bipolar membrane fuel cells.

Preparation and characterization of fluorophenylboronic acid-functionalized affinity monolithic columns for the selective enrichment of cis-diol-containing biomolecules.

PubMed

Li, Qianjin; Liu, Zhen

2015-01-01

Boronate affinity monolithic columns have been developed into an important means for the selective recognition and capture of cis-diol-containing biomolecules, such as glycoproteins, nucleosides and saccharides. The ligands of boronic acids are playing an important role in boronate affinity monolithic columns. Although several boronate affinity monoliths with high affinity toward cis-diol-containing biomolecules have been reported, only few publications are focused on their detailed procedures for preparation and characterization. This chapter describes in detail the preparation and characterization of a boronate affinity monolithic column applying 2,4-difluoro-3-formyl-phenylboronic acid (DFFPBA) as a ligand. The DFFPBA-functionalized monolithic column not only exhibited an ultrahigh boronate affinity toward cis-diol-containing biomolecules, but also showed great potential for the selective enrichment of cis-diol-containing biomolecules in real samples.

Preparation and Characterization of Guar-Montmorillonite Nanocomposites

PubMed Central

Mansa, Rola; Detellier, Christian

2013-01-01

Polymer-clay nanocomposites are highly sought-after materials, mainly due to their applicability in a variety of avenues. From the standpoint of the preparation of these nanocomposites, however, organic compatibility with clay and adherence to “green chemistry” concepts and principles can be limiting factors. As such, the objective was to prepare a biopolymer-modified clay nanocomposite using a simple and environmentally friendly method of preparation, whereby pre-treatment of the clay for organic compatibility was bypassed. Novel montmorillonite nanocomposites were prepared using neutral guar gum and cationic guar gum. X-ray diffraction (XRD) and transmission electron microscopy (TEM) confirmed the formation of intercalated structures. A monolayer configuration of cationic guar within the interlayer space was indicated by XRD results, while treatment with neutral guar gum resulted in the observance of both monolayer and bilayer configurations. Additionally, TEM results indicated partial exfoliation. Results attributed from 13C cross polarization/magic angle spinning nuclear magnetic resonance spectroscopy (CP/MAS NMR) of the nanocomposites indicated peaks corresponding to the guar constituent, confirming the adsorption of the biopolymer. Inductively coupled plasma emission spectrometry (ICP-ES) results indicated the exchange of cations present in neutral guar gum with the sodium cations of montmorillonite, in the case of the neutral guar nanocomposites. PMID:28788384

Preparation and Characterization of Activated Carbon from Palm Kernel Shell

NASA Astrophysics Data System (ADS)

Andas, J.; Rahman, M. L. A.; Yahya, M. S. M.

2017-08-01

In this study, a high quality of activated carbon (AC) was successfully synthesized from palm kernel shell (PKS) via single step KOH activation. Several optimal conditions such as impregnation ratio and activation temperature were investigated. The prepared activated carbon under the optimum condition of impregnation ratio (1:1.5 raw/KOH) and activation temperature (800 °C) was characterized using Na2S2O3 volumetric method, CHNS/O analysis and Scanning Electron Microscope (SEM). Na2S2O3 volumetric showed an iodine number of 994.83 mgg-1 with yield % of 8.931 %. CHNS/O analysis verified an increase in C content for KOH-AC (61.10 %) in comparison to the raw PKS (47.28 %). Well-formation of porous structure was evidenced through SEM for KOH-AC. From this study, it showed a successful conversion of agricultural waste into value added porous material under benign condition.

Structural characterization of pharmaceutical heparins prepared from different animal tissues.

PubMed

Fu, Li; Li, Guoyun; Yang, Bo; Onishi, Akihiro; Li, Lingyun; Sun, Peilong; Zhang, Fuming; Linhardt, Robert J

2013-05-01

Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. Three heparins from porcine, ovine, and bovine were characterized through state-of-the-art carbohydrate analysis methods with a view profiling their physicochemical properties. Differences in molecular weight, monosaccharide and disaccharide composition, oligosaccharide sequence, and antithrombin III-binding affinity were observed. These data provide some insight into the variability of heparins obtained from these three species and suggest some analytical approaches that may be useful in confirming the species origin of a heparin active pharmaceutical ingredient. Copyright © 2013 Wiley Periodicals, Inc.

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

PubMed

Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

2017-03-01

Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Preparation and Characterization of Cyclotrimethylenetrinitramine (RDX) with Reduced Sensitivity

PubMed Central

Wang, Yuqiao; Li, Xin; Chen, Shusen; Ma, Xiao; Yu, Ziyang; Jin, Shaohua; Li, Lijie; Chen, Yu

2017-01-01

The internal defects and shape of cyclotrimethylenetrinitramine (RDX) crystal are critical parameters for the preparation of reduced sensitivity RDX (RS-RDX). In the current study, RDX was re-crystallized and spheroidized to form the high-quality RDX that was further characterized by purity, apparent density, size distribution, specific surface area, impact sensitivity, and shock sensitivity. The effects of re-crystallization solvent on the growth morphology of RDX crystal were investigated by both theoretical simulation and experiment test, and consistent results were obtained. The high-quality RDX exhibited a high purity (≥99.90%), high apparent density (≥1.811 g/cm3), spherical shape, and relatively low impact sensitivity (6%). Its specific surface area was reduced more than 30%. Compared with conventional RDXs, the high-quality RDX reduced the shock sensitivities of PBXN-109 and PBXW-115 by more than 30%, indicating that it was a RS-RDX. The reduced sensitivity and good processability of the high-quality RDX would be significant in improving the performances of RDX-based PBXs. PMID:28825661

Preparation and characterization of bio-diesels from various bio-oils.

PubMed

Lang, X; Dalai, A K; Bakhshi, N N; Reaney, M J; Hertz, P B

2001-10-01

Methyl, ethyl, 2-propyl and butyl esters were prepared from canola and linseed oils through transesterification using KOH and/ or sodium alkoxides as catalysts. In addition, methyl and ethyl esters were prepared from rapeseed and sunflower oils using the same catalysts. Chemical composition of the esters was determined by HPLC for the class of lipids and by GC for fatty acid compositions. The bio-diesel esters were characterized for their physical and fuel properties including density, viscosity, iodine value, acid value, cloud point, pure point, gross heat of combustion and volatility. Methyl and ethyl esters prepared from a particular vegetable oil had similar viscosities, cloud points and pour points, whereas methyl, ethyl, 2-propyl and butyl esters derived from a particular vegetable oil had similar gross heating values. However, their densities, which were 2 7% higher than those of diesel fuels, statistically decreased in the order of methyl approximately 2-propyl > ethyl > butyl esters. Butyl esters showed reduced cloud points (-6 degrees C to -10 degrees C) and pour points (-13 degrees C to -16 degrees C) similar to those of summer diesel fuel having cloud and pour points of -8 degrees C and -15 degrees C, respectively. The viscosities of bio-diesels (3.3-7.6 x 10(-4) Pa s at 40 degrees C) were much less than those of pure oils (22.4-45.1 x 10(-4) Pa s at 40 degrees C) and were twice those of summer and winter diesel fuels (3.50 and 1.72 x 10(-4) Pa s at 40 degrees C), and their gross heat contents of approximately 40 MJ/kg were 11% less than those of diesel fuels (approximately 45 MJ/kg). For different esters from the same vegetable oil, methyl esters were the most volatile, and the volatility decreased as the alkyl group grew bulkier. However, the bio-diesels were considerably less volatile than the conventional diesel fuels.

Preparation and electrochemical characterization of polyaniline/activated carbon composites as an electrode material for supercapacitors.

PubMed

Oh, Misoon; Kim, Seok

2012-01-01

Polyaniline (PANI)/activated carbon (AC) composites were prepared by a chemical oxidation polymerization. To find an optimum ratio between PANI and AC which shows superior electrochemical properties, the preparation was carried out in changing the amount of added aniline monomers. The morphology of prepared composites was investigated by scanning electron microscopy (SEM) and transmission electron microscope (TEM). The structural and thermal properties were investigated by Fourier transform infrared spectra (FT-IR) and thermal gravimetric analysis (TGA), respectively. The electrochemical properties were characterized by cyclic voltammetry (CV). Composites showed a summation of capacitances that consisted of two origins. One is double-layer capacitance by ACs and the other is faradic capacitance by redox reaction of PANI. Fiber-like PANIs are coated on the surface of ACs and they contribute to the large surface for redox reaction. The vacancy among fibers provided the better diffusion and accessibility of ion. High capacitances of composites were originated from the network structure having vacancy made by PANI fibers. It was found that the composite prepared with 5 ml of aniline monomer and 0.25 g of AC showed the highest capacitance. Capacitance of 771 F/g was obtained at a scan rate of 5 mV/s.

Preparation, Characterization, and UV Irradiation of Mars Soil Analogues Under Simulated Martian Conditions to Support Detection of Molecular Biomarkers

NASA Astrophysics Data System (ADS)

Fornaro, T.; Brucato, J. R.; ten Kate, I. L.; Siljeström, S.; Steele, A.; Cody, G. D.; Hazen, R. M.

2018-04-01

We present laboratory activities of preparation, characterization, and UV irradiation processing of Mars soil analogues, which are key to support both in situ exploration and sample return missions devoted to detection of molecular biomarkers on Mars.

Preparation, Characterization, and Enhanced Thermal and Mechanical Properties of Epoxy-Titania Composites

PubMed Central

Rubab, Zakya; Siddiqi, Humaira M.; Saeed, Shaukat

2014-01-01

This paper presents the synthesis and thermal and mechanical properties of epoxy-titania composites. First, submicron titania particles are prepared via surfactant-free sol-gel method using TiCl4 as precursor. These particles are subsequently used as inorganic fillers (or reinforcement) for thermally cured epoxy polymers. Epoxy-titania composites are prepared via mechanical mixing of titania particles with liquid epoxy resin and subsequently curing the mixture with an aliphatic diamine. The amount of titania particles integrated into epoxy matrix is varied between 2.5 and 10.0 wt.% to investigate the effect of sub-micron titania particles on thermal and mechanical properties of epoxy-titania composites. These composites are characterized by X-ray photoelectron (XPS) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric (TG), and mechanical analyses. It is found that sub-micron titania particles significantly enhance the glass transition temperature (>6.7%), thermal oxidative stability (>12.0%), tensile strength (>21.8%), and Young's modulus (>16.8%) of epoxy polymers. Epoxy-titania composites with 5.0 wt.% sub-micron titania particles perform best at elevated temperatures as well as under high stress. PMID:24578638

Preparation and Characterization of Ato Nanoparticles by Coprecipitation with Modified Drying Method

NASA Astrophysics Data System (ADS)

Liu, Shimin; Liang, Dongdong; Liu, Jindong; Jiang, Weiwei; Liu, Chaoqian; Ding, Wanyu; Wang, Hualin; Wang, Nan

Antimony-doped tin oxide (ATO) nanoparticles were prepared by coprecipitation by packing drying and traditional direct drying (for comparison) methods. The as-prepared ATO nanoparticles were characterized by TG, XRD, EDS, TEM, HRTEM, BET, bulk density and electrical resistivity measurements. Results indicated that the ATO nanoparticles obtained by coprecipitation with direct drying method featured hard-agglomerated morphology, high bulk density, low surface area and low electrical resistivity, probably due to the direct liquid evaporation during drying, the fast shrinkage of the precipitate, the poor removal efficiency of liquid molecules and the hard agglomerate formation after calcination. Very differently, the ATO product obtained by the packing and drying method featured free-agglomerated morphology, low bulk density, high surface area and high electrical resistivity ascribed probably to the formed vapor cyclone environment and liquid evaporation-resistance, avoiding fast liquid removal and improving the removal efficiency of liquid molecules. The intrinsic formation mechanism of ATO nanoparticles from different drying methods was illustrated based on the dehydration process of ATO precipitates. Additionally, the packing and drying time played key roles in determining the bulk density, morphology and electrical conductivity of ATO nanoparticles.

The Preparation and Characterization of INTEC HAW Phase I Composition Variation Study Glasses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musick, C. A.; Peeler, D. K.; Piepel, G. F.

1999-03-01

A glass composition variation study (CVS) is in progress to define formulations for the vitrification of high activity waste (HAW) proposed to be separated from dissolved calcine stored at the Idaho National Engineering and Environmental Laboratory (INEEL). Estimates of calcine and HAW compositions prepared in FY97 were used to define test matrix glasses. The HAW composition is of particular interest because high aluminum, zirconium, phosphorous and potassium, and low iron and sodium content places it outside the realm of vitrification experience in the Department of Energy (DOE) complex. Through application of statistical techniques, a test matrix was defined for Phasemore » 1 of the CVS. From this matrix, formulations were systematically selected for preparation and characterization with respect to homogeneity, viscosity, liquidus temperature (TL), and leaching response when subjected to the Product Consistency Test (PCT). Based on the properties determined, certain formulations appear suitable for further development including use in planning Phase 2 of the study. It is recommended that glasses to be investigated in Phase 2 be limited to 3-5 wt % phosphate. The results of characterizing the Phase 1 glasses are presented in this document. A full analysis of the composition-property relationships of glasses being developed for immobilizing HAWs will be performing at the completion of CVS phases. This analysis will be needed for the optimization of the glass formulations of vitrifying HAW. Contributions were made to this document by personnel working at the INEEL, Pacific Northwest National Laboratories (PNNL), and the Savannah River Technology Center (SRTC).« less

Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion.

PubMed

Zeng, Zhaowu; Zhou, Guanglin; Wang, Xiaoli; Huang, Eric Zhijian; Zhan, Xiaori; Liu, Jun; Wang, Shuling; Wang, Anming; Li, Haifeng; Pei, Xiaolin; Xie, Tian

2010-09-07

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m(-1) in surface tension, (8.273 ± 0.018) mg·mL(-1) in content of β-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC(0→24h)) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L(-1) and 1.896 mg·h·L(-1) respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability.

Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion

PubMed Central

Zeng, Zhaowu; Zhou, Guanglin; Wang, Xiaoli; Huang, Eric Zhijian; Zhan, Xiaori; Liu, Jun; Wang, Shuling; Wang, Anming; Li, Haifeng; Pei, Xiaolin; Xie, Tian

2010-01-01

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m−1 in surface tension, (8.273 ± 0.018) mg·mL−1 in content of β-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC0→24h) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L−1 and 1.896 mg·h·L−1 respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability. PMID:20856831

Ultrastructural characterization of tooth-biomaterial interfaces prepared with broad and focused ion beams.

PubMed

Coutinho, E; Jarmar, T; Svahn, F; Neves, A A; Verlinden, B; Van Meerbeek, B; Engqvist, H

2009-11-01

Current available techniques for transmission electron microscopy (TEM) of tooth-biomaterial interfaces are mostly ineffective for brittle phases and impair integrated chemical and morphological characterization. The aims of this study were (1) to determine the applicability of new focused ion beam (FIB) and broad ion beam (BIB) techniques for TEM preparation of tooth-biomaterial interfaces; (2) to characterize the interfacial interaction with enamel and dentin of a conventional glass-ionomer (Chemfil Superior, DeTrey Dentsply, Germany), a 2-step self-etch (Clearfil SE, Kuraray, Japan) and a 3-step etch-and-rinse (OptiBond FL, Kerr, USA) adhesives; and (3) to characterize clinically relevant interfaces obtained from actual Class-I cavities. After bonding to freshly extracted human third molars, non-demineralized and non-stained sections were obtained using the FIB/BIB techniques and examined under TEM. The main structures generally disclosed in conventional ultramicrotomy samples were recognized in FIB/BIB-based ones. There were not any major differences between FIB and BIB concerning the resulting ultrastructural morphology. FIB/BIB-sections enabled to clearly resolve sub-micron hydroxyapatite crystals on top of hard tissues and the interface between matrix and filler in all materials, even at nano-scale. Some investigated interfaces disclosed areas with a distinct "fog" or "melted look", which is probably an artifact due to surface damage caused by the high-energy beam. Interfaces with enamel clearly disclosed the distinct "keyhole" shape of enamel rods sectioned at 90 degrees , delimited by a thin electron-lucent layer of inter-rod enamel. At regions where enamel crystals ran parallel with the interface, we observed a lack of interaction and some de-bonding along with interfacial void formation. The FIB/BIB methods are viable and reliable alternatives to conventional ultramicrotomy for preparation of thin sections of brittle and thus difficult to cut biomaterial

Preparation and characterization of cobalt-substituted anthrax lethal factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saebel, Crystal E.; Carbone, Ryan; Dabous, John R.

2011-12-09

Highlights: Black-Right-Pointing-Pointer Cobalt-substituted anthrax lethal factor (CoLF) is highly active. Black-Right-Pointing-Pointer CoLF can be prepared by bio-assimilation and direct exchange. Black-Right-Pointing-Pointer Lethal factor binds cobalt tightly. Black-Right-Pointing-Pointer The electronic spectrum of CoLF reveals penta-coordination. Black-Right-Pointing-Pointer Interaction of CoLF with thioglycolic acid follows a 2-step mechanism. -- Abstract: Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressingmore » Bacillus megaterium cells in the presence of CoCl{sub 2}, and (ii) direct exchange by treatment of zinc-LF with CoCl{sub 2}. Independent of the method employed, the protein was found to contain one Co{sup 2+} per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co{sup 2+} ion to be five-coordinate, an observation similar to that reported for other Co{sup 2+}-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co{sup 2+}:TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.« less

Preparation and Characterization of Mesoporous Zirconia Made by Using a Poly (methyl methacrylate) Template

NASA Astrophysics Data System (ADS)

Duan, Guorong; Zhang, Chunxiang; Li, Aimei; Yang, Xujie; Lu, Lude; Wang, Xin

2008-03-01

Superfine powders of poly (methyl methacrylate) (PMMA) have been prepared by means of an emulsion polymerization method. These have been used as templates in the synthesis of tetragonal phase mesoporous zirconia by the sol gel method, using zirconium oxychloride and oxalic acid as raw materials. The products have been characterized by infrared spectroscopy, X-ray diffraction analysis, transmission electron microscopy, N2 adsorption-desorption isotherms, and pore size distribution. The results indicate that the average pore size was found to be 3.7 nm.

Preparation and characterization of zinc sulphide nanocomposites based on acrylonitrile butadiene rubber

NASA Astrophysics Data System (ADS)

Ramesan, M. T.; Nihmath, A.; Francis, Joseph

2013-06-01

Rubber composite based on acrylonitrile butadiene rubber (NBR) reinforced with nano zinc sulphide (ZnS) have been prepared via vulcanization process and characterized by several techniques. Processing characteristics such as scorch time, optimum cure time decreases with increase in concentration of nano filler in acrylonitrile butadiene rubber. Mechanical properties such as tensile and tear strength increases with increase in concentration of nano filler up to 7 phr of loading thereafter the value decreases, whereas hardness, and flame resistance increases with the dosage of fillers. These enhanced properties are due to the homogenous dispersion of nano fillers in NBR matrix, which is evidenced from the structure that evaluated using X-ray diffraction (XRD) and scanning electron microscopy (SEM).

Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

PubMed Central

Ahmed, Tarek A; Aljaeid, Bader M

2016-01-01

Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

Tungstocobaltate-pillared layered double hydroxides: Preparation, characterization, magnetic and catalytic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Xiaocui; Baicheng College of Higher Medicine, Baicheng 137000; Fu Youzhi

2008-06-15

A new polyoxometalate anion-pillared layered double hydroxide (LDH) was prepared by aqueous ion exchange of a Mg-Al LDH precursor in nitrate form with the tungstocobaltate anions [CoW{sub 12}O{sub 40}]{sup 5-}. The physicochemical properties of the product were characterized by the methods of powder X-ray diffraction, elemental analysis, infrared spectroscopy, thermogravimetric analysis and cyclic voltammetry. It was confirmed that [CoW{sub 12}O{sub 40}]{sup 5-} was intercalated between the brucite-type layers of the LDHs without a change in the structure. Magnetic measurement shows the occurrence of antiferromagnetic interactions between the magnetic centers. The investigation of catalytic performance for this sample exhibits high activitymore » for the oxidation of benzaldehyde by hydrogen peroxide. - Graphical abstract: A tungstocobaltate anion [CoW{sub 12}O{sub 40}]{sup 5-} pillared layered double hydroxide (LDH) was prepared by aqueous ion exchange with a Mg-Al LDH precursor in nitrate form, demonstrating that [CoW{sub 12}O{sub 40}]{sup 5-} was intercalated between the brucite-type layers of the LDHs without change in structure. Magnetic measurement shows the occurrence of antiferromagnetic interactions between the magnetic centers. The investigation of catalytic performance for this sample exhibits high activity for the oxidation of benzaldehyde by hydrogen peroxide.« less

Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research.

PubMed

Ray, Balmiki; Chopra, Nipun; Long, Justin M; Lahiri, Debomoy K

2014-09-16

Culturing primary cortical neurons is an essential neuroscience technique. However, most cultures are derived from rodent brains and standard protocols for human brain cultures are sparse. Herein, we describe preparation, maintenance and major characteristics of a primary human mixed brain culture, including neurons, obtained from legally aborted fetal brain tissue. This approach employs standard materials and techniques used in the preparation of rodent neuron cultures, with critical modifications. This culture has distinct differences from rodent cultures. Specifically, a significant numbers of cells in the human culture are derived from progenitor cells, and the yield and survival of the cells grossly depend on the presence of bFGF. In the presence of bFGF, this culture can be maintained for an extended period. Abundant productions of amyloid-β, tau and proteins make this a powerful model for Alzheimer's research. The culture also produces glia and different sub-types of neurons. We provide a well-characterized methodology for human mixed brain cultures useful to test therapeutic agents under various conditions, and to carry forward mechanistic and translational studies for several brain disorders.

Preparation and characterization of collagen/hydroxypropyl methylcellulose (HPMC) blend film.

PubMed

Ding, Cuicui; Zhang, Min; Li, Guoying

2015-03-30

This study aimed to prepare and characterize the collagen/HPMC blend film (1/1). Thermogravimetric analysis and differential scanning calorimetry were used to investigate the thermal properties of the film. Both thermal decomposition temperature and denaturation temperature of the blend film were higher than those of the collagen film due to the intermolecular hydrogen bonding interaction between collagen and HPMC, which was demonstrated by Fourier transform infrared spectroscopy. Additionally, the morphologies, mechanical properties and hydrophilicity of films were examined. The blend film exhibited a more homogeneous and compact structure compared with that of the collagen film, as observed from scanning electron microscopy and atomic force microscopy. The tensile strength, ultimate elongation and hydrophilicity of the blend film were superior to those of the pure collagen film. Furthermore, the introduction of polyethylene glycol 1500 had almost no influence on the thermal properties of the blend film but obviously improved its stretch-ability and smoothness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation, characterization and catalytic application of CoFe2O4 nanoparticles in the synthesis of benzimidazoles

NASA Astrophysics Data System (ADS)

Borade, Ravikumar M.; Shinde, Pavan R.; Kale, Swati B.; Pawar, Rajendra P.

2018-05-01

A highly efficient magnetically recoverable cobalt ferrite nano-catalyst was prepared by sol-gel autocombustion method using glycine as green fuel. The prepared material has been characterized by X-ray powder diffraction and scanning. An investigation of its catalytic activity showed it to be a heterogeneous Lewis acid catalyst for the synthesis of substituted benzimidazoles. The aqueous ethanol used as green solvent for the reaction. The nm size range of these particles facilitates the catalysis process, as an increased surface area available for the reaction. The easy separation of the catalyst by an external magnet and their recovery and reuse in next cycle reaction are additional benefits.

Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin.

PubMed

Liu, Meina; Cao, Wen; Sun, Yinghua; He, Zhonggui

2014-12-30

The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The (1)H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC-MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0-t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanoparticles Prepared From N,N-Dimethyl-N-Octyl Chitosan as the Novel Approach for Oral Delivery of Insulin: Preparation, Statistical Optimization and In-vitro Characterization

PubMed Central

Shamsa, Elnaz Sadat; Mahjub, Reza; Mansoorpour, Maryam; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2018-01-01

In this study, N,N-Dimethyl-N-Octyl chitosan was synthesized. Nanoparticles containing insulin were prepared using PEC method and were statistically optimized using the Box-Behnken response surface methodology. The independent factors were considered to be the insulin concentration, concentration and pH of the polymer solution, while the dependent factors were characterized as the size, zeta potential, PdI and entrapment efficiency. The optimized nanoparticles were morphologically studied using SEM. The cytotoxicity of the nanoparticles on the Caco-2 cell culture was studied using the MTT cytotoxicity assay method, while the permeation of the insulin nanoparticles across the Caco-2 cell monolayer was also determined. The optimized nanoparticles posed appropriate physicochemical properties. The SEM morphological studies showed spherical to sub-spherical nanoparticles with no sign of aggregation. The in-vitro release study showed that 95.5 ± 1.40% of the loaded insulin was released in 400 min. The permeability studies revealed significant enhancement in the insulin permeability using nanoparticles prepared from octyl chitosan at 240 min (11.3 ± 0.78%). The obtained data revealed that insulin nanoparticles prepared from N,N-Dimethyl-N-Octyl chitosan can be considered as the good candidate for oral delivery of insulin compared to nanoparticles prepared from N,N,N-trimethyl chitosan.

Late conversion from tacrolimus to a belatacept-based immuno-suppression regime in kidney transplant recipients improves renal function, acid-base derangement and mineral-bone metabolism.

PubMed

Schulte, Kevin; Vollmer, Clara; Klasen, Vera; Bräsen, Jan Hinrich; Püchel, Jodok; Borzikowsky, Christoph; Kunzendorf, Ulrich; Feldkamp, Thorsten

2017-08-01

Calcineurin inhibitor (CNI)-induced nephrotoxicity and chronic graft dysfunction with deteriorating glomerular filtration rate (GFR) are common problems of kidney transplant recipients. The aim of this study was to analyze the role of belatacept as a rescue therapy in these patients. In this retrospective, observational study we investigated 20 patients (10 females, 10 males) who were switched from a CNI (tacrolimus) to a belatacept-based immunosuppression because of CNI intolerance or marginal transplant function. Patient follow-up was 12 months. Patients were converted to belatacept in mean 28.8 months after transplantation. Reasons for conversion were CNI intolerance (14 patients) or marginal transplant function (6 patients). Mean estimated GFR (eGFR) before conversion was 22.2 ± 9.4 ml/min at baseline and improved significantly to 28.3 ± 10.1 ml/min at 4 weeks and to 32.1 ± 12.6 ml/min at 12 months after conversion. Serum bicarbonate significantly increased from 24.4 ± 3.2 mmol/l at baseline to 28.7 ± 2.6 mmol/l after 12 months. Conversion to belatacept decreased parathyroid hormone and phosphate concentrations significantly, whereas albumin levels significantly increased. In 6 cases an acute rejection preceded clinically relevant CNI toxicity; only two patients suffered from an acute rejection after conversion. Belatacept was well tolerated and there was no increase in infectious or malignant side effects. A late conversion from a tacrolimus-based immunosuppression to belatacept is safe, effective and significantly improves renal function in kidney transplant recipients. Additionally, the conversion to belatacept has a beneficial impact on acid-base balance, mineral-bone and protein metabolism, independently of eGFR.

Preparation, characterization, and anti-Helicobacter pylori activity of Bi3+-Hericium erinaceus polysaccharide complex.

PubMed

Zhu, Yang; Chen, Yao; Li, Qian; Zhao, Ting; Zhang, Ming; Feng, Weiwei; Takase, Mohammed; Wu, Xueshan; Zhou, Zhaoxiang; Yang, Liuqing; Wu, Xiangyang

2014-09-22

Two new Bi3+-Hericium erinaceus polysaccharide (BiHEP) complexes were prepared using Bi3+ and two purified polysaccharides from H. erinaceus (HEPs), respectively. The complexes were characterized by elemental analysis, FT-IR, CD, SEM, AFM, XRD, and TG. The anti-Helicobacter pylori (Hp) activities in vitro by agar dilution assay of the complexes were evaluated. The molecular weights of HEPs were 197 and 20 kDa, respectively. All the analyses confirmed the formation of new BiHEP complexes with lower content of Bi3+ compared with colloidal bismuth subcitrate (CBS), the most utilized bismuth preparation clinically. Furthermore, HEPs themselves have definite inhibition effects on Hp, and BiHEP complexes have lower content of Bi exhibited strong inhibition effects on Hp (MIC=20 μg/mL), similar to that of CBS with higher content of Bi. The study provides a basis for further development of multiple treatments of Hp infection or new medicines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation and characterization of antibacterial electrospun chitosan/poly (vinyl alcohol)/graphene oxide composite nanofibrous membrane

NASA Astrophysics Data System (ADS)

Yang, Shuai; Lei, Peng; Shan, Yujuan; Zhang, Dawei

2018-03-01

In this paper, chitosan (CS)/poly (vinyl alcohol) (PVA)/graphene oxide (GO) composite nanofibrous membranes were prepared via electrospinning. Such nanofibrous membranes have been characterized and investigated for their morphological, structural, thermal stability, hydrophilic and antibacterial properties. SEM images showed that the uniform and defect-free nanofibers were obtained and GO sheets, shaping spindle and spherical, were partially embedded into nanofibers. FTIR, XRD, DSC and TGA indicated the good compatibility between CS and PVA. There were strong intermolecular hydrogen bonds between the chitosan and PVA molecules. Contact angle measurement indicated that while increasing the content of GO, the distance between fibers increased and water drop showed wetting state on the surface of nanofibrous membranes. As a result, the contact angle decreased significantly. Meanwhile, good antibacterial activity of the prepared nanofibrous membranes were exhibited against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus.

Preparation and characterization of N-benzoyl-O-acetyl-chitosan.

PubMed

Cai, Jinping; Dang, Qifeng; Liu, Chengsheng; Fan, Bing; Yan, Jingquan; Xu, Yanyan; Li, Jingjing

2015-01-01

A novel amphipathic chitosan derivative, N-benzoyl-O-acetyl-chitosan (BACS), was prepared by using the selective partial acylation of chitosan (CS), benzoyl chloride, and acetic acid under high-intensity ultrasound. The chemical structure and physical properties of BACS were characterized by FTIR, (1)H NMR, TGA, and XRD techniques. The degrees of substitution of benzoyl and acetyl for the chitosan derivatives were 0.26 and 1.15, respectively, which were calculated from the peak areas in NMR spectra by using the combined integral methods. The foaming properties of CS and BACS were determined and the results suggested BACS had better foam capacity and stability than those of chitosan. In addition, the antimicrobial activities of CS and BACS were also investigated against two species of bacteria (Escherichia coli and Staphylococcus aureus) and a fungus (Aspergillus niger), the results indicated that the antibacterial and antifungal activities of BACS were much stronger than those of the parent chitosan. These findings suggested that BACS was preferable for use as a food additive with a dual role of both foaming agent and food preservative. Copyright © 2015 Elsevier B.V. All rights reserved.

Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment

NASA Astrophysics Data System (ADS)

Asadi, Asadollah

2014-04-01

The aim of this study was to formulate and characterize streptomycin-loaded PLGA-alginate nanoparticles for their potential therapeutic use in Salmonella subsp. enterica ATCC 14028 infections. The streptomycin nanoparticle was prepared by solvent diffusion method, and the other properties such as size, zeta potential, loading efficacy, release kinetics, and antimicrobial strength were evaluated. The survey shows that nanoparticles may serve as a carrier of streptomycin and may provide localized antibacterial activity in the treatment of Salmonellosis. Electron microscopy showed spherical particles with indentations. The average size of the nanoparticles was 90 nm. At pH 7.2, the release kinetics of streptomycin from the nanoparticles was successfully illustrated as an initial burst defined by a first order equation that after this stage, it has a drastic tendency to obtain steady state. Nevertheless, nanoparticles showed loading efficacy nearly about 70-75 %. In addition, the tendency of concentration of streptomycin released from nanoparticles to reach antibacterial activity was similar to that of free streptomycin against PLGA-alginate, but it had threefold more antimicrobial strength in comparison with free streptomycin. This work shows the potential use of streptomycin-loaded PLGA-alginate nanoparticles and its capability.

Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice.

PubMed

Noguchi, Atsushi; Tominaga, Mitsutoshi; Takahashi, Nobuaki; Matsuda, Hironori; Kamata, Yayoi; Umehara, Yoshie; Ko, Kyi Chan; Suga, Yasushi; Ogawa, Hideoki; Takamori, Kenji

2017-04-01

Topical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood. This study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms. AD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA ® -Real system. Transepidermal water loss (TEWL) before and after treatment was measured using a Tewameter ® TM210. Skin collected from each group was analyzed histologically. After the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant

Preparation and characterization of MWCNT nanofiller incorporated polymer composite for lithium battery applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pradeepa, P.; Raj, S. Edwin; Selvakumar, K.

Poly (ethyl methacrylate) based polymer electrolyte films were prepared by solution casting technique incorporating multi-walled carbon nanotube (MWCNT) as filler and characterized using XRD and Ac impedance analysis. The electrical conductivity is increased with increasing filler concentration (upto 6wt %), which is attributed to the formation of charge transfer complexes. The maximum ionic conductivity value is found to be 1.171×10{sup −3} Scm{sup −1} at 303K for PEMA (19wt %) -LiClO{sub 4} (8wt %) -MWCNT (6wt %) -PC (67wt %) electrolyte system. The temperature dependent ionic conductivity plot seems to obey Vogel -Tamman-Fulcher relation.

Preparation, characterization, and catalytic activity of zirconocene bridged on surface of silica gel

NASA Astrophysics Data System (ADS)

El Majdoub, Lotfia; Shi, Yasai; Yuan, Yuan; Zhou, Annan; Abutartour, Abubaker; Xu, Qinghong

2015-10-01

Zirconocene catalyst supported on silica gel was prepared for olefin polymerization by surface modification of calcined silica with SiCl4, and the reaction between the modified silica and cyclopentadienyl sodium and ZrCl4. The catalyst was characterized by using Fourier-transform infrared (FT-IR) spectrometer, thermogravimetric (TG), and differential scanning calorimetric (DSC) analytic spectrometer. It was found that the metallocene structure could be formed and connected on silica surface by chemical bond. Initial catalytic tests showed that the supported metallocene was catalytically active (methylaluminoxane as a cocatalyst), producing polymer with higher molecular weight than the metallocene just immobilized on the surface of silica gel.

Preparation and characterization of specific and high-affinity monoclonal antibodies against morphine.

PubMed

Rahbarizadeh, F; Rasaee, M J; Madani, R; Rahbarizadeh, M H; Omidfar, K

2000-10-01

A C6-hemisuccinate derivative of morphine was prepared and conjugated to bovine serum albumin. High titer antibody producing spleen cells were removed and fused with myeloma cells of Sp2/0 origin. A C3-hemisuccinate derivative of morphine was prepared and conjugated to enzyme penicillinase used as a tracer molecule. A novel enzyme-linked immunoadsorbent assay was developed using this conjugate to screen and characterize the monoclonal antibody produced in these experiments. After two successive limiting dilutions, antibodies produced by 5 clones with good affinities ranging from 10(8) to 10(12) M(-1) and less cross-reaction (least for codeine and other structurally related molecules) were selected. These clones were found to be of IgG class with kappa light chain. Subclass determination showed that two of the clones produced IgG2b and three of them produced IgG1 type of antibody. Affinity purifications were performed for the selected clone (MOR-I). Purified antibody was coated onto the wells of microtiter plate. The standard curve was constructed with a sensitivity of 100 pg/mL covering up to 10 ng/mL in buffer and urine. The slope of the standard curve for selected clone in buffer and urine was calculated to be -0.7 and -0.64, respectively.

CHITOSAN-CELLULOSE COMPOSITE MATERIALS: PREPARATION, CHARACTERIZATION AND APPLICATION FOR REMOVAL OF MICROCYSTIN

PubMed Central

Tran, Chieu D.; Duri, Simon; Delneri, Ambra; Franko, Mladen

2013-01-01

We developed a simple and one-step method to prepare biocompatible composites from cellulose (CEL) and chitosan (CS). [BMIm+Cl−], an ionic liquid (IL), was used as a green solvent to dissolve and prepare the [CEL+CS] composites. Since majority (>88%) of IL used was recovered for reuse by distilling the aqueous washings of [CEL+CS], the method is recyclable. XRD, FTIR, NIR, 13C CP-MAS-NMR and SEM were used to monitor the dissolution and to characterize the composites. The composite was found to have combined advantages of their components: superior mechanical strength (from CEL) and excellent adsorption capability for microcystin-LR, a deadly toxin produced by cyanobacteria (from CS). Specifically, the mechanical strength of the composites increased with CEL loading; e.g., up to 5X increase in tensile strength was achieved by adding 80% of CEL into CS. Kinetic results of adsorption confirm that unique properties of CS remain intact in the composite, i.e., it is not only a very good adsorbent for microcystin but also is better than all other available adsorbents. For example, it can adsorb 4X times more microcystin than the best reported adsorbent. Importantly, the microcystin adsorbed can be quantitatively desorbed to enable the composite to be reused with similar adsorption efficiency. PMID:23542326

Preparation and characterization of green graphene using grape seed extract for bioapplications.

PubMed

Yaragalla, Srinivasarao; Rajendran, Rajakumari; Jose, Jiya; AlMaadeed, Mariam A; Kalarikkal, Nandakumar; Thomas, Sabu

2016-08-01

The development of functionalized graphene materials concerning health and environmental aspects via green approaches is currently the most recent topic in the field of nanoscience and nanotechnology. Herein, we report the green reduction of graphene oxide (GO) to reduced graphene oxide (RGO) using grape seed extract (GSE). Structural properties of the prepared RGO were investigated using Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, thermogravimetric analysis (TGA), UV-Visible spectroscopy and X-ray diffraction analysis. These all characterization techniques clearly revealed that the RGO has been successfully prepared. Moreover, the average thickness (4.2nm) of RGO layers was also confirmed by transmission electron microscopy (TEM). Optical properties such as band gap and photoluminescence of the synthesized RGO were evaluated. The band gap of RGO was found to be 3.84eV and it showed emission in the visible region. Efficient antimicrobial activity against Escherichia coli and Staphylococcus aureus was observed with 4μgml(-1) & 5μgml(-1) of RGO and also the cell wall damage of these strains has been proved by atomic force microscopy (AFM). The in vitro study of RGO (500μg) disclosed the effective anti-proliferative activity (88%) against HCT-116 cell lines. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and Characterization of Extruded Composites Based on Polypropylene and Chitosan Compatibilized with Polypropylene-Graft-Maleic Anhydride.

PubMed

Carrasco-Guigón, Fernando Javier; Rodríguez-Félix, Dora Evelia; Castillo-Ortega, María Mónica; Santacruz-Ortega, Hisila C; Burruel-Ibarra, Silvia E; Encinas-Encinas, Jose Carmelo; Plascencia-Jatomea, Maribel; Herrera-Franco, Pedro Jesus; Madera-Santana, Tomas Jesus

2017-01-25

The preparation of composites of synthetic and natural polymers represent an interesting option to combine properties; in this manner, polypropylene and chitosan extruded films using a different proportion of components and polypropylene-graft-maleic anhydride (PPgMA) as compatibilizer were prepared. The effect of the content of the biopolymer in the polypropylene (PP) matrix, the addition of compatibilizer, and the particle size on the properties of the composites was analyzed using characterization by fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), tensile strength, and contact angle, finding that in general, the addition of the compatibilizer and reducing the particle size of the chitosan, favored the physicochemical and morphological properties of the films.

Preparation and characterization of hydroxyapatite-coated iron oxide particles by spray-drying technique.

PubMed

Donadel, Karina; Felisberto, Marcos D V; Laranjeira, Mauro C M

2009-06-01

Magnetic particles of iron oxide have been increasingly used in medical diagnosis by magnetic resonance imaging and in cancer therapies involving targeted drug delivery and magnetic hyperthermia. In this study we report the preparation and characterization of iron oxide particles coated with bioceramic hydroxyapatite by spray-drying. The iron oxide magnetic particles (IOMP) were coated with hydroxyapatite (HAp) by spray-drying using two IOMP/HAp ratios (0.7 and 3.2). The magnetic particles were characterized by way of scanning electronic microscopy, energy dispersive X-ray, X-ray diffraction, Fourier transformed infrared spectroscopy, flame atomic absorption spectrometry,vibrating sample magnetometry and particle size distribution (laser diffraction). The surface morphology of the coated samples is different from that of the iron oxide due to formation of hydroxyapatite coating. From an EDX analysis, it was verified that the surface of the coated magnetic particles is composed only of HAp, while the interior containsiron oxide and a few layers of HAp as expected. The results showed that spray-drying technique is an efficient and relatively inexpensive method for forming spherical particles with a core/shell structure.

Preparation and characterization of nanocomposite polymer electrolytes poly(vinylidone fluoride)/nanoclay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahmawati, Suci A.; Sulistyaningsih,; Putro, Alviansyah Z. A.

2016-02-08

Polymer electrolytes are defined as semi solid electrolytes used as separator in lithium ion battery. Separator used as medium for transfer ions and to prevent electrical short circuits in battery cells. To obtain the optimal battery performance, separator with high porosity and electrolyte uptake is required. This can reduce the resistance in the transfer of ions between cathode and anode. The main objective of this work is to investigate the impact of different solvent (Dimethyl acetamide (DMAc), N-methyl-2-pyrrolidone (NMP) and dimethyl formamide (DMF)), pore forming agent poly(vinylpyrolidone) (PVP) and nanoclay as filler in addition of membrane using phase inversion methodmore » on the morphology, porosity, electrolyte uptake and degree of crystallinity. The membrane was prepared by the phase inversion method by adding PVP and Nanoclay using different solvents. The phase inversion method was prepared by dissolving Nanoclay and PVP in solvent for 1-2 hours, and then add the PVDF with stirring for 4 hours at 60°C. The membranes were characterized by porosity test, electrolyte uptake test, scanning electron microscope (SEM), and X-ray diffraction (XRD). The results showed that DMAc as solvent gives the highest value of porosity and electrolyte uptake. The addition of nanoclay and PVP enlarge the size of the pores and reduce the degree of crystallinity. So, the usage of DMAc as solvent is better than NMP or DMF.« less

Preparation and characterization of Chitosan/Konjac glucomannan/CdS nanocomposite film with low infrared emissivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Feng-Ying; Zhou, Yu-Ming, E-mail: fchem@seu.edu.cn; Sun, Yan-qing

Novel organic-inorganic nanocomposite films were prepared with Chitosan (CS), Konjac glucomannan (KGM) and CdS by one-step synthesis. As-prepared films were characterized by IR spectra, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and infrared emissometer (IR). The results indicated that grown CdS dendrites were formed with reaction time of 12 h for Cd{sup 2+} and CS/KGM, and were well dispersed in CS/KGM with an average diameter of 40 nm. The CS/KGM/CdS nanocomposite films had significantly low infrared emissivity. When the mole ratio of CdS to summation of CS and KGM construction units was 1.0 with CdS size of 10-20 nm,more » the film got the lowest infrared emissivity value of 0.011, which could be attributed to the strong synergism effect existing between CS/KGM and CdS dendrites.« less

Preparation and Characterization of Microencapsulated Phase Change Materials for Use in Building Applications.

PubMed

Giro-Paloma, Jessica; Al-Shannaq, Refat; Fernández, Ana Inés; Farid, Mohammed M

2015-12-26

A method for preparing and characterizing microencapsulated phase change materials (MPCM) was developed. A comparison with a commercial MPCM is also presented. Both MPCM contained paraffin wax as PCM with acrylic shell. The melting temperature of the PCM was around 21 °C, suitable for building applications. The M-2 (our laboratory made sample) and Micronal ® DS 5008 X (BASF) samples were characterized using SEM, DSC, nano-indentation technique, and Gas Chromatography/Mass spectrometry (GC-MS). Both samples presented a 6 μm average size and a spherical shape. Thermal energy storage (TES) capacities were 111.73 J·g -1 and 99.3 J·g -1 for M-2 and Micronal ® DS 5008 X, respectively. Mechanical characterization of the samples was performed by nano-indentation technique in order to determine the elastic modulus ( E ), load at maximum displacement ( P m ), and displacement at maximum load ( h m ), concluding that M-2 presented slightly better mechanical properties. Finally, an important parameter for considering use in buildings is the release of volatile organic compounds (VOC's). This characteristic was studied at 65 °C by CG-MS. Both samples showed VOC's emission after 10 min of heating, however peaks intensity of VOC's generated from M-2 microcapsules showed a lower concentration than Micronal ® DS 5008 X.

Preparation and Characterization of Microencapsulated Phase Change Materials for Use in Building Applications

PubMed Central

Giro-Paloma, Jessica; Al-Shannaq, Refat; Fernández, Ana Inés; Farid, Mohammed M.

2015-01-01

A method for preparing and characterizing microencapsulated phase change materials (MPCM) was developed. A comparison with a commercial MPCM is also presented. Both MPCM contained paraffin wax as PCM with acrylic shell. The melting temperature of the PCM was around 21 °C, suitable for building applications. The M-2 (our laboratory made sample) and Micronal® DS 5008 X (BASF) samples were characterized using SEM, DSC, nano-indentation technique, and Gas Chromatography/Mass spectrometry (GC-MS). Both samples presented a 6 μm average size and a spherical shape. Thermal energy storage (TES) capacities were 111.73 J·g−1 and 99.3 J·g−1 for M-2 and Micronal® DS 5008 X, respectively. Mechanical characterization of the samples was performed by nano-indentation technique in order to determine the elastic modulus (E), load at maximum displacement (Pm), and displacement at maximum load (hm), concluding that M-2 presented slightly better mechanical properties. Finally, an important parameter for considering use in buildings is the release of volatile organic compounds (VOC’s). This characteristic was studied at 65 °C by CG-MS. Both samples showed VOC’s emission after 10 min of heating, however peaks intensity of VOC’s generated from M-2 microcapsules showed a lower concentration than Micronal® DS 5008 X. PMID:28787812

Preparation and Characterization of Selenium Incorporated Guar Gum Nanoparticle and Its Interaction with H9c2 Cells

PubMed Central

Soumya, Rema Sreenivasan; Vineetha, Vadavanath Prabhakaran; Reshma, Premachandran Latha; Raghu, Kozhiparambil Gopalan

2013-01-01

This study deals with the preparation and characterization of selenium incorporated guar gum nanoparticle (SGG), and its effect on H9c2 cardiomyoblast. Herein, nanoprecipitation techniques had been employed for the preparation of SGG nanoparticle. The prepared nanoparticle had been subjected to various types of analytical techniques like transmission electron microscopy (TEM), X-ray diffraction (XRD) and particle size analysis to confirm the characteristics of nanoparticle as well as for selenium incorporation. Physical characterization of nanoparticle showed that the size of nanoparticles increase upto ∼69–173 nm upon selenium incorporation from ∼41–132 nm. Then the prepared nanoparticles were evaluated for its effect on H9c2 cells. In this regard, the effect of nanoparticle on various vital parameters of H9c2 cells was studied. Parameters like cell viability, uptake of selenium incorporated guar gum nanoparticle by the cells, effect of SGG on DNA integrity, apoptosis, reactive oxygen species generation, alteration in transmembrane potential of mitochondria and cytoskeletal integrity had been investigated. Viability results showed that up to 25 nM of SGG was safe (10.31%) but beyond that it induces cytotoxicity. Cellular uptake of selenium showed that cell permeability for SGG is significantly high compared to normal selenium (7.2 nM of selenium for 25 nM SGG compared with 5.2 nM selenium for 25 nM sodium selenite). There was no apoptosis with SGG and also it protects DNA from hydroxyl radical induced breakage. Likewise no adverse effect on mitochondria and cytoskeleton was observed for 25 nM of SGG. Overall results reveal that SGG is highly suitable for biomedical research application. PMID:24098647

Preparation and characterization of polymeric nanocomposite films for application as protective coatings

NASA Astrophysics Data System (ADS)

Gagliardi, S.; Rondino, F.; D'Erme, C.; Persia, F.; Menchini, F.; Santarelli, M. L.; Paulke, B.-R.; Enayati, A. L.; Falconieri, M.

2017-08-01

Addiction of ceramic nanoparticles to acrylic polymers provides a simple and effective means to produce paints with important properties, such as mechanical resistance and tailored wettability, even though for optimal performances, an engineered nanoparticle distribution would be desirable. In this paper we report on the realization and on the morphological and functional characterization of nanocomposites where the nanophase is distributed on the surface of acrylic polymer films, in order to enhance the expression of surface-related properties. To this aim, commercial titanium oxide and silicon oxide nanopowders were dispersed in water and the suspensions were air-sprayed on polymeric films prepared by paint brushing, thus producing a nanostructured ceramic surface coating. Control of the pH of suspensions and acrylic acid functionalization of the surface of titania were used together with high power ultrasonic treatments in order to control dimension of the aggregates in the sprayed suspensions. Optical microscopy, mechanical profilometry, and atomic force microscopy were used to characterize the nanocomposite surface morphology and correlate it to the coating functional properties, evaluated through mechanical abrasion tests and contact angle measurements; also, colorimetry on coated stones was performed in order to test the impact of the coatings on the aesthetical appearance and their photostability under UV irradiation. Results show that the nanostructured ceramic layer slightly improves the resistance of coatings to mechanical abrasion in case of polymer films prepared from latexes. The nanocomposite surface layer does not affect the wettability of the polymer, which remained slightly hydrophilic; this behavior is likely due to inadequate distribution of the nanophase. On the other hand UV-induced superhydrophilicity was observed when the concentration of surface titania nanoparticles is about 0.6 mg/cm2. Colorimetric analysis on historical and Carrara

Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton

PubMed Central

Edwards, J. Vincent; Fontenot, Krystal R.; Prevost, Nicolette T.; Pircher, Nicole; Liebner, Falk; Condon, Brian D.

2016-01-01

Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA) made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride as a direct cellulose dissolving medium. Subsequent casting, coagulation, solvent exchange and supercritical carbon dioxide drying afforded homogeneous cellulose II aerogels of fibrous morphology. The cotton-based aerogel had a porosity of 99% largely dominated by mesopores (2–50 nm) and an internal surface of 163 m2·g−1. A fluorescent tripeptide-substrate (succinyl-alanine-proline-alanine-4-amino-7-methyl-coumarin) was tethered to NA by (1) esterification of cellulose C6 surface hydroxyl groups with glycidyl-fluorenylmethyloxycarbonyl (FMOC), (2) deprotection and (3) coupling of the immobilized glycine with the tripeptide. Characterization of the NA and PepNA included techniques, such as elemental analysis, mass spectral analysis, attenuated total reflectance infrared imaging, nitrogen adsorption, scanning electron microscopy and bioactivity studies. The degree of substitution of the peptide analog attached to the anhydroglucose units of PepNA was 0.015. The findings from mass spectral analysis and attenuated total reflectance infrared imaging indicated that the peptide substrate was immobilized on to the surface of the NA. Nitrogen adsorption revealed a high specific surface area and a highly porous system, which supports the open porous structure observed from scanning electron microscopy images. Bioactivity studies of PepNA revealed a detection sensitivity of 0.13 units/milliliter for human neutrophil elastase, a diagnostic biomarker for inflammatory diseases. The

Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton.

PubMed

Edwards, J Vincent; Fontenot, Krystal R; Prevost, Nicolette T; Pircher, Nicole; Liebner, Falk; Condon, Brian D

2016-10-26

Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA) made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride as a direct cellulose dissolving medium. Subsequent casting, coagulation, solvent exchange and supercritical carbon dioxide drying afforded homogeneous cellulose II aerogels of fibrous morphology. The cotton-based aerogel had a porosity of 99% largely dominated by mesopores (2-50 nm) and an internal surface of 163 m²·g -1 . A fluorescent tripeptide-substrate (succinyl-alanine-proline-alanine-4-amino-7-methyl-coumarin) was tethered to NA by (1) esterification of cellulose C6 surface hydroxyl groups with glycidyl-fluorenylmethyloxycarbonyl (FMOC), (2) deprotection and (3) coupling of the immobilized glycine with the tripeptide. Characterization of the NA and PepNA included techniques, such as elemental analysis, mass spectral analysis, attenuated total reflectance infrared imaging, nitrogen adsorption, scanning electron microscopy and bioactivity studies. The degree of substitution of the peptide analog attached to the anhydroglucose units of PepNA was 0.015. The findings from mass spectral analysis and attenuated total reflectance infrared imaging indicated that the peptide substrate was immobilized on to the surface of the NA. Nitrogen adsorption revealed a high specific surface area and a highly porous system, which supports the open porous structure observed from scanning electron microscopy images. Bioactivity studies of PepNA revealed a detection sensitivity of 0.13 units/milliliter for human neutrophil elastase, a diagnostic biomarker for inflammatory diseases. The

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differing manifestations of hepatitis C and tacrolimus on hospitalized diabetes mellitus occurring after kidney transplantation.

PubMed

Abbott, Kevin C; Bernet, Victor J; Agodoa, Lawrence Y; Yuan, Christina M

2005-09-01

Previous studies suggest the association of recipient hepatitis C seropositivity (HCV+) and use of tacrolimus (TAC) with post-transplant diabetes mellitus (PTDM) may differ by manifestations of type I or type II diabetes, but this has not been assessed in the era of current immunosuppression. We performed a retrospective cohort study of 10,342 Medicare primary renal transplantation recipients without evidence of diabetes at the time of listing in the United States Renal Data System between January 1, 1998 and July 31, 2000, followed until December 31, 2000. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for time to DKA or HHS, stratified by diabetes status at the time of transplant. In Cox regression analysis, use of TAC at discharge was independently associated with shorter time to DKA (AHR, 1.88; 95% CI, 1.05-3.37, p=0.034) but not HHS. In contrast, recipient HCV+ was independently associated with shorter time to HHS (AHR, 3.90; 1.59-9.60, p=.003), but not DKA. There was no interaction between TAC and HCV+ for either outcome. These results confirm earlier findings that TAC and HCV+ may mediate the risk of PTDM through different mechanisms, even in the modern era.

Hydroxyapatite/MCM-41 and SBA-15 Nano-Composites: Preparation, Characterization and Applications

PubMed Central

Anunziata, Oscar A.; Martínez, Maria L.; Beltramone, Andrea R.

2009-01-01

Composites of hydroxyapatite (HaP) and highly ordered large pore mesoporous silica molecular sieves such as, Al-SBA-15 and Al-MCM-41 (denoted as SBA-15 and MCM-41, respectively) were developed, characterized by XRD, BET, FTIR, HRTEM and NMR-MAS, and applied to fluoride retention from contaminated water. The proposed procedure by a new route to prepare the HaP/SBA-15 and HaP/MCM-41, composites generates materials with aluminum only in tetrahedral coordination, according to the 27Al NMR-MAS results. Free OH- groups of HaP nanocrystals, within the hosts, allowed high capacity fluoride retention. The activity of fluoride retention using HaP/MCM-41 or HaP/SBA-15 was 1-2 orders of magnitude greater, respectively, than with pure HaP.

Desulfurization of Cysteine-Containing Peptides Resulting from Sample Preparation for Protein Characterization by MS

PubMed Central

Wang, Zhouxi; Rejtar, Tomas; Zhou, Zhaohui Sunny; Karger, Barry L.

2010-01-01

In this paper, we have examined two cysteine modifications resulting from sample preparation for protein characterization by MS: (1) a previously observed conversion of cysteine to dehydroalanine, now found in the case of disulfide mapping and (2) a novel modification corresponding to conversion of cysteine to alanine. Using model peptides, the conversion of cysteine to dehydroalanine via β-elimination of a disulfide bond was seen to result from the conditions of typical tryptic digestion (37 °C, pH 7.0– 9.0) without disulfide reduction and alkylation.. Furthermore, the surprising conversion of cysteine to alanine was shown to occur by heating cysteine containing peptides in the presence of a phosphine (TCEP). The formation of alanine from cysteine, investigated by performing experiments in H2O or D2O, suggested a radical-based desulfurization mechanism unrelated to β-elimination. Importantly, an understanding of the mechanism and conditions favorable for cysteine desulfurization provides insight for the establishment of improved sample preparation procedures of protein analysis. PMID:20049891

Preparation and Characterization of Extruded Composites Based on Polypropylene and Chitosan Compatibilized with Polypropylene-Graft-Maleic Anhydride

PubMed Central

Carrasco-Guigón, Fernando Javier; Rodríguez-Félix, Dora Evelia; Castillo-Ortega, María Mónica; Santacruz-Ortega, Hisila C.; Burruel-Ibarra, Silvia E.; Encinas-Encinas, Jose Carmelo; Plascencia-Jatomea, Maribel; Herrera-Franco, Pedro Jesus; Madera-Santana, Tomas Jesus

2017-01-01

The preparation of composites of synthetic and natural polymers represent an interesting option to combine properties; in this manner, polypropylene and chitosan extruded films using a different proportion of components and polypropylene-graft-maleic anhydride (PPgMA) as compatibilizer were prepared. The effect of the content of the biopolymer in the polypropylene (PP) matrix, the addition of compatibilizer, and the particle size on the properties of the composites was analyzed using characterization by fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), tensile strength, and contact angle, finding that in general, the addition of the compatibilizer and reducing the particle size of the chitosan, favored the physicochemical and morphological properties of the films. PMID:28772464

X-ray absorption and Mössbauer spectroscopies characterization of iron nanoclusters prepared by the gas aggregation technique.

PubMed

Sánchez-Marcos, J; Laguna-Marco, M A; Martínez-Morillas, R; Céspedes, E; Menéndez, N; Jiménez-Villacorta, F; Prieto, C

2012-11-01

Partially oxidized iron nanoclusters have been prepared by the gas-phase aggregation technique with typical sizes of 2-3 nm. This preparation technique has been reported to obtain clusters with interesting magnetic properties such as very large exchange bias. In this paper, a sample composition study carried out by Mössbauer and X-ray absorption spectroscopies is reported. The information reached by these techniques, which is based on the iron short range order, results to be an ideal way to have a characterization of the whole sample since the obtained data are an average over a very large amount of the clusters. In addition, our results indicate the presence of ferrihydrite, which is a compound typically ignored when studying this type of systems.

Preparation and characterization of the nanoporous ultrathin multilayer films based on molybdenum polyoxometalate (Mo 38) n

NASA Astrophysics Data System (ADS)

Wang, L.; Jiang, M.; Wang, E. B.; Duan, L. Y.; Hao, N.; Lan, Y.; Xu, L.; Li, Z.

2003-11-01

Ultrathin multilayer films of the wheel-shaped molybdenum polyoxometalate cluster (Mo 38) n and poly(allylamine hydrochloride)(PAH) have been prepared by the layer-by-layer (LbL) self-assembly method. The ((Mo 38) n/PAH) m multilayer films have been characterized by X-ray photoelectron spectra (XPS) and atomic force microscopy (AFM). UV-VIS measurements reveal regular film growth with each (Mo 38) n adsorption. The electrochemistry behavior of the film at room temperature was investigated.

A search for new CYP3A4 variants as determinants of tacrolimus dose requirements in renal-transplanted patients.

PubMed

Tavira, Beatriz; Coto, Eliecer; Diaz-Corte, Carmen; Alvarez, Victoria; López-Larrea, Carlos; Ortega, Francisco

2013-08-01

The CYP3A5*3 and CYP3A4*1B alleles have been related with tacrolimus (Tac) dose requirements. The rare CYP3A4*22 variant has also been associated with a significantly lower Tac dose. We genotyped the three single-nucleotide polymorphisms in 206 kidney-transplanted patients who received Tac as the primary immunosuppressor. CYP3A5*1 and CYP3A4*1B allele carriers received a significantly higher Tac dose (P<0.01) compared with wild-type homozygotes. We did not find significant differences between the CYP3A4*22 genotypes, either nominally or according to the CYP3A5 genotype (expressers vs. nonexpressers). Sequencing of CYP3A4 coding exons in a total of 15 patients revealed only one nonreported missense change (p.P227>T) in one patient. We concluded that CYP3A5*3 and CYP3A4*1B were the main determinants of the Tac dose-adjusted blood concentration in our cohort of renal-transplanted patients.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

PubMed Central

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-01-01

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. PMID:28398222

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

PubMed

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-04-11

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly( γ -glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca 2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

Preparation and characterization of carbon nanofibrous/hydroxyapatite sheets for bone tissue engineering.

PubMed

Abd El-Aziz, A M; El Backly, Rania M; Taha, Nahla A; El-Maghraby, Azza; Kandil, Sherif H

2017-07-01

Critical size bone defects are orthopedic defects that will not heal without intervention or that will not completely heal over the natural life time of the animal. Although bone generally has the ability to regenerate completely however, critical defects require some sort of scaffold to do so. In the current study we proposed a method to obtain a carbon nanofibrous/Hydroxyapatite (HA) bioactive scaffold. The carbon nanofibrous (CNF) nonwoven fabrics were obtained by the use of the electrospinning process of the polymeric solution of poly acrylonitrile "PAN" and subsequent stabilization and carbonization processes. The CNFs sheets were functionalized by both hydroxyapatite (HA) and bovine serum albumin (BSA). The HA was added to the electrospun solution, but in case of (BSA), it was adsorbed after the carbonization process. The changes in the properties taking place in the precursor sheets were investigated using the characterization methods (SEM, FT-IR, TGA and EDX). The prepared materials were tested for biocompatibility via subcutaneous implantation in New Zealand white rabbits. We successfully prepared biocompatible functionalized sheets, which have been modified with HA or HA and BSA. The sheets that were functionalized by both HA and BSA are more biocompatible with fewer inflammatory cells of (neutrophils and lymphocytes) than ones with only HA over the period of 3weeks. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation, characterization, and antibacterial activity studies of silver-loaded poly(styrene-co-acrylic acid) nanocomposites.

PubMed

Song, Cunfeng; Chang, Ying; Cheng, Ling; Xu, Yiting; Chen, Xiaoling; Zhang, Long; Zhong, Lina; Dai, Lizong

2014-03-01

A simple method for preparing a new type of stable antibacterial agent was presented. Monodisperse poly(styrene-co-acrylic acid) (PSA) nanospheres, serving as matrices, were synthesized via soap-free emulsion polymerization. Field-emission scanning electron microscopy micrographs indicated that PSA nanospheres have interesting surface microstructures and well-controlled particle size distributions. Silver-loaded poly(styrene-co-acrylic acid) (PSA/Ag-NPs) nanocomposites were prepared in situ through interfacial reduction of silver nitrate with sodium borohydride, and further characterized by transmission electron microscopy and X-ray diffraction. Their effects on antibacterial activity including inhibition zone, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetics were evaluated. In the tests, PSA/Ag-NPs nanocomposites showed excellent antibacterial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. These nanocomposites are considered to have potential application in antibacterial coatings on biomedical devices to reduce nosocomial infection rates. Copyright © 2013 Elsevier B.V. All rights reserved.

Liposomes Containing Gadodiamide: Preparation, Physicochemical Characterization, and In Vitro Cytotoxic Evaluation.

PubMed

Maia, Ana Luiza Chaves; Fernandes, Christian; de Oliveira, Cynthia Nara Pereira; Teixeira, Claudia Salviano; Oliveira, Mariana Silva; Soares, Daniel Cristian Ferreira; Ramaldes, Gilson Andrade

2017-01-01

The aim of this study was to develop, characterize and assess the cytotoxic activity of pHsensitive (pHL-Gd), stealth pH-sensitive (SpHL-Gd), and conventional (convL-Gd) liposomes containing gadodiamide (Gd-DTPA-BMA). Formulations were prepared by reverse-phase evaporation method and their physicochemical properties were evaluated by means of particle size, zeta potential, and Gd-DTPA-BMA entrapment. SpHL-Gd was considered being the most promising liposome, since it combines stealth and fusogenic characteristics that might contribute to achieve higher therapeutic efficiency. Their drug encapsulation percentages have been optimized satisfactorily. The addition of Gd-DTPA-BMA at 125 μmol/mL in the SpHL-Gd preparation allowed obtaining liposomes with appropriate encapsulation percentage (20.3 ± 0.1%) and entrapment (25.4 ± 0.1 μmol/mL). The cytotoxic studies on the 4T1 breast cancer cell line demonstrated that liposomes-loaded with Gd-DTPA-BMA inhibited cancer cell. pHL-Gd and SpHL-Gd liposomes showed higher activity than convL-Gd and free Gd-DTPA-BMA, indicating that the pH-sensitive characteristic was important to improve intracellular delivery. The presence of polyethylene glycol (PEG) in the SpHL-Gd formulation did not affect the pH-sensitivity and internalization. Therefore, the results of this study suggest the feasibility of liposomes containing Gd-DTPA-BMA as a new promising controlled delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preparation and characterization of a novel adsorbent from Moringa oleifera leaf

NASA Astrophysics Data System (ADS)

Bello, Olugbenga Solomon; Adegoke, Kayode Adesina; Akinyunni, Opeyemi Omowumi

2017-06-01

A new and novel adsorbent was obtained by impregnation of Moringa oleifera leaf in H2SO4 and NaOH, respectively. Prepared adsorbents were characterized using elemental analysis, FT-IR, SEM, TGA and EDX analyses, respectively. The effects of operational parameters, such as pH, moisture content, ash content, porosity and iodine number on these adsorbents were investigated and compared with those of commercial activated carbon (CAC). EDX results of acid activated M. oleifera leaf have the highest percentage of carbon by weight (69.40 %) and (76.11 %) by atom, respectively. Proximate analysis showed that the fixed carbon content of acid activated M. oleifera leaf (69.14 ± 0.01) was the highest of all adsorbents studied. Conclusively, the present investigation shows that acid activated M. oleifera leaf is a good alternative adsorbent that could be used in lieu of CAC for recovery of dyes and heavy metal from aqueous solutions and other separation techniques.

Polymeric Nanoparticles of Brazilian Red Propolis Extract: Preparation, Characterization, Antioxidant and Leishmanicidal Activity

NASA Astrophysics Data System (ADS)

do Nascimento, Ticiano Gomes; da Silva, Priscilla Fonseca; Azevedo, Lais Farias; da Rocha, Louisianny Guerra; de Moraes Porto, Isabel Cristina Celerino; Lima e Moura, Túlio Flávio Accioly; Basílio-Júnior, Irinaldo Diniz; Grillo, Luciano Aparecido Meireles; Dornelas, Camila Braga; Fonseca, Eduardo Jorge da Silva; de Jesus Oliveira, Eduardo; Zhang, Alex Tong; Watson, David G.

2016-06-01

The ever-increasing demand for natural products and biotechnology derived from bees and ultra-modernization of various analytical devices has facilitated the rational and planned development of biotechnology products with a focus on human health to treat chronic and neglected diseases. The aim of the present study was to prepare and characterize polymeric nanoparticles loaded with Brazilian red propolis extract and evaluate the cytotoxic activity of "multiple-constituent extract in co-delivery system" for antileishmanial therapies. The polymeric nanoparticles loaded with red propolis extract were prepared with a combination of poly-ɛ-caprolactone and pluronic using nanoprecipitation method and characterized by different analytical techniques, antioxidant and leishmanicidal assay. The red propolis nanoparticles in aqueous medium presented particle size (200-280 nm) in nanometric scale and zeta analysis (-20 to -26 mV) revealed stability of the nanoparticles without aggregation phenomenon during 1 month. After freeze-drying method using cryoprotectant (sodium starch glycolate), it was possible to observe particles with smooth and spherical shape and apparent size of 200 to 400 nm. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and thermal analysis revealed the encapsulation of the flavonoids from the red propolis extract into the polymeric matrix. Ultra performance liquid chromatography coupled with diode array detector (UPLC-DAD) identified the flavonoids liquiritigenin, pinobanksin, isoliquiritigenin, formononetin and biochanin A in ethanolic extract of propolis (EEP) and nanoparticles of red propolis extract (NRPE). The efficiency of encapsulation was determinate, and median values (75.0 %) were calculated using UPLC-DAD. 2,2-Diphenyl-1-picryhydrazyl method showed antioxidant activity to EEP and red propolis nanoparticles. Compared to negative control, EEP and NRPE exhibited leishmanicidal activity with an IC50 value of ≅38.0 �

Preparation and characterization of mucoadhesive nanoparticles of poly (methyl vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for vaginal administration.

PubMed

Aguilar-Rosas, Irene; Alcalá-Alcalá, Sergio; Llera-Rojas, Viridiana; Ganem-Rondero, Adriana

2015-01-01

Traditional vaginal preparations reside in the vaginal cavity for relatively a short period of time, requiring multiple doses in order to attain the desired therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to prolong the residence time in the vaginal cavity. In the current study, mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with well-known antiviral properties) were prepared and characterized. Nanoparticles were generated by a solvent displacement method. Incorporation of GA was performed during nanoprecipitation, followed by adsorption of drug once nanoparticles were formed. The prepared nanoparticles were characterized in terms of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by differential scanning calorimetry) and the in vitro interaction of nanoparticles with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The preparation method led to nanoparticles of a mean diameter of 198.5 ± 24.3 nm, zeta potential of -44.8 ± 2.8 mV and drug loading of 15.07 ± 0.86 µg/mg polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles without GA adsorbed. The data obtained suggest the promise of using mucoadhesive nanoparticles of PVM/MA for intravaginal delivery of GA.

Preparation and characterization of natural bentonite in to nanoparticles by co-precipitation method

NASA Astrophysics Data System (ADS)

Sirait, Makmur; Bukit, Nurdin; Siregar, Nurdin

2017-01-01

The nanoparticle based on natural bentonite from Pahae village had been prepared using co-precipitation method. Bentonite was dried in the oven at 100°C during a week. Bentonite is crushed using a mortal and milled by planetary ball mill to obtain the powder form. Further, the bentonite powder is activated with chemical reaction by dissolves the 50 g bentonite to 100 ml of HCl at 10 M. The magnetic stirrer was employed to mix the solution at 300 rpm and temperature 70°C. After that, the bentonite solution is washed using distilled water until the pH is neutral. The bentonite powder is calcined at temperature of 600°C for 1 hour with fix increment 150°C. Finally, the powder is given High Energy Milling (HEM) treatment for 30 minutes to obtain the particle size. The X-ray Difractometer (XRD) and Scanning Electron Microscope (SEM) were used to characterize. From the characterization results it is reported that the average of bentonite nanoparticle size is 35.26 nm and the chemical constituents of natural bentonite Pahae are Al, Si, Ca, Fe and Ti.

Error baseline rates of five sample preparation methods used to characterize RNA virus populations.

PubMed

Kugelman, Jeffrey R; Wiley, Michael R; Nagle, Elyse R; Reyes, Daniel; Pfeffer, Brad P; Kuhn, Jens H; Sanchez-Lockhart, Mariano; Palacios, Gustavo F

2017-01-01

Individual RNA viruses typically occur as populations of genomes that differ slightly from each other due to mutations introduced by the error-prone viral polymerase. Understanding the variability of RNA virus genome populations is critical for understanding virus evolution because individual mutant genomes may gain evolutionary selective advantages and give rise to dominant subpopulations, possibly even leading to the emergence of viruses resistant to medical countermeasures. Reverse transcription of virus genome populations followed by next-generation sequencing is the only available method to characterize variation for RNA viruses. However, both steps may lead to the introduction of artificial mutations, thereby skewing the data. To better understand how such errors are introduced during sample preparation, we determined and compared error baseline rates of five different sample preparation methods by analyzing in vitro transcribed Ebola virus RNA from an artificial plasmid-based system. These methods included: shotgun sequencing from plasmid DNA or in vitro transcribed RNA as a basic "no amplification" method, amplicon sequencing from the plasmid DNA or in vitro transcribed RNA as a "targeted" amplification method, sequence-independent single-primer amplification (SISPA) as a "random" amplification method, rolling circle reverse transcription sequencing (CirSeq) as an advanced "no amplification" method, and Illumina TruSeq RNA Access as a "targeted" enrichment method. The measured error frequencies indicate that RNA Access offers the best tradeoff between sensitivity and sample preparation error (1.4-5) of all compared methods.

Error baseline rates of five sample preparation methods used to characterize RNA virus populations

PubMed Central

Kugelman, Jeffrey R.; Wiley, Michael R.; Nagle, Elyse R.; Reyes, Daniel; Pfeffer, Brad P.; Kuhn, Jens H.; Sanchez-Lockhart, Mariano; Palacios, Gustavo F.

2017-01-01

Individual RNA viruses typically occur as populations of genomes that differ slightly from each other due to mutations introduced by the error-prone viral polymerase. Understanding the variability of RNA virus genome populations is critical for understanding virus evolution because individual mutant genomes may gain evolutionary selective advantages and give rise to dominant subpopulations, possibly even leading to the emergence of viruses resistant to medical countermeasures. Reverse transcription of virus genome populations followed by next-generation sequencing is the only available method to characterize variation for RNA viruses. However, both steps may lead to the introduction of artificial mutations, thereby skewing the data. To better understand how such errors are introduced during sample preparation, we determined and compared error baseline rates of five different sample preparation methods by analyzing in vitro transcribed Ebola virus RNA from an artificial plasmid-based system. These methods included: shotgun sequencing from plasmid DNA or in vitro transcribed RNA as a basic “no amplification” method, amplicon sequencing from the plasmid DNA or in vitro transcribed RNA as a “targeted” amplification method, sequence-independent single-primer amplification (SISPA) as a “random” amplification method, rolling circle reverse transcription sequencing (CirSeq) as an advanced “no amplification” method, and Illumina TruSeq RNA Access as a “targeted” enrichment method. The measured error frequencies indicate that RNA Access offers the best tradeoff between sensitivity and sample preparation error (1.4−5) of all compared methods. PMID:28182717

Preparation and characterization of PANI@G/CWO nanocomposite for enhanced 2-nitrophenol sensing

NASA Astrophysics Data System (ADS)

Khan, Anish; Khan, Aftab Aslam Parwaz; Rahman, Mohammed M.; Asiri, Abdullah M.; Inamuddin; Alamry, Khalid A.; Hameed, Salem A.

2018-03-01

A new material by polymer insertion via graphene oxide into cerium tungstate was prepared by very simple oxidation-reduction method. Aniline polymerization was done on the surface of graphene oxide (GO) which was reduced to graphene (G) simultaneously mixed with separately prepared inorganic matrices of cerium tungstate (Ce2(WO4)3 (CWO)). PANI@G/CWO was characterized by various spectroscopic methods as SEM, FTIR, TGA, XRD and XPS to confirm its possibilities. Selective 2-nitrophenol sensor was fabricated on flat glassy carbon electrode (GCE) and PANI@G/CWO nanocomposites in the form of thin layer. It was found excellent sensitivity as well as long life spam with broad dynamic concentration range (LDR) that showed efficient electrochemical performance towards 2-nitrophenol on fabricated chemical sensor by PANI@G/CWO. The linear calibration curve (r2 = 0.9914) with wide range of 2-nitrophenol concentration (1.0 nM-1.0 mM) was found having the detection limit of 0.87 nM while the sensitivity of the sensor was around 1.229 μ A μM-1 cm-2. It was introduced a new route for the development of a versatile phenolic sensor based on PANI@G/CWO nanocomposites by I-V method that is proved more selective and sensitive for environmental toxic materials.

Preparation and characterization of polymer nanocomposites coated magnetic nanoparticles for drug delivery applications

NASA Astrophysics Data System (ADS)

Prabha, G.; Raj, V.

2016-06-01

In the present research work, the anticancer drug 'curcumin' is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe3O4) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Curcumin drug loaded Fe3O4-CS, Fe3O4-CS-PEG and Fe3O4-CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183-390 nm with a zeta potential value of 26-41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behavior of curcumin drug loaded Fe3O4-CS, Fe3O4-CS-PEG and Fe3O4-CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium and it was proved that the drug release depends upon the pH medium in addition to the nature of matrix.

Preparation and characterization Al3+-bentonite Turen Malang for esterification fatty acid (palmitic acid, oleic acid and linoleic acid)

NASA Astrophysics Data System (ADS)

Abdulloh, Abdulloh; Aminah, Nanik Siti; Triyono, Mudasir, Trisunaryanti, Wega

2016-03-01

Catalyst preparation and characterization of Al3+-bentonite for esterification of palmitic acid, oleic acid and linoleic acid has been done. Al3+-bentonite catalyst was prepared from natural bentonite of Turen Malang through cation exchange reaction using AlCl3 solution. The catalysts obtained were characterized by XRD, XRF, pyridine-FTIR and surface area analyser using the BET method. Catalyst activity test of Al3+-bentonite for esterification reaction was done at 65°C using molar ratio of metanol-fatty acid of 30:1 and 0.25 g of Al3+-bentonite catalyst for the period of ½, 1, 2, 3, 4 and 5 hours. Based on the characterization results, the Al3+-bentonite Turen Malang catalyst has a d-spacing of 15.63 Ǻ, acid sites of Brönsted and Lewis respectively of 230.79 µmol/g and 99.39 µmol/g, surface area of 507.3 m2/g and the average of radius pore of 20.09 Å. GC-MS analysis results of the oil phase after esterification reaction showed the formation of biodiesel (FAME: Fatty acid methyl ester), namely methyl palmitate, methyl oleate and methyl linoleate. The number of conversions resulted in esterification reaction using Al3+-bentonite Turen Malang catalyst was 74.61%, 37.75%, and 20, 93% for the esterification of palmitic acid, oleic acid and linoleic acid respectively.

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.

PubMed

Andrews, Louise M; de Winter, Brenda C M; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H N; Koch, Birgit C P; van Gelder, Teun; Hesselink, Dennis A

2017-02-01

Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.

Structural characterization of nanocrystalline cadmium sulphide powder prepared by solvent evaporation technique

NASA Astrophysics Data System (ADS)

Pandya, Samir; Tandel, Digisha; Chodavadiya, Nisarg

2018-05-01

CdS is one of the most important compounds in the II-VI group of semiconductor. There are numerous applications of CdS in the form of nanoparticles and nanocrystalline. Semiconductors nanoparticles (also known as quantum dots), belong to state of matter in the transition region between molecules and solids, have attracted a great deal of attention because of their unique electrical and optical properties, compared to bulk materials. In the field of optoelectronic, nanocrystalline form utilizes mostly in the field of catalysis and fluid technology. Considering these observations, presented work had been carried out, i.e. based on the nanocrystalline material preparation. In the present work CdS nano-crystalline powder was synthesized by a simple and cost effective chemical technique to grow cadmium sulphide (CdS) nanoparticles at 200 °C with different concentrations of cadmium. The synthesis parameters were optimized. The synthesized powder was structurally characterized by X-ray diffraction and particle size analyzer. In the XRD analysis, Micro-structural parameters such as lattice strain, dislocation density and crystallite size were analysed. The broadened diffraction peaks indicated nanocrystalline particles of the film material. In addition to that the size of the prepared particles was analyzed by particle size analyzer. The results show the average size of CdS particles ranging from 80 to 100 nm. The overall conclusion of the work can be very useful in the synthesis of nanocrystalline CdS powder.

Preparation and characterization of nanosized Ag/SLN composite and its viability for improved occlusion

NASA Astrophysics Data System (ADS)

Cynthia Jemima Swarnavalli, G.; Dinakaran, S.; Divya, S.

2016-10-01

Nanocomposites consisting of silver and solid lipid nanoparticles (SLN) elicit interest for their synergistic effect based enhanced properties in skin hydration. The nanocomposite preparation aims at combining the antimicrobial activity of silver with skin hydration performance of SLN. The nanocomposites designated Ag/SAN (silver/stearic acid nanoparticles), Ag/PAN (silver/palmitic acid nanoparticles) were prepared by incorporating silver nanoparticles into the dispersion of SLN and sonicating for 10 min followed by heating for 1 h at 50 °C in a thermostat. The occlusive property of the two nanocomposites was evaluated in comparison with the pure SLN by adopting de Vringer-de Ronde in vitro occlusion test. The incorporation of silver nanoparticles has improved occlusion factor by 10 % in the case of both composites at SLN concentration of 0.14 mmol. Characterization studies include XRD, DSC, HRSEM, DLS and zeta potential measurement. High resolution scanning electron microscopy (HRSEM) images divulge that the nanoparticles of composite (Ag/SAN) shows halo effect where the hydrophobic stearic acid is oriented at the core and is surrounded by silver nanoparticles while Ag/PAN shows cashew shaped SLN dispersed in silver nanoparticles matrix.

Sirolimus and tacrolimus rather than cyclosporine A cause bone loss in healthy adult male rats.

PubMed

Rubert, Mercedes; Montero, Mercedes; Guede, David; Caeiro, Jose-Ramón; Martín-Fernández, Marta; Díaz-Curiel, Manuel; de la Piedra, Concepción

2015-06-01

The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on bone mass, femoral microstructure, femoral biomechanical properties, and bone remodeling in healthy adult male rats. Forty-eight 5-month-old male Wistar rats were used. CsA (2 mg/kg/day), FK-506 (3 mg/kg/day), RAPA (1.25 mg/kg/day), or water (0.5 ml/rat/day, control group) were administered orally for 3 months. After sacrifice, mean values of immunosuppressants in blood were: CsA (670.4 ng/ml), FK-506 (19.2 ng/ml), and RAPA (4.8 ng/ml). Levels of biochemical parameters were normal in all groups. Femoral BMD was decreased in FK-506 and RAPA groups and lumbar BMD in FK-506 group. Trabecular volume fraction (BV/TV) decreased only in FK-506 group. RAPA and CsA affected femoral cortical structure, but FK-506 did not. FK-506 produced an increase in bone remodeling, and CsA a decrease. FK-506 group showed a decrease in biomechanical parameters relative to all groups. RAPA group showed a decrease in ultimate stress vs control group, and CsA group presented an increase in biomechanical parameters versus control group. We found that administration of both RAPA and FK-506 as monotherapy for healthy rats produced osteopenia. CsA treatment only produces slight damages in the cortical zone of the femur.

Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

PubMed Central

2013-01-01

Background and the aim of the study The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data. PMID:24355133

Preparation and characterization of V/TiO{sub 2} nanocatalyst with magnetic nucleus of iron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feyzi, Mostafa; Rafiee, Hamid Reza, E-mail: rafieehr@yahoo.com; Ranjbar, Shahram

2013-11-15

Graphical abstract: - Highlights: • Fe-V/TiO{sub 2} nanocatalyst is prepared. • Combination of sol–gel and wetness impregnation methods. • Facile separation of catalyst from medium by magnet. - Abstract: A magnetic composite containing V/TiO{sub 2} was prepared by combination of sol–gel and wetness impregnation methods. The effects of synthesis temperature, different weight percents of Fe supported on TiO{sub 2}, vanadium loading and the heating rate of calcination on the structure and morphology of nanocatalyst were investigated. The optimum conditions for synthesized catalyst were 40 wt.% of Fe, 15 wt.% of V and synthesis temperature equal to 30 °C. Characterization ofmore » catalyst is carried out using XRD, TGA, DSC, SEM, FTIR and N{sub 2} physisorption measurements. The magnetic character of nanocatalyst was measured using VSM, which showed the typical paramagnetic behavior of sample at room temperature with a saturation magnetization value equal to 8.283 emu/g. The nanocatalyst has a particle size about 56 nm and can easily be separated from medium by a magnet.« less

Characterization of Lone Pine, California, tremolite asbestos and preparation of research material

USGS Publications Warehouse

Harper, Martin; Van Gosen, Bradley S.; Crankshaw, Owen S; Doorn, Stacy S; Ennis, J. Todd; Harrison, Sara E

2014-01-01

Well-characterized amphibole asbestos mineral samples are required for use as analytical standards and in future research projects. Currently, the National Institute for Standards and Technology Standard Reference Material samples of asbestos are listed as ‘Discontinued’. The National Institute for Occupational Safety and Health (NIOSH) has a goal under the Asbestos Roadmap of locating and characterizing research materials for future use. Where an initial characterization analysis determines that a collected material is appropriate for use as a research material in terms of composition and asbestiform habit, sufficient amounts of the material will be collected to make it publicly available. An abandoned mine near Lone Pine, California, contains a vein of tremolite asbestos, which was the probable source of a reference material that has been available for the past 17 years from the Health and Safety Laboratory (HSL) in the UK. Newly collected fibrous vein material from this mine was analyzed at Research Triangle Institute (RTI International) with some additional analysis by the US Geological Survey’s Denver Microbeam Laboratory. The analysis at RTI International included: (i) polarized light microscopy (PLM) with a determination of principal optical properties; (ii) X-ray diffraction; (iii) transmission electron microscopy, including energy dispersive X-ray spectroscopy and selected-area electron diffraction; and (iv) spindle stage analysis using PLM to determine whether individual fibers and bundles of the samples were polycrystalline or single-crystal cleavage fragments. The overall findings of the study indicated that the material is tremolite asbestos with characteristics substantially similar to the earlier distributed HSL reference material. A larger quantity of material was prepared by sorting, acid-washing and mixing for sub-division into vials of ~10g each. These vials have been transferred from NIOSH to RTI International, from where they can be

Characterization of Lone Pine, California, Tremolite Asbestos and Preparation of Research Material

PubMed Central

Harper, Martin; Van Gosen, Bradley; Crankshaw, Owen S.; Doorn, Stacy S.; Ennis, Todd J.; Harrison, Sara E.

2016-01-01

Well-characterized amphibole asbestos mineral samples are required for use as analytical standards and in future research projects. Currently, the National Institute for Standards and Technology Standard Reference Material samples of asbestos are listed as ‘Discontinued’. The National Institute for Occupational Safety and Health (NIOSH) has a goal under the Asbestos Roadmap of locating and characterizing research materials for future use. Where an initial characterization analysis determines that a collected material is appropriate for use as a research material in terms of composition and asbestiform habit, sufficient amounts of the material will be collected to make it publicly available. An abandoned mine near Lone Pine, California, contains a vein of tremolite asbestos, which was the probable source of a reference material that has been available for the past 17 years from the Health and Safety Laboratory (HSL) in the UK. Newly collected fibrous vein material from this mine was analyzed at Research Triangle Institute (RTI International) with some additional analysis by the US Geological Survey’s Denver Microbeam Laboratory. The analysis at RTI International included: (i) polarized light microscopy (PLM) with a determination of principal optical properties; (ii) X-ray diffraction; (iii) transmission electron microscopy, including energy dispersive X-ray spectroscopy and selected-area electron diffraction; and (iv) spindle stage analysis using PLM to determine whether individual fibers and bundles of the samples were polycrystalline or single-crystal cleavage fragments. The overall findings of the study indicated that the material is tremolite asbestos with characteristics substantially similar to the earlier distributed HSL reference material. A larger quantity of material was prepared by sorting, acid-washing and mixing for sub-division into vials of ~10 g each. These vials have been transferred from NIOSH to RTI International, from where they can be

Flavourzyme, an Enzyme Preparation with Industrial Relevance: Automated Nine-Step Purification and Partial Characterization of Eight Enzymes.

PubMed

Merz, Michael; Eisele, Thomas; Berends, Pieter; Appel, Daniel; Rabe, Swen; Blank, Imre; Stressler, Timo; Fischer, Lutz

2015-06-17

Flavourzyme is sold as a peptidase preparation from Aspergillus oryzae. The enzyme preparation is widely and diversely used for protein hydrolysis in industrial and research applications. However, detailed information about the composition of this mixture is still missing due to the complexity. The present study identified eight key enzymes by mass spectrometry and partially by activity staining on native polyacrylamide gels or gel zymography. The eight enzymes identified were two aminopeptidases, two dipeptidyl peptidases, three endopeptidases, and one α-amylase from the A. oryzae strain ATCC 42149/RIB 40 (yellow koji mold). Various specific marker substrates for these Flavourzyme enzymes were ascertained. An automated, time-saving nine-step protocol for the purification of all eight enzymes within 7 h was designed. Finally, the purified Flavourzyme enzymes were biochemically characterized with regard to pH and temperature profiles and molecular sizes.

Preparation and characterization of high purity β-chitin from squid pens (Loligo chenisis).

PubMed

Cuong, Hoang Ngoc; Minh, Nguyen Cong; Van Hoa, Nguyen; Trung, Trang Si

2016-12-01

Squid pens were extracted by a NaOH solution at 80°C for 10h to remove protein and minerals. The as-prepared β-chitin had a high molecular weight (8.5±0.1×10 3 kDa), a low protein content (0.63±0.02wt.%), and a negligible amount of minerals. This method avoids the conventional method for the removal of minerals from shrimp and crab shells by HCl. The purity of resulting products was measured by NMR and FTIR. Moreover, the morphology and crystallinity of β-chitin was characterized by SEM and XRD. The β-chitin with long chains and high purity is suitable for producing high quantity β-chitosan for various potential applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation, characterization and antibacterial properties against E. coli K88 of chitosan nanoparticle loaded copper ions

NASA Astrophysics Data System (ADS)

Du, Wen-Li; Xu, Ying-Lei; Xu, Zi-Rong; Fan, Cheng-Li

2008-02-01

The present study was conducted to prepare and characterize chitosan nanoparticle loaded copper ions, and evaluate their antibacterial activity. Chitosan nanoparticles were prepared based on ionotropic gelation, and then the copper ions were loaded. The particle size, zeta potential and morphology were determined. Antibacterial activity was evaluated against E. coli K88 by determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in vitro. Results showed that the antibacterial activity was significantly enhanced by the loading of copper ions compared to those of chitosan nanoparticles and copper ions. The MIC and MBC of chitosan nanoparticle loaded copper ions were 21 times and 42 times lower than those of copper ions, respectively. To confirm the antibacterial mechanism, morphological changes of E. coli K88 treated by chitosan nanoparticle loaded copper ions were dynamically observed with an atomic force microscope (AFM). It was found that chitosan nanoparticle loaded copper ions killed E. coli K88 through damage to the cell membrane.

Preparation of biocompatible magnetite-carboxymethyl cellulose nanocomposite: characterization of nanocomposite by FTIR, XRD, FESEM and TEM.

PubMed

Habibi, Neda

2014-10-15

The preparation and characterization of magnetite-carboxymethyl cellulose nano-composite (M-CMC) material is described. Magnetite nano-particles were synthesized by a modified co-precipitation method using ferrous chloride tetrahydrate and ferric chloride hexahydrate in ammonium hydroxide solution. The M-CMC nano-composite particles were synthesized by embedding the magnetite nanoparticles inside carboxymethyl cellulose (CMC) using a freshly prepared mixture of Fe3O4 with CMC precursor. Morphology, particle size, and structural properties of magnetite-carboxymethyl cellulose nano-composite was accomplished using X-ray powder diffraction (XRD), transmission electron microscopy (TEM), Fourier transformed infrared (FTIR) and field emission scanning electron microscopy (FESEM) analysis. As a result, magnetite nano-particles with an average size of 35nm were obtained. The biocompatible Fe3O4-carboxymethyl cellulose nano-composite particles obtained from the natural CMC polymers have a potential range of application in biomedical field. Copyright © 2014 Elsevier B.V. All rights reserved.

Polymeric Nanoparticles of Brazilian Red Propolis Extract: Preparation, Characterization, Antioxidant and Leishmanicidal Activity.

PubMed

do Nascimento, Ticiano Gomes; da Silva, Priscilla Fonseca; Azevedo, Lais Farias; da Rocha, Louisianny Guerra; de Moraes Porto, Isabel Cristina Celerino; Lima E Moura, Túlio Flávio Accioly; Basílio-Júnior, Irinaldo Diniz; Grillo, Luciano Aparecido Meireles; Dornelas, Camila Braga; Fonseca, Eduardo Jorge da Silva; de Jesus Oliveira, Eduardo; Zhang, Alex Tong; Watson, David G

2016-12-01

The ever-increasing demand for natural products and biotechnology derived from bees and ultra-modernization of various analytical devices has facilitated the rational and planned development of biotechnology products with a focus on human health to treat chronic and neglected diseases. The aim of the present study was to prepare and characterize polymeric nanoparticles loaded with Brazilian red propolis extract and evaluate the cytotoxic activity of "multiple-constituent extract in co-delivery system" for antileishmanial therapies. The polymeric nanoparticles loaded with red propolis extract were prepared with a combination of poly-ε-caprolactone and pluronic using nanoprecipitation method and characterized by different analytical techniques, antioxidant and leishmanicidal assay. The red propolis nanoparticles in aqueous medium presented particle size (200-280 nm) in nanometric scale and zeta analysis (-20 to -26 mV) revealed stability of the nanoparticles without aggregation phenomenon during 1 month. After freeze-drying method using cryoprotectant (sodium starch glycolate), it was possible to observe particles with smooth and spherical shape and apparent size of 200 to 400 nm. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and thermal analysis revealed the encapsulation of the flavonoids from the red propolis extract into the polymeric matrix. Ultra performance liquid chromatography coupled with diode array detector (UPLC-DAD) identified the flavonoids liquiritigenin, pinobanksin, isoliquiritigenin, formononetin and biochanin A in ethanolic extract of propolis (EEP) and nanoparticles of red propolis extract (NRPE). The efficiency of encapsulation was determinate, and median values (75.0 %) were calculated using UPLC-DAD. 2,2-Diphenyl-1-picryhydrazyl method showed antioxidant activity to EEP and red propolis nanoparticles. Compared to negative control, EEP and NRPE exhibited leishmanicidal activity with an IC50 value of ≅38

Preparation and characterization of nanocrystalline cellulose/Eucommia ulmoides gum nanocomposite film.

PubMed

Sun, Qianqian; Zhao, Xinkun; Wang, Dongmei; Dong, Juane; She, Diao; Peng, Pai

2018-02-01

The nanocomposite films were prepared using Eucommia ulmoides gum (EUG) matrix reinforced with nanocrystalline cellulose (NCC) at different concentrations. Subsequently, the obtained films were characterized by Raman spectra, AFM, XRD, TGA, and DSC. Meanwhile, the wettability, mechanical, and water vapor barrier properties of these films were analyzed. AFM noticed that the average sizes of NCC were 81.95×50.17×13.06nm, while the size of molecular chain for EUG was 2530×57.33×1.28nm. In comparison with control film, a certain amount of NCC obviously improved elongation at break and enhanced their crystallinity and ΔH m . More importantly, NCC/EUG nanocomposite films presented lower thermal stability, glass transition temperature (T g ), melting temperature (T m ), and water vapor permeability (WVP) values, especially the WVP values of 4% NCC film were the lowest as 0.28×10 -9 , 0.30×10 -9 , and 0.58×10 -9 g/m/h/Pa at RH 34%, 55%, and 76%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and characterization of self-crosslinked organic/inorganic proton exchange membranes

NASA Astrophysics Data System (ADS)

Zhong, Shuangling; Cui, Xuejun; Dou, Sen; Liu, Wencong

A series of silicon-containing sulfonated polystyrene/acrylate (Si-sPS/A) nanoparticles are successfully synthesized via simple emulsion polymerization method. The Si-sPS/A latexes show good film-forming capability and the self-crosslinked organic/inorganic proton exchange membranes are prepared by pouring the Si-sPS/A nanoparticle latexes into glass plates and drying at 60 °C for 10 h and 120 °C for 2 h. The potential of the membranes in direct methanol fuel cells (DMFCs) is characterized preliminarily by studying their thermal stability, ion-exchange capacity, water uptake, methanol diffusion coefficient, proton conductivity and selectivity (proton conductivity/methanol diffusion coefficient). The results indicate that these membranes possess excellent thermal stability and methanol barrier due to the existence of self-crosslinked silica network. In addition, the proton conductivity of the membranes is in the range of 10 -3-10 -2 S cm -1 and all the membranes show much higher selectivity in comparison with Nafion ® 117. These results suggest that the self-crosslinked organic/inorganic proton exchange membranes are particularly promising in DMFC applications.

Preparation and physicochemical characterization of 5 niclosamide solvates and 1 hemisolvate.

PubMed

van Tonder, Elsa C; Mahlatji, Mabatane D; Malan, Sarel F; Liebenberg, Wilna; Caira, Mino R; Song, Mingna; de Villiers, Melgardt M

2004-02-23

The purpose of the study was to characterize the physicochemical, structural, and spectral properties of the 1:1 niclosamide and methanol, diethyl ether, dimethyl sulfoxide, N,N' dimethylformamide, and tetrahydrofuran solvates and the 2:1 niclosamide and tetraethylene glycol hemisolvate prepared by recrystallization from these organic solvents. Structural, spectral, and thermal analysis results confirmed the presence of the solvents and differences in the structural properties of these solvates. In addition, differences in the activation energy of desolvation, batch solution calorimetry, and the aqueous solubility at 25 degrees C, 24 hours, showed the stability of the solvates to be in the order: anhydrate > diethyl ether solvate > tetraethylene glycol hemisolvate > methanol solvate > dimethyl sulfoxide solvate > N,N' dimethylformamide solvate. The intrinsic and powder dissolution rates of the solvates were in the order: anhydrate > diethyl ether solvate > tetraethylene glycol hemisolvate > N,N' dimethylformamide solvate > methanol solvate > dimethyl sulfoxide solvate. Although these nonaqueous solvates had higher solubility and dissolution rates than the monohydrous forms, they were unstable in aqueous media and rapidly transformed to one of the monohydrous forms.

Formulation, Preparation, and Characterization of Polyurethane Foams

ERIC Educational Resources Information Center

Pinto, Moises L.

2010-01-01

Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

CYP3A5 and ABCB1 polymorphisms influence tacrolimus concentrations in peripheral blood mononuclear cells after renal transplantation.

PubMed

Capron, Arnaud; Mourad, Michel; De Meyer, Martine; De Pauw, Luc; Eddour, Djamila Chaib; Latinne, Dominique; Elens, Laure; Haufroid, Vincent; Wallemacq, Pierre

2010-05-01

This prospective study investigated the effect of genetic polymorphisms in a biotransformation enzyme (CYP3A5) and a transporter protein (ABCB1) on tacrolimus (Tac) whole blood concentrations in renal transplantation, and more specifically on peripheral blood mononuclear cell (PBMC) drug concentrations, after renal transplantation. A total of 96 renal transplant recipients were genotyped for the exon 11 (1199G>A), 21 (3435C>T) and 26 (2677G>T/A) polymorphisms in the ABCB1 gene and for the intron 3 polymorphism in the CYP3A5 gene. Tac blood and PBMC concentrations were determined at day 7 after transplantation and at steady state, and then compared with recipient genotypes. The ABCB1 1199G>A, 3435C>T and 2677G>T/A SNPs, appeared to reduce the activity of P-glycoprotein towards Tac, increasing Tac PBMC concentrations. The impact of ABCB1 genetic polymorphisms on Tac blood concentrations was negligible. As increased Tac intracellular concentrations might in turn enhance immunosuppressive status and prevention or rejection, ABCB1 recipient genotyping might be useful to better individualize the Tac immunosuppressive therapy in renal transplantation.

The preparation and characterization of a lithium borate glass prepared by the gel technique

NASA Technical Reports Server (NTRS)

Weinberg, M. C.; Neilson, G. F.; Smith, G. L.; Dunn, B.; Moore, G. S.; Mackenzie, J. D.

1985-01-01

The preparation of an amorphous lithium borate gel by the metal organic procedure is described. In addition, a preliminary evaluation of the behavior of the gel upon heating is given. In particular the crystallization tendency of the gel is studied with the aid of DTA and X-ray diffraction, and the structural changes in the gel are monitored with the aid of IR spectroscopy. The glass produced from the lithium borate gel is compared to both the gel precursor material and a glass of similar composition prepared by conventional techniques. Specifically, the relevant water contents, crystallization behavior, and structural features are contrasted.

Preparation and characterization of novel biocompatible cryogels of poly (vinyl alcohol) and egg-albumin and their water sorption study.

PubMed

Bajpai, A K; Saini, Rajesh

2006-01-01

Polyvinyl alcohol (PVA) and egg albumin are water-soluble, biocompatible and biodegradable polymers and have been widely employed in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of poly (vinyl alcohol) and egg albumin were prepared by cyclic freezing/thawing processes of aqueous solutions containing PVA and egg albumin. The FTIR analysis of prepared cryogels indicated that egg albumin was successfully introduced into the formed hydrogel possibly via hydrogen bonds among hydroxyl groups, amide groups and amino groups present in PVA and egg albumin. The gels were also characterized thermally and morphologically by DSC and SEM-techniques, respectively. The prepared so called 'cryogels' were evaluated for their water uptake potential and influence of various factors such as chemical architecture of the spongy hydrogels, pH and temperature of the swelling bath were investigated on the degree of water sorption by the cryogels. The effect of salt solution and various simulated biological fluids on the swelling of cryogel was also studied. The in vitro biocompatibility of the prepared cryogel was also judged by methods such as protein (BSA) adsorption, blood clot formation and percentage hemolysis measurements.

Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

NASA Astrophysics Data System (ADS)

Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

2017-09-01

Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

Polyacrylamide-hydroxyapatite composite: Preparation, characterization and adsorptive features for uranium and thorium

NASA Astrophysics Data System (ADS)

Baybaş, Demet; Ulusoy, Ulvi

2012-10-01

The composite of synthetically produced hydroxyapatite (HAP) and polyacrylamide was prepared (PAAm-HAP) and characterized by BET, FT-IR, TGA, XRD, SEM and PZC analysis. The adsorptive features of HAP and PAAm-HAP were compared for UO22+ and Th4+. The entrapment of HAP into PAAm-HAP did not change the structure of HAP. Both structures had high affinity to the studied ions. The adsorption capacity of PAAm-HAP was than that of HAP. The adsorption dependence on pH and ionic intensity provided supportive evidences for the effect of complex formation on adsorption process. The adsorption kinetics was well compatible to pseudo second order model. The values of enthalpy and entropy changes were positive. Th4+ adsorption from the leachate obtained from a regional fluorite rock confirmed the selectivity of PAAm-HAP for this ion. In consequence, PAAm-HAP should be considered amongst favorite adsorbents for especially deposition of nuclear waste containing U and Th, and radionuclide at secular equilibrium with these elements.

Preparation and characterization of ZnO/graphene nanocomposite for improved photovoltaic performance

NASA Astrophysics Data System (ADS)

Jayabal, P.; Gayathri, S.; Sasirekha, V.; Mayandi, J.; Ramakrishnan, V.

2014-11-01

Zinc oxide (ZnO) nanoparticles and ZnO/graphene (ZG) nanocomposite were synthesized via simple chemical route and its application as a photoanode for dye-sensitized solar cell (DSSC) was demonstrated. The prepared ZnO and ZG were structurally characterized by X-ray diffraction and micro-Raman techniques. The scanning electron micrograph of ZG revealed the spherical-shaped ZnO nanoparticles of particle size 160 nm was anchored on the two-dimensional graphene sheets. UV-Vis absorption spectroscopy showed that the ZG nanocomposite has enriched visible light absorption. The DSSCs were fabricated using the synthesized ZnO and ZG nanocomposite as photoanode and the effect of low-cost organic dyes on the photovoltaic performances of the solar cells were investigated. Comprehensive performances of ZG are better than that of ZnO-based DSSCs. The ZG DSSCs show power conversion efficiency (PCE) of 1.5 and 0.98 % for RB and EY sensitized electrodes, respectively. Moreover, the ZG dominates in many aspects due to the presence of graphene.

Poly (γ-glutamic acid)/beta-TCP nanocomposites via in situ copolymerization: Preparation and characterization.

PubMed

Shu, Xiu-Lin; Shi, Qing-Shan; Feng, Jin; Yang, Yun-Hua; Zhou, Gang; Li, Wen-Ru

2016-07-01

A series biodegradable poly (γ-glutamic acid)/beta-tricalcium phosphate (γ-PGA/TCP) nanocomposites were prepared which were composed of poly-γ-glutamic acid polymerized in situ with β-tricalcium phosphate and physiochemically characterized as bone graft substitutes. The particle size via dynamic light scattering, the direct morphological characterization via transmission electron microscopy and field emission scanning electron microscope, which showed that γ-PGA and β-TCP were combined compactly at 80℃, and the γ-PGA/TCP nanocomposites had homogenous and nano-sized grains with narrow particle size distributions. The water uptake and retention abilities, in vitro degradation properties, cytotoxicity in the simulated medium, and protein release of these novel γ-PGA/TCP composites were investigated. Cell proliferation in composites was nearly twice than β-TCP when checked in vitro using MC3T3 cell line. We also envision the potential use of γ-PGA/TCP systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering applications. These observations suggest that the γ-PGA/TCP are novel nanocomposites with great potential for application in the field of bone tissue engineering. © The Author(s) 2016.

[Preparation and characterization of a polyvinylpyrrolidone water-based magnetic fluid].

PubMed

Xie, Jian-feng; Zhang, Yang-de; Zeng, Zhao-wu; Wang, Xiao-li; Liu, Xing-yan; Zhou, Wei-hua

2008-03-01

To prepare a stable water-based magnetic fluid. A water-based magnetic fluid was prepared by addition of polyvinylpyrrolidone (PVP) as the coating agent for the magnetic particles. After preparation of Fe3O4 by co-precipitation method, PVP was added for its coating, followed by ultrasonic agitation and purification. The magnetic nanoparticles of homogeneously small size and water-based magnetic fluid were obtained, which had good dispersion in water with strong magnetism. PVP can be used as a surfactant to stabilize the magnetic fluid.

13C NMR and XPS characterization of anion adsorbent with quaternary ammonium groups prepared from rice straw, corn stalk and sugarcane bagasse

NASA Astrophysics Data System (ADS)

Cao, Wei; Wang, Zhenqian; Zeng, Qingling; Shen, Chunhua

2016-12-01

Despite amino groups modified crop straw has been intensively studied as new and low-cost adsorbent for removal of anionic species from water, there is still a lack of clear characterization for amino groups, especially quaternary ammonium groups in the surface of crop straw. In this study, we used 13C NMR and XPS technologies to characterize adsorbents with quaternary ammonium groups prepared from rice straw, corn stalk and sugarcane bagasse. 13C NMR spectra clearly showed the presence of quaternary ammonium groups in lignocelluloses structure of modified crop straw. The increase of nitrogen observed in XPS survey spectra also indicated the existence of quaternary ammonium group in the surface of the adsorbents. The curve fitting of high-resolution XPS N1s and C1s spectra were conducted to probe the composition of nitrogen and carbon contained groups, respectively. The results showed the proportion of quaternary ammonium group significantly increased in the prepared adsorbent's surface that was dominated by methyl/methylene, hydroxyl, quaternary ammonium, ether and carbonyl groups. This study proved that 13C NMR and XPS could be successfully utilized for characterization of quaternary ammonium modified crop straw adsorbents.

Pretransplant Tacrolimus Dose Requirements Predict Early Posttransplant Dose Requirements in Blood Group AB0-Incompatible Kidney Transplant Recipients.

PubMed

Shuker, Nauras; de Man, Femke M; de Weerd, Annelies E; van Agteren, Madelon; Weimar, Willem; Betjes, Michiel G H; van Gelder, Teun; Hesselink, Dennis A

2016-04-01

The aim of this study was to investigate whether pretransplant tacrolimus (Tac) dose requirements of patients scheduled to undergo living donor kidney transplantation correlate with posttransplantation dose requirements. The predictive value of Tac dose requirements (defined as the ratio of the Tac predose concentration, C0, divided by the total daily Tac dose, D) pretransplantation on this same parameter posttransplantation was assessed retrospectively in a cohort of 57 AB0-incompatible kidney transplant recipients. These patients started immunosuppressive therapy 14 days before transplant surgery. All patients were using a stable dose of glucocorticoids and were at steady-state Tac exposure before transplantation. Tac dose requirements immediately before transplantation (C0/Dbefore) explained 63% of the Tac dose requirements on day 3 after transplantation: r = 0.633 [F (1, 44) = 75.97, P < 0.01]. No other clinical and demographic variables predicted Tac dose requirements early after transplantation. Steady-state Tac dose requirement before transplantation largely predicted posttransplantation Tac dose requirements in AB0-incompatible kidney transplant recipients. The importance of this finding is that the posttransplantation Tac dose can be individualized based on a patient's pretransplantation Tac concentration/dose ratio. Pretransplant Tac phenotyping therefore has the potential to improve transplantation outcomes.

Post-marketing surveillance of the safety and effectiveness of tacrolimus in 3,267 Japanese patients with rheumatoid arthritis.

PubMed

Takeuchi, Tsutomu; Kawai, Shinichi; Yamamoto, Kazuhiko; Harigai, Masayoshi; Ishida, Kota; Miyasaka, Nobuyuki

2014-01-01

A post-marketing surveillance (PMS) program was implemented to assess the safety and effectiveness of tacrolimus (TAC) in Japanese rheumatoid arthritis (RA) patients and to identify risk factors related to adverse drug reactions (ADRs). Patients were registered centrally and monitored for all adverse events (AEs) for 24 weeks. Effectiveness was evaluated using the Disease Activity Score 28-CRP (DAS28-CRP). Data from 3,172 patients (mean age 62.2 years) were evaluated in the safety analysis. Of the safety population, 78.5 %were female and 25.9 % were in Steinbrocker's functional class 3 or 4. TAC was prescribed as monotherapy in 52.5 % and the most common concomitant disease modifying antirheumatic drug (DMARD) was methotrexate, used in 28.9 % of the patients. The incidence of AEs, serious AEs (SAEs), ADRs and serious ADRs were 41.2, 6.4, 36.0, and 4.9 %, respectively. The most frequent serious ADR category was infections and infestations. Age ≥ 65 years, concurrent renal dysfunction, and concurrent diabetes mellitus were identified as significant risk factors for ADR. Based on EULAR response criteria, 65.4 % of the patients showed moderate or good response. The results demonstrate that TAC is well tolerated by Japanese patients with active RA, including those receiving concomitant methotrexate, in the real world.

Preparation and characterization of TiO2 coated Fe nanofibers for electromagnetic wave absorber.

PubMed

Jang, Dae-Hwan; Song, Hanbok; Lee, Young-In; Lee, Kun-Jae; Kim, Ki Hyeon; Oh, Sung-Tag; Lee, Sang-Kwan; Choa, Yong-Ho

2011-01-01

Recently, electromagnetic interference (EMI) and electromagnetic compatibility (EMC) have become serious problems due to the growth of electronic device and next generation telecommunication. It is necessary to develop new electromagnetic wave absorbing material to overcome the limitation of electromagnetic wave shielding materials. The EMI attenuation is normally related to magnetic loss and dielectric loss. Therefore, magnetic material coating dielectric materials are required in this reason. In this study, TiO2 coated Fe nanofibers were prepared to improve their properties for electromagnetic wave absorption. Poly(vinylpyrrolidone) (PVP) and Iron (III) nitrate nonahydrate (Fe(NO3)3 x 9H2O) were used as starting materials for the synthesis of Fe oxide nanofibers. Fe oxide nanofibers were prepared by electrospinning in an electric field and heat treatment. TiO2 layer was coated on the surface of Fe oxide nanofibers using sol-gel process. After the reduction of TiO2 coated Fe oxide nanofibers, Fe nanofibers with a TiO2 coating layer of about 10 nm were successfully obtained. The morphology and structure of fibers were characterized by SEM, TEM, and XRD. In addition, the absorption properties of TiO2 coated Fe nanofibers were measured by network analyzer.

No-load sirolimus with tacrolimus and steroids is safe and effective in renal transplantation.

PubMed

Tellis, V; Schechner, R; Mallis, M; Rosegreen, S; Glicklich, D; Moore, N; Greenstein, S

2005-03-01

Basiliximab (BX) induction, tacrolimus (TAC), and steroids have sharply reduced acute cellular rejection at our institution. However, late graft loss has continued, for which sirolimus (SL) was introduced into the protocol. From July 1, 2001 to December 31, 2003, 152 live donor (LD) renal transplant recipients received TAC (level 15 to 20 ng/mL) and steroids, with BX induction. One hundred twenty-two patients (Group 1) received SL (3 mg/d African-americans; 2 mg/d for others) starting on days 2 and 3. The SL level was adjusted to 8 to 10 ng/d, usually by weeks 3 to 4 posttransplant. The TAC doses were then progressively reduced. Records were reviewed for demographics, immunosuppressive drug levels, serum cholesterol and blood pressure, and complications. Graft and patient survival rates were calculated. Comparison was made to 53 LD recipients transplanted from July 1, 1998, to June 30, 2001 (Group 2) receiving BX, steroids and TAC, without SL. Recipients of deceased donor kidneys were excluded because of variability in kidney quality, ischemic time, and patient management. Demographics were similar between groups: African Americans, 25% to 35%; mean age 36 years; mean HLA mismatch 3.7. Wound problems and infection were minimal in both groups. Mean serum creatinine and cholesterol and systolic and diastolic blood pressure measured periodically up to 1 year were similar, as was the incidence of rejection. In 25% of patients, SL was discontinued. Gradual introduction of SL appears to be associated with minimal wound problems. With more aggressive reduction in TAC, better renal function, and better long-term graft survival may be attainable. We currently lower TAC levels to 5 ng/mL by 3 months.

Preparation, Characterization and Photocatalytic Activity of Ag/TiO2 Nanoparticle Semiconductor Catalysts

NASA Astrophysics Data System (ADS)

Zhang, Yaoyao; Li, Mengyao; Guo, Yinli

2018-01-01

A series of Ag-doped TiO2 powder photocatalysts were prepared by the sol-gel method. The phase structure and morphology of the samples were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The persistent organic pollutant sodium pentachlorophenol ate (PCP-Na) was selected as the target pollutant, and the photocatalytic property of the material Ag/TiO2 was evaluated by PCP-Na degradation rate. It was found that the calcination at 450 °C was conducive to form the anatase structure with high catalytic activity, and the catalytic activity was higher when the silver mole fraction of Ag/TiO2 was 0.50%. The influence of Ag/TiO2 dosage, hydrogen peroxide volume, silver mole fraction and PCP-Na initial concentration was investigated by the single factor experiment.

Synthesis and spectroscopic characterization of gold nanobipyramids prepared by a chemical reduction method

NASA Astrophysics Data System (ADS)

Thanh Ngo, Vo Ke; Phat Huynh, Trong; Giang Nguyen, Dang; Phuong Uyen Nguyen, Hoang; Lam, Quang Vinh; Dat Huynh, Thanh

2015-12-01

Gold nanobipyramids (NBPs) have attracted much attention because they have potential for applications in smart sensing devices, such as medical diagnostic equippments. This is due to the fact that they show more advantageous plasmonic properties than other gold nanostructures. We describe a chemical reduction method for synthesizing NBPs using conventional heating with ascorbic acid reduction and cetyltrimethylamonium bromide (CTAB) + AgNO3 as capping agents. The product was characterized by ultraviolet-visible spectroscopy (UV-vis), Fourier transmission infrared spectroscopy (FTIR), transmission electron microscopy (TEM), x-ray powder diffraction (XRD). The results showed that gold nanoparticles were formed with bipyramid shape (tip-to-tip distance of 88.4 ± 9.4 nm and base length of 29.9 ± 3.2 nm) and face-centered-cubic crystalline structure. Optimum parameters for preparation of NBPs are also found.

Preparation of eugenol-based polyurethane

NASA Astrophysics Data System (ADS)

Li, Yupeng; Luo, Fang; Cheng, Chuanjie

2018-03-01

The regenerative eugenol was used as the starting material to prepare diol species by two steps, with a total yield of 28%. Furthermore, the prepared diol reacts with 1,6-hexadiisocyanate(HDI) to afford the corresponding polyurethane (PU). The structure of intermediates and PU are characterized by 1H-NMR or IR.

Preparation and Characterization of Ni-Doped TiO2 Materials for Photocurrent and Photocatalytic Applications

PubMed Central

Ganesh, Ibram; Gupta, A. K.; Kumar, P. P.; Sekhar, P. S. C.; Radha, K.; Padmanabham, G.; Sundararajan, G.

2012-01-01

Different amounts of Ni-doped TiO2 (Ni = 0.1 to 10%) powders and thin films were prepared by following a conventional coprecipitation and sol-gel dip coating techniques, respectively, at 400 to 800°C, and were thoroughly characterized by means of XRD, FT-IR, FT-Raman, DRS, UV-visible, BET surface area, zeta potential, flat band potential, and photocurrent measurement techniques. Photocatalytic abilities of Ni-doped TiO2 powders were evaluated by means of methylene blue (MB) degradation reaction under simulated solar light. Characterization results suggest that as a dopant, Ni stabilizes TiO2 in the form of anatase phase, reduces its bandgap energy, and adjusts its flat band potentials such that this material can be employed for photoelectrochemical (PEC) oxidation of water reaction. The photocatalytic activity and photocurrent ability of TiO2 have been enhanced by doping of Ni in TiO2. The kinetic studies revealed that the MB degradation reaction follows the Langmuir-Hinshelwood first-order reaction relationship. PMID:22619580

A novel smart injectable hydrogel prepared by microbial transglutaminase and human-like collagen: Its characterization and biocompatibility.

PubMed

Zhao, Leilei; Li, Xian; Zhao, Jiaqi; Ma, Saijian; Ma, Xiaoxuan; Fan, Daidi; Zhu, Chenhui; Liu, Yannan

2016-11-01

Various tissue scaffold materials are increasingly used to repair skin defects by cross-linking because of the ability to fill and implant in any form via operation. However, crosslinker residues cannot be easily removed from scaffold materials prepared by chemical crosslinking methods, limiting their use for skin tissue engineering. Here, microbial transglutaminase (MTGase), a nontoxic crosslinker with high specific activity and reaction rate under mild conditions, was employed crosslinks in human-like collagen (HLC) to yield novel smart MTGase crosslinked with human-like collagen (MTGH) hydrogels, which are sensitive to temperature and/or enzymes. Various ratios of MTGase/HLC were performed, and their physicochemical properties were characterized, including the swelling ratio, the elastic modulus, the morphology and the porosity. The degradation behavior and mechanism of MTGase in concentration-dependent manner involved in formation hydrogels were identifying in vitro. The cell attachment in vitro and biocompatibility in vivo were also investigated. The results demonstrated that the use of different concentrations of MTGase to crosslink HLC produced products with different degradation times and biocompatibilities. The 50U/g MTGase-prepared MTGH hydrogels had a higher density of crosslinks, which made them more resistant to degradation by collagenase I and collagenase II. However, 40U/g MTGase-prepared MTGH hydrogels were more suitable for cell attachment. In addition, compared with the Collagen Implant I® (SUM) used in animal experiments, the 40U/g MTGase-prepared MTGH hydrogels had a lower toxicity and better biocompatibility. Therefore, 40U/g MTGase crosslinked with HLC should be used to prepare MTGH hydrogels for potential application as soft materials for skin tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

PubMed

Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

2016-04-01

A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

Preparation, Processing, and Characterization of Oriented Polycrystalline Zeolite and Aluminophosphate Membranes

NASA Astrophysics Data System (ADS)

Stoeger, Jared Andrew

Since the advent of zeolite membranes, speculation on their industrial applicability has been closely monitored, although widespread commercialization has been hampered by limitations in fabrication and post-synthesis processing. Economical, energy-efficient technology breakthroughs require an evaluation of a range of material candidates which show robustness and reliability. Straightforward manufacturing techniques should be devised to generate thousands of square meters of membrane area; however, this demands control of structural characteristics on the scale of nanometers. As described in this dissertation, the path forward will be forged by exploiting the intrinsic crystalline properties of zeolites or aluminophosphates for the next advancement in membrane technology. A facile method is described for the preparation of silicalite-1 (MFI zeolite type) membranes using the secondary growth technique on symmetric porous stainless steel tubes. Activation through rapid thermal processing (RTP), a lamp-based heat-treatment process used as a critical fabrication step in silicon integrated circuit manufacturing, is proven to reduce the density of non-zeolitic transport pathways which are detrimental to high-resolution molecular sieving. RTP-treated membranes are shown to have enhanced performance in the binary separation of vapor-phase isomers (p-/o-xylene), gas-phase isomers (n-/i-butane), and alcohol/water when compared to membranes activated at a much slower heating rate but otherwise similarly-prepared. The performance is discussed in the context of the market potential for industrially-attractive separations: the recovery of p-xylene from an isomeric mixture or alcohol biofuels from aqueous post-fermentation streams. Hydrothermal growth techniques for the preparation and characterization of continuous aluminophosphate (AFI zeolite type) membranes with a preferential crystallographic alignment on porous alpha-Al2O3 disc supports are demonstrated. A mechanism is

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

PubMed Central

Shen, Xiujin; Jiang, Hong; Ying, Meike; Xie, Zhoutao; Li, Xiayu; Wang, Haibing; Zhao, Jie; Lin, Chuan; Wang, Yucheng; Feng, Shi; Shen, Jia; Weng, Chunhua; Lin, Weiqiang; Wang, Huiping; Zhou, Qin; Bi, Yan; Li, Meng; Wang, Lingyan; Zhu, Tongyu; Huang, Xiaoru; Lan, Hui-Yao; Zhou, Jing; Chen, Jianghua

2016-01-01

Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway. PMID:27580845

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose

PubMed Central

Andrews, Louise M.; de Winter, Brenda C.M.; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H.N.; Koch, Birgit C.P.; van Gelder, Teun; Hesselink, Dennis A.

2017-01-01

Background Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. Methods For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Results Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. Conclusions This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients. PMID:28361113

Preparation and characterization of photoactive composite kaolinite/TiO(2).

PubMed

Mamulová Kutláková, K; Tokarský, J; Kovář, P; Vojtěšková, S; Kovářová, A; Smetana, B; Kukutschová, J; Čapková, P; Matějka, V

2011-04-15

Preparation of nanocomposite kaolinite/TiO(2), using hydrolysis of titanyl sulfate in the presence of kaolin was addressed. A variable (kaolin)/(titanyl sulfate) ratio has been used in order to achieve the desired TiO(2) content in prepared nanocomposites. Calcination of the composites at 600 °C led to the transformation of the kaolinite to metakaolinite and to origination of metakaolinite/TiO(2) composites. The prepared samples were investigated using X-ray fluorescence spectroscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetry and diffuse reflectance spectroscopy in the UV-VIS region. Structural ordering of TiO(2) on the kaolinite particle surface was modeled using empirical force field atomistic simulations in the Material Studio modeling environment. Photodegradation activity of the composites prepared was evaluated by the discoloration of Acid Orange 7 aqueous solution. Copyright © 2011 Elsevier B.V. All rights reserved.

Tacrolimus and mycophenolate regimen and subclinical tubulo-interstitial inflammation in low immunological risk renal transplants.

PubMed

Torres, Irina B; Reisaeter, Anna V; Moreso, Francesc; Âsberg, Anders; Vidal, Marta; Garcia-Carro, Clara; Midtvedt, Karsten; Reinholt, Finn P; Scott, Helge; Castellà, Eva; Salcedo, Maite; Dörje, Christina; Sellarés, Joana; Azancot, Maria A; Perello, Manel; Holdaas, Hallvard; Serón, Daniel

2017-11-01

The aim was to evaluate the relationship between maintenance immunosuppression, subclinical tubulo-interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA) in surveillance biopsies performed in low immunological risk renal transplants at two transplant centers. The Barcelona cohort consisted of 109 early and 66 late biopsies in patients receiving high tacrolimus (TAC-C 0 target at 1-year 6-10 ng/ml) and reduced MMF dose (500 mg bid at 1-year). The Oslo cohort consisted of 262 early and 237 late biopsies performed in patients treated with low TAC-C 0 (target 3-7 ng/ml) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC-C 0 in the early (OR: 0.75, 95% CI: 0.61-0.92; P = 0.006) and late biopsies (OR: 0.69, 95% CI: 0.50-0.95; P = 0.023) from Barcelona. In the Oslo cohort, it was associated with low MMF in early biopsies (OR: 0.90, 95% CI: 0.83-0.98; P = 0.0101) and with low TAC-C 0 in late biopsies (OR: 0.77, 95% CI: 0.61-0.97; P = 0.0286). MMF dose was significantly reduced in Oslo between early and late biopsies. IF/TA was not associated with TAC-C 0 or MMF dose in the multivariate analysis. Our data suggest that in TAC- and MMF-based regimens, TAC-C 0 levels are associated with subclinical inflammation in patients receiving reduced MMF dose. © 2017 Steunstichting ESOT.

Preparation, characterization and conductivity study of nitro-mercurated styrene butadiene rubber/silver doped zinc oxide nanocomposites

NASA Astrophysics Data System (ADS)

Anilkumar, T.; Naik, Adarsh Ajith; Ramesan, M. T.

2017-06-01

Here we report the preparation of nitromercurated styrene butadiene rubber (NMSBR)/silver doped zinc oxide nanocomposite by inexpensive and ecofriendly two roll mill mixing. The composites were characterized by UV, FTIR, XRD, SEM, TGA and conductivity measurements. UV and FTIR spectrum indicated the interfacial interaction between the polymer and nanoparticles.XRD and SEM images showed the uniform arrangement of nanoparticles within the macromolecular chain. TGA study indicated the better thermal resistance of the composite. The dielectric properties and AC conductivity ofnanocomposites were much greater than nitromercurated SBR and they may be used as multifunctional materials for nanoelectronic devices.

CYP3A5*3 and ABCB1 61A>G Significantly Influence Dose-adjusted Trough Blood Tacrolimus Concentrations in the First Three Months Post-Kidney Transplantation.

PubMed

Hu, Rong; Barratt, Daniel T; Coller, Janet K; Sallustio, Benedetta C; Somogyi, Andrew A

2018-03-30

Tacrolimus (TAC) is a first-line immunosuppressant used to prevent organ rejection after kidney transplantation. There is large inter-individual variability in its pharmacokinetics. Single nucleotide polymorphisms (SNPs) in genes encoding TAC metabolizing enzymes cytochromes P450 3A4/5 (CYP3A4/5), P-glycoprotein efflux transporter (ABCB1), their expression regulator pregnane X receptor (NR1I2) and CYP3A co-factor cytochrome P450 reductase (POR) have been studied for their effects on tacrolimus disposition. However, except for CYP3A5*3, controversies remain about their roles in predicting dose-adjusted trough blood TAC concentrations (C 0 /D). This study aimed to investigate the effects of ABCB1 (61A>G, 1199G>A, 1236C>T, 2677G>T and 3435C>T), CYP3A4*22, CYP3A5*3, NR1I2 (8055C>T, 63396C>T and -25385C>T) and POR*28 SNPs on TAC C 0 /D. In total, 165 kidney transplant recipients were included in this study. SNPs were genotyped by probe-based real-time polymerase chain reaction. Associations between log-transformed whole blood TAC C 0 /D (measured at 1 and 3 months post-transplant) and genotypes/haplotypes were assessed by linear mixed effects analysis, controlling for age, sex and haematocrit. It was observed that CYP3A5 expressors (*1/*1 + *1/*3) (p = 5.5 × 10 -16 ) and ABCB1 61G allele carriers (p = 0.001) had lower log-transformed TAC C 0 /D (56% and 26% lower geometric mean TAC C 0 /D, respectively) and accounted for approximately 30% and 4%, respectively, of log-transformed TAC C 0 /D variability in the first 3 months post-transplant. In conclusion, CYP3A5*3 is a major, and ABCB1 61A>G is a novel, although minor, genetic factor affecting TAC C 0 /D in kidney transplant recipients. © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Synthesis and characterization of zeolites prepared from industrial fly ash.

PubMed

Franus, Wojciech; Wdowin, Magdalena; Franus, Małgorzata

2014-09-01

In this paper, we present the possibility of using fly ash to produce synthetic zeolites. The synthesis class F fly ash from the Stalowa Wola SA heat and power plant was subjected to 24 h hydrothermal reaction with sodium hydroxide. Depending on the reaction conditions, three types of synthetic zeolites were formed: Na-X (20 g fly ash, 0.5 dm(3) of 3 mol · dm(-3) NaOH, 75 °C), Na-P1 (20 g fly ash, 0.5 dm(3) of 3 mol · dm(-3) NaOH, 95 °C), and sodalite (20 g fly ash, 0.8 dm(3) of 5 mol · dm(-3) NaOH + 0.4 dm(3) of 3 mol · dm(-3) NaCl, 95 °C). As synthesized materials were characterized to obtain mineral composition (X-ray diffractometry, Scanning electron microscopy-energy dispersive spectrometry), adsorption properties (Brunauer-Emmett-Teller surface area, N2 isotherm adsorption/desorption), and ion exchange capacity. The most effective reaction for zeolite preparation was when sodalite was formed and the quantitative content of zeolite from X-ray diffractometry was 90 wt%, compared with 70 wt% for the Na-X and 75 wt% for the Na-P1. Residues from each synthesis reaction were the following: mullite, quartz, and the remains of amorphous aluminosilicate glass. The best zeolitic material as characterized by highest specific surface area was Na-X at almost 166 m(2) · g(-1), while for the Na-P1 and sodalite it was 71 and 33 m(2) · g(-1), respectively. The ion exchange capacity decreased in the following order: Na-X at 1.8 meq · g(-1), Na-P1 at 0.72 meq · g(-1), and sodalite at 0.56 meq · g(-1). The resulting zeolites are competitive for commercially available materials and are used as ion exchangers in industrial wastewater and soil decontamination.

Preparation, physical characterization, and stability of Ferrous-Chitosan microcapsules using different iron sources

NASA Astrophysics Data System (ADS)

Handayani, Noer Abyor; Luthfansyah, M.; Krisanti, Elsa; Kartohardjono, Sutrasno; Mulia, Kamarza

2017-11-01

Dietary modification, supplementation and food fortification are common strategies to alleviate iron deficiencies. Fortification of food is an effective long-term approach to improve iron status of populations. Fortification by adding iron directly to food will cause sensory problems and decrease its bioavailability. The purpose of iron encapsulation is: (1) to improve iron bioavailability, by preventing oxidation and contact with inhibitors and competitors; and (2) to disguise the rancid aroma and flavor of iron. A microcapsule formulation of two suitable iron compounds (iron II fumarate and iron II gluconate) using chitosan as a biodegradable polymer will be very important. Freeze dryer was also used for completing the iron microencapsulation process. The main objective of the present study was to prepare and characterize the iron-chitosan microcapsules. Physical characterization, i.e. encapsulation efficiency, iron loading capacity, and SEM, were also discussed in this paper. The stability of microencapsulated iron under simulated gastrointestinal conditions was also investigated, as well. Both iron sources were highly encapsulated, ranging from 71.5% to 98.5%. Furthermore, the highest ferrous fumarate and ferrous gluconate loaded were 1.9% and 4.8%, respectively. About 1.04% to 9.17% and 45.17% to 75.19% of Fe II and total Fe, were released in simulated gastric fluid for two hours and in simulated intestinal fluid for six hours, respectively.

Preparation and Characterization of Myosin Proteins.

ERIC Educational Resources Information Center

Caldwell, Elizabeth; Eftink, Maurice R.

1985-01-01

Students complete five experimental projects at the end of a senior-level biochemistry course which involves the isolation and characterization of myosin and its water-soluble subfragments. Procedures used and results obtained are provided for such projects as viscosity and ATPase measurements and gel electrophoresis experiments. (JN)

Preparation and Preliminary Characterization of Crystallizing Fluorescent Derivatives of Chicken Egg White Lysozyme

NASA Technical Reports Server (NTRS)

Sumida, John; Forsythe, Elizabeth L.; Pusey, Marc L.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

Fluorescence is one of the most versatile and powerful tools for the study of macromolecules. While most proteins are intrinsically fluorescent, working at crystallization concentrations require the use of covalently prepared derivatives added as tracers. This approach requires derivatives that do not markedly affect the crystal packing. We have prepared fluorescent derivatives of chicken egg white lysozyme with probes bound to one of two different sites on the protein molecule. Lucifer yellow and 5-(2-aminoethyl)aminonapthalene-1-sulfonic acid (EDANS) have been attached to the side chain carboxyl of Asp(sup 101) using a carbodiimide coupling procedure. Asp(sup 101) lies within the active site cleft, and it is believed that the probes are "buried" within that cleft. Lucifer yellow and MANS probes with iodoacetamide reactive groups have been bound to His(sup 15), located on the "back side" of the molecule relative to the active site. All the derivatives fluoresce in the solution and the crystalline states. Fluorescence characterization has focused on determination of binding effects on the probe quantum yield, lifetime, absorption and emission spectra, and quenching by added solutes. Quenching studies show that, as postulated, the Asp(sup 101)-bound probes are partially sheltered from the bulk solution by their location within the active site cleft. Probes bound to His(sup 15) have quenching constants about equal to those for the free probes, indicating that this site is highly exposed to the bulk solution.

Preparation and Preliminary Characterization of Crystallizing Fluorescent Derivatives of Chicken Egg White Lysozyme

NASA Technical Reports Server (NTRS)

Sumida, John P.; Forsythe, Elizabeth L.; Pusey, Marc L.

2001-01-01

Fluorescence is one of the most versatile and powerful tools for the study of macromolecules. While most proteins are intrinsically fluorescent, working at crystallization concentrations require the use of covalently prepared derivatives added as tracers. This approach requires derivatives that do not markedly affect the crystal packing. We have prepared fluorescent derivatives of chicken egg white lysozyme with probes bound to one of two different sites on the protein molecule. Lucifer yellow and 5-(2-aminoethyl)aminonapthalene-i-sulfonic acid (EDANS) have been attached to the side chain carboxyl of Asp(sup 101) using a carbodiimide coupling procedure. Asp(sup 101) lies within the active site cleft, and it is believed that the probes are 'buried' within that cleft. Lucifer yellow and MANS probes with iodoacetamide reactive five groups have been bound to His(sup 15), located on the 'back side' of the molecule relative to the active site. All the derivatives fluoresce in the solution and the crystalline states. Fluorescence characterization has focused on determination of binding effects on the probe quantum yield, lifetime, absorption and emission spectra, and quenching by added solutes. Quenching studies show that, as postulated, the Asp(sup 101)-bound probes are partially sheltered from the bulk solution by their location within the active site cleft. Probes bound to His(sup 15) have quenching constants about equal to those for the free probes, indicating that this site is highly exposed to the bulk solution.

Preparation and preliminary characterization of crystallizing fluorescent derivatives of chicken egg white lysozyme

NASA Astrophysics Data System (ADS)

Sumida, John P.; Forsythe, Elizabeth L.; Pusey, Marc L.

2001-11-01

Fluorescence is one of the most versatile and powerful tools for the study of macromolecules. While most proteins are intrinsically fluorescent, working at crystallization concentrations require the use of covalently prepared derivatives added as tracers. This approach requires derivatives that do not markedly affect the crystal packing. We have prepared fluorescent derivatives of chicken egg white lysozyme with probes bound to one of two different sites on the protein molecule. Lucifer yellow and 5-(2-aminoethyl)aminonapthalene-1-sulfonic acid (EDANS) have been attached to the side chain carboxyl of Asp 101 using a carbodiimide coupling procedure. Asp 101 lies within the active site cleft, and it is believed that the probes are "buried" within that cleft. Lucifer yellow and EDANS probes with iodoacetamide reactive groups have been bound to His 15, located on the "back side" of the molecule relative to the active site. All the derivatives fluoresce in the solution and the crystalline states. Fluorescence characterization has focused on determination of binding effects on the probe quantum yield, lifetime, absorption and emission spectra, and quenching by added solutes. Quenching studies show that, as postulated, the Asp 101-bound probes are partially sheltered from the bulk solution by their location within the active site cleft. Probes bound to His 15 have quenching constants about equal to those for the free probes, indicating that this site is highly exposed to the bulk solution.

Efficient Pb(II) removal using sodium alginate-carboxymethyl cellulose gel beads: Preparation, characterization, and adsorption mechanism.

PubMed

Ren, Huixue; Gao, Zhimin; Wu, Daoji; Jiang, Jiahui; Sun, Youmin; Luo, Congwei

2016-02-10

Alginate-carboxymethyl cellulose (CMC) gel beads were prepared in this study using sodium alginate (SA) and sodium CMC through blending and cross-linking. The specific surface area and aperture of the prepared SA-CMC gel beads were tested. The SA-CMC structure was characterized and analyzed via infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Static adsorption experiment demonstrated that Pb(II) adsorption of SA-CMC exceeded 99% under the optimized conditions. In addition, experiments conducted under the same experimental conditions showed that the lead ion removal efficiency of SA-CMC was significantly higher than that of conventional adsorbents. The Pb(II) adsorption process of SA-CMC followed the Langmuir adsorption isotherm, and the dynamic adsorption model could be described through a pseudo-second-order rate equation. Pb(II) removal mechanisms of SA-CMC, including physical, chemical, and electrostatic adsorptions, were discussed based on microstructure analysis and adsorption kinetics. Chemical adsorption was the main adsorption method among these mechanisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

PubMed

Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

2014-12-01

The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

Expanding the Chemistry of Rhenium Metal–Metal Bonded Fluoro Complexes: Facile Preparation and Characterization of Paddlewheel Complexes

DOE PAGES

Balasekaran, Samundeeswari Mariappan; Sattelberger, Alfred P.; Hagenbach, Adelheid; ...

2017-12-08

Quadruply bonded rhenium(III) dimers with the stoichiometry Re 2L 4F 2 (1, L = hexahydro-2H-pyrimido[1,2a]pyrimidinate (hpp –); 2, L = diphenyl formamidinate (dpf –)) were prepared from the solid-state melt reactions (SSMRs) between (NH 4) 2[Re 2F 8]·2H 2O and HL. Then those compounds were characterized in the solid state by single-crystal X-ray diffraction and in solution by UV–visible spectroscopy and cyclic voltammetry. The compound [Re 2(hpp) 4F 2]PF 6 (3) was prepared from the one-electron oxidation of Re 2(hpp) 4F 2 with [Cp 2Fe]PF 6. Compounds 1–3 are isostructural with the corresponding chloro derivatives. In summation, compound 1 undergoesmore » two one-electron oxidations. Comparison with its higher halogen homologues reveals that Re 2(hpp) 4F 2 (1) is more easily oxidized than its chloro and bromo analogues.« less

Expanding the Chemistry of Rhenium Metal–Metal Bonded Fluoro Complexes: Facile Preparation and Characterization of Paddlewheel Complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balasekaran, Samundeeswari Mariappan; Sattelberger, Alfred P.; Hagenbach, Adelheid

Quadruply bonded rhenium(III) dimers with the stoichiometry Re 2L 4F 2 (1, L = hexahydro-2H-pyrimido[1,2a]pyrimidinate (hpp –); 2, L = diphenyl formamidinate (dpf –)) were prepared from the solid-state melt reactions (SSMRs) between (NH 4) 2[Re 2F 8]·2H 2O and HL. Then those compounds were characterized in the solid state by single-crystal X-ray diffraction and in solution by UV–visible spectroscopy and cyclic voltammetry. The compound [Re 2(hpp) 4F 2]PF 6 (3) was prepared from the one-electron oxidation of Re 2(hpp) 4F 2 with [Cp 2Fe]PF 6. Compounds 1–3 are isostructural with the corresponding chloro derivatives. In summation, compound 1 undergoesmore » two one-electron oxidations. Comparison with its higher halogen homologues reveals that Re 2(hpp) 4F 2 (1) is more easily oxidized than its chloro and bromo analogues.« less

21 CFR 184.1148 - Bacterially-derived carbohydrase enzyme preparation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Bacterially-derived carbohydrase enzyme preparation... carbohydrase enzyme preparation. (a) Bacterially-derived carbohydrase enzyme preparation is obtained from the... Bacillus subtilis or B. amyloliquefaciens. The preparation is characterized by the presence of the enzymes...

Preparation and characterization of RuO2/polypyrrole electrodes for supercapacitors

NASA Astrophysics Data System (ADS)

Li, Xiang; Wu, Yujiao; Zheng, Feng; Ling, Min; Lu, Fanghai

2014-11-01

Polypyrrole (PPy) embedded RuO2 electrodes were prepared by the composite method. Precursor solution of RuO2 was coated on tantalum sheet and annealed at 260 °C for 2.5 h to develop a thin film. PPy particles were deposited on RuO2 films and dried at 80 °C for 12 h to form composite electrode. Microstructure and morphology of RuO2/PPy electrode were characterized using Fourier transform infrared spectrometer, X-ray diffraction and scanning electron microscopy, respectively. Our results confirmed that counter ions are incorporated into RuO2 matrix. Structure of the composite with amorphous phase was verified by X-ray diffraction. Analysis by scanning electron microscopy reveals that during grain growth of RuO2/PPy, PPy particle size sharply increases as deposition time is over 20 min. Electrochemical properties of RuO2/PPy electrode were calculated using cyclic voltammetry. As deposition times of PPy are 10, 20, 25 and 30 min, specific capacitances of composite electrodes reach 657, 553, 471 and 396 F g-1, respectively. Cyclic behaviors of RuO2/PPy composite electrodes are stable.

Preparation and characterization of biocompatible silver nanoparticles using pomegranate peel extract.

PubMed

Nasiriboroumand, Majid; Montazer, Majid; Barani, Hossein

2018-02-01

The potential application of any nanoparticles, including silver nanoparticles (AgNPs), strongly depends on their stability against aggregation. In the current study, an aqueous extract of pomegranate peel was used as a stabilizer during synthesis of AgNPs. Nanoparticles have been prepared by the chemical reduction method from an aqueous solution of silver nitrate in the presence of sodium borohydride as a reducing agent. The AgNPs were characterized by dynamic light scattering (DLS), zeta-potential measurements, UV-Vis spectroscopy and transmission electron microscopy (TEM). The antibacterial efficiency of AgNPs against Escherichia coli was investigated. The size, polydispersity index, FWHM, and colloidal stability of nanoparticles in dispersion depends on the extract concentrations. In the presence of pomegranate peel extract, the nanoparticles suspension shows colloidal stability at least for a week. Our studies show that synthesized AgNPs with the above described procedure were stable at pH = 3-12 and in the temperature range of 25-85 °C. Additionally, AgNPs exhibit antibacterial properties, especially at the lowest amount of extract to silver ratio (K Extract/Ag ). Copyright © 2018. Published by Elsevier B.V.

Structural Characterization of Melanin Pigments from Commercial Preparations of the Edible Mushroom Auricularia auricula

PubMed Central

Prados-Rosales, Rafael; Toriola, Stacy; Nakouzi, Antonio; Chatterjee, Subhasish; Stark, Ruth; Gerfen, Gary; Tumpowsky, Paul; Dadachova, Ekaterina; Casadevall, Arturo

2016-01-01

Many of the most widely consumed edible mushrooms are pigmented, and these have been associated with some beneficial health effects. Nevertheless, the majority of the reported compounds associated with these desirable properties are non-pigmented. We have previously reported that melanin pigment from the edible mushroom Auricularia auricula can protect mice against ionizing radiation, although no physicochemical characterization was reported. Consequently, in this study we have characterized commercial A. auricula mushroom preparations for melanin content and carried out structural characterization of isolated insoluble melanin materials using a panel of sophisticated spectroscopic and physical/imaging techniques. Our results show that approximately 10% of the dry mass of A. auricula is melanin and that the pigment has physicochemical properties consistent with those of eumelanins, including hosting a stable free radical population. Electron microscopy studies show that melanin is associated with the mushroom cell wall in a manner similar to that of melanin from the model fungus C. neoformans. Elemental analysis of melanin indicated C, H, and N ratios consistent with 5,6-dihydroxyindole-2-carboxylic acid/5,6-dihydroxyindole and 1,8-dihydroxynaphthalene eumelanin. Validation of the identity of the isolated product as melanin was achieved by EPR analysis. A. auricula melanin manifested structural differences, relative to the C. neoformans melanin, with regard to the variable proportions of alkyl chains or oxygenated carbons. Given the necessity for new oral and inexpensive radioprotective materials coupled with the commercial availability of A. auricula mushrooms, this product may represent an excellent source of edible melanin. PMID:26244793