Academic literature on the topic 'TA 7.5 UL 2013'

This study aims to investigate the renoprotective effect of recombinant human erythropoietin (rhEPO) treatment could preserve tubular epithelial cell regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for histopathological and immunohistochemical study. The expression of S100A4, TGF-β1, BMP-7, Smad2/3, Smad1/5/8, andp16INK4awas determined by western blot and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and interstitial fibrosis within 3 to 14 days. An increase in TGF-β1, Smad2/3, S100A4, andp16INK4aexpression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys.p16INK4awas positively correlated with TGF-β1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8 in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF-β, Smad2/3, S100A4, andp16INK4aand preserved the downregulation of BMP-7 and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by modulating senescence and EMT which could be a part of therapeutic option in patients with chronic kidney disease.

Perakitan klon karet unggul terus menerus dilakukan sejak tahun 1980-an di Balai Penelitian Sungei Putih, Pusat Penelitian Karet. Teknik perakitan dilakukan secara konvensional dengan persilangan alami dan buatan. Setelah itu dilakukan seleksi, pengujian pendahuluan, pengujian lanjutan, dan pengujian adaptasi. Tujuan perakitan adalah mendapatkan klonyang memiliki potensi hasil dan sifat-sifat agronomis lebih baik dari padaklon saat ini. Keunggulan suatu klon ditentukan oleh faktor genetik yang dikandungnya dan diekspresikan dalam bentuk morfologis, susunan anatomis dan proses fisiologis yang menunjang pertumbuhan, potensi hasil dan daya adaptasi terhadap lingkungan. Sepuluh tahun terakhir (2006 s.d 2015), total bunga yang disilangkan adalah 224.248 bunga, dengan jumlah tanaman F1 sebanyak 2.451 genotipe. Kebun F1 terbangun sebanyak lima lokasi yaitu F1 HP 2000, F1 HP 2001 s.d 2005, F1 HP 2006 s.d 2009, F1 HP 2010 s.d 2012, F1 HP 2013, danF1 HP 2014, 2015.Kebun pengujian pendahuluan terbangun delapan lokasi yaitu UP/1/93, UP/2/94, UP/3/96, UP/4/98, UP/5/99, UP/6/01, UP/7/04 dan UP/8/12.Kebun pengujian lanjutan terbangun sebanyak delapan lokasi yaitu UL/14/97, UL 15/99, UL/16/99, UL/17/99, UL/18/02, UL/21/04, UL/OB/04, UL/22/05. Kebun penggujian adaptasi terbangun tiga lokasi yaitu UA/1/05, UA2/05, UA/3/10. Siklus perakitan klon unggul membutuhkan waktu yang lama (±30 tahun) dan biaya yang besar (Rp. 0,77 milyar) yaitu biaya dikebun persilangan buatan Rp. 30,5 juta, di kebun F1 Rp. 77,2 juta, di kebun pengujian pendahuluan Rp. 209,9 juta, dikebun pengujian lanjutan Rp. 219,7 juta, dan di kebun pengujian adaptasi Rp. 230,4 juta. The assembly of superior rubber clones has been continuously carried out since the 1980s at the Rubber Research Center, Sungai Putih. The assembly technique is done conventionally with natural and artificial crosses, selection, preliminary testing, follow-up testing, and adaptation testing. This assembly aims to get clones that have potential results and better agronomic properties than current clones. The superiority of a clone is determined by its genetic factors and was expressed in morphological forms, anatomical arrangements and physiological processes that support growth, production and adaptability to the environment. In the last ten years (2006 to 2015), the total number of flowers crossed was 224,248 flowers, with total F1 genotypes of 2,451. F1 Gardens were built in five locations such as F1 HP 2000, F1 HP 2001 to 2005, F1 HP 2006 to 2009, F1 HP 2010 to 2012, F1 HP 2013, and F1 HP 2014 to 2015. Preliminary testing plant were built in eight locations such as UP / 1/93, UP / 2/94, UP / 3/96, UP / 4/98, UP / 5/99, UP / 6/01, UP / 7/04 and UP / 8/12. The advanced testing plant were built in eight locations, such as UL / 14/97, UL 15/99, UL / 16/99, UL / 17/99, UL / 18/02, UL / 21/04, UL / OB / 04, UL / 22/05. Adaptation testing plant were built in three locations such as UA / 1/05, UA2 / 05, UA / 3/10. The superior clone assembly cycle requires a long time (± 30 years) and requires a large cost (Rp. 0.77 billion), consisting of Rp. 30.5 million for an artificial crossing garden, Rp. 77.2 million for F1 garden , Rp. 209.9 million for preliminary testing garden, Rp. 219.7 million for further test plantation, and Rp. 230.4 million for adaptation testing in the garden.

Background: Triamcinolone acetonide (TA) is commonly used in vitreous surgery to visualize the posterior hyaloid and internal limiting membrane. Some TA can accumulate in the macular hole during surgery which can persist postoperatively. Case: A 17-year-old boy underwent successful macular hole surgery with TA-assisted induction of posterior vitreous detachment. Sub-foveal deposit of TA was observed postoperatively, which got absorbed at 7 weeks with complete closure of the macular hole, and best corrected visual acuity improved from 20/100 preoperatively to 20/60. Conclusion: Residual TA after macular hole surgery may not hamper the anatomical and functional outcome. Similar cases have been reported in the literature and most of them show no harmful effect of TA on macular hole closure and visual recovery. Nepal J Ophthalmol 2013; 5(9):114-116 DOI: http://dx.doi.org/10.3126/nepjoph.v5i1.7837

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia due to autoantibody-mediated destruction of platelets. Multiple therapies targeting antibody production, the reticuloendothelial system and platelet production are used to treat ITP, including glucocorticoids, intravenous immune globulin (IVIG), Rituximab, splenectomy and thrombopoietin-receptor agonists. The response to therapy is heterogeneous, supporting the concept that multiple mechanisms are ultimately responsible for thrombocytopenia. In vitro complement fixation assays have shown that serum obtained from 50% of patients with ITP is able to fix complement to the platelet surface. Autoantibodies to platelet surface antigens GPIIb/IIIa and/or GPIb/IX have also been shown to activate complement via the classical pathway. We suspect that complement fixation/activation plays an important role in platelet destruction in ITP. Proposed mechanisms include C3b deposition on the platelet surface leading to opsonization, direct damage to platelets by C5b-9, and a role for complement in the imbalance in T-cell regulator/effector activity. T-cell activity has been proposed to stimulate B-cell production of autoantibodies against platelet surface antigens. C1 esterase inhibitor (C1INH) is a member of the serine protease inhibitor family and interacts with C1 esterase to block activation of the classical pathway of complement activation. Case reports have demonstrated that C1INH can prevent C3-mediated lysis of PNH erythrocytes (DeZern 2014) and attenuate hemolysis in a patient with DAT C3d positive autoimmune hemolytic anemia (Wouters 2013). Based on these data, we hypothesized 1) complement activation/deposition may play an important role in persistent thrombocytopenia in refractory ITP, and 2) blockade of the classical pathway with C1INH may lead to prolonged platelet survival. Two female patients with a history of autoimmune disease (systemic lupus erythematosus (SLE) and Sjogren's) and primary refractory ITP [steroids, IVIG, Rituximab, and Romiplostim (23-38 days)] were treated with C1INH, Berinert 20 units/kg. Within 8 hours of first C1INH dose, platelet count improved significantly in both patients. Given the rapid increase in platelet count, each patient received two additional doses of C1INH. Both patients demonstrated a continued increase in platelet count with no further C1NH therapy. In patient 1, platelet count normalized on day 63 and remains normal without additional therapy 194 days post C1INH treatment. In patient 2, platelet count has risen to 568K 14 days after C1INH administration. These cases clinically illustrate a thought provoking relationship between antigen/antibody complexes, complement activation, and platelet destruction in ITP. We suspect a potential biphasic response to C1INH therapy. We hypothesize immediate inhibition of the classical pathway and subsequent decrease of C3b deposition on platelet surface may be responsible for the acute rise in platelet count, while a reset of T-cell regulatory/effector function via complement blockade may be accountable for the longevity of platelet count increase and normalization seen in our patients. Refractory ITP may involve antibody-mediated complement activation via the classical pathway. The destruction of platelets may be driven by C3b-mediated phagocytosis and/or by C5b-9-mediated membrane damage, as well as by modulation of the immune system and T regulator cell function. In our patients, the commercially available C1INH, Berinert, was well-tolerated and platelet count improvement was noted almost immediately after administration and has appeared to be sustained. Future studies evaluating treatments that target inhibition of the complement pathway may be an effective alternative or adjunctive therapy for refractory immune thrombocytopenia. Table 1. Platelet Counts Baseline Diagnosis Prior to 1st C1NH dose 8 hours post 1st C1NH dose Prior to 2nd C1NH dose 8 hours post 2nd C1NH dose Prior to 3rd C1NH dose Post 3rd C1NH dose 7 days post 1st C1NH dose 10 days post 1st C1NH dose 14 days post 1st C1INH dose Patient 162yo F H/O SLE 160 K/UL 0 K/UL 2 K/UL 12 K/UL 5 K/UL 9 K/UL 15 K/UL 30 K/UL 38 K/UL 105/UL 139K/UL Patient 247yo F H/O Sjogren's Unknown 1 K/UL 4K/UL 8K/UL 9 K/UL 18 K/UL 18 K/UL 25 K/UL 122 K/UL 469 K/UL 568 K/UL Disclosures Off Label Use: Berinert and its use in ITP.. Broome:Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding.

1. Kostiuk O. M. Teoretyko-pravovi zasady normatyvnoho tlumachennia : avtoreferat dys. ... kand. yuryd. nauk: 12.00.01 «Teoriia ta istoriia derzhavy i prava; istoriia politychnykh i pravovykh uchen» Kostiuk Olha Mykolaivna; Ivano-Frankiv. un-t prava im. korolia Danyla Halytskoho. Ivano-Frankivsk, 2017. S. 3. 2. Rishennia Konstytutsiinoho Sudu Ukrainy vid 2 lystopada 2004 roku № 15-rp/2004. u spravi za konstytutsiinym podanniam Verkhovnoho Sudu Ukrainy shchodo vidpovidnosti Konstytutsii Ukrainy (konstytutsiinosti) polozhen statti 69 Kryminalnoho kodeksu Ukrainy (sprava pro pryznachennia sudom bilsh miakoho pokarannia) https://zakon. rada.gov.ua/laws/show/v015p710-04#Text 3. Rishennia YeSPL vid 28 zhovtnia 1999 roku u spravi «Brumaresku proty Rumunii», zaiava № 28342/95, § 61. 4. Danishevska V. Kliuchovi zasady ta pidkhody do vyrishennia konfliktiv tlumachennia zakoniv. Vzaiemni zdobutky Yevropeiskoi Komisii «Za demokratiiu cherez pravo» i orhaniv konstytutsiinoi yustytsii ta problemy tlumachennia u konstytutsiinomu sudochynstvi : zbirnyk materialiv i tez Mizhnarodnoi onlain-konferentsii (m. Kyiv, 25 chervnia 2020 r.). Kyiv: VAITE, 2020. S. 60. 5. Todyka Yu. M. Sposoby tlumachennia Konstytutsii i zakoniv Ukrainy Konstytutsiinym Sudom. Visnyk Akademii pravovykh nauk Ukrainy. Kharkiv: Pravo, 2001. № 2 (25). S. 51-59. https://dspace.nlu.edu.ua/ bitstream/123456789/4565/1/Toduka_51.pdf 6. Yevropeiska Komisiia «Za demokratiiu cherez pravo» Mirylo pravovladdia. Komentar. HLOSARII. Strasburh,18 bereznia 2016 roku. Doslidzhennia №711/2013 http://newjustice.org.ua/wp-content/uploads/2017/09/Rule_of_ Law_Checklist_UKR.pdf 7. Postanova Kasatsiinoi palaty Verkhovnoho Sudu vid 14 bereznia 2018 roku u spravi № 917/1503/17. 8. Selivanov A. O., Stryzhak A. A. Pytannia teorii konstytutsiinoho pravosuddia v Ukraini: aktualni pytannia suchasnoho rozvytku konstytutsiinoho pravosuddia. Kyiv : Lohos, 2010. 275 s. 9. Radchenko O. I. Ofitsiine tlumachennia zakonu v konteksti udoskonalennia natsionalnoho mekhanizmu zakhystu prav liudyny v Ukraini http://webcache.googleusercontent.com/search?q=cache:l3C1xwQGyHYJ:univd.edu.ua/ science-issue/issue/2996+&cd=9&hl=ru&ct=clnk&gl=ua 10. Postanova Kabinetu Ministriv Ukrainy vid 2 lypnia 2014 r. № 228 «Pro zatverdzhennia Polozhennia pro Ministerstvo yustytsii Ukrainy» https://zakon.rada.gov.ua/laws/show/228-2014-%D0%BF#Text 11. Shevchuk S. Holovna ideia pravosuddia – z bezlichi formalnostei zrobyty spravedlyve rishennia. «Iurydychna hazeta», 6 zhovtnia 2015 r. 12. Kostytskyi M., Kushakova-Kostytska N. Tlumachennia Konstytutsii ta zakoniv Ukrainy Konstytutsiinym Sudom Ukrainy ta inshymy orhanamy sudochynstva: spilnist ta vidminnist. Vzaiemni zdobutky Yevropeiskoi Komisii «Za demokratiiu cherez pravo» i orhaniv konstytutsiinoi yustytsii ta problemy tlumachennia u konstytutsiinomu sudochynstvi : zbirnyk materialiv i tez Mizhnarodnoi onlain-konferentsii (m. Kyiv, 25 chervnia 2020 r.). Kyiv :VAITE, 2020. S. 91-92. 13. Terletskyi D. Konstytutsiina skarha yak natsionalnyi zasib yurydychnoho zakhystu: yurydychni naslidky. URL: https://uplan.org.ua/analytics/konstytutsiina-skarha-iak-natsionalnyi-zasib-iurydychnoho-zakhystu-iurydychni-naslidky

This research aim to investigate the urban thermal environment profile and land cover classification in the Jakarta Metropolitan Area (JMA) in 1989 and 2013. Thermal environment conducted by installing fix point ground measurement of air temperature and land surface temperature. The land cover classification was carried out by using Landsat TM 5 and Landsat 7 ETM+ data sets. The diurnal variation of air temperature shows that Urban Heat Island (UHI) was occurring in urban and suburban JMA, which can be seen the slower cooling period in the urban area than suburban areas. Positive correlation between air temperature (Ta) and land surface temperature (Ts) on the brush (r2 = 0.78) and the asphalt surface (r2= 0.88) is clearly shown during the study. The rapid urbanization was detected during 1989 to 2013 where the urban sprawl is spread over to the whole area of JMA. Urban built up is the dominant of high increase due to years, while vegetation is decreasing.

INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR).AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function.MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun” were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used.RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a “mixed” rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR + IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease.CONCLUSION: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.

Abstract Introduction: Traditional prognostic factors for adult acute lymphocytic leukemia (ALL) include age, white blood count at diagnosis, and cytogenetic (CG) risk. We sought to identify a more detailed prognostic risk score for newly diagnosed adult patients (pts) based on these and other pre-treatment characteristics. Methods: 82 newly diagnosed ALL pts given induction chemotherapy (IC) at our institution between the years 2003-2011 were included, and data were obtained by chart review. Institutional review board approval was obtained. Variables examined included: gender, age, immunophenotype, CG risk, pre-IC body mass index (BMI), pre-IC and day 28 serum albumin, absolute lymphocyte (ALC) and neutrophil (ANC) counts, positive culture (blood or other) during IC, positive imaging suggestive of infection (during IC), and allogeneic hematopoietic cell transplant (AHCT). CG risk was ascribed by CALGB criteria (Blood 1999; 93: 3983). BMI was defined by: underweight (≤ 18.5), normal (> 18.5-25.0), overweight (> 25.0-30.0), moderately obese (> 30.0-35.0), severely obese (> 35.0-40.0), and very severely obese (> 40.0). The primary endpoint was overall survival (OS) which was measured from IC to death or last follow-up. Proportional hazards models were used for univariable and multivariable analyses. In the multivariable analysis stepwise variable selection was used to identify independent predictors. Results were internally validated using a bootstrap algorithm. For convenience measured factors were discretized using a recursive partitioning algorithm. Prognostic groups were formed by assigning “points” to each factor that were based on the magnitude of the estimated regression coefficients of the final model, and then summing the total number of points present. Results: Median age at diagnosis was 43 yrs (range 18-78); 58% male. 71% of pts (58/82) had a B-cell immunophenotype. CG risk included: normal: 15 pts (18%), high: 41 pts (50%), miscellaneous: 9 pts (11%), and unknown: 17 pts (21%). Twenty-four pts (29%) were Ph+. The majority of pts (70%: 57/82) received the CALGB 19802 regimen (Cancer 2013; 119: 90) for IC +/- a tyrosine kinase inhibitor (if they were Ph+). 27% of pts (22/ 82) received AHCT in CR1. Estimated median OS is 41.5 months (95% CI: 15.5-N/A). In univariable analysis age, pre-induction BMI, Day 28 ALC, pre- and Day 28 albumin, Day 28 ANC, Day 28 platelet count, evidence of infection, and CG risk were all seen to impact outcome. In multivariable analysis pre-IC BMI and albumin, age, and Day 28 ALC were identified as independent predictors. Assigning 1 “points” each for age >50, albumin prior to IC ≤ 3.2 g/dL, or Day 28 ALC ≤ 50 /uL and 2 points for BMI ≥ 35, 3 prognostic groups were defined: favorable (0 points) 32% of pts (26/80): estimated 5-yr OS of 68% +/-11%; intermediate (1 points) (29% of pts, 23/80): estimated 5 yr OS of 39% +/-11%, and unfavorable (≥ 2 points) (39% of pts, 31/80) with estimated 5 yr OS of 17% +/- 7% (Figure 1). Conclusion: We have constructed a simple prognostic model for newly diagnosed adults with ALL. This model will need to be validated in a larger group of uniformly treated patients. Table 1 Prognostic Factors for OS in Univariable and Multivariable Analysis Factor Univariable (HR (95% C.I.)) Multivariable (HR (95% C.I.)) Age at dx (≤50 vs. >50) 3.29 (1.80-5.99), p=.0001 2.83 (1.45-5.53), p=.002 Pre-IC BMI (<35 vs. >35) 2.95 (1.57-5.52), p=0.0008 3.88 (1.84-8.17), p=.0004 Pre-IC albumin (≥ 3.2 vs. < 3.2 g/dl) 2.61 (1.43-4.77), p=0.002 2.66 (1.33-5.30), p=.0006 Day 28 ALC (> 50/uL vs. ≤50/uL) 3.57 (1.61-7.91), p=0.002 3.11 (1.33-7.28), p=.009 CG risk 2.03 (0.98-4.22); p=0.06 ------ Day 28 albumin (>2.3 vs. ≤2.3 g/dl) 3.37 (1.66-6.83), p=0.0008 ------ Day 28 ANC (>200/uL vs. ≤200/uL) 4.51 (1.94-10.51), p=.0005 ------ Day 28 platelets (>75K/uL vs. ≤75K/uL) 2.44 (1.26-4.72), p=.008 ------ Any positive culture (no vs. yes) 2.19 (1.19-4.04), p=0.01 ------ Blood culture positive for bacteria (no vs. yes) 2.34 (1.28-4.30), p=0.006 ------ Positive imaging suggestive of infection (no vs. yes) 2.44 (1.34-4.46), p=0.004 ------ Positive blood culture and image (no vs. yes) 1.96 (1.07-3.57), p=0.03 ------ Figure 1 Prognostic Groups Figure 1. Prognostic Groups Disclosures No relevant conflicts of interest to declare.

Abstract Background: Hematopoietic stem cell release is regulated by the sympathetic nervous system through the β (3) adrenergic receptor [Mendez-Ferrer et al. Nature 2008]. Peripheral sympathetic nerve neurons express the G-CSF receptor and stimulation of peripheral sympathetic nerve neurons with G-CSF reduced norepinephrine (NE) reuptake significantly, suggesting that G-CSF potentiates the sympathetic tone by increasing NE availability [Lucas et al Blood 2012]. Based on preclinical data, we investigated the NE reuptake inhibitor desipramine in HSC mobilization. Despite augmentation with Plerixafor (CXCR4 inhibitor), 20% of all patients fail to mobilize 6*10^6 CD34 cells/kg in myeloma and the collection rate with G-CSF alone is 51.1% [Diperiso et al Blood 2012]. The cost of upfront plerixafor is $9,081 per patient while desipramine costs $40. We undertook a feasibility study of adult patients with MM undergoing autologous transplantation (ASCT) to study safety and efficacy of mobilization with desipramine and G-CSF. Patients & Methods: From 2013- 2014, 10 patients between the ages of 18-70, eligible for ASCT were enrolled. Desipramine 100mg daily was administered for 7 days, starting 4 days prior to starting G-CSF (D-3) and continue along with G-CSF for a total of 7 days. CBC and CD34 counts were determined on Day+5. If CD34 counts were > 10/ul, stem cell collection was commenced and if < 10/ul, plerixafor was added as salvage therapy. The endpoints were safety and efficacy in mobilizing CD34 cells for ASCT in patients with multiple myeloma. This trial was registered at clinicaltrials.gov as NCT01899326. Results Six of ten patients enrolled completed the protocol and underwent stem cell transplantation. Reasons for not completing were 1. Lack of insurance coverage 2. Non-compliance with study treatment 3. Disease relapse prior to ASCT. Five patients did not have any grade 3 or 4 adverse events and 1 had disease-related Grade 4 hypercalcemia and Grade 2 AKI at the time of stem cell mobilization. No patients had significant treatment related adverse effects. All 6 patients who completed the protocol achieved the target collection of 5*10^6 CD34 cells/kg. Four patients achieved 6*10^6 CD34 cells/kg or more and the remaining 2 patients achieved 5.52 and 5.92 *10^6 CD34 cells/kg respectively. Among the 6 patients, 2 patients received salvage plerixafor. The median time to achieve WBC >1000/ul, ANC >500/ul and platelets>20k was 11.5, 11, 13.5 days Table 1. Age Ind. Regimne Disease status P PB CD34/ul CD34 collected *10^6 / kg Total CD34/kg collected Engraftment (Days to) Adverse effects from desipramine D1 D2 D3 D4 D2 D3 D4 ANC >0.5 Platelets> 20k G1,G2 G3,G4 1 62 Free λ VRD VGPR N 45.8 66.0 7.01 7.01 12 13 none none 2 50 Free λ VRD VGPR N 88.0 143.5 12.22 12.22 12 12 none none 3 58 IgA VCD VGPR N 38.0 67.7 31.6 4.22 2.75 6.97 13 17 none none 4 70 IgAκ VRD VGPR Y 2.40 40.2 16.6 4.31 1.61 5.92 12 14 none none 5 56 IgGκ VCD VGPR Y 8.70 11.9 37.1 19.4 1.33 4.57 1.61 7.51 11 12 none none 6 70 IgGλ VD RD Relapse N 76.2 97.1 5.54 5.54 11 20 AKI hypercalcemia P-Plerixafor; V-Velcade; R-Lenalidomide; D-Dexamethasone; C-Cyclophosphamide Conclusions Overall G-CSF + Desipramine combination appears to be safe, well tolerated and shows signs of efficacy. G-CSF and desipramine was successful in 4/6 (66%) and all achieved the stem cell collection in 2 days or less. Desipramine, GCSF and Plerixafor was successful in all (6/6) patients to achieve a target of 5*10^6 CD34 cells/kg. The mean number of CD34 cells collected in the desipramine+ G-CSF mobilisers was 7.24*10^6 CD34 cells/kg which, based on historical data, is higher than what would be expected with G-CSF alone even though 3/4 of these patients had lenalidomide as induction therapy. Based on these results, a phase II clinical study evaluating the efficacy of G-CSF with desipramine with or without salvage plerixafor in multiple myeloma and lymphoma will be initiated. Disclosures Barta: Seattle Genetics: Research Funding.

Abstract Mobilization failure is seen in 10-15% of patients undergoing G-CSF or Chemo mobilization and the use of plerixafor is limited by its cost in developing countries. This phase II study is being undertaken to study whether the addition of Meloxicam to standard G-CSF will improve rates of mobilization (CTRI/2014/06/004671). After informed consent, patients received Meloxicam 15 mg once daily for 5 days from Day -7 to -3 and G-CSF 5 ug/kg BD from Day -4 to -1. Peripheral blood stem cell harvest was performed on Day 0 and on the following day is the initial harvest CD34 dose was < 4 x 106 CD34/Kg. Patients with myeloma proceeded immediately to an autologous transplant (auto SCT) with Single agent Melphalan conditioning while patients with lymphoma and acute myeloid leukemia had cryopreservation of harvest and then proceeded with transplant using either BEAM or BuCy2 conditioning. Between November 2013 till July 2014, 25 patients (20 males and 5 females) with a median age of 51 years (range: 25-63) received meloxicam with G-CSF. There was no toxicity in any of the patients during the 5 days of administration of meloxicam. A cell dose of > 2 x 106 CD34/kg was achieved in 21 (84%) with a cell dose of > 3 x 106 CD34/kg being achieved in a single harvest in 15 (60%). Four patients needed additional cyclophosphamide mobilization to achieve the target cell doses. Analysis of peripheral blood CD34 counts revealed that 20 (80%) had counts > 20/ul on Day 0 [median count of 65.5/ul (range: 21.1 – 313.02) and of these 15 (60%) had achieved counts of > 20/ul on Day -1 itself [median count of 45.3/ul (range: 21.4 – 130.2)]. None of the patients had toxicity related to meloxicam. Subsequently 21 patients underwent auto SCT and their data was compared with 50 age and disease matched controls who had mobilization and auto SCT at our centre between January 2013 and March 2014. Though mobilization rates and cell doses were not significantly different, the use of meloxicam and G-CSF was associated with faster neutrophil engraftment. Following auto SCT, there was lower Grade III – IV toxicity, lower transfusion requirement of red cells and reduction in the duration of hospital stay post SCT [Table 1]. Conclusion: The addition of meloxicam to G-CSF improves stem cell mobilization and is associated with faster engraftment, no additional toxicity, lower supportive care and lower duration of hospitalization. It is also potentially possible that we may be able to harvest the patients a day earlier depending upon the peripheral blood CD 34 counts achieved. This data warrants a prospective randomized trial comparing Meloxicam + G-CSF with G-CSF alone as a mobilization strategy prior to autologous stem cell transplantation. Table 1 – Comparison of demographic data, mobilization characteristics and post transplant outcome in patients using meloxicam + G-CSF compared with historical controls Abstract 2455. Table 1VariablesMeloxicam + GCSF (n = 25)G-CSF alone (n = 50)P valueMedian age (years)51 (25 – 63)50 (18 -65)0.902Sex M: F20: 536:140.577Diagnosis MM NHL/HD APML/AML15 (60%) 8 (32%) 2 (8%)32 (64%) 14 (28%) 4 (8%)Successful mobilization (> 2 x 106 CD34/kg after 2 harvets)21 (84%)42 (84%)1.000CD 34 > 5 x 106 /kg12 (48%)18 (36%)0.138CD 34 > 3 x 106/Kg20 (80%)32 (64%)0.191Conditioning regimen High dose Melphalan BEAM Bu/Cy215 (60%) 8 (32%) 2 (8%)32 (64%) 14 (28%) 4 (8%)ANC > 500/cumm (days)11.09 + 0.5311.53 + 0.920.044ANC > 1000/cumm (days)11.61 + 0.4511.95 + 0.990.216Platelet count >20000/cumm (days)14.7 + 4.516.4 + 6.30.291Platelet count >50000/cumm (days)17.4 + 7.524.7 + 19.30.143Platelet count >100000/cumm (days)23.1 + 11.951.2 + 58.20.025Number of red cell units transfused1.19 + 1.12.31 + 2.450.031Number of platelet units transfused12 + 9.117 + 160.327No of pts with Grade III-IV toxicity7/21 (31.8%)33/47 (59.5%)0.040Duration of hospital stay from day 0 (days)16 + 3.320 + 7.30.025 Disclosures Srivastava: Octapharma: Consultancy, Other.

Manas K. Ghorai of the Indian Institute of Technology, Kanpur depended (J. Org. Chem. 2013, 78, 2311) on memory of chirality during deprotonation to convert 1 to the aziridine 3. X. Peter Zhang of the University of South Florida demonstrated (Angew. Chem. Int. Ed. 2013, 52, 5309) that Co-catalyzed enantioselective aziridination is compatible with fluoro-aromatics such as 5. David M. Hodgson of the University of Oxford prepared (J. Org. Chem. 2013, 78, 1098) the azetidine 8 by double deprotonation of 7 followed by acylation. Laurel L. Schafer of the University of British Columbia assembled (Org. Lett. 2013, 15, 2182) 11 by Ta-catalyzed aminoalkylation of 10 with 9, followed by cyclization. Nicholas A. Magnus of Eli Lilly reduced (J. Org. Chem. 2013, 78, 5768) the ketone 12 to the alcohol 13 with high de and ee. Pei-Qiang Huang of Xiamen University effected (J. Org. Chem. 2013, 78, 1790) the reductive addition of 14 to 15 to give 16. The titanocene protocol reported (Angew. Chem. Int. Ed. 2013, 52, 3494) by Xiao Zheng, also of Xiamen University, effectively mediated similar transformations. En route to (–)-quinocarcin, Nobutaka Fujii and Hiroaki Ohno of Kyoto University cyclized (Chem. Eur. J. 2013, 19, 8875) 17 to 18 with high diastereoselectivity. Dipolar cycloaddition, long a workhorse of pyrrolidine synthesis, has been improved by enantioselective organocatalysis. For instance, Liu-Zhu Gong of the University of Science and Technology of China combined (Org. Lett. 2013, 15, 2676) 19, 20, and 21 to give the triester 22. Qi-Lin Zhou of Nankai University reduced (Angew. Chem. Int. Ed. 2013, 52, 6072) the tetrahydropyridine 23 to 24 in high ee. Takaaki Sato and Noritaka Chida of Keio University cyclized (Chem. Eur. J. 2013, 19, 678) the intermediate from reduction of 25 to the piperidine 26. Yasumasa Hamada of Chiba University devised (Tetrahedron Lett. 2013, 54, 1562) the rearrangement of 27 to the piperidine 28. In a synthesis of (–)-hippodamine, Shigeo Katsumura of Kwansei Gakuin University used (Org. Lett. 2013, 15, 2758) the chiral auxiliary 29 to direct the combination of 30 with 31 to give 32.