L-Asparaginase Loaded Inside Red Cells Has An Acceptable Tolerability Profile On Bilirubin Value

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2642-2642 ◽  
Author(s):  
Celine Plisson ◽  
Mathilde Hunault ◽  
Xavier Thomas ◽  
Thibault Legay ◽  
Yves Bertrand ◽  
...  
Keyword(s):  
Half Life ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
Principal Investigator ◽  
Red Cells ◽  
Control Group ◽  
Breakdown Product ◽  
Tolerability Profile ◽  
Major Drawback ◽  
Acceptable Tolerability Profile

Abstract L-asparaginase has been a major drug in the treatment of acute lymphoblastic leukemia (ALL) over the past decades, its efficacy has been demonstrated in a broad range of patient clinical profiles. However frequence and severity of toxicities, of which allergic reactions, have been a major drawback. L-asparaginase loaded inside homologous red cells, suspended in SAG-mannitol preservative solution, (GRASPA) is a new available formulation for administering L-asparaginase in combination with standard chemotherapy in different ALL populations, including frail patients older than 55years. Tolerability and efficacy of GRASPA in patients with ALL have been investigated in successive clinical trials (GRASPALL 2005-01 and GRASPALL/GRAALL-SA2-2008). The global toxicity of this new L-asparaginase formulation is decreased, in all age groups, with fewer hypersensitive reactions. A significant reduction of the coagulation disorders in patients <55 years old has also been reported. The pharmacokinetics is improved, with a half-life of about 30 days compared to 1 day for the free formulation. GRASPA has been proposed as a new approach to maintain the complete activity of L-asparaginase while reducing its antibody mediated toxicity. The red blood cells (RBC) act as a micro bioreactor and protect the enzyme against circulating antibodies. Plasma asparagine diffuses through the RBC membrane to the intra cellular compartment where it is cleaved by the entrapped L-asparaginase. In addition, encapsulation into RBC has been shown to extend the duration of drug action, allowing a reduction in the number of injections. Hepatic toxicity has often been reported with regular L-aparaginase associated with chemotherapy in ALL patients. Therefore this, and more specifically the occurrence of hyperbilirubinemia, with GRASPA, need to be studied. Indeed, bilirubin is a major breakdown product of hemoglobin. Hemoglobin is derived from red cells that have outlived their natural life and subsequently have been trapped inside the spleen. During splenic degradation of RBC, hemoglobin is separated from iron and cell membrane components. Hemoglobin is then transferred to the liver where it undergoes its further metabolic transformations in a process called conjugation. As the liver becomes irritated, the total bilirubin may rise and this lead to hyperbilirubinemia. GRASPA is containing a weak fraction of extracellular hemoglobin (2 g/dl maximum the day of injection), and the red cell half-life has been shown similar to that of non-processed red cells (about 30 days). We investigated in our clinical studies, whether there is any relationship between GRASPA administration and the occurrence of hyperbilirubinemia. In a first study in 12 relapsed-ALL patients <55 years old, at the dosages of 100 and 150IU/kg, we observed 1/6 case of transient hyperbilirubinemia (due to cytolysis) in the adult population and 0/6 case in the children stratum. In the same study, 1/3 adults (due to cytolysis) and 2/3 children, from the control group receiving the native E.Coli L-asparaginase, developped hyperbilirubinemia. In a non-randomised study, 27 newly diagnosed ALL patients over 55 year-old were investigated. At the same dosages, 4/27 experienced hyperbilirubinemia (including 1 with increasing bilirubinemia before treatment). These results are in accordance with data from the literature (W. Stock, 2011, leuk. & lymph.). Interestingly, GRASPA was also administrated in monotherapy in 12 patients with pancreatic carcinoma. Results showed that up to the highest dose tested (150IU/kg) all patients had normal bilirubinemia values. In conclusion, using red cells to vehicle L-asparaginase does not increase the risk of hyperbilirubimenia, and has an acceptable tolerability profile for fragile patients. Disclosures: Plisson: Orphan Europe: Employment. Hunault:ERYTECH Pharma: Principal Investigator Other. Thomas:ERYTECH Pharma: Principal Investigator Other; Orphan Europe: Consultancy. Legay:ERYTECH Pharma: Principal Investigator Other. Bertrand:ERYTECH Pharma: Principal Investigator Other. Andre:ERYTECH Pharma: clinical trial investigator Other. Godfrin:ERYTECH Pharma: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea

2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske
Keyword(s):  
Late Onset ◽  
Adult Population ◽  
Additive Models ◽  
Atopic Asthma ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Single Nucleotide ◽  
Gender And Age

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

scholarly journals PIM2 and NF-κβ gene expression in a sample of AML and ALL Egyptian patients and its relevance to response to treatment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shymaa Kamal El Din Abed El Rahman ◽  
Sanaa Sayed Abd Elshafy ◽  
Mohamed Samra ◽  
Hala Mohammed Ali ◽  
Rabab Afifi Mohamed
Keyword(s):  
Overall Survival ◽  
Acute Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Expression Level ◽  
Response To Treatment ◽  
Control Group ◽  
Poor Overall Survival ◽  
Healthy Control ◽  
Complete Blood Counts

Abstract Background The relation between PIM2 and the transcriptional factor NF κβ have been controversial in literature. The significance of PIM2 and NF-κβ genes expression on the incidence of acute leukemia (AML and ALL) and its relevance to the response rate was evaluated. Sixty de novo acute leukemia patients were stratified in 2 groups: 30 acute myeloid leukemia (AML) and 30 acute lymphoblastic leukemia (ALL) patients and compared to 30 sex- and age-matched controls. The expression level of PIM2 and NF κβ genes was measured using quantitative real-time polymerase chain reaction (QRT-PCR). The patients were followed with clinical examination and complete blood counts. Results The expression level of PIM2 gene was significantly higher in AML patients (P<0.001) compared to the control group. The mean expression level of NF κβ gene was significantly high in AML and ALL patients compared to the healthy control group (P=0.037 and P<0.001; respectively). The overall survival in AML patients was higher in NF κβ gene low expressers compared to high expressers (P=0.047). The number of AML patients who achieved complete remission was significantly higher in PIM2 gene low expressers in comparison to PIM2 gene high expressers (P=0.042). Conclusion PIM2 and NF κβ genes might have a role in the pathogenesis of acute leukemia, poor overall survival, and failure of response to induction therapy.

scholarly journals Assessment of Selected Spatio-Temporal Gait Parameters on Subjects with Pronated Foot Posture on the Basis of Measurements Using OptoGait. A Case-Control Study

Sensors ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 2805
Author(s):  
Inmaculada Requelo-Rodríguez ◽  
Aurora Castro-Méndez ◽  
Ana María Jiménez-Cebrián ◽  
María Luisa González-Elena ◽  
Inmaculada C. Palomo-Toucedo ◽  
...  
Keyword(s):  
Gait Cycle ◽  
Population Aging ◽  
Adult Population ◽  
Control Group ◽  
Cycle Duration ◽  
Foot Posture ◽  
Complex Control System ◽  
Risk Of Falls ◽  
Spatio Temporal ◽  
Asymptomatic Subjects

Walking is part of daily life and in asymptomatic subjects it is relatively easy. The physiology of walking is complex and when this complex control system fails, the risk of falls increases. As a result, gait disorders have a major impact on the older adult population and have increased in frequency as a result of population aging. Therefore, the OptoGait sensor is intended to identify gait imbalances in pronating feet to try to prevent falling and injury by compensating for it with treatments that normalize such alteration. This study is intended to assess whether spatiotemporal alterations occur in the gait cycle in a young pronating population (cases) compared to a control group (non-pronating patients) analyzed with OptoGait. Method: a total of n = 142 participants consisting of n = 70 cases (pronators) and n = 72 healthy controls were studied by means of a 30 s treadmill program with a system of 96 OptoGait LED sensors. Results: Significant differences were found between the two groups and both feet in stride length and stride time, gait cycle duration and gait cadence (in all cases p < 0.05). Conclusions: pronating foot posture alters normal gait patterns measured by OptoGait; this finding presents imbalance in gait as an underlying factor. Prevention of this alteration could be considered in relation to its relationship to the risk of falling in future investigations.

THE UPTAKE OF TRITIATED LYSINE VASOPRESSIN BY RAT AND PIG PITUITARY NEURAL LOBES IN VITRO

1971 ◽  
Vol 50 (4) ◽  
pp. 669-677 ◽  
Author(s):  
B. A. EDWARDS
Keyword(s):  
Tap Water ◽  
Exchange Chromatography ◽  
Control Group ◽  
Breakdown Product ◽  
Nacl Solution ◽  
Water Control ◽  
Neural Lobe ◽  
Lysine Vasopressin ◽  
And Control

SUMMARY Uptake of tritiated lysine vasopressin ([3H]LVP) was studied in halved neural lobes of rats (which had been given either tap water (control group) or 2% (w/v) NaCl solution as drinking water for 4 days) as well as in slices of pig neural lobe. Uptake of radioactivity into the neural lobes was shown but analysis of the extracts of incubated lobes of both species by ion exchange chromatography showed that very little of it remained in the tissue as hormone. In addition, some radioactivity was associated with trichloroacetic acid-insoluble proteins. After 90 min of incubation, and after correction for the breakdown, the uptake of unchanged [3H]LVP, expressed as a tissue: medium ratio, was 0·14 ± 0·04 and 0·09 ± 0·03 (mean ± s.e.m.) for the saline-treated and control rats respectively, while the tissue: medium ratios for the breakdown product(s) were 6·47 ± 0·45 and 5·50 ± 0·36. The results suggest uptake of [3H]LVP into the cell with almost complete intracellular breakdown of the hormone.

Quantifying Coronal Permanent Tooth Discoloration Caused by Different Pulpotomy Materials

2021 ◽  
Vol 45 (5) ◽  
pp. 306-311
Author(s):  
Hanaa Azem ◽  
Sigalit Blumer ◽  
Benjamin Peretz ◽  
Sohad Haj-Yahya ◽  
Shlomo Elbahary
Keyword(s):  
Color Space ◽  
Mineral Trioxide Aggregate ◽  
Permanent Tooth ◽  
Control Group ◽  
Major Drawback ◽  
Tooth Structure ◽  
Color Changes ◽  
Base Materials ◽  
Tooth Discoloration ◽  
Over Time

Introduction: Bioceramic materials, gray and white mineral trioxide aggregate (GMTA, WMTA), have been shown to have high rates of success in various endodontic applications. A major drawback is their tendency to discolor teeth compared to Biodentine (BD), that has been claimed not to discolor teeth. The aim of this study was to compare tooth discoloration after applying different pulpotomy base materials (BD, GMTA and WMTA). Study design: Forty human incisors teeth were used in this study. Coronal access was achieved by a Tungsten Carbide drill, and the pulp chambers were accessed and chemo-mechanically debrided. Each material was placed in the pulp chamber, up to the cervical sectioning level. All specimens were incubated at 37°C and 100% humidity for three months and have been evaluated before the study and weekly. Color was assessed according to the CIE L*a*b* color space system. Results: ΔE of all experimental groups (GMTA, WMTA and BD) were significantly different from the control group at all time points (P&lt;0.05). Color changes in the GMTA and WMTA groups, had no statistically significant differences, but showed higher discoloration compared to BD group in the cervical part of the crown, since week 1 (P&lt;0.05). WMTA group showed significant discoloration in the cervical part as of week 1 (P&lt;0.05), and gradually increased over time (Figure 2). BD group showed no significantly discoloration over time. GMTA group showed the significant discoloration at week 1 and week 14 (P&lt;0.05). Conclusions: both GMTA and WMTA pulpotomy materials may discolor tooth structure over time in an extracted permanent anterior tooth model. When choosing bioceramic pulpotomy material, BD may be preferable in esthetic area.

scholarly journals Mental health history—a contributing factor for poorer outcomes in burn survivors

2018 ◽  
Vol 6 ◽  
Author(s):  
Frank Li ◽  
Danielle Coombs
Keyword(s):  
Mental Health ◽  
Length Of Stay ◽  
Average Length ◽  
Adult Population ◽  
Total Body Surface Area ◽  
Control Group ◽  
Health History ◽  
Health Group ◽  
Burn Survivors ◽  
Mental Health History

Abstract Background A pre-morbid mental health history is common in patients with severe burn injuries. This creates challenges in providing rehabilitation. The aim of this study is to cross examine the possible impact of psychological co-morbidities on outcomes. Methods A notes audit was carried out examining patients that were admitted to Concord Hospital Burns Unit in a 3-year period (2010–2012). Patients with total body surface area (TBSA) of 20% or greater and aged between 16 and 50 years were included. Subjects were divided into a mental health group and a control group. SPSS version 21 statistic program was used for analysis the data. Results Data collected included length of stay, time to achieve independence, %TBSA, types of burns and surgery required. Results of 69 files showed that the average length of stay per %TBSA was nearly double in the patients with a mental health problem (1.47 vs 0.88). They also had a higher rate of re-graft (52% vs 22%) due to infection and poor nutrition. The average time for patients to achieve independence in daily living activity was significantly higher (p = 0.046) in the mental health group (36.2 days) versus the control group (24.1 days). Conclusion Patients with a mental health history may have poorer general health. This may result in a higher failure rate of grafting, leading to a requirement of re-graft. Hence, it took a longer time to achieve independence, as well as a longer hospital stay. A mental health history in burn survivors can be a contributing factor for poorer outcomes in the adult population.

scholarly journals Role of IL13 genetic polymorphism in the development of bronchial asthma in children

2020 ◽  
Vol 22 (5) ◽  
pp. 907-914
Author(s):  
S. Yu. Tereschenko ◽  
M. V. Smolnikova ◽  
E. V. Kasparov ◽  
E. V. Shakhtshneider ◽  
M. A. Malinchik ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Adult Population ◽  
Allergic Inflammation ◽  
Control Group ◽  
Genotype Frequencies ◽  
Gene Associations ◽  
Caucasian Origin ◽  
Online Calculator ◽  
Asthma In Children ◽  
Severity Of The Disease

Bronchial asthma is a multifactorial disease, with both environmental factors and genetic predisposal affecting its development. A number of gene associations have been obtained between polymorphisms of cytokine genes produced by different types of immune cells and asthma development. Interleukin-13 is involved in allergic inflammation, increased bronchial hypersensitivity, regulation of eosinophil levels and IgE production by B cells, thus making it promising for studying IL13 gene polymorphisms in bronchial asthma coupled to development of the disease. The aim of this study was to investigate possible association between asthma and IL13 rs1800925 polymorphism in the children of Caucasian origin in Eastern Siberia. Four groups of patients with asthma were examined (mean age 12.8±1.2 years): with a controlled (n = 95) and uncontrolled course (n = 107), with severe (n = 71) and moderate severity (n = 131) diseases. The control group consisted of healthy individuals: children (n = 33) and adults (n = 102). DNA was isolated with sorbent method; genotyping was carried out using RT-PCR using specific oligonucleotide primers and fluorescent TaqMan probes. The allele and genotype frequencies were compared by the χ-square test using an online calculator. The odds ratio (OR) with a 95% confidence interval (CI) was performed to link genetic markers with pathological phenotypes. The CT IL13 rs1800925 genotype was shown to be associated with moderate asthma and cases of uncontrollable clinical course, whereas the TT genotype was associated with severe asthma. Thus, rs1800925 polymorphism of IL13 gene (the T* variant is known to be associated with increased IL-13 expression) may be associated with bronchial asthma in children. Our data are consistent with results of other authors. E.g., Liu Z. et al. revealed an association between rs1800925 IL13 and the risk of developing asthma in children, with CT and TT genotypes being more common in the patient group. Radhakrishnan A. et al., was studied rs1800925 IL13 in adult population of Malaysia and found that the T* allele frequency in the group of patients significantly exceeds the frequency of this allele in the control group. Thus, the results of our study showed that IL13 rs1800925 polymorphism is associated with bronchial asthma in children, especially, with level of its control and severity of the disease.

scholarly journals Shortened platelet half-life in multiple myeloma

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 514-520
Author(s):  
E Fritz ◽  
H Ludwig ◽  
W Scheithauer ◽  
H Sinzinger
Keyword(s):  
Multiple Myeloma ◽  
Half Life ◽  
Serum Levels ◽  
Statistical Correlation ◽  
Control Group ◽  
Healthy Controls ◽  
Platelet Factor ◽  
Healthy Control

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

scholarly journals Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

2021 ◽  
Author(s):  
Runhong Yu ◽  
Shiwei Yang ◽  
Yufeng Liu ◽  
Zunmin Zhu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Western Blot ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Immunohistochemical Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Children ◽  
Expression Levels ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Purpose: Study was by intention to screen serum autoantibodies that may contribute to the early detection of B-cell acute lymphoblastic leukemia (B-ALL) in children.Patients and methods: The total protein from three pooled B-ALL cell lines(NALM-6, REH and BALL-1 cells) was separated using two-dimensional gel electrophoresis(2-DE), which was followed by Western blot by mixed serum from B-ALL patients (n=20) or healthy children(n=20). We obtained and analyzed the images of 2-D gel and Western blot by PDQuest software,and then identify the spots of immune responses in B-ALL samples compared with those in control samples.The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against α-enolase and voltage-dependent anion-selective channel protein 1(VDAC1) were further validated on the use of enzyme-linked immunosorbent assay(ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis.Results: Six protein dots were identified with MS as Aconitase,apoptosis-inducing factor(AIF),dihydrolipoamide dehydrogenase(DLD), α-enolase,medium-chain acyl-CoA dehydrogenase(MCAD) and VDAC 1.The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23%, respectively, which were significantly higher than those in normal controls(4% and 0). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. Conclusion: This study incidates that α-enolase and VDAC1 may be the antigen associated with B-ALL .α-enolase and VDAC1 autoantibodies may develop into potential serological markers of B-ALL in children.Other proteins also need to be confirmed in a large number of serum samples.

scholarly journals Determination of Advanced Oxidation Protein Products, E3 SUMO-Protein Ligase NSE2[NSMCE2], as a Marker to Predict Child Acute Lymphoblastic Leukemia

2014 ◽  
Vol 11 (1) ◽  
pp. 128-138 ◽  
Author(s):  
Baghdad Science Journal
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Blood Cell ◽  
White Blood Cell ◽  
Total Protein ◽  
Lymphoblastic Leukemia ◽  
Advanced Oxidation ◽  
Control Group ◽  
Advanced Oxidation Protein Products ◽  
Sumo Protein

Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow (spongy tissue in the center of bone). In ALL, too many bone marrow stem cells develop into a type of white blood cell called lymphocytes. These abnormal lymphocytes are not able to fight infection very well. The aim of this study was to investigate possible links between E3 SUMO-Protein Ligase NSE2 [NSMCE2] and increase DNA damage in the childhood patients with Acute lymphoblastic leukemia (ALL). Laboratory investigations including hemoglobin(Hb) ,white blood cell (WBC) , serum total protein , albumin ,globulin , in addition to serum total antioxidant activity (TAA) , Advanced oxidation protein products(AOPP) and E3 SUMO-Protein Ligase NSE2[NSMCE2]. Blood samples were collected from 60 patients diagnosed to Acute lymphoblastic leukemia (ALL) after one month treatment with induction therapy. Age and sex matched 30 healthy persons selected as control.serum total protein , albumin and globulin showed A significant decrease in patients group when compared to control group( P

Sign in / Sign up

Export Citation Format

Share Document