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2.
Molecules ; 28(2)2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36677563

ABSTRACT

The doping of magnesium on lithium aluminium borate phosphor is reported in this study. A solid-state sintering technique was employed as the borate samples were synthesized. This report focuses on the structural, optical, thermoluminescence, and kinetic analyses of the main glow peak. The structural properties of lithium aluminium borates improved due to the magnesium dopants used. Differences in the crystallite size and particle size were 38.85-67.35 nm and 50-60 nm, respectively, and these results were obtained from the analyzed X-ray diffractogram and scanning electron spectroscopy. The energy band gaps obtained from the direct transition of borate phosphor materials were within the range of 3.00-4.40 eV, and the doped samples gave a higher energy band gap. A decrease in the TGA (%) exhibited a weight loss or water loss for the undoped, 0.1% Mg, and 0.3% Mg-doped lithium aluminium borate materials. The glow curve measured at a heat rate of 1 °C·s-1 after irradiation to 50 Gy revealed four peaks related to the magnesium doped lithium aluminium borate. The main glow peak was observed at 86 °C. Activation energy was extracted from the main glow peak by using kinetic analysis which involves the initial rise, deconvolution, and variable heating rate approach, and it was approximately 0.67 ± 0.03 eV. A shift in the main glow peak curve from 86 to 110 °C was recognized for the magnesium-doped lithium aluminium borate when it was irradiated from 1 to 300 Gy.

3.
PLoS One ; 17(9): e0273940, 2022.
Article in English | MEDLINE | ID: mdl-36048833

ABSTRACT

BACKGROUND: Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. METHODS: Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. RESULTS: Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15). CONCLUSION: Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. CLINICAL TRIAL INFORMATION: Scientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Enalapril , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Blood Pressure/physiology , Child , Enalapril/pharmacology , Enalapril/therapeutic use , Hemodynamics , Humans , Tilt-Table Test
4.
J Exp Zool A Ecol Integr Physiol ; 337(3): 258-267, 2022 03.
Article in English | MEDLINE | ID: mdl-34843175

ABSTRACT

Fipronil is used to control pests to improve farm yield, however, indiscriminate use of fipronil has been reported to endanger crabs leading to their extinction. Therefore, this study investigated the impact of fipronil on several hematological and biochemical parameters of blue land crabs. We exposed blue land crabs to either fipronil or to a control treatment; fipronil reduced the protein content of the crab and also led to hematological and oxidative damages to the crabs' oxy-hemocyanin. Based on our results, there is need for guided use of agrochemicals such as fipronil to avoid/reduce their adverse effects on economically important species such as crabs.


Subject(s)
Brachyura , Water Pollutants , Animals , Brachyura/physiology , Pyrazoles , Water Pollutants/toxicity
5.
Sci Rep ; 11(1): 22503, 2021 Nov 18.
Article in English | MEDLINE | ID: mdl-34795300

ABSTRACT

In this study, five mathematical models were fitted in the absence of space charge with experimental data to find a more appropriate model and predict the emission current density of the graphene-based thermionic energy converter accurately. Modified Richardson Dushman model (MRDE) shows that TEC's electron emission depends on temperature, Fermi energy, work function, and coefficient of thermal expansion. Lowest Least square value of [Formula: see text] makes MRDE most suitable in modelling the emission current density of the graphene-based TEC over the other four tested models. The developed MRDE can be adopted in predicting the current emission density of two-dimensional materials and also future graphene-based TEC response.

6.
Ann Clin Transl Neurol ; 8(8): 1635-1645, 2021 08.
Article in English | MEDLINE | ID: mdl-34166574

ABSTRACT

OBJECTIVE: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). METHODS: Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations. RESULTS: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%. INTERPRETATION: These new hemodynamic criteria reliably differentiate cOH from VVS.


Subject(s)
Blood Pressure/physiology , Heart Rate/physiology , Hypotension, Orthostatic/diagnosis , Practice Guidelines as Topic , Syncope, Vasovagal/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Syncope, Vasovagal/physiopathology , Young Adult
7.
Clin Neurophysiol Pract ; 6: 16-21, 2021.
Article in English | MEDLINE | ID: mdl-33490738

ABSTRACT

OBJECTIVE: Spinal cord injury is a devastating complication after endovascular thoracic and thoracoabdominal aneurysm repair (EVAR). Motor evoked potentials (MEPs) can be monitored to detect spinal cord injury, but may also be affected by peripheral ischemia caused by femoral artery sheaths. We aimed to determine the incidence of peripheral ischemia during EVAR, and whether central and peripheral ischemia can be distinguished using compound muscle action potentials (CMAPs). METHODS: We retrospectively analyzed all EVAR procedures between March 1st 2015 and January 1st 2020 during which MEPs were monitored. Peripheral ischemia was defined as both a reduction in MEP amplitudes reversed by removing the femoral sheaths and no clinical signs of immediate post-procedural paraparesis. All other MEP decreases were defined as central ischemia. RESULTS: A significant MEP decrease occurred in 14/27 (52%) of all procedures. Simultaneous CMAP amplitude reduction was observed in 7/8 (88%) of procedures where peripheral ischemia occurred, and never in procedures with central ischemia. CONCLUSIONS: MEP reductions due to peripheral ischemia are common during EVAR. A MEP-reduction without a CMAP decrease indicates central ischemia. SIGNIFICANCE: CMAP measurements can help to distinguish central from peripheral ischemia, potentially reducing the chance of misinterpreting of MEP amplitude declines as centrally mediated, without affecting sensitivity.

8.
Nanomaterials (Basel) ; 10(8)2020 Aug 08.
Article in English | MEDLINE | ID: mdl-32784377

ABSTRACT

Nanocomposite films grown by incorporating varying concentrations of Yttrium, a d-block rare-earth ion, into the binary chalcogenide Arsenic selenide host matrix is here presented. Films were grown via the wet-chemical electro-deposition technique and characterized for structural, optical, surface morphology, and photoluminescence (PL) properties. The X-ray Diffraction (XRD) result of the host matrix (pristine film) showed films of monoclinic structure with an average grain size of 36.2 nm. The composite films, on the other hand, had both cubic YAs and tetragonal YSe structures with average size within 36.5-46.8 nm. The fairly homogeneous nano-sized films are shown by the Scanning Electron Microscopy (SEM) micrographs while the two phases of the composite films present in the XRD patterns were confirmed by the Raman shifts due to the cleavage of the As-Se host matrix and formation of new structural units. The refractive index peaked at 2.63 within 350-600 nm. The bandgap energy lies in the range of 3.84-3.95 eV with a slight decrease with increasing Y addition; while the PL spectra depict emission bands across the Vis-NIR spectral regions. Theoretically, the density functional theory (DFT) simulations provided insight into the changes induced in the structure, bonding, and electronic properties. Besides reducing the bandgap of the As2Se3, the yttrium addition has induced a lone pair p-states of Se contributing nearby to Fermi energy level. The optical constants, and structural and electronic features of the films obtained present suitable features of film for IR applications as well as in optoelectronics.

9.
Circ Res ; 127(5): e126-e138, 2020 08 14.
Article in English | MEDLINE | ID: mdl-32460687

ABSTRACT

RATIONALE: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope requires methods that reflect BP physiology accurately. OBJECTIVE: To assess the relative contributions of cardioinhibition and vasodepression to tilt-induced vasovagal syncope using novel methods. METHODS AND RESULTS: We studied the parameters determining BP, that is, stroke volume (SV), heart rate (HR), and total peripheral resistance (TPR), in 163 patients with tilt-induced vasovagal syncope documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of an HR decrease (HR) before syncope and used logarithms of SV, HR, and TPR ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined 3 stages before syncope and 2 after it based on direction changes of these parameters. The earliest BP decrease occurred 9 minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 seconds before syncope. At that time, SV had a strong negative effect on BP, TPR a lesser negative effect, while HR had increased (all P<0.001). At the onset of cardioinhibition, the median HR was at 98 bpm higher than baseline. Cardioinhibition thus initially only represented a reduction of the corrective HR increase but was nonetheless accompanied by an immediate acceleration of the ongoing BP decrease. At syncope, SV and HR contributed similarly to the BP decrease (P<0.001), while TPR did not affect BP. CONCLUSIONS: The novel methods allowed the relative effects of SV, HR, and TPR on BP to be assessed separately, although all act together. The 2 major factors lowering BP in tilt-induced vasovagal syncope were reduced SV and cardioinhibition. We suggest that the term vasodepression in reflex syncope should not be limited to reduced arterial vasoconstriction, reflected in TPR, but should also encompass venous pooling, reflected in SV.


Subject(s)
Autonomic Nervous System/physiopathology , Blood Pressure Determination , Cardiovascular System/innervation , Electrocardiography , Hemodynamics , Posture , Syncope, Vasovagal/diagnosis , Tilt-Table Test , Adult , Arterial Pressure , Female , Heart Rate , Humans , Male , Middle Aged , Predictive Value of Tests , Signal Processing, Computer-Assisted , Stroke Volume , Syncope, Vasovagal/physiopathology , Time Factors , Vascular Resistance
10.
RSC Adv ; 10(22): 13139-13148, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-35492092

ABSTRACT

Planar perovskite solar cells (PPSCs) have received great attention in recent years due to their intriguing properties, which make them a good choice for photovoltaic applications. In this work, the effect of alkali and transition metal-doped TiO2 (cesium-doped TiO2 (Cs-TiO2) and yttrium-doped TiO2 (Y-TiO2)) compact layers on the optical, structural and the photovoltaic performance of the PPSCs have been investigated. The perovskite layer syntheses were carried out by depositing a lead iodide (PbI2) layer via spin-coating; converting PbI2 into methyl ammonium iodide (CH3NH3PbI3) by chemical vapor deposition (CVD) and spin-coating at 60 min and 60 s conversion times respectively. The as-deposited PPSCs were studied layer-by-layer using an X-ray diffractometer, scanning electron microscope, and UV-vis diffuse reflectance, transmittance and absorbance. The power conversion efficiency for stable processed perovskite solar cells were 3.61% and 12.89% for air and vacuum processed, respectively.

11.
J Photochem Photobiol B ; 199: 111601, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31470270

ABSTRACT

Human pathogenic diseases are on the rampage in the list of debilitating diseases globally. The endless quest to salvage this menace through various therapies via innocuous agents is essential to overcome these drug-resistant pathogens. This study engaged a benign, facile, biocompatible, cost-effective and eco-friendly approach to synthesized iron oxide nanoparticles (FeO-NPs) via a composite of Psidium guavaja-Moringa oleifera (PMC) leaf extract to address six most debilitating bacterial strain in vitro as an antibacterial agent. Physicochemical analysis of PMC formed nanoparticles (PMC_NPs) was effectuated through Fourier Transform Infrared Spectroscopy (FT-IR), UV-Visible Spectroscopy, X-ray Diffraction Spectroscopy (XRD), Transmission Electron Microscopy (TEM), and Vibrating Sample Magnetometer (VSM). The PMC_NPs inhibited the growth of six human pathogens with higher activity at lower concentrations. It is noteworthy from our observations that, the bacterial strains show functional susceptibility to the PMC_NPs at lower concentrations compared to the orthodox antibacterial drugs. Photocatalytic degradation was observed with a decrease in the absorbance of Methylene blue dyes with the help of PMC_NPs apropos irradiation time under visible light irradiation. Consequently, PMC_NPs serve as an enhanced substitute for the orthodox antibacterial drugs in therapeutic biomedical field sequel to its pharmacodynamics against the bacterial strains at lower concentrations and also serves as a good component for water purification.


Subject(s)
Anti-Bacterial Agents/chemistry , Magnetite Nanoparticles/chemistry , Moringa oleifera/chemistry , Plant Extracts/chemistry , Psidium/chemistry , Bacteria/drug effects , Biosynthetic Pathways , Catalysis , Green Chemistry Technology/methods , Humans , Methylene Blue/chemistry , Particle Size , Photochemical Processes , Surface Properties
12.
J Hazard Mater ; 375: 281-289, 2019 08 05.
Article in English | MEDLINE | ID: mdl-31078988

ABSTRACT

Zea mays L. dry husk extract was used to bio synthesize copper oxide nanoparticles. Red coloured cubic Cu2O nanoparticles were obtained for the first time via this simple, eco- friendly, green synthesis route. The Cu2O nanoparticles were thermally oxidized to pure monoclinic CuO nanoparticles at 600 °C. The phases of the copper oxides were confirmed from the x-ray diffraction (XRD) studies. The nanoparticle sizes as obtained from high resolution transmission electron microscope (HRTEM) analysis range from 10 to 26 nm, 36-73 nm and 30-90 nm for the unannealed Cu2O, 300 °C and 600 °C annealed CuO respectively. The values of the bandgap energies obtained from diffuse reflectance of the nanoparticles are 2.0, 1.30 and 1.42 eV respectively for the unannealed, 300 °C, and 600 °C annealed copper oxide nanoparticles. The 600 °C annealed copper oxide nanoparticles showed 91% and 90% degradation ability for methylene blue dye (BM) and textile effluent (TE) respectively under visible light irradiation. While CuO_300 is more effective to inhibit the growth of Escherichia coli 518,133 and Staphylococcus aureus 9144, Cu2O is better for Pseudomonas aeruginosa and Bacillus licheniformis. The results confirm the photo-catalytic and anti-microbial effectiveness of the copper oxide nanoparticles.


Subject(s)
Anti-Bacterial Agents/metabolism , Copper/metabolism , Metal Nanoparticles , Waste Disposal, Fluid/methods , Zea mays/metabolism , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/growth & development , Catalysis , Copper/chemistry , Copper/pharmacology , Copper/radiation effects , Green Chemistry Technology , Industrial Waste , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Methylene Blue/chemistry , Photolysis , Textiles , Water Pollutants, Chemical/chemistry
13.
J Immunother Cancer ; 7(1): 16, 2019 01 21.
Article in English | MEDLINE | ID: mdl-30665463

ABSTRACT

Increasing evidence suggests that antibody-drug conjugates (ADCs) can enhance anti-tumor immunity and improve clinical outcome. Here, we elucidate the therapeutic efficacy and immune-mediated mechanisms of a novel HER2-targeting ADC bearing a potent anthracycline derivate as payload (T-PNU) in a human HER2-expressing syngeneic breast cancer model resistant to trastuzumab and ado-trastuzumab emtansine. Mechanistically, the anthracycline component of the novel ADC induced immunogenic cell death leading to exposure and secretion of danger-associated molecular signals. RNA sequencing derived immunogenomic signatures and TCRß clonotype analysis of tumor-infiltrating lymphocytes revealed a prominent role of the adaptive immune system in the regulation of T-PNU mediated anti-cancer activity. Depletion of CD8 T cells severely reduced T-PNU efficacy, thus confirming the role of cytotoxic T cells as drivers of the T-PNU mediated anti-tumor immune response. Furthermore, T-PNU therapy promoted immunological memory formation in tumor-bearing animals protecting those from tumor rechallenge. Finally, the combination of T-PNU and checkpoint inhibition, such as α-PD1, significantly enhanced tumor eradication following the treatment. In summary, a novel PNU-armed, HER2-targeting ADC elicited long-lasting immune protection in a murine orthotopic breast cancer model resistant to other HER2-directed therapies. Our findings delineate the therapeutic potential of this novel ADC payload and support its clinical development for breast cancer patients and potentially other HER2 expressing malignancies.


Subject(s)
Anthracyclines/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Immunoconjugates/therapeutic use , Mammary Neoplasms, Experimental/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Receptor, ErbB-2/antagonists & inhibitors , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Female , Humans , Immunologic Memory/drug effects , Mammary Neoplasms, Experimental/immunology , Mice, Inbred BALB C , Receptor, ErbB-2/genetics , Trastuzumab/therapeutic use
14.
Front Immunol ; 9: 2490, 2018.
Article in English | MEDLINE | ID: mdl-30450096

ABSTRACT

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) has been identified as a highly relevant tumor-associated antigen in a variety of cancer indications of high unmet medical need, including renal cell carcinoma and osteosarcoma, making it an attractive target for targeted cancer therapy. Here, we describe the de novo discovery of fully human ROR2-specific antibodies and potent antibody drug conjugates (ADCs) derived thereof by combining antibody discovery from immune libraries of human immunoglobulin transgenic animals using the Transpo-mAb mammalian cell-based IgG display platform with functional screening for internalizing antibodies using a secondary ADC assay. The discovery strategy entailed immunization of transgenic mice with the cancer antigen ROR2, harboring transgenic IgH and IgL chain gene loci with limited number of fully human V, D, and J gene segments. This was followed by recovering antibody repertoires from the immunized animals, expressing and screening them as full-length human IgG libraries by transposon-mediated display in progenitor B lymphocytes ("Transpo-mAb Display") for ROR2 binding. Individual cellular "Transpo-mAb" clones isolated by single cell sorting and capable of expressing membrane-bound as well as secreted human IgG were directly screened during antibody discovery, not only for high affinity binding to human ROR2, but also functionally as ADCs using a cytotoxicity assay with a secondary anti-human IgG-toxin-conjugate. Using this strategy, we identified and validated 12 fully human, monoclonal anti-human ROR2 antibodies with nanomolar affinities that are highly potent as ADCs and could be promising candidates for the therapy of human cancer. The screening for functional and internalizing antibodies during the early phase of antibody discovery demonstrates the utility of the mammalian cell-based Transpo-mAb Display platform to select for functional binders and as a powerful tool to improve the efficiency for the development of therapeutically relevant ADCs.


Subject(s)
Antibodies, Monoclonal, Humanized/isolation & purification , Antibodies, Monoclonal/isolation & purification , Immunoconjugates/isolation & purification , Neoplasms/therapy , Precursor Cells, B-Lymphoid/physiology , Animals , Antigens, Neoplasm/immunology , Cell Line, Tumor , Drug Evaluation, Preclinical , Humans , Immunization , Immunoconjugates/pharmacology , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Light Chains/genetics , Immunotoxins/pharmacology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neoplasms/immunology , Receptor Tyrosine Kinase-like Orphan Receptors/immunology , Single-Cell Analysis , VDJ Exons/genetics
15.
Regen Med ; 13(4): 427-441, 2018 06.
Article in English | MEDLINE | ID: mdl-29985755

ABSTRACT

AIM: This study aimed to evaluate the effect of two platelet preparations used in the clinic, pure platelet-rich plasma (P-PRP) and the supernatant of calcium-activated P-PRP (S-PRP), on the phenotype of human macrophages. MATERIALS & METHODS: Surface markers and cytokine production of human monocyte-derived macrophages were analyzed after 24 h stimulation with P-PRP or S-PRP. RESULTS: P-PRP and S-PRP present no difference in the expression of CD206, a M2 tissue-repair macrophage-related marker. However, these same macrophages presented different levels of CD163, CD86 as well as different IL-10 secretion capacities after 24 h incubation. CONCLUSION: These platelet preparations do not have an equivalent biological effect over macrophages, which suggest that they may present different clinical regenerative potentials.


Subject(s)
Antigens, CD/biosynthesis , Calcium/pharmacology , Interleukin-10/blood , Macrophages/cytology , Macrophages/metabolism , Platelet-Rich Plasma , Adolescent , Adult , Cells, Cultured , Female , Humans , Male , Middle Aged
16.
Mol Cancer Ther ; 16(5): 879-892, 2017 05.
Article in English | MEDLINE | ID: mdl-28258164

ABSTRACT

Antibody-drug conjugates (ADC) are highly potent and specific antitumor drugs, combining the specific targeting of mAbs with the potency of small-molecule toxic payloads. ADCs generated by conventional chemical conjugation yield heterogeneous mixtures with variable pharmacokinetics, stability, safety, and efficacy profiles. To address these issues, numerous site-specific conjugation technologies are currently being developed allowing the manufacturing of homogeneous ADCs with predetermined drug-to-antibody ratios. Here, we used sortase-mediated antibody conjugation (SMAC) technology to generate homogeneous ADCs based on a derivative of the highly potent anthracycline toxin PNU-159682 and a noncleavable peptide linker, using the anti-HER2 antibody trastuzumab (part of Kadcyla) and the anti-CD30 antibody cAC10 (part of Adcetris). Characterization of the resulting ADCs in vitro and in vivo showed that they were highly stable and exhibited potencies exceeding those of ADCs based on conventional tubulin-targeting payloads, such as Kadcyla and Adcetris. The data presented here suggest that such novel and highly potent ADC formats may help to increase the number of targets available to ADC approaches, by reducing the threshold levels of target expression required. Mol Cancer Ther; 16(5); 879-92. ©2017 AACR.


Subject(s)
Anthracyclines/administration & dosage , Antibodies, Monoclonal/administration & dosage , Immunoconjugates/administration & dosage , Neoplasms/drug therapy , Ado-Trastuzumab Emtansine , Aminoacyltransferases/chemistry , Animals , Anthracyclines/chemistry , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Bacterial Proteins/chemistry , Brentuximab Vedotin , Cell Line, Tumor , Cysteine Endopeptidases/chemistry , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Doxorubicin/chemistry , Humans , Immunoconjugates/chemistry , Immunoconjugates/immunology , Ki-1 Antigen/chemistry , Ki-1 Antigen/immunology , Maytansine/analogs & derivatives , Maytansine/chemistry , Maytansine/immunology , Mice , Neoplasms/immunology , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/immunology , Trastuzumab/administration & dosage , Trastuzumab/chemistry , Trastuzumab/immunology , Xenograft Model Antitumor Assays
17.
Eye (Lond) ; 31(4): 519-528, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28338667

ABSTRACT

PurposeThe purpose of the study was to investigate the outcomes of primary photodynamic therapy (PDT) for small pigmented posterior pole choroidal melanoma.Patients and methodsProspective interventional consecutive case series of 15 patients with small pigmented posterior pole choroidal melanoma, who were treated with three sessions of PDT and followed-up thereafter. Risk factors for failure were assessed and outcome measures at presentation were compared to those at last follow-up visit.ResultsTumor control was achieved in 12 (80%) patients in a median follow-up time of 15 months (mean 14, range 8-18). Three patients failed treatment, diagnosed in a median time of 5 months (mean 4, range 3-6), after first PDT. In all failed cases, lesions were 100% pigmented; de novo melanoma rather than transformed nevi and showed a radial growth pattern rather than increased thickness. All failed cases were subsequently successfully treated with radiotherapy. In this cohort, subretinal fluid (SRF) was significantly reduced (P<0.001), vision did not deteriorate (P=0.11) and even improved in patients with subfoveal SRF at presentation (P=0.018), tumor height significantly decreased (P=0.037) and no complications were recorded.ConclusionPrimary PDT was found to be a safe and efficient treatment modality for small pigmented posterior pole choroidal melanoma, achieving short-term tumor control in 80% of patients. PDT offers patients the opportunity to preserve vision by avoiding the retinopathy associated with conventional radiation treatments for choroidal melanoma. However, the long-term local control of these tumors remains uncertain.


Subject(s)
Choroid Neoplasms/drug therapy , Melanoma/drug therapy , Photochemotherapy , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Adult , Aged , Aged, 80 and over , Choroid Neoplasms/pathology , Female , Fluorescein Angiography , Follow-Up Studies , Humans , Male , Melanoma/pathology , Middle Aged , Outcome Assessment, Health Care , Prospective Studies , Treatment Outcome , United Kingdom , Verteporfin , Visual Acuity
18.
MAbs ; 8(4): 726-40, 2016.
Article in English | MEDLINE | ID: mdl-26986818

ABSTRACT

In vitro antibody display and screening technologies geared toward the discovery and engineering of clinically applicable antibodies have evolved from screening artificial antibody formats, powered by microbial display technologies, to screening of natural, full-IgG molecules expressed in mammalian cells to readily yield lead antibodies with favorable properties in production and clinical applications. Here, we report the development and characterization of a novel, next-generation mammalian cell-based antibody display and screening platform called Transpo-mAb Display, offering straightforward and efficient generation of cellular libraries by using non-viral transposition technology to obtain stable antibody expression. Because Transpo-mAb Display uses DNA-transposable vectors with substantial cargo capacity, genomic antibody heavy chain expression constructs can be utilized that undergo the natural switch from membrane bound to secreted antibody expression in B cells by way of alternative splicing of Ig-heavy chain transcripts from the same genomic expression cassette. We demonstrate that stably transposed cells co-express transmembrane and secreted antibodies at levels comparable to those provided by dedicated constructs for secreted and membrane-associated IgGs. This unique feature expedites the screening and antibody characterization process by obviating the need for intermediate sequencing and re-cloning of individual antibody clones into separate expression vectors for functional screening purposes. In a series of proof-of-concept experiments, we demonstrate the seamless integration of antibody discovery with functional screening for various antibody properties, including binding affinity and suitability for preparation of antibody-drug conjugates.


Subject(s)
Antibodies, Monoclonal/analysis , Cell Surface Display Techniques/methods , High-Throughput Screening Assays/methods , Immunoglobulin G/analysis , Animals , DNA Transposable Elements , Drug Evaluation, Preclinical/methods , Genetic Vectors , Humans
19.
Int J Med Chem ; 2014: 735602, 2014.
Article in English | MEDLINE | ID: mdl-25505991

ABSTRACT

Iron (III) complexes of ciprofloxacin, amoxicillin, and cloxacillin were synthesized and their aqueous solubility profiles, relative stabilities, and antimicrobial properties were evaluated. The complexes showed improved aqueous solubility when compared to the corresponding ligands. Relative thermal and acid stabilities were determined spectrophotometrically and the results showed that the complexes have enhanced thermal and acid stabilities when compared to the pure ligands. Antimicrobial studies showed that the complexes have decreased activities against most of the tested microorganisms. Ciprofloxacin complex, however, showed almost the same activity as the corresponding ligand. Job's method of continuous variation suggested 1 : 2 metals to ligand stoichiometry for ciprofloxacin complex but 1 : 1 for cloxacillin complex.

20.
CCH, Correo cient. Holguín ; 18(2): 363-371, abr.-jun. 2014. ilus
Article in Spanish | LILACS | ID: lil-714385

ABSTRACT

El síndrome de Brugada es una manifestación clínico-electrocardiográfica caracterizada por una mutación de los canales de sodio cardíaco, más frecuente en varones. La clínica se caracteriza por episodios sincopales a repetición o de muerte súbita, en pacientes sin cardiopatía estructural evidente. El patrón típico se caracteriza por una imagen de bloqueo de rama derecha con elevación del ST de V1 a V3 y T negativa. Es vital el diagnóstico de este síndrome porque sin tratamiento la incidencia de muerte súbita es muy alta; es la implantación de un desfibrilador automático el único tratamiento útil. Se reporta el caso de una mujer de 32 años atendida por episodios presincopales recurrentes, con electrocardiogramas iniciales normales, patrón de Brugada tipo I oculto o intermitente, test de procainamida positivo y estudio electrofisiológico negativo, a la cual se le implantó un cardioversor desfibrilador automático.


Brugada syndrome is a clinical-electrocardiographic manifestation characterized by a mutation of the cardiac sodium channel, more common in males, that is characterized by recurrent episodes of syncope and sudden death in patients without apparent structural heart disease. The typical pattern is characterized by an image of right bundle branch block with ST elevation in V1 to V3 and T negative. It is vital to the diagnosis of this syndrome because without treatment the incidence of sudden death is very high, the implantation of an automatic defibrillator is the only useful treatment. A young woman aged 32 attended by recurrent presyncopal episodes was reported in this article. The patient presented normal baseline electrocardiograms, with hidden or intermittent pattern of Brugada type I. The procainamide test was positive and electrophysiological study was negative, a cardioverter defibrillator was implanted.

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