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1.
Materials (Basel) ; 15(6)2022 Mar 16.
Article in English | MEDLINE | ID: mdl-35329644

ABSTRACT

This study focused on the vibrating fluidized-bed-type powder feeder used in HVAF thermal spraying equipment. This feeder has been used in thermal spraying equipment and industrial applications. However, particulate materials' flow mechanism and stable transport characteristics have not been fully understood. This study experimentally investigated the fluidization characteristics, powder dispersion state, and powder transportation characteristics of Al2O3 particles during vertical vibration fluidization. The material used was Al2O3 particles of 2.9 µm and 3808 kg/m3, classified as the group C particles in the Geldart diagram. As experimental conditions, the fluidized air velocity to the bottom of the powder bed and the vibration intensity in the vertical direction changed. The critical fluidization air velocity was defined to evaluate the generating powder flow by vertical vibrating fluidization. As a result, good fluidization of the powder bed of Al2O3 was obtained by the vertical vibration, as well as an airflow that was higher than the critical fluidization air velocity. Regarding powder transportation characteristics, it was clarified that the fluidized air velocity at the bottom of the powder dispersion vessel and the pressure difference from the powder dispersion vessel to the transportation part significantly affect the mass flow rate.

2.
JCI Insight ; 4(8)2019 04 18.
Article in English | MEDLINE | ID: mdl-30996138

ABSTRACT

Biased agonism is a paradigm that may explain the selective activation of a signaling pathway via a GPCR that activates multiple signals. The autoantibody-induced inactivation of the calcium-sensing receptor (CaSR) causes acquired hypocalciuric hypercalcemia (AHH). Here, we describe an instructive case of AHH in which severe hypercalcemia was accompanied by an increased CaSR antibody titer. These autoantibodies operated as biased allosteric modulators of CaSR by targeting its Venus flytrap domain near the Ca2+-binding site. A positive allosteric modulator of CaSR, cinacalcet, which targets its transmembrane domain, overcame this autoantibody effect and successfully corrected the hypercalcemia in this patient. Hence, this is the first study to our knowledge that identifies the interaction site of a disease-causing GPCR autoantibody working as its biased allosteric modulator and demonstrates that cinacalcet can correct the AHH autoantibody effects both in vitro and in our AHH patient. Our observations provide potentially new insights into how biased agonism works and how to design a biased allosteric modulator of a GPCR. Our observations also indicate that the diagnosis of AHH is important because the severity of hypercalcemia may become fatal if the autoantibody titer increases. Calcimimetics may serve as good treatment options for some patients with severe AHH.


Subject(s)
Autoantibodies/metabolism , Calcium-Regulating Hormones and Agents/administration & dosage , Cinacalcet/administration & dosage , Hypercalcemia/drug therapy , Receptors, Calcium-Sensing/metabolism , Aged, 80 and over , Allosteric Regulation/drug effects , Autoantibodies/immunology , Autoantigens/immunology , Binding Sites/drug effects , Calcium/blood , Calcium/metabolism , HEK293 Cells , Humans , Hypercalcemia/blood , Hypercalcemia/diagnosis , Hypercalcemia/immunology , Male , Receptors, Calcium-Sensing/immunology , Receptors, G-Protein-Coupled/immunology , Severity of Illness Index , Signal Transduction/drug effects , Signal Transduction/immunology , Treatment Outcome
3.
Clin Endocrinol (Oxf) ; 91(1): 195-200, 2019 07.
Article in English | MEDLINE | ID: mdl-30903705

ABSTRACT

OBJECTIVE: Central hypothyroidism (CH) is a well-known adverse effect of bexarotene treatment for cutaneous T-cell lymphoma (CTCL). While concomitant levothyroxine therapy is recommended in these cases, associations between ethnic variation or susceptibility and bexarotene-induced CH have not yet been reported. This study aimed to characterize the kinetics and dose dependency of bexarotene-induced CH in Japanese patients. DESIGN AND PATIENTS: Sixty-six Japanese patients with CTCL were retrospectively investigated by evaluating thyroid function during the early phase of bexarotene therapy. RESULTS: At one week after bexarotene initiation, TSH and FT4 values significantly declined. However, this effect was not bexarotene dose-dependent at least at the dose of 96-320 mg/m2 . Approximately 1 month later, 61 patients exhibited hypothyroidism at a relatively low dose of bexarotene (average 251 mg/m2 /day). Forty-five study cases showed this effect at 1 week. Simple regression analyses indicated that higher pretreatment TSH values (at a cut-off value of 1.30:73% sensitivity, 57% specificity) or lower normal (within the lower half of the reference range) pretreatment FT4 values (84% sensitivity, 57% specificity) were predictive of hypothyroidism at 1 week. The remaining 21 cases showed euthyroidism at 1 week, at which TSH values may roughly predict their thyroid function at 1 month (at a cut-off value of 0.05:100% sensitivity, 80% specificity). CONCLUSIONS: Preventive treatment with levothyroxine is recommended for Japanese CTCL patients prior to bexarotene therapy. Minimally, it should be considered for patients with a pretreatment TSH above 1.30, a lower normal pretreatment FT4, or a TSH below 0.05 at 1 week.


Subject(s)
Bexarotene/adverse effects , Hypothyroidism/chemically induced , Adult , Aged , Aged, 80 and over , Bexarotene/therapeutic use , Female , Humans , Hypothyroidism/blood , Lymphoma, T-Cell, Cutaneous/blood , Lymphoma, T-Cell, Cutaneous/drug therapy , Male , Middle Aged , Regression Analysis , Retrospective Studies , Thyrotropin/blood , Thyroxine/blood
4.
Analyst ; 137(14): 3238-41, 2012 Jul 21.
Article in English | MEDLINE | ID: mdl-22645735

ABSTRACT

The J-aggregate of diprotonated tetraphenylporphyrin (H(4)TPP(2+)) formed at the dodecane-water interface showed circular dichroism spectra corresponding to the chirality of 2-alkyl alcohols, longer than 2-butanol, added to the dodecane phase. The phenomenon suggested the preferential interaction between the nano-sized J-aggregates and the chiral alcohols at the interface, and provided a potential use of the J-nanoaggregate as a chiral recognition probe.


Subject(s)
Alcohols/chemistry , Alkanes/chemistry , Nanostructures/chemistry , Porphyrins/chemistry , Absorption , Protons , Stereoisomerism
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