Study of the Kinetics of the Thyroid Hormones and the Peripheral Conversion Rate of Thyroxine to Triiodothyronine in Acute Renal Insufficiency under Experimental Conditions

1980 ◽  
Vol 12 (10) ◽  
pp. 529-536 ◽  
Author(s):  
F. Pablo-Dávila ◽  
J. Miralles-García ◽  
E. Hernández-Miguel ◽  
C. Iglesias ◽  
J. Corrales-Hernández ◽  
...  
Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1003
Author(s):  
Michiaki Matsumoto ◽  
Tadashi Hano

The non-enzymatic synthesis of N-benzyloxycarbonyl-L-phenylalanyl-L-leucine (Cbz-Phe-Leu) from lipophilic N-benzyloxycarbonyl-L-phenylalanine (Cbz-Phe) and hydrophilic L-leucine (Leu), by N, N’-dicyclohexylcarbodiimide (DCC) as a condensing agent, was carried out using a reversed micellar system composed of bis(2-ethylhexyl) sodium sulfosuccinate (AOT) as a surfactant and isooctane. We successfully synthesized Cbz-Phe-Leu in a short time and investigated the effects of its operational conditions, the DCC concentration, w0, and the pH on the kinetic parameters and the maximum yields. For dipeptide synthesis, we had to add an excess of DCC with the substrates because of the side reactions of Cbz-Phe. From the pH dependency of the reactivity, a partially cationic form of Leu was better for a synthesis reaction because of the enrichment of Leu at the interface by anionic AOT. The optimum water content on the dipeptide synthesis was w0 = 28 due to the competition of the peptide synthesis and the side reactions. The maximum yield of Cbz-Phe-Leu was 0.565 at 80 h under optimum experimental conditions.


1976 ◽  
Vol 49 (4) ◽  
pp. 937-959 ◽  
Author(s):  
S. Cesca ◽  
M. Bruzzone ◽  
A. Priola ◽  
G. Ferraris ◽  
P. Giusti

Abstract New catalyst systems based on alkylaluminum derivatives and halogen or interhalogen compounds were found highly efficient in the synthesis of high-molecular-weight IIR at temperatures above − 50°C. The reaction mechanism was studied in detail for the system Et2AlCl + Cl2. The reactions occurring between chlorine, isobutene, Et2AlCl, and the solvent (CH3Cl) were elucidated and studied under various experimental conditions (e.g. presence or absence of light, simultaneous presence of the copolymerization system components, temperature, type of halogen, use of model compound of isobutene). It was concluded that halogenium ions, i.e. Cl+, Br+, or I+, are the initiating species. Kinetic and conductometric investigations showed that scarcely dissociated ion pairs, e.g. Cl+[Et2AlCl2]−, were formed in the absence of monomer; but in the presence of isobutene, a noticeable increase of the electrical conductivity and rapid polymerization occurred. The maximum polymerization rate was first order with respect to the concentrations of monomer, Cl2, and Et2AlCl. In the homopolymerization of isobutene, transfer to monomer and termination reactions were negligible. The MW of IIR was found to be mainly dependent on the concentrations of the catalyst components, on isoprene concentration, and on temperature. The reactivity ratio of isobutene with isoprene was found to be r1=2.5±0.5 at −35°C, while the activation energies relative to MW were −5.8 ± 0.4, kcal/mol for polyisobutene, and −5.7 ± 0.7 and − 4.3 ± 0.5 kcal/mol for IIR containing, respectively, 1.3 and 1.9 mol% of isoprene. The evaluation of some physicochemical and technological properties of typical IIR produced with the system Et2AlCl + Cl2, indicated that isoprene is randomly distributed along the chains and that the MWD is monomodal, while the glass transition temperature, tensile properties, mechanical-dynamic spectra, and kinetics of vulcanization are very similar to those of commercial IIR. Very preliminary data, referring to several classes of new catalyst systems yielding IIR having good properties, were also obtained. The syncatalyst systems here described can work in a homogeneous phase consisting of an aliphatic hydrocarbon besides methyl chloride, still giving IIR with high MW. Therefore, a completely homogeneous process can be envisioned for the synthesis of IIR at −50°C thus avoiding a great part of the fouling problems of the slurry process. The economic advantage of using “high” temperatures of polymerization is briefly discussed in terms of energy savings.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2518-2518
Author(s):  
Thorsten Oliver Goetze ◽  
Daniel Wilhelm Mueller ◽  
Mohammad-Reza Rafiyan ◽  
Dragan Kiselicki ◽  
Timursah Habibzade ◽  
...  

2518 Background: Stratum D of the INSIGHT platform trial evaluates s.c. eftilagimod alpha (efti, IMP321) combined with avelumab in advanced solid tumors. Efti is an MHC class II agonist which activates antigen-presenting cells followed by CD8 T-cell activation. Combination with PD-1/PD-L1 blockade aims at enhanced efficacy. Methods: This IIT platform trial consists of 5 strata: intratumoral (A) or intraperitoneal efti (B); s.c. efti with SOC (C) or with PD-L1 inhibition (D). Strat E is currently under development and starts soon with a new efti combination. This abstract focuses on preliminary data of Strat D. Patients (pts) received 800mg avelumab i.v. q2w along with s.c. efti: 6mg in cohort 1 (coh 1, 6 pts), 30mg in cohort 2 (coh 2, 6 pts). Primary endpoint: safety. Results: Recruitment has been completed with 12 pts (coh 1: gastric, gallbladder, colon cancer, pleural mesothelioma; coh 2: gastric, gastroesophageal, anal, rectum, cervix uteri). No dose limiting toxicities (DLTs) occurred. 10 serious adverse events (SAEs) were reported, none of them considered causally related (4 in 3 pts of coh 1 [1 acute renal insufficiency grade 5 in 1 pt, 2 preileus grade 3 in 1 pt, hearing impaired grade 4 in 1 pt] and 6 in 4 pts of coh 2 [1 anal hemorrhage and 1 gallbladder obstruction in 1 pt, 1 eye pain and 1 surgery to replace the feeding tube in 1 pt, each grade 3, 1 skin infection grade 2, 1 diffuse myocardial fibrosis grade 5]. 1 AE of special interest (AESI) possibly related with avelumab (sarcoidosis grade 1) occurred in coh 1. 2 pts completed max treatment duration with 24 cycles. In coh 1, 47 adverse events (AEs; grade 1-2, 29; grade 3, 14; grade 4, 3; grade 5, 1) occurred in 5 pts. Most common grade 1-2 AEs were nausea, pain in 33%, 33% of the pts. Most common grade 3 AEs were ileus, vomiting in 33%, 33% of the pts. 2 AEs grade 4 (hearing impaired, sepsis) and 1 AE grade 5 (acute renal insufficiency) were reported. All AEs grade 3-5 were considered causally unrelated. In coh 2, 51 adverse events (AEs; grade 1-2, 29; grade 3, 19; grade 4, 2; grade 5, 1) occurred in 5 pts. The most common grade 1-2 AE was hypothyroidism in 33% of the pts. 1 AE grade 5 (diffuse myocardial fibrosis) was reported. Only 1 AE grade 3-5 was considered causally related (urinary tract infection grade 3 related with avelumab). 5 pts showed partial response as best response (2 coh 1: colon, pleural mesothelioma; 3 coh 2: gastric, anal, cervical), 1 stable disease with clinical progression (coh 2) (all but one of these pts still alive), 5 disease progressions acc. to RECIST 1.1 (3 coh 1, 2 coh 2), 1 clinical progression (coh 1). Signals of activity were also observed in pre-treated MSS/PD-L1low pts. Conclusions: Combined treatment with avelumab 800mg and efti 6mg (coh 1) or 30 mg efti (coh 2) seems feasible and safe. No unexpected AEs occurred. Signals of efficacy with CPI combination were seen (DCR 50%). Clinical trial information: NCT03252938.


1999 ◽  
Vol 92 (11) ◽  
pp. 1093-1094 ◽  
Author(s):  
ANTHONY F. LAWSON ◽  
PHILLIP A. GREEN ◽  
ALLAN S. BRETT

2005 ◽  
Vol 475-479 ◽  
pp. 1137-1140
Author(s):  
Lili Zhao ◽  
Feng Gao ◽  
Wei Min Wang ◽  
Chang Sheng Tian

The oriented 0.67Pb (Mg1/3Nb2/3)O3-0.33PbTiO3 (PMNT) polycrystals were prepared by the conventional ceramic technique and the templated grain growth method adding excess PbO in the matrix. Kinetics of the development of oriented structure was investigated systemically. In the presence of PbO liquid phase, the oriented PMNT polycrystals mainly grow by the dissolution-precipitation mechanism. The diffusion is determined by the sintering temperature and the PbO-excess content in the matrix. The thickness of oriented PMNT polycrystals displays a t1/3 dependence, which is characteristic of diffusion-controlled growth. For the thicker oriented structure, 20% excess PbO in the PMNT matrix and 1150oC for 10h are the proper experimental conditions. Moreover, the addition of PbO in the matrix hardly affects the final composition of ceramic matrix.


2013 ◽  
Vol 26 (1) ◽  
pp. 37-48 ◽  
Author(s):  
S.M. Nanjundaiah ◽  
J.P. Stains ◽  
K.D. Moudgil

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, bone erosion, and cartilage destruction in the joints. It is increasingly being realized that inflammation might play an important role in inducing bone damage in arthritis. However, there is limited validation of this concept in vivo in well-controlled experimental conditions. We addressed this issue using the adjuvant arthritis (AA) model of RA. In AA, the draining lymph nodes are the main sites of activation of pathogenic leukocytes, which then migrate into the joints leading to the induction of arthritis. We tested the temporal kinetics of mediators of bone damage [e.g., receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteopontin (OPN)] and inflammation (pro-inflammatory cytokines and chemokines) in the draining lymph node cells (LNC) at different phases of AA, and then examined their inter-relationships. Our study revealed that, together with cytokines/chemokines, some of the mediators of bone remodeling are also produced in LNC. Various cytokines/chemokines showed distinct kinetics of expression as well as patterns of correlation with mediators of bone remodeling at different phases of the disease. Pro-inflammatory cytokines such as TNF-α are known to play an important role in bone damage. Interestingly, there was a positive correlation between TNF-α and RANKL, between RANKL and each of the 3 chemokines tested (RANTES, MIP-1α, and GRO/KC), and between TNF-α and RANTES. Our results in the AA model lend support to the concept of osteo-immune crosstalk during the course of autoimmune arthritis.


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