Incorporation of Aramids into Polybenzimidazoles to Achieve Ultra-High Thermoresistance and Toughening Effects.

Polybenzimidazoles (PBIs) are recognized for their remarkable thermal stability due to their unique molecular structure, which is characterized by aromaticity and rigidity. Despite their remarkable thermal attributes, their tensile properties limit their application. To improve the mechanical performance of PBIs, we made a vital modification to their molecular backbone to improve their structural flexibility. Non-π-conjugated components were introduced into PBIs by grafting meta-polyamide (MA) and para-polyamide (PA) onto PBI backbones to form the copolymers PBI-co-MA and PBI-co-PA. The results indicated that the cooperation between MA and PA significantly enhanced mechanical strain and overall toughness. Furthermore, the appropriate incorporation of aromatic polyamide components (20 mol% for MA and 15% for PA) improved thermal degradation temperatures by more than 30 °C. By investigating the copolymerization of PBIs with MA and PA, we unraveled the intricate relationships between composition, molecular structure, and material performance. These findings advance copolymer design strategies and deepen the understanding of polymer materials, offering tailored solutions that address thermal and mechanical demands across applications.

Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse.

Human arylacetamide deacetylase (AADAC) is a major esterase responsible for the hydrolysis of clinical drugs such as flutamide, phenacetin, and rifampicin. Thus, AADAC is considered to be a relevant enzyme in preclinical drug development, but there is little information about species differences with AADAC. This study investigated the species differences in the tissue distribution and enzyme activities of AADAC. In human, AADAC mRNA was highly expressed in liver and the gastrointestinal tract, followed by bladder. In rat and mouse, AADAC mRNA was expressed in liver at the highest level, followed by the gastrointestinal tract and kidney. The expression levels in rat tissues were approximately 7- and 10-fold lower than those in human and mouse tissues, respectively. To compare the catalytic efficiency of AADAC among three species, each recombinant AADAC was constructed, and enzyme activities were evaluated by normalizing with the expression levels of AADAC. Flutamide and phenacetin hydrolase activities were detected by the recombinant AADAC of all species. In flutamide hydrolysis, liver microsomes of all species showed similar catalytic efficiencies, despite the lower AADAC mRNA expression in rat liver. In phenacetin hydrolysis, rat liver microsomes showed approximately 4- to 6.5-fold lower activity than human and mouse liver microsomes. High rifampicin hydrolase activity was detected only by recombinant human AADAC and human liver and jejunum microsomes. Taken together, the results of this study clarified the species differences in the tissue distribution and enzyme activities of AADAC and facilitate our understanding of species differences in drug hydrolysis.

Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine.

Rifamycins such as rifampicin, rifabutin, and rifapentine are used for the treatment of tuberculosis and induce various drug-metabolizing enzymes. Rifamycins have been reported to be mainly deacetylated by esterase(s) expressed in human liver microsomes (HLM) to 25-deacetylrifamycins, but the responsible enzyme remained to be determined. In this study, we found that recombinant human arylacetamide deacetylase (AADAC) could efficiently deacetylate rifamycins, whereas human carboxylesterases, which are enzymes responsible for the hydrolysis of many prodrugs, showed no activity. The involvement of AADAC in the deacetylation of rifamycins in HLM was verified by the similarities of the K(m) and K(i) values and the inhibitory characteristics between recombinant AADAC and HLM. Rifamycins exhibited potent cytotoxicity to HepG2 cells, but their 25-deacetylated metabolites did not. Luciferase assay using a reporter plasmid containing CYP3A4 direct repeat 3 and everted repeat 6 motifs revealed that 25-deacetylrifamycins have lesser potency to transactivate CYP3A4 compared with the parent drugs. Supporting these results, HepG2 cells infected with a recombinant adenovirus expressing human AADAC showed low cytotoxicity and induction potency of CYP3A4 by rifamycins. In addition, CYP3A4 induction in human hepatocytes by rifamycins was increased by transfecting siRNA for human AADAC. Thus, we found that human AADAC was the enzyme responsible for the deacetylation of rifamycins and would affect the induction rate of drug-metabolizing enzymes by rifamycins and their induced hepatotoxicity.

Some biochemical and histochemical properties of human liver serine dehydratase.

In rat, serine dehydratase (SDH) is abundant in the liver and known to be a gluconeogenic enzyme, while there is little information about the biochemical property of human liver serine dehydratase because of its low content and difficulty in obtaining fresh materials. To circumvent these problems, we purified recombinant enzyme from Escherichia coli, and compared some properties between human and rat liver serine dehydratases. Edman degradation showed that the N-terminal sequence of about 75% of human serine dehydratase starts from MetSTART-Met2-Ser3- and the rest from Ser3-, whereas the N-terminus of rat enzyme begins from the second codon of MetSTART-Ala2-. The heterogeneity of the purified preparation was totally confirmed by mass spectrometry. Accordingly, this observation in part fails to follow the general rule that the first Met is not removed when the side chain of the penultimate amino acid is bulky such as Met, Arg, Lys, etc. There existed the obvious differences in the local structures between the two enzymes as revealed by limited-proteolysis experiments using trypsin and Staphylococcus aureus V8 protease. The most prominent difference was found histochemically: expression of rat liver serine dehydratase is confined to the periportal region in which many enzymes involved in gluconeogenesis and urea cycle are known to coexist, whereas human liver serine dehydratase resides predominantly in the perivenous region. These findings provide an additional support to the previous notion suggested by physiological experiments that contribution of serine dehydratase to gluconeogenesis is negligible or little in human liver.

[Long-term outcomes and complications associated with the use of a Groningen voice prosthesis].

We have been using the Groningen voice prosthesis as a method of voice restoration after total laryngectomy for approximately five years. During this period, the Groningen voice prosthesis has been used in 19 patients and a total of 125 unit replacements have been performed. No serious complications have occurred to date. Upon examination of the voice restoration results, exchange frequency, and complications, we noted that 15 out of 19 patients (78.9%) were able to maintain a good voice quality, including cases with long-term observation periods. Voice restoration was difficult in the remaining 4 cases. The overall mean exchange period was 4.5 months, with 2.5 months being the shortest exchange interval in cases without complications. The mean exchange period for cases without complications was 6.1 months. No serious complications, such as a foreign body in the trachea, were encountered. However, several problems with water leakage occurred and were managed appropriately. Aspiration pneumonia from repeated water leakage did not occur, and no cases of TE shunt closure were encountered. These problems may occur with further aging. Thorough follow-ups will be continued in the future.

BRPK, a novel protein kinase showing increased expression in mouse cancer cell lines with higher metastatic potential.

A novel protein kinase named BRPK was isolated and partially characterized. BRPK was expressed at a higher level in three carcinoma cell lines with higher metastatic potential. Mouse and human BRPK cDNAs are well conserved and encode 580 and 581 amino acids, respectively. BRPK has a serine/threonine-type protein kinase domain, and the recombinant proteins of BRPK were capable of autophosphorylation. The results of a comparative sequence analysis indicated a possible link of BRPK to BRAP2. BRAP2 is known to bind the nuclear localization signal of BRCA1. We cloned mouse BRAP2 cDNA and showed the presence of isoforms.