scholarly journals Spontaneous Production of Glutathione-Conjugated Forms of 1,2-Dichloropropane: Comparative Study on Metabolic Activation Processes of Dihaloalkanes Associated with Occupational Cholangiocarcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Toyoda ◽  
Tappei Takada ◽  
Hiroshi Suzuki

Recently, epidemiological studies revealed a positive relationship between an outbreak of occupational cholangiocarcinoma and exposure to organic solvents containing 1,2-dichloropropane (1,2-DCP). In 1,2-DCP-administered animal models, we previously found biliary excretion of potentially oncogenic metabolites consisting of glutathione- (GSH-) conjugated forms of 1,2-DCP (GS-DCPs); however, the GS-DCP production pathway remains unknown. To enhance the understanding of 1,2-DCP-related risks to human health, we examined the reactivity of GSH with 1,2-DCP in vitro and compared it to that with dichloromethane (DCM), the other putative substance responsible for occupational cholangiocarcinoma. Our results showed that 1,2-DCP was spontaneously conjugated with GSH, whereas this spontaneous reaction was hardly detected between DCM and GSH. Further analysis revealed that glutathione S-transferase theta 1 (GSTT1) exhibited less effect on the 1,2-DCP reaction as compared with that observed for DCM. Although GSTT1-mediated bioactivation of dihaloalkanes could be a plausible explanation for the production of reactive metabolites related to carcinogenesis based on previous studies, this catalytic pathway might not mainly contribute to 1,2-DCP-related occupational cholangiocarcinoma. Considering the higher catalytic activity of GSTT1 on DCM as compared with that on 1,2-DCP, our findings suggested differences in the activation processes associated with 1,2-DCP and DCM metabolism.

2021 ◽  
Author(s):  
Yingying Xu ◽  
Yuchen Li ◽  
Han Zhang ◽  
Jinglei Nie ◽  
Jie Ren ◽  
...  

H-protein, one of the four component proteins (H, T, P and L) of glycine cleavage system (GCS), is generally considered a shuttle protein interacting with the other three GCS-proteins via a lipoyl swinging arm. We report that without P-, T- and L-proteins, lipoylated H-protein (Hlip) enables GCS reactions in both glycine cleavage and synthesis directions in vitro. This apparent catalytic activity is closely related to the cavity on the H-protein surface where the lipoyl arm is attached. Heating or mutation of selected residues in the cavity destroys or reduces the stand-alone activity of Hlip, which can be restored by adding the other three GCS-proteins. Systematic study of the Hlip-catalyzed overall GCS reactions and the individual reaction steps provides a first step towards understanding the stand-alone function of Hlip. The results in this work provide some inspiration for further understanding the mechanism of the GCS and give some interesting implications on the evolution of the GCS.


2020 ◽  
Vol 51 (Special) ◽  
Author(s):  
Ali & Saleh

This study was designed to study the capacitation of caudal spermatozoa in vitro by different levels of heparin, estrogen for in vitro fertilization (IVF) in the Iraqi local sheep. Results of sperm capcitation (massive motility percentage) by applying three levels of heparin (50, 100, 150) IU in relation to breeding season showed no significant differences during breeding season with the three levels, which were (82.23 ± 0.58), While results by applying the higher level of heparin (150) IU out of breeding season showed significantly (P<0.05) more and active motility Which were (62.07 ± 0.62) than the other levels (56.85 ± 0.61). At the same time applications result of three estrogen levels (20, 40, 60) mg on sperm capcitation showed Positive relationship between concentrations and (massive motility percentage), which showed the highest concentration gave the best results during and out of breeding season (87.20 ± 0.60) and (65.86 ± 0.62) respectively. with significant differences (P<0.05) between the three levels. While the results of the in vitro fertilization (IVF) index which reflected the sperm capcitation were recorded with the highest estrogen concentration during breeding season (22.70 %) compared with the best heparin level (20 %) while she was (10.45 %), (8.70 %) out of breeding season Sequentially, in which the highest estrogen concentration gives a best capacitation and IVF index level compared with the high heparin level over the year.


Author(s):  
Riccardo Oggiano ◽  
Andrea Pisano ◽  
Angela Sabalic ◽  
Cristiano Farace ◽  
Grazia Fenu ◽  
...  

AbstractThe present review represents an update about the knowledge of the possible role of Cadmium (Cd) in amyotrophic lateral sclerosis (ALS) initiation and its progression. ALS is a neurodegenerative disease that occurs in adulthood; its etiology is unknown and leads to death within a few years from its appearance. Among the various possible causes that can favor the development of the disease, heavy metals cannot be excluded. Cadmium is a heavy metal that does not play a biological role, but its neurotoxicity is well known. Numerous in vitro studies on cell and animal models confirm the toxicity of the metal on the nervous system, but these data are not accompanied by an epidemiological evidence, and, thus, an unclear correlation between Cd and the onset of the disease can be pointed out. On the other hand, a possible multifactorial and synergic mechanism in which Cd may have a role can explain the ALS onset. More efforts in new clinical, biochemical, and epidemiological studies are necessary to better elucidate the involvement of Cd in this lethal disease.


1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.


2014 ◽  
Vol 1 (1) ◽  
pp. 47-56
Author(s):  
Milan Palat

Bu çalışmanın amacı, Türkiye’den göç ve Almanya’nın ekonomik göstergeleri arasındaki ilişkiyi, nicel metot yöntemleri kullanarak değerlendirmektir. Türkiye’nin belirsiz Avrupa ile bütünleşme beklentilerine rağmen  Avrupa Birliğinin köklü üyelerine olan Türk göçü devam edecektir. Çok sayıda Türk azınlığın yaşadığı ve hayat standartlarının yüksek olduğu Almanya, Hollanda ve Fransa’ya  büyük bir göç dalgası gerçekleşebilir. Çalışmanın istatistiksel bölümünün sonuçları, toplam göç ile gayri safi yurtiçi hasıladaki büyüme arasında pozitif, toplam göç ile işsizlik arasındaki negatif ve tahmin edilen bağımlılık yönüyle uygunluk içerisinde olan toplam göç ile aylık gelir arasında pozitif ilişki olduğunu göstermektedir. Türkiye’den göçle işsizlik arasındaki ilişki, toplam göçle olan ilişkiden daha düşüktür. Ancak, Almanya’daki yabancı mevcudiyeti ile Türkiye’den göç arasında bir ilişki bulunmaktadır. Bu durum, var olan göçmen topluluğunun olduğu yerin, yeni göçmenleri, köken bağlarına dayanarak cezbetmesi ve maliyet- riskler sebebiyle göçün düşük seviye de olduğuna dayanan kuramsal Ağ teorisi görüşü ile uygunluk göstermektedir. Göç ve işsizlik arasında gözlenen ilişki, Almanya’ya göçün  işgücü piyasasında talepte meydana gelen değişime karşılık geldiği gerçeğini göstermektedir. İşsizlik ve göç olgularının meydana geliş zamanlarında bir aralık  olsa bile  göç, Alman emek pazarında var olan dengesizliklerin azaltılmasında nispeten etkili bir mekanizma gibi görünmektedir. ENGLISH TITLE & ABSTRACTTurkish Immigration to the European Union: The Case of GermanyThe objective of the paper was to evaluate the relationships between immigration from Turkey and economic indicators in Germany using  quantitative methods. Despite Turkey’s unclear European integration prospects, it is predicted that Turkish immigration to  established member countries of the EU will continue. The strongest waves may flow to Germany, Netherlands or France, where numerous Turkish minorities are already present and where the living standards are high. Results from the statistical analysis of the paper showed a positive correlation between immigration total and the growth of gross domestic product. On the other hand, a negative correlation of immigration total and unemployment was found and a positive relationship between immigration total and income total which is in agreement with the expected dependency direction. With regards to  immigration from Turkey it is less correlated to unemployment than immigration total. But there is a correlation between immigration from Turkey and the stock of foreigners in Germany This is in accordance with the theoretical concept of network theory where an existing community of migrants keeps attracting new migrants because the costs and risks associated with migration are lower, thanks to established linkages to the country of origin. The observed correlation of migration and unemployment points to the fact that immigration to Germany responds to changes in demand in the labour market. Even though a time lag may occur in the case of unemployment and immigration, migration appears to be a relatively effective mechanism to offset existing imbalances in German labour markets. 


1965 ◽  
Vol 50 (2) ◽  
pp. 301-309 ◽  
Author(s):  
Jürg Müller

ABSTRACT An extract of human urine, which was previously shown to stimulate aldosterone production by rat adrenal sections, was further purified. Evidence was obtained that its aldosterone-stimulating effect was due to the presence of ammonium ions. Addition of ammonium chloride and of urine extract to the incubation medium caused identical increases in aldosterone production in vitro. In addition to ammonium ions, rubidium and caesium ions also stimulated aldosterone production up to 250% that of control values without a significant effect on corticosterone production. Similar dose-response curves were obtained when increasing concentrations of potassium, ammonium, rubidium and caesium ions were tested. Aldosterone production was maximal at concentrations of 7 mval/1 and was significantly lower at higher concentrations. When ammonium chloride and ACTH were simultaneously added to the incubation medium, the production of aldosterone and of corticosterone was lower than with ACTH alone. On the other hand, the stimulating activity on aldosterone and corticosterone production by »TPN« (NADP) and glucose-6-phosphate was enhanced by the simultaneous addition of ammonium chloride.


1974 ◽  
Vol 77 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Gustav Wägar

ABSTRACT Whether the short-term regulation of thyroidal protein synthesis by TSH occurs at the transcriptional or the translational level was tested by measuring the effect of actinomycin D (act D) on the TSH-induced stimulation of L-14C-leucine incorporation into the thyroidal proteins of rats. TSH was injected 6 h before the rats were killed. The thyroid glands were then removed and incubated in vitro in the presence of L-14C-leucine for 2 h. The pronounced stimulation of leucine incorporation in the TSH-treated animals was depressed as compared with controls but still significant even when the animals had been pre-treated with 100 μg act D 24 and 7 h before sacrifice. On the other hand, act D strongly decreased incorporation of 3H-uridine into RNA. Short-term regulation of thyroidal protein synthesis by TSH appears to be partly but not wholly dependent on neosynthesis of RNA. Hence regulation may partly occur at the translation level of protein synthesis.


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