A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogesis. 2-(Allylthio) prazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicant sand elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 ($AFB_1$)-induced three-step medium-term hepatocarcinogenesis model. Reduction of $AFB_1$-DNA adduct by 2-AP appeared to result from the decreased formation of $AFB_1$-8,9-epoxide via suppression of cytochrome P450, while induction of GST 2-AP increases the excretion of glutathione-conjugated $AFB_1$ . 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-KB activation is not involved in the induction of the detoxifying enzymes. the mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.
Sitovs, Andrejs;Voiko, Laura;Kustovs, Dmitrijs;Kovalcuka, Liga;Bandere, Dace;Purvina, Santa;Giorgi, Mario
Journal of Veterinary Science
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v.21
no.2
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pp.32.1-32.13
/
2020
Levofloxacin pharmacokinetic profiles were evaluated in 6 healthy female rabbits after intravenous (I/V), intramuscular (I/M), or subcutaneous (S/C) administration routes at a single dose of 5 mg/kg in a 3 × 3 cross-over study. Plasma levofloxacin concentrations were detected using a validated Ultra Performance Liquid Chromatography method with a fluorescence detector. Levofloxacin was quantifiable up to 10 h post-drug administration. Mean AUC0-last values of 9.03 ± 2.66, 9.07 ± 1.80, and 9.28 ± 1.56 mg/h*L were obtained via I/V, I/M, and S/C, respectively. Plasma clearance was 0.6 mL/g*h after I/V administration. Peak plasma concentrations using the I/M and S/C routes were 3.33 ± 0.39 and 2.91 ± 0.56 ㎍/mL. Bioavailability values, after extravascular administration were complete, - 105% ± 27% (I/M) and 118% ± 40% (S/C). Average extraction ratio of levofloxacin after I/V administration was 7%. Additionally, levofloxacin administration effects on tear production and osmolarity were evaluated. Tear osmolarity decreased within 48 h post-drug administration. All 3 levofloxacin administration routes produced similar pharmacokinetic profiles. The studied dose is unlikely to be effective in rabbits; however, it was calculated that a daily dose of 29 mg/kg appears effective for I/V administration for pathogens with MIC < 0.5 ㎍/mL.
Incident duration prediction is one of the most important steps of the overall incident management process. An accurate and reliable estimate of the incident duration can be the main difference between an effective incident management operation and an unacceptable one since, without the knowledge of such time durations, traffic impact can not be estimated or calculated. This research presents several multiple linear regression models for incident duration prediction using data consisting of 384 incident cases. The main source of various incident cases was the Traffic Incident Reports filled out by the Motorist Assistant Units of the Korea Highway Corporation. The models were proposed separately according to the time of day(daytime vs. nighttime) and the fatality/injury incurred (fatality/injury vs. property damage only). Two models using an integrated dataset, one with an intercept and the other without it, were also calibrated and proposed for the generality of model application. Some findings are as follows ; ?Variables such as vehicle turnover, load spills, the number of heavy vehicles involved and the number of blocked lanes were found to significantly affect incident duration times. ?Models, however, tend to overestimate the duration times when a dummy variable, load spill, is used. It was simply because several of load spill incidents had excessively long clearance times. The precision was improved when load spills were further categorized into "small spills" and "large spills" based on the size of vehicles involved. ?Variables such as the number of vehicles involved and the number of blocked lanes found not significant when a regression model was calibrated with an intercept. whereas excluding the intercept from the model structure signifies those variables in a statistical sense.
Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time ($22.5{\pm}10.6hr$) and the mean parasite clearance time ($27.3{\pm}12.2hr$) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P<0.0001). The resistance intensities decreased as follows: chloroquine>piperaquine>pyronarididine>artesunate. The inhibitory dose 50 ($IC_{50}$) was $3.77{\times}10^{-6}mol/L$, $2.09{\times}10^{-6}mol/L$, $0.09{\times}10^{-6}mol/L$, and $0.05{\times}10^{-6}mol/L$, and the mean concentrations for complete inhibition (CIMC) of schizont formation were $5.60{\times}10^{-6}mol/L$, $9.26{\times}10^{-6}mol/L$, $0.55{\times}10^{-6}mol/L$, and $0.07{\times}10^{-6}mol/L$, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.
Objective: This study ascertained effects of roughage quality, period of day at meal termination and time lapse after feeding on digesta load in the rumen. Methods: Veld hay was untreated (poor roughage quality, PRQ), improved (improved roughage quality, IRQ) by treating with urea or semi-improved by spraying with urea (semi-improved roughage quality, SIRQ). Experiment 1a used four rumen fistulated sheep to determine in-sacco degradability. Twelve sheep ($56.3{\pm}4.59kg$) were blocked by weight and randomly allocated to IRQ (n = 6) and PRQ (n = 6) to determine solid and liquid passage rates. In experiment 1b, nine sheep ($37.6{\pm}9.34kg$) were blocked by weight and randomly allocated to IRQ (n = 4) and PRQ (n = 5) to determine digestibility. Sixteen sheep ($36.47{\pm}9.46kg$) were blocked by body weight and randomly allocated to IRQ (n = 8) and PRQ (n = 8). Two sheep were slaughtered for each sampling time in each treatment (IRQ and PRQ) at 0, 6, 12, and 24 h after feeding to determine rumen load. In experiment 2, eighteen goats ($25.4{\pm}9.08kg$) were blocked by weight and randomly allocated to IRQ (n = 6), SIRQ (n = 6), and PRQ (n = 6). Then all 18 goats were slaughtered soon after meal termination in the morning; afternoon and evening to determine the effect of period of day on rumen fill. Results: Rate of degradation and effective degradability were enhanced by improvement of roughage quality. Roughage quality had no effect on digestibility, but digestibility was higher in goats than sheep. Fractional passage rate of particles was higher for IRQ than PRQ, but similar for liquids. Digesta fractional clearance rates at 24 h after feeding were 0.018/h (IRQ) and 0.006/h (PRQ). Period of day had an influence on rumen load. Neutral detergent fibre load for goats were above 2.03 kg/100 kg body weight for all diet treatments. Conclusion: Following starvation, passage rate had negligible effects on emptying of rumen load.
Ham, Sangwoo;Kim, Hyojung;Hwang, Seojin;Kang, Hyunook;Yun, Seung Pil;Kim, Sangjune;Kim, Donghoon;Kwon, Hyun Sook;Lee, Yun-Song;Cho, MyoungLae;Shin, Heung-Mook;Choi, Heejung;Chung, Ka Young;Ko, Han Seok;Lee, Gum Hwa;Lee, Yunjong
Molecules and Cells
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v.42
no.6
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pp.480-494
/
2019
Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.
Seo, Hyung-bum;Lee, Chan;Cho, Im-hak;Heo, Gi-yoon;Kang, Hee-kyung;Han, Chang-woo;Kim, So-yeon;Choi, Jun-yong;Park, Seong-ha;Yun, Young-ju;Hong, Jin-woo;Kwon, Jung-nam;Lee, In
The Journal of Internal Korean Medicine
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v.41
no.6
/
pp.1191-1199
/
2020
We studied the effect of Korean medicine treatment on the clearance of vancomycin-resistant enterococcus (VRE) colonization and on improvement in symptoms in a stroke patient. The patient was continuously followed up with stool VRE cultures while being treated with herbal medicine, Chunglijagam-tang, acupuncture, and oxygen therapy. We also checked the coccygeal pressure sore condition and the oxygen levels during therapy. No VRE colonization was found after treatment and the oxygen levels and pressure sores had improved. This study proved that Korean medicine treatment could be effective for the clearance of VRE colonization and improvement of symptoms.
The author in an attempt to evaluate hemodynamic changes in the clinical stages of Korean hemorrhagic fever measured plasma volume, cardiac output and effective renal plasma flow utilizing radioisoto es during various phases of the disease. Cardiac output was measured by radiocardiography with external monitoring method using RIHSA. Effective renal plasma flow was obtained from blood clearance curve drawn by external monitoring after radiohippuran injection according to the method described by Razzak et al. The study was carried out in thirty-eight cases of Korean hemorrhagic fever and the following conclusions were obtained. 1. Plasma volume was increased in the patients during the oliguric-and hypertensive diuretic phases, while it was normal in the patients during the normotensive-diuretic phase. 2. Cardiac index was increased in the patients during the oliguric phase and was slightly increased in the patients at the hypertensive diuretic phase. It was normal in the other phases. 3. Total peripheral resistance was increased in the hypertensive patients during diuretic phase, while it was normal in the rest of phases. 4. Effective renal plasma flow was significantly reduced in the patients during the oliguric and diuretic phases as well as at one month after the oliguric onset. There was no significant difference between the oliguric and the early diuretic phases. Renal plasma flow in the group of patients at one month after the oliguric onset was about 45% of the normal, however, it returned to normal level at six months after the onset. 5. Clinical syndrome of relative hypervolemia was observed in some patients during the oliguric phase or hypertensive diuretic phase. Characteristic hemodynamic findings were high cardiac output and normal to relatively increased peripheral resistance in these cases. Relatively increased circulating blood volume due to decreased effective vascular space was suggested for the mechanism of relative hypervolemia. 6. Cardiac hemodynamic alteration returned to normal during late stage of the diuretic phase, while renal hemodynamic changes were normalized at six months after the onset.
In 1965, Rosenberg reported that platinum compounds not only inhibit growth and cell division of E. coli but also has anti-tumor activity. Since then, through animal and clinical experiments by Welsch(1971), Speer(1972), Rossof(1972), Hill(1974), and Wittes(1975), it was proved that Cis-platinum has excellent supressive effects on malignant tumor, especially on head and neck cancer. Accordingly, Cis-platinum is now widely used, sometimes without any other durg, or sometimes with Bleomycin and Methotrexate etc. Inspite of the strong anticancer effect, the use of Cis-platinum is quite often discouraged because of the reports that Cis-platinum causes auditory impairment at high frequencies above the speech range due to inner ear damage and irreversible change in the renal tubules. Since Kohonen et al(1965), Standnicki et al(1974) reported that Cisplatinum has toxic effects at the basal turn of the cochlea using guinea pig, many studies on ototoxicity after infusion of Cis-platinum have been carried out using animals. But the studies on ototoxicity in human beings can hardly be found except in reports by Piel et al(1974) and Hong et al (1979). So the authors did a study which tried to clarify the ototoxic effect by comparing the hearing level after infusion of Cis-plastinum with the hearing level before infusion of Cis-plastinum in 30 patients who was treated with Cis-platinum and admitted to the dept. of otolaryngology of Yonsei University Hospital during 2 years and a half from July. 1979 to March. 1982 and the following results were obtained. 1) The results of auditory evaluation, using the pure tone average, hearing loss of 4kHz and 8kHz, Speech Reception Threshold, PB score, SISI showed that the difference of dosage does not change the hearing level after infusion of Cis-platinum and before infusion of Cis-platinum. 2) Cis-platinum had no effect on the hearing level of patients with conductive hearing loss, or with sensorineural hearing loss, as well as with normal hearing level. 3) The infusion of Cis-platinum did not cause any change in creatinine clearance, creatinine, uric acid, but only one case showed that Cis-platinum caused severe nephrotoxicity. 4) The infusion of Cis-plastinum did not cause any change in hemoglobin, leukocyte count, platelet count and there was no correlation with the amount of infusion. 5) To see the side effect of hydration practiced with the infusion of Cis-platinum, the electrolytes, particularly the K level in the serum was measured. But the results did not show any change. 6) Judging from the results of this study mentioned above, ototoxicity caused by infusion of Cis-platinum can be prevented by sufficient hydration. Also the results might say that the appropriate method of infusion of Cis-platinum might be effective in the patients with head and neck cancer who had sensorineural hearing loss for whom the infusion of Cis-platinum has been absolutely cotraindicated.
Spraying method from the paddy-field levee is known to give insufficient penetration of the spray droplets to the rice stem of the densely grown plants, which is generally encountered at the last stage of rice growth. This study was intended to investigate the spraying system to solve this existing problem. As an approach, it was attempted to develop the boom-with-nozzle, between-the-row application system. Several types of nozzles and their different arrangements in the boom were tested in the field to measure the penetration-reaching distance and the uniformity of spray droplet distribution. The results of the study are summarized as follows: 1. Field experiments by the spraying method from the paddy-field levee showed to have practically no penetration of the spray droplets to the portion of the plant stem with the normal flow volume generally applied and thus need for improving present spraying method. 2. It was found that, considering both the uniformity of the spray droplet distribution and performance rate, the most efficient type of nozzle in the between-the-row boom-type spraying system was one that has core-insert hollow-cone with some clearance between the cone and tip. 3. When tested by applying the spraying method of between-the-row, the nozzle pressure did not affect the uniformity of spray droplet distribution. However, the nozzle pressure had a positive effect on the penetrating-reaching distance of the facing side of the rice stem and did not affect much on that of the opposite face of the stem. It was also found that the maximum pressure to affect the penetration-reaching distance was about $10kg/cm^2$. 4. The uniformity of the spray droplet distribution in the between-the-row system was greatly affected by the height and orientation of the nozzles in the boom. Based on experimental work for the different type of the boom-with-nozzle arrangements, it is recommended that the position of nozzle is set at about 0.45 m above the ground and two nozzles in the boom are oriented to be faced with each other with some angle such that the droplet stream from the nozzle would not directly face with each other.
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