The authors investigated the biodegradability and toxicity of polyoxyethylene-alkyl citric diester-triethanolamine(PAT), which is one of new non-ionic detergents. 1) The PAT is very biodegradable, which 50% is biodegraded for one day and 100% for eight days by the activated sludge treatment and 40% for one day and 93% for eight days by the aerobic domestic sewage treatment. 2) $LD_{50}$ of PAT for chicken, mouse, and rat by oral adminstration are 7.1g/kg, 8.4g/kg and 14.0g/kg reactively. 3) $TL_{m}$ of PAT for goldfish is 64.0mg/l in 24bours. 4) No reaction for humun skin is determined by PAT.
Cancer is the leading cause of death and is on the rise worldwide. Until 2010, the development of targeted treatment was mainly focused on the growth mechanisms of cancer. Since then, drugs with mechanisms related to tumor immunity, especially immune checkpoint inhibitors, have proven effective, and most pharmaceutical companies are striving to develop related drugs. Programmed cell death-1 and programmed cell death ligand-1 inhibitors have shown great success in various cancer types. They showed durable and sustainable responses and were approved by the U.S. Food and Drug Administration. However, the response to inhibitors showed low percentages of cancer patients; 15% to 20%. Therefore, combination strategies with immunotherapy and conventional treatments were used to overcome the low response rate. Studies on combination therapy have typically reported improvements in the response rate and efficacy in several cancers, including non-small cell lung cancer, small cell lung cancer, breast cancer, and urogenital cancers. The combination of chemotherapy or targeted agents with immunotherapy is one of the leading pathways for cancer treatment.
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.
Pharmaceutical byproduct sludge and cosmetic industry wastewater sludge can be used as a raw material of compost. Effects of three types of pharmaceutical byproduct sludge and one type of cosmetic industry wastewater sludge on soil properties and red pepper growth were investigated in a field based concrete pot ($2{\times}2m$). These sludges and pig manure ($5Mg\;ha^{-1}$, dry basis) were incorporated into the upper of loam soil 30 days prior to transplanting red pepper. Changes in soil properties and contents of heavy metals and toxic organic compounds in soil and plant were measured. And also plant growth measurement and bioassay of soil phytotoxicity were included. Contents of heavy metals were increased in the soils treated with the sludges. Plant growth in the sludge treatments were mostly inferior to that of NPK treatment, especially in early stage. Content of N in plant was lower in all sludge treatments at early and middle growth stages, and it was especially caused by characteristics and concentration of nitrogen and organic matter of sludges. Total yield of red pepper was highest in the NPK treatment and followed by pharmaceutical sludge 3, pig manure, pharmaceutical sludge 1, and pharmaceutical sludge 2, and the yield of cosmetic sludge treatment was considerably lower than others. HEM and PAHs contents in soil of cosmetic sludge treatment were $4.80mg\;kg^{-1}$ and $2,263.2{\mu}g\;kg^{-1}$, respectively. Root elongation of lettuce exposed to the water extract of soil treated with cosmetic sludge was about 20% of that found in the test with soil extract of non fertilization treatment. At present, raw materials of compost were authorized according to the contents of organic matter, heavy metals and product processing. Toxic organic compounds analysis and bioassay would be helpful for authorization and assessment of suitability of raw materials of compost.
5-Fluorouracil (5-FU) is an antimetabolic of the pyrimidine derivatives that is used in chemotherapy for the treatment of several types of cancer. 5-FU have poor oral absorption and short biological half-time and strong side effects. Microneedle introduced to find a solution of problems. Microneedle device with roll was manufactured for transdermal delivery of various drugs. 5-FU was mixed in non-ionic surfactant such as tween 20 and tween 80. Camscope was used to analysis the permeation magnitude of treated skin by microneedle and trypan blue staining. The 5-FU solution with surfactant measured by ZETA-potential analysis system for stability of solution. The skin permeation rate of 5-FU determined by HPLC. We confirmed that cross treated skin was dyed more deeply than parallel treated skin through trypan blue staining. The results indicate that skin permeation rate of 5-FU was increased with the treatment types and treatment times.
The purpose of this study was to evaluate the clinical efficacy and safety of NRM which was newly developed as a combination product containing antacids, digestive enzyme and herbal drugs, and OTA powder, called OHTA'S ISAN on the morret, for the treatment of various symptoms in upper gastrointestinal diseases. 63 patients were recruited, 36 as a treated group with NRM and 27 as a controlled one with OTA. Patients were randomly allocated to receive either NRM or OTA t.i.d. for treatment of upper G-1 symptoms and undergone endoscopic, symptomatic and clinical laboratory assessments before and after 2 weeks. The results were as follows; 1. The general improvement rates of subjective symptoms in upper G-1 diseases were observed in 100%(32/32) for NRM and in 92%(23/25) for OTA. 2. The overall effective rates in terms of the symptoms and endoscopic findings were 88.9%(32/36) for NRM and 85.2%(23/27) ,or OTA respectively. 3. In NRM group, no significant side effects by NRM were observed except a mild and transient vomiting in one patient, but in OTA group treatment was discontinued due to nousea in one patient, However, there were no clinically significant changes detected in the laboratory parameters. According to the result of this trial, it is cocluded that NRM was safe and effective and (but not statistically significant) was superior to OTA in the treatment of gastrointestinal diseases caused by gastritis, gastric and duodenal ulcer, functional gastrointestinal disorder, non-ulcer dyspepsia etc.
This study is to enhance drug penetration via skin and investigate anti-inflammation effect following adoption of ultrasound. For this goal gel containing triamcinolone was prepared and the skin penetration rate and the change effects of blood plasma ingredients and serum enzyme were investigated. Using Franz type diffusion cell and the skin of hairless mouse, the permeation enhancing effect of ultrasound was tested. After the injury by direct trauma, the blood test was performed by measuring WBC, lymphocyte, and neutrophyl, and by analyzing CPK and LDH. The ultrasound transducer whose technical specification is geometric area(GA) $1.4\;cm^2$, effective radiation area(ERA) $0.8\;cm^2$, and beam non-uniformity ratio(BNR) 6.0 max was used. The influence of frequency having an effect on skin permeation rate was higher in the case of using 1MHz and continuous treatment. The temperature of receptor phase was not influenced in skin permeation by phonophoresis. Skin permeation increase attended by intensity of ultrasound, the permeation of triamcinolone was accelerated at $2.5\;w/cm^2\;than\;1.0\;w/cm^2$. Following muscle injury phonophoretic group the number of WBC, neutrophil and lympholyte were decreased significantly as compared with both control group and ultrasound group. The result of variation of serum CPK and LDH activity conformed to the phonophoretic effect as same pattern with the variation of WBC, neutrophil and lymphocyte.
Objective: It is to evaluate the drug interaction monitoring program as a pilot project to develop a pharmaceutical care model in a medical intensive care unit and to analyze the influencing factors of drug interactions. Method: Electronic medical records were retrospectively investigated for 116 patients who had been hospitalized in a medical intensive care unit from October to December in 2014. The prevalence of adverse reaction with risk rating higher than 'D' was investigated by Lexi-$Comp^{(R)}$ Online database. The factors related with potential drug interaction and with treatment outcomes were analyzed. Results: The number of patients with a potential interaction of drug combination was 92 (79.3%). Average ages, the length of stay in the intensive care unit and the numbers of prescription drugs showed significant differences between drug interaction group and non-drug interaction group. Opioids (14.4%), antibiotics (7.2%), and diuretics (7.2%) were most responsible drug classes for drug interactions and the individual medications included furosemide (6.4%), tramadol (4.9%), and remifentanil (4.5%). There were 950 cases with a risk rating of 'C' (84.6%), 142 cases with a risk rating of 'D' (12.6%), and 31 cases with a risk rating of 'X' (avoid combination) (2.8%). The factors affecting drug interactions were the number of drugs prescribed (p < 0.0001) and the length of stay at intensive care unit (p < 0.01). The patients in intensive care unit showed a high incidence of adverse reactions related to potential drug interaction. Therefore, drug interaction monitoring program as a one of pharmaceutical care services was successfully piloted and it showed to prevent adverse reaction and to improve therapeutic outcomes. Conclusion: Active participation of a pharmacist in the drug management at the intensive care unit should be considered.
The antitumor activity of crude saponin mixture obtained from Luffa tuberosa (Roxb.) (Fam; Cucurbitaceae) hairy roots (CSLT) in mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC-bearing mice receiving 150 and $300{\mu}g/kg$ body weight, (i.p) of CSLT have shown a dose dependent elevation in tumor-tree survival and a highest number of survivors were observed after administration of CSLT $(300{\mu}g/kg)$, which was considered as an optimum dose for its antineoplastic action. The mean survival time (MST) for this dose was approximately $47.1{\pm}0.74d$, when compared with $19.0{\pm}0.36d$ of untreated control. Administration of $300{\mu}g/kg$ CSLT resulted in 130% long-term increased survival time. The measurement of body weight, tumor volume, packed cell volume, viable and non-viable count indicated the efficacy of CSLT in tumor-bearing mice, there was a significant recovery in hematological profiles, and there was depletion in lipid peroxidation levels, and the antioxidant enzyme activities such as GSH, SOD and CAT were restored to near the normal levels. The CSLT was found to be devoid of conspicuous short-term toxicity in the mice when animals were intraperitoneally injected with 250, 500, 750 and $1000{\mu}g/kg$ bodyweight. The treated mice showed conspicuous toxic symptoms only at a dose of $1500{\mu}g/kg$. Mortality of the animals was monitored up to 14 d post drug treatment, $1/7^{th}$ of the $LD_{50}$ dose has been considered for the optimal antineoplastic activity.
Zhong, Yong-Mei;Hisao Nishijo;Teruko Uwano;Hidetishi Yamaguchi;Taketosho Ono
Proceedings of the Ginseng society Conference
/
1998.06a
/
pp.1-11
/
1998
Ameliorating mechanisms of red ginseng on learning deficits were investigated in the following 3 experiments; its effects on 1) place learning deficits in aged rats and in young rats with selective hippocampal lesions (behavioral study), 2) long-term potentiation in the hippocampal formation (neuro- physiological study), and 3) ChAT (choline acetyl transferase) activity in various brain regions of aged rats (pharmacological study). In the behavioral study, first, performance in the place learning tasks were compared among 3 groups of young and aged rats; control young intact rats (10-12 week old) treated with water, aged rats (28-32 month old) treated with water, and aged rats (28-32 month old) treated with red ginseng (100 mghglday) suspended in water. Second, performance in the place learning tasks was compared among 3 groups of young rats; control intact rats treated with water, rats with bilateral hippocampal lesions treated with water, and rats with bilateral hippocampal lesions treated with red ginseng (100 mg/kg/day). Each rat in these 2 behavioral experiments was tested with the 3 types of the place learning tasks in a circular open field using intracranial self-stimulation (ICSS) as reward. The ICSS reward was delivered if the rat (1) moved distance of 100-160 cm (DMT): (2) entered an experiment-determined reward place within the open field, and this place was randomly varied in sequential trials (RRPST); or (3) entered 2 specific places, and did a shuttle behavior between the 2 places (PLT). Performance of the aged rats in the ginseng group was not significantly different from that of control young rats in ICSS (current intensity, bar press rates), DMT and RRPST. However, treatment with red ginseng significantly ameliorated place-navigation learning deficits in aged rats in the PLT. Similarly, red ginseng ameliorated learning and memory deficits in young rats with hippocampal lesions in the same tasks. In the neurophysiological study using young rats, perfusion of hippocampal slices with non-sapon in fraction of red ginseng significantly enhanced magnitudes of the long-term potentiation (LfP) in the CA3 subfield. In the pharmacological study, treatment with red ginseng did not affect ChAT activity in aged rat brain including the hippocampal formation. These results strongly suggest that red ginseng ameliorates learning and memory deficits in aged rats through actions on the CA3 subfield of the hippocampal formation, which were independent of the presynaptic components of the cholinergic system
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