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Two -week Oral Toxicity Study of 1- (4-methylpiperazinyl) -3- phenylisoquinoline (CWJ-a-5) in sprague-Dawley (SD) Rats (1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5)의 Sprague-Dawley(SD) 랫드를 이용한 2주간 반복 경구투여 독성시험)

  • 강부현;조원제;김대덕;김용범;차신우;장순재
    • Toxicological Research
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    • v.18 no.1
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    • pp.47-57
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    • 2002
  • The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

Post-operative analgesia of 2% lignocaine with or without magnesium sulfate for inferior alveolar nerve block in symptomatic mandibular molars - a randomized double blind controlled clinical trial

  • Chandrasekaran, Charanya;Vijay, Amirtharaj L;Sekar, Mahalaxmi;Mary, Nancy S
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.20 no.3
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    • pp.147-154
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    • 2020
  • Background: Single inferior alveolar nerve block is ineffective in achieving adequate pulpal anesthesia in 30-80% of patients due to anatomical variations, local tissue pH, central sensitization, and several factors. Various supplementary techniques and combination of adjuvants with lignocaine are used to overcome these failures. Magnesium sulfate (MgSO4), one such adjuvant, acts at the N-methyl-D-aspartate glutamate receptor resulting in effective anesthesia. The aim of this prospective, randomized, double-blind, clinical controlled trial was to evaluate the onset, anesthetic efficacy, duration and post-operative analgesia of 2% lignocaine with and without the addition of MgSO4 in patients with symptomatic irreversible pulpitis and apical periodontitis. Methods: Fourty-two patients were randomly divided into three groups: 2% lignocaine (group 1) and 2% lignocaine with MgSO4 (75 mg) and (150 mg) in groups 2 and 3, respectively. Pre-operative vitals and Heft Parker-Visual Analogue Scale (HP-VAS) pain scores were recorded. The onset of anesthesia, anesthetic efficacy, and duration of anesthesia were evaluated post administration of the local anesthetic solution. The post-operative analgesia was examined at intervals of 2, 6, 12, 24, and 48 h. Results: Administration of 150 mg MgSO4 hastens the onset of anesthesia (1.29 min) and produces better anesthetic efficacy (3.29 HP-VAS) compared to group 2 (2.07 min and 9.14 HP-VAS) and group 1 (3.29 min and 35.79 HP-VAS), respectively. The duration of anesthesia was significantly higher in group 3 (247.07 min) compared to that of groups 2 and 1 (190 min and 110.21 min) with P < 0.05. Conclusion: Combining 75 mg or 150 mg of MgSO4 with lignocaine is more effective than 2% lignocaine and 75 mg of MgSO4 is adequate for endodontic procedures.

Effectiveness of High-Volume Therapeutic Plasma Exchange for Acute and Acute-on-Chronic Liver Failure in Korean Pediatric Patients

  • Lim, Hyeji;Kang, Yunkoo;Park, Sowon;Koh, Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.6
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    • pp.481-488
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    • 2022
  • Purpose: Liver transplantation (LT) is the only curative treatment for acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). In high-volume therapeutic plasma exchange (HV-TPE), extracorporeal liver support filters accumulate toxins and improve the coagulation factor by replacing them. In this study, we aimed to evaluate the effectiveness of HV-TPE in pediatric patients with ALF and ACLF. Methods: We reviewed the records of children waiting for LT at Severance Hospital who underwent HV-TPE between 2017 and 2021. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin (TB and DB), gamma-glutamyl transferase (GGT), ammonia, and coagulation parameter-international normalized ratio (INR) were all measured before and after HV-TPE to analyze the liver function. The statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Co., Armonk, NY, USA). Results: Nine patients underwent HV-TPE with standard medical therapy while waiting for LT. One had neonatal hemochromatosis, four had biliary atresia, and the other four had ALF of unknown etiology. Significant decreases in AST, ALT, TB, DB, GGT, and INR were noted after performing HV-TPE (930.38-331.75 IU/L, 282.62-63.00 IU/L, 11.75-5.59 mg/dL, 8.10-3.66 mg/dL, 205.62-51.75 IU/L, and 3.57-1.50, respectively, p<0.05). All patients underwent LT, and two expired due to acute complications. Conclusion: HV-TPE could remove accumulated toxins and improve coagulation. Therefore, we conclude that HV-TPE can be regarded as a representative bridging therapy before LT.

Effects of the Fermented Black Garlic Extract on Lipid Metabolism and Hepatoprotection in Mice (발효흑마늘 추출물이 흰쥐의 지질대사 및 간기능 개선에 미치는 영향)

  • Chung, Soo Yeon;Han, Kyung-Hoon;Bae, Song-Hwan;Han, Sung Hee;Lee, Yong Kwon
    • The Korean Journal of Food And Nutrition
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    • v.33 no.1
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    • pp.17-26
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    • 2020
  • This study was conducted to evaluate the functionality of fermented black garlic extracts under various conditions. Black garlic powder was prepared by aging for 0~72 hours at 80℃ depending on relative humidity (RH). It showed the highest antioxidant effects among the samples; the total antioxidant activity of black garlic powders at RH 75%, 84%, and 90% for 72 hours was increased 31.9 times, 28.2 times, and 22.6 times compared with that of the fresh garlic powder, respectively. Also, the alliin content was gradually decreased. S-ally-L-cysteine and S-ethyl-cysteine levels were increased; the highest values were 495.9 ㎍/g and 1,769.7 ㎍/g after aging for 72 hours at RH 75%. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were increased following high fat diet feeding, but the rise was obviously reduced by administration of black garlic extract. The total cholesterol, LDL/VLDL-cholesterol, and triglyceride contents in serum were significantly lower in methionine and choline deficient (MCD) diet treatment groups than in the positive control group. The concentration was increased following the intake of black garlic and fermented black garlic extracts. Therefore, black garlic extracts could be an ideal material as a dietary supplement in healthy functional foods to improve the effects on fatty liver.

Silymarin Modulates Cisplatin-Induced Oxidative Stress and Hepatotoxicity in Rats

  • Mansour, Heba Hosny;Hafez, Hafez Farouk;Fahmy, Nadia Mohamed
    • BMB Reports
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    • v.39 no.6
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    • pp.656-661
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    • 2006
  • Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP -induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.

Predictors of Short-Term Outcome of Kasai Portoenterostomy for Biliary Atresia in Infants: a Single-Center Study

  • Yassin, Noha Adel;El-Tagy, Gamal;Abdelhakeem, Omar Nagy;Asem, Noha;El-Karaksy, Hanaa
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.23 no.3
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    • pp.266-275
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    • 2020
  • Purpose: The outcome predictors of Kasai portoenterostomy (KPE) for biliary atresia (BA) are controversial. This study aimed to identify possible short-term outcome predictors of KPE for BA in infants. Methods: This retrospective study included infants with BA who underwent KPE between January 2015 and December 2017 and were followed up for at least 6 months after surgery at the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt. The short-term outcome was jaundice clearance within 6 months following surgery. All data were compared between the jaundice free group and those with persistent jaundice to identify the predictors of jaundice clearance. Results: The study included 75 infants. The mean age at the time of surgery was 82.43±22.77 days (range, 37-150 days), and 28 (37.3%) infants cleared their jaundice within 6 months postoperative. Age at surgery did not significantly affect the outcome (p=0.518). Infants with persistent jaundice had significantly higher pre-operative levels of aspartate aminotransferase (AST) than those who were jaundice free (p=0.041). Receiver operating characteristic curve analysis showed that preoperative AST ≤180 IU/L was predictive of a successful KPE, with sensitivity 74.5% and specificity 60.7%. Infants with bile plugs in liver biopsy had a 6-fold higher risk of persistent jaundice than those without bile plugs (95% confidence interval: 1.59-20.75, p=0.008). Conclusion: Jaundice clearance after KPE for BA can be predicted using preoperative AST and presence of bile plugs in liver biopsy.

Isolation and Electrical Characterization of the Rat Spinal Dorsal Horn Neurons (랫드 척수후각 단일세포 분리 및 특성에 관한 연구)

  • Han, Seong-Kyu;Ryu, Pan-Dong
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.283-292
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    • 1996
  • The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region. In this study, single neurons of the spinal dorsal horn were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by patch clamp technique. Transverse slice ($(300{\mu}m$) of lumbar spinal cords from young rats$(7{\sim}14\;days)$ were sequentially treated with two pretenses(pronase 0.75 mg/ml and thermolysin 0.75 mg/ml), then single neurons were mechanically dissociated. These neurons showed near-intact morphology such as multipolar, ellipsoidal and bipolar, and pyramidal cells and we recorded the typical whole cell currents of $K^+$, $Ca^{2+}$ and ligand-operated channels from these neurons. Glutamate $(30{\mu}M)$ and N-methyl-D-aspartate(NMDA, $30{\mu}M)$ induced inward currents of $117{\pm}12.4$ pA(n=5) and $49{\pm}6.9$ pA(n=3), respectively. Glycine $(1{\mu}M)$ potentiated glutamate-induced currents $4{\sim}5$ times and NMDA-induced currents $8{\sim}10$ times. In addition, glycine $(30{\mu}M)$ induced Inward current ($31{\pm}6.1$ nA, n=2), which was rapidly desensitized after the peak to a new steady-state level. However, the inward currents induced by ${\gamma}-amino$ butyric acid(GABA, $1{\mu}M$) decreased continuously after the peak($226{\pm}41.6$ pA, n=3) under the similar experimental condition. The ionic currents and pharmacological responses of isolated neurons in this work were similar to those observed in vivo or in vitro spinal cord slice, indicating that acutely isolated neurons could be effectively used for further pharmacological studies.

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Effect of dietary supplementation of garlic powder and phenyl acetic acid on productive performance, blood haematology, immunity and antioxidant status of broiler chickens

  • Ismail, I.E.;Alagawany, M.;Taha, A.E.;Puvaca, N.;Laudadio, V.;Tufarelli, V.
    • Animal Bioscience
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    • v.34 no.3_spc
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    • pp.363-370
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    • 2021
  • Objective: The effect of garlic powder (GP) and phenyl acetic (PA) acid throughout the fattening period of broiler chickens on performance, blood parameters, immune, and antioxidant parameters as well as carcass traits was evaluated. Methods: A total of 210 day-old Cobb broiler chicks were randomly distributed into seven dietary treatments having five replications with six chicks per replicate. The first group (control) fed a basal diet without supplements, whereas the 2nd, 3rd, and 4th group were fed basal diet plus 0.25, 0.50, and 0.75 g GP/kg diet, respectively and the group 5th, 6th, and 7th were fed on the basal diet plus 0.25, 0.50, and 0.75 g PA/kg diet. Results: Broiler body weight and gain at 21 and 42 days were increased (p<0.05) with diets supplemented with GP and PA. Red blood cells and hemoglobin were improved in chickens fed diets enriched with GP. Broiler chickens received diets containing either GP or PA recorded the higher values (p<0.05) of total protein, globulin, high-density lipoprotein, immunoglobulin M (IgM), and IgG, superoxide dismutase and total antioxidant capacity; while, blood total cholesterol, low-density lipoprotein, aspartate-aminotransferase, and malondialdehyde were lowered (p<0.05) compared to control-diet. Liver and immune-related organs weight were improved (p<0.05) in broilers fed diet supplemented with GP and PA. Conclusion: Feeding of GP or PA in diet had positive effects on performance traits and immunological, antioxidant and physiological status of broilers. Thus, the use of tested feed additives as an eco-friendly alternative to antibiotics produced a positive effect on animal health.

BLOOD BIOCHEMICAL PROFILE AND HISTOPATHOLOGY OF VITAL ORGANS IN RABBITS FED ON PROCESSED NEEM (Azadirachta indica) KERNEL MEAL INCORPORATED DIETS

  • Gowda, S.K.;Katiyar, R.C.;Sharma, A.K.;Sastry, V.R.B.
    • Asian-Australasian Journal of Animal Sciences
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    • v.9 no.4
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    • pp.471-476
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    • 1996
  • Blood biochemical and histopathological changes in vital organs of rabbits were studied after 19 wk of feeding composite diets (75 concentrate : 25 roughage) incorporating either urea (2%, wt/wt) ammoniated or alkali (1.5%, wt/wt) treated neem kernel meal (NKM) replacing peanut meal protein of control diet by either 50 or 100%. The blood biochemical constituents (Haemoglobin, Alanine amino transferase, Aspartate amino transferase, Total protein, Blood urea nitrogen &Cholesterol) in rabbits fed on processed NKM diet at either levels, were comparable to the values of thos on control diet except a lowered (p < 0.05) blood glucose concentration in processed NKM fed rabbits as compared to that in control diet fed ones. Histological examination revealed increased goblet cell activity, stunting of jejunal villi, mild tubular degeneration in kidney and hepatic fibro-cellular reaction in rabbits fed on urea ammoniated and alkali treated NKM diets with less marked changes in the latter. Testicular changes with variable degree of disorganization and vacuolation of spermatogonial cells were noticed in rabbits fed higher levels of urea-ammoniated and alkali treated NKM. Thus, alkali treatment and urea-ammoniation were effective in detoxification of meal, but the processing technology is to be further perfected to prevent cumulative effect of residual neem bitters in long term feeding.

Hepatoprotective and antifibrotic effects of extracts from Persicae Semen (도인 추출물의 간보호 및 항섬유화 효과)

  • Na Ji-Xing;Park Eun-Jeon;Sohn Dong-Hwan;Ko Geon-Il
    • Herbal Formula Science
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    • v.12 no.2
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    • pp.109-117
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    • 2004
  • This study was carried out to investigate the liver protective effects of extracts from Persicae Semen (WT-003, WT-005, WT-006). The acute hepatic injury was induced by intraperitoneal injection of alpha-naphtylisothiocyanate (75 mg/kg, p.o.) and treated with WT-006 (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day). The experimental hepatic fibrosis was induced by bile duct ligation/scission(BDL/S), duration of 4 weeks and treated with WT-003, WT-005 or WT-006 (200 mg/kg/days for 4 week). In acute liver injury, WT-006 (200 or 400 mg/kg) lowered serum alanine transferase(ALT) and aspartate transferase(AST) significantly. In fibrotic rats, WT-006 treatment inhibited the hydroxyproline deposition in liver and lowered serum AST, ALT and ALP, significantly. These results suggest WT-006 extract, which does not contain amygdalin, from Persicae Semen have liver protective and antifibrotic effects in rats.

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