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Pharmacokinetics and Pharmacodynamics of Pimobendan-Pentoxifylline Liquid Mixture After Oral Administration in Dogs

  • Ro, Woong-bin;Song, Doo-won;Kim, Ki-hun;Jeong, Sang-hee;Kang, Min-hee
    • Journal of Veterinary Clinics
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    • v.36 no.3
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    • pp.159-165
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    • 2019
  • Pimobendan is an inodilator used to treat canine heart failure, and pentoxifylline is reported to be beneficial for microcirculation and heart disease. The purpose of this study was to evaluate the pharmacokinetic and pharmacodynamic profiles of a novel pimobendan-pentoxifylline liquid mixture after oral administration to dogs. Eight healthy Beagle dogs were included in the study. The dogs were divided into the control group (orally administered water; n = 4) and experimental group (orally administered pimobendan-pentoxifylline liquid mixture [pimobendan 0.25 mg/kg, pentoxifylline 15 mg/kg]; n = 4). Plasma samples were obtained and echocardiographic indices were measured for 24 hours after administration. The concentrations of pimobendan and pentoxifylline were quantified by using a liquid chromatography-mass spectrometer (LC-MS). The elimination half-life ($T_{1/2}$) was $32.96{\pm}9.80mins$ for pimobendan and $29.49{\pm}6.67mins$ for pentoxifylline. The time to reach maximum concentration ($T_{max}$) were $52.50{\pm}31.22mins$ for pimobendan and $41.25{\pm}18.87mins$ for pentoxifylline. The maximum blood concentration ($C_{max}$) was $96.92{\pm}75.64ng/mL$ for pimobendan and $7074.07{\pm}3261.1ng/mL$ for pentoxifylline. Of the echocardiographic indices, fractional shortening (FS) and left ventricular internal diameter at end systole (LVIDs) were significantly altered at 1-3 hours after the administration of pimobendan-pentoxifylline liquid mixture. The pimobendan-pentoxifylline liquid mixture was well tolerated by the dogs, with no adverse effects observed during the study.

Occupational Exposure to Metals in Shooting Ranges: A Biomonitoring Study

  • Vandebroek, Eline;Haufroid, Vincent;Smolders, Erik;Hons, Luc;Nemery, Benoit
    • Safety and Health at Work
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    • v.10 no.1
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    • pp.87-94
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    • 2019
  • Background: Lead (Pb) exposure in shooting ranges has been reduced by various measures such as jacketed ammunition and lead-free primers. Nevertheless, this may lead to exposure to other metals, potentially resulting in adverse health effects. Methods: In a cross-sectional study, 35 subjects from seven different shooting ranges were studied: four shooting instructors, 10 police officers, 15 Special Forces, and six maintenance staff members. Metals and metalloids were determined in blood and urine by inductively coupled plasma-mass spectrometry. Results: The concentrations of most elements did not differ significantly between groups or compared to reference values, except for Sb and Pt in urine and Pb in blood. Mean values for Sb were considerably higher in urine from the Special Forces ($0.34{\mu}g/L$), the maintenance staff ($0.13{\mu}g/L$), and shooting instructors ($0.32{\mu}g/L$) compared to the police officers before shooting ($0.06{\mu}g/L$) and a Belgian reference value ($0.04{\mu}g/L$). For Pt, the Special Forces showed higher mean urinary concentrations ($0.078{\mu}g/L$) compared to a Belgian reference value (<$0.061{\mu}g/L$). Mean values for blood lead were markedly higher in the Special Forces ($3.9{\mu}g/dL$), maintenance staff ($5.7{\mu}g/dL$), and instructors ($11.7{\mu}g/dL$) compared to police officers ($1.4{\mu}g/dL$). One instructor exceeded the biological exposure index for blood Pb ($38.8{\mu}g/dL$). Conclusion: Since both Pb and Sb were found to be higher in shooting range employees, especially among frequent shooters, it is advisable to provide appropriate protective equipment, education, and medical follow-up for shooting range personnel in addition to careful choice of ammunition.

Effect of Glycyrrhizae Radix Water Extract on the depression induced by LPS in Rats (LPS로 유발된 우울증에 대한 감초(甘草)의 효과)

  • Ko, Sung-Youl;Kim, Do-Hoon;Lee, Tae-Hee
    • The Korea Journal of Herbology
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    • v.29 no.5
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    • pp.9-16
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    • 2014
  • Objectives : Investigation of the antidepressant effect of Glycyrrhizae Radix (GR) through the anti-inflammatory effect. Methods : Depression in rats was induced by LPS (i,p.3days). The rats were treated with GR100 mg/kg (GR 100) or GR400 mg/kg (GR 400). The depressive immobility was examined with Tail Suspension Test(TST) and Forced Swimming Test(FST). The expression of nuclear factor-${\kappa}B$(NF-${\kappa}B)$, $I{\kappa}B$ was measured with western blotting. The concentration of corticosterone, cytokine in plasma was measured with ELISA. The expression of c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coeluleus(LC) were measured with immunostaining method. Results : In the TST, GR400 group significantly decreased immobility time compared with the LPS group. In the FST, GR100, GR400 group significantly decreased immobility time comparing with the LPS group. c-Fos expression in GR100 and GR400 group was decreased comparing with the lipoplysaccharide(LPS) group. The $I{\kappa}B$ expression of GR100 and GR400 group was increased comparing with the LPS group. The level of corticosterone of GR100 group was decreased comparing with the LPS group. The concentration of cytokine of GR100 and GR400 group was decreased comparing with the LPS group. TH expression in the LC was increased in LPS group, but in GR100 and GR400 group was not shown significant decrease. Conclusion : According to this results obtained, GR has antidepressant effects by the anti inflammatory action through the suppression of HPA axis activity, not through the action against the catecholaminergic system.

The Regulatory Effect of Angelica gigas Nakai on Immune Enhancement and Cytokine Production in vivo and in vitro (참당귀(Angelica gigas Nakai)의 체력증진 및 면역조절효과)

  • Jeon, Yong-Deok;Kim, Su-Jin
    • Korean Journal of Plant Resources
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    • v.35 no.4
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    • pp.411-416
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    • 2022
  • Natural products are important sources for drug development because they have a wide variety of useful biological properties. Angelica gigas Nakai (AGN) has been used as an herbal medicine for treatment of colds, pain, and anemia. The present study was designed to evaluate the regulatory effect of AGN on immune enhancement in vivo and in vitro. To investigate the immune-enhancing effect of AGN, we used forced swimming test (FST) experimental model. Mice were orally administered by AGN or distilled water for 14 days and then immobility time and biological parameters in serum were measured. The results showed that immobility time in AGN treatment group was significantly reduced in comparison with the control group. Plasma levels of blood urea nitrogen and lactate dehydrogenase in AGN group was significantly decreased compared with control group. Additionally, we showed that AGN treatment significantly increased immune-related cytokines such as interleukin (IL)-4, IL-2, and interferon (IFN)-𝛾 levels in Molt-4 cells. Collectively, the findings provide experimental evidence that AGN may be effective in improving immune function.

Anti-inflammatory Effect of Biotin and Plant extracts

  • Y. J. Joo;S. W. Jung;Kim, B. R.;Kim, I. Y.;Lee, J. D.;H. C. Ryoo;Lee, S. H.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.601-610
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    • 2003
  • Biotin is a water-soluble vitamin used as a skin conditioning agent and promotes the formation of intercellular lipid layers through increased lipid synthesis, which improves the skin's natural barrier function. The anti-inflammatory effects of biotin have been investigated using in vitro assay models, such as MTT assay, measurements of concentrations of nitric oxide(NO), prostaglandin E2(PGE$_2$), and inhibition rate of 5-lipoxygenase(5-LOX). In comparison with biotin, other plant extracts were tested at the same time which were kudzu vine extract, sage extract, paeonia extract, and dipotassium glycyrrhetinate. Nitric oxide is a signal molecule with functions such as neurotransmission, local vascular relaxation, and anti-inflammation in many physiological and pathological processes. NO can cause apoptosis and necrosis of target cells such as keratinocytes and is generated from L-arginine by nitric oxide synthase (NOS). Prostanoids, including prostaglandins and thromboxanes, are generated by the phospholipase $A_2$/cyclooxygenase(COX) pathway, and leukotrienes are generated by the 5-lipoxygenase pathway from arachidonic acid. Prostaglandin E2 recently have been shown to be beneficial in the resolution of tissue injury and inflammation, also has been implicated as an immunosuppressive agent and plasma levels of PGE$_2$ are elevated in patients sustaining thermal injury. Lipoxygenase metabolites from arachidonic acid have been implicated in inflammation, anti-inflammatory activity of the raw materials was evaluated in vitro by the offered inhibition of lipoxygenase.

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Raoultella ornithinolytica as a Potential Candidate for Bioremediation of Heavy Metal from Contaminated Environments

  • Laila Ibrahim Faqe Salih;Rezan Omer Rasheed;Sirwan Muhsin Muhammed
    • Journal of Microbiology and Biotechnology
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    • v.33 no.7
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    • pp.895-908
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    • 2023
  • Disposal of waste containing heavy metals into the environment is a major threat to human health and can result in toxic or chronic poisoning in aquatic life. In the current study, metal-resistant Raoultella ornithinolytica was isolated from metal-contaminated samples collected from the Tanjaro River, located southwest of Sulaymaniyah, Iraq. R. ornithinolytica was identified by partial amplification of 16S rRNA. The uptake potency of heavy metals was assessed using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and indicated that R. ornithinolytica removed 67, 89, 63.4, 55.6, 56.5, 65, and 61.9% of Cd, Pb, Cr, Ni, Zn, Co, and Fe, respectively. These removal rates were influenced by temperature, pH, and contact time; at 35℃ and pH 5 with a change in the incubation time, the reduction rate improved from 89 to 95% for Pb, from 36.4 to 45% for Cu, and from 55.6 to 64% for Ni. Gene analysis indicated that R. ornithinolytica contained pbrT, chrB, nccA, iroN, and czcA genes, but the pcoD gene was absent. Energy-dispersive X-ray spectroscopy (EDS) images showed evidence of metal ion binding on the cell wall surface with different rates of binding. Transmission electron microscopy (TEM) detected different mechanisms for metal particle localization; cell surface adsorption was the main mechanism for Pb, Zn, and Co uptake, while Cd, Ni, and Fe were accumulated inside the cell. The current study describes, for the first time, the isolation of R. ornithinolytica from metal-contaminated water, which can be used as an eco-friendly biological expedient for the remediation and detoxification of metals from contaminated environments.

Evaluation of preslaughter losses, meat quality, and physiological characteristics of broilers in response to crating density for the standard of animal welfare and to seasonal differences

  • Myunghwan Yu;Elijah Ogola Oketch;Jun Seon Hong;Shan Randima Nawarathne;Yuldashboy Vohobjonov;Jung Min Heo
    • Korean Journal of Agricultural Science
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    • v.49 no.4
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    • pp.927-936
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    • 2022
  • The effects of seasonal differences and crating densities on the preslaughter losses, breast meat quality, and physiological indices of broilers were determined. A total of 600 broilers aged 35 days were divided into 10 treatment groups based on five crating densities (10.3, 11.5, 12.8, 14.1, 15.4 birds·m-2) with two seasons (i.e., summer and winter) to give six replicates and were placed at various locations in the truck. The birds were transported in crates having dimensions of 1.0 m × 0.78 m × 0.26 m. The transportation distance was 20 km for 40 minutes (average 30 - 50 km·h-1) during the early morning. The results revealed that broilers transported at densities of 14.1 and 15.4 birds·m-2 recorded lower (p < 0.05) pH, water-holding capacity (WHC), and muscle redness compared to those at densities of 11.5 birds·m-2. Furthermore, higher (p < 0.05) cooking loss was found in birds stocked at more than 14.1 birds·m-2 compared to the other treatments. However, no effect (p > 0.05) with different crating densities on body weight loss, carcass traits, glucose, lactate, or muscle yellowness was observed. Crating density of 14.1 birds·m-2 showed lower (p < 0.05) cortisol contents compared with birds at 10.3 and 15.4 birds·m-2. Winter transportation had higher (p < 0.05) relative breast meat weight, cooking loss, muscle redness, and cortisol contents whereas summer transportation had higher (p < 0.05) glucose and lactate contents in the blood plasma of broilers. In conclusion, the stocking of 12.8 birds·m-2 is recommended to minimize stress responses and undesirable changes that could negatively affect muscle quality.

A Study on Antiulcer Effects of Opuntia dillenii Haw. on Stomach Ulcer Induced by Water-immersion Stress in Rats (랫드의 스트레스성 위궤양에 대한 Opuntia dillenii Haw.(선인장)의 항궤양작용에 관한 연구)

  • 이후장;이용욱;김정현
    • Journal of Food Hygiene and Safety
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    • v.13 no.1
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    • pp.53-61
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    • 1998
  • This study was performed to investigate the antiulcer effects of Opuntia dillenii Haw. on the stomach ulcer induced by restraint and water-immersion stress in rats. For this experiment, 48 male Sprague-Dawley strain were used. The experimental groups were divided into four: a control (C) and 3 Opuntia dillenii Haw. treatment groups (E-1, E-2, E-3). Each dose of Opuntia dillenii Haw. was 30 mg/kg bw (E-1), 60 mgfKg bw (E-2) and 120 mg/kg bw (E-3). The rats were allocated to each group by 12 and observed for 4 weeks. The results were as following: 1. The stomach surface pH in each group showed no significant difference, but the values of Opuntia dillenii Haw. treatment groups were higher than the value of the control group. 2. The gastric wall mucus was increased in all Opuntia dillenii Haw. treatment groups compared with the control group. Especially in E-1 difference was higher (p<0.05) and in E-2 difference was significantly higher (p<0.01). 3. At shear rate 11.25, 45.0, 90.0, $225\;sec^{-1}$, whole blood viscosity and plasma viscosity were measured. Most of the values of Opuntia dillenii Haw. treatment groups were low compared with that of the control group. At shear rate 90.0, $225\;sec^{-1}$ the values of whole blood viscosity in E-1 were significantly low (p<0.05) and at shear rate 11.25, $45.0\;sec^{-1}$, more significant (p<0.01). At shear rate 11.25, 45.0, 90.0, $225\;sec^{-1}$ the values of whole blood viscosity in E-2 were significantly low (p<0.01). At shear rate $90.0\;sec^{-1}$ the value of plasma viscosity in E-1 was significantly low (p<0.05) and at shear rate 90.0, $225\;sec^{-1}$ the values of plasma viscosity in E-2 we resignificantly low (p<0.01). 4. Less severe ulcers were obsered in Opuntia dillenii Haw. treatment groups than in the control group. Especially E-1 groups tissues had only slight ulcers and necrosis of tissue was not observed in this group. From the results of this study, it can be concluded that the oral administratio-n of Opuntia dillenii Haw. results in protection of stomach ulcer by stimulating the secretion of gastric mucus and improving the gastric mucosal microcirculation.

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Effects of Fruits and Stems of Opuntia ficus-indica on Blood Glucose and Lipid Metabolism in Streptozotocin-induced Diabetic Rats (손바닥선인장의 열매와 줄기가 Streptozotocin으로 유발된 당뇨 쥐의 혈당 및 지질대사에 미치는 영향)

  • Yoon, Jin-A;Son, Yong-Suk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.2
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    • pp.146-153
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    • 2009
  • This study was conducted to examine the effects of fruits and stems of Opuntia ficus-indica var. saboten Makino on water intake, feed intake, body weight, blood glucose level and glucose tolerance in streptozotocin (STZ)-induced diabetic rats. Forty Sprague-Dawley male rats were divided into non-diabetic control (NC), diabetic control (DC), 8% Opuntia fruit (DOF), 5% Opuntia stem (DO-5) and 10% Opuntia stem (DO-10) groups. Fruits and stems of Opuntia ficus-indica were freeze-dried and ground before use in the experiment. Animals were fed experimental diet for 3 weeks. DOF, DO-5 and DO-10 groups showed lower water and feed intake as well as less body weight loss than DC group. The fasting blood glucose levels were 100 mg/dL for NC and 379 mg/dL for DC. Fasting glucose level of DOF was a significantly low level of 28% (p<0.05), whereas DO-5 and DO-10 had a decrease of 5% and 9% compared to DC. As for the glucose tolerance test, the highest blood glucose levels for NC and DC-10 group were observed at 30 minutes after glucose injection while those of DOF and DO-5 groups were after 60 minutes. DOF and DO-5 plasma insulin level improved. Plasma total cholesterol, triglyceride, non-esterified fatty acid (NEFA) and LDL-cholesterol concentrations were also lower in DOF, DO-5 and DO-10 groups, although HDL-cholesterol level was only slightly affected by experimental diets compared to DC. These results suggest that the feeding of Opuntia ficus-indica fruits and stems improved blood glucose and lipid metabolism in STZ-induced diabetic rats.

Lipid-Lowering Action of Powder and Water Extract of Mulberry Leaves in C57BL/6 Mice Fed High-Fat Diet (고지방식이를 급여한 C57BL/6 마우스에서 뽕잎분말과 열수추출물의 지질저하 작용)

  • Cho, Young-Sook;Shon, Mi-Yae;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.4
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    • pp.405-410
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    • 2007
  • This study was to investigate the hypolipidemic effect of powdered mulberry leaves (PML) and water extract of powdered mulberry leaves (WML) on high-fat fed mice. Male C57BL/6 mice were divided into four groups; a normal group (N), a high-fat (HF) group, a high-fat group supplemented with PML (HF-PML) and a high-fat group supplemented with WML (HF-WML). The PML or WML was added to a standard diet based on 1% dried mulberry loaves (1g PML/100g diet and 0.22g WML/100g diet) for 6 weeks. Body weight and organ weights were not different among thle groups in high-fat fed mice, whereas food intake and daily energy intake were significantly (p<0.05) lowered in the HF-PML group. In plasma and liver, the supplementation of PML and WML significantly (p<0.05) lowered cholesterol and triglyceride concentrations compared to the HF group. The HDL-cholesterol/total cholesterol ratio was significantly (p<0.05) higher in the HF-PML and HF-WML groups than in the B:.w group. The fecal triglyceride and cholesterol concentrations were significantly (p<0.05) increased in the HF-PML and HF-WML groups compared to the HF group. Hepatic lipid regulating enzyme activities, fatty acid synthase, fatty acid ${\beta}-oxidation$ and carnitine palmitoyl transferase were significantly lower in the HF group than in the N group. However, the activities of these hepatic lipid regulating enzymes activities were significantly (p<0.05) elevated in the HF-PML and HF-WML groups compared to the HF group. Accordingly, these results suggest that PML and WML improve plasma and hepatic lipid levels partly by increasing fecal lipid excretion and enhancing hepatic lipid regulating enzymes activities.