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Pharmacokinetics of thalidomide in dogs: can feeding affect it? A preliminary study

  • Pierini, Alessio;Sartini, Irene;Giorgi, Mario;Lebkowska-Wieruszewska, Beata;Lisowski, Andrzej;Poapolathep, Amnart;Marchetti, Veronica
    • Journal of Veterinary Science
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    • v.21 no.5
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    • pp.60.1-60.11
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    • 2020
  • Background: Tumor-associated neoangiogenesis is a crucial target for antitumor therapies. Thalidomide (TAL) is a promising anti-neoangiogenetic drug that has recently been used in the treatment of several malignancies in dogs. Objectives: The aim of the study was to assess the pharmacokinetics of TAL after single oral administration in dogs. Additionally, the influence of feeding on the pharmacokinetic profile of TAL in dogs has been preliminarily investigated. Methods: Six healthy adult female Labradors were enrolled according to a randomized single-dose, 2-treatment, 2-phase, paired 2 × 2 cross-over study design. The dogs were administered a single 400 mg capsule of TAL in fasted and fed conditions. Blood was collected from 15 min to 48 h after dosing, and TAL quantified in plasma by a validated high-performance liquid chromatography method. The pharmacokinetics of TAL were analyzed using a non-compartmental approach. Results: TAL concentration was quantifiable up to 10 h and 24 h after fasted and fed conditions, respectively. Cmax (fasted, 1.34 ± 0.12 ㎍/mL; fed, 2.47 ± 0.19 ㎍/mL) and Tmax (fasted, 3 h; fed, 10 h) differed substantially between the 2 groups. AUC and t1/2λz were significantly higher in fed (42.46 ± 6.64 mg × h/L; 17.14 ± 4.68 h) compared to fasted (12.38 ± 1.13 mg × h/L; 6.55 ± 1.25 h) dogs. The relative oral bioavailability of TAL for the fasted group was low (36.92% ± 3.28%). Conclusions: Feeding affects the pharmacokinetics of oral TAL in dogs, showing a delayed, but higher absorption with different rate of elimination. These findings are of importance in clinical veterinary settings, and represent a starting point for further related studies.

Computed tomographic features of gastric and esophageal content in dogs undergoing CT myelography and factors influencing the presence of esophageal fluid

  • Benzimra, Caroline;Cerasoli, Ilaria;Rault, Delphine;Chalvet-Monfray, Karine;Cauvin, Eddy;Couturier, Laurent;Gatel, Laure
    • Journal of Veterinary Science
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    • v.21 no.6
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    • pp.84.1-84.11
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    • 2020
  • Background: Gastroesophageal reflux (GER) has been reported to be a common finding in dogs under general anesthesia. Objectives: The aim of this retrospective study was to assess the esophageal and gastric contents in a population of dogs undergoing computed tomographic myelography (myeloCT) examination and to evaluate the factors influencing the presence of esophageal fluid (gastric content, duration of anesthesia, body position, and intrinsic factors). Methods: Esophageal and gastric contents of 83 non-brachycephalic dogs were retrospectively assessed based on plain and myelo-CT scans. Age, weight, breed, sex, and the time between the 2 computed tomography [CT] scans were included. Results: Esophageal fluid was present in 19% (16/83) of the animals, and 14% (12/83) and 46% (37/83), respectively, had fluid or food material in their stomachs. The frequency of observing esophageal fluid on myelo-CT scans was significantly increased compared with plain CT scans (p = 0.006). The presence of gastric fluid was significantly associated with an increased frequency of observing esophageal fluid compared to other gastric contents (p = 0.049; odds ratio, 3.1). The presence of esophageal fluid was not correlated with alimentary gastric contents (p = 0.17). Increased body weight and duration of anesthesia were significantly associated with an increased frequency of observing esophageal fluid (p = 0.022, p = 0.021). Conclusions: Unlike alimentary gastric contents, fluid gastric contents were correlated with the presence of esophageal fluid upon myelo-CT. The observation of fluid in the esophagus may be consistent with GER. This study provides data additional to pH monitoring studies of GER and may support previous studies recommending shorter pre-anesthetic fasting periods in dogs.

Net energy and its establishment of prediction equations for wheat bran in growing pigs

  • Zhiqian, Lyu;Yifan, Chen;Fenglai, Wang;Ling, Liu;Shuai, Zhang;Changhua, Lai
    • Animal Bioscience
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    • v.36 no.1
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    • pp.108-118
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    • 2023
  • Objective: The objective of this experiment was to determine the net energy (NE) value of 6 wheat bran and 1 wheat shorts by indirect calorimetry and establish the NE prediction equations of wheat bran fed to growing barrows. Methods: Forty-eight growing barrows (28.5±2.4 kg body weight) were allotted in a completely randomized design to 8 dietary treatments that included a corn-soybean meal basal diet, 6 wheat bran diets and 1 wheat shorts diet. The inclusion level of wheat bran or wheat shorts in diets is 30%. Results: The addition of wheat bran reduced the apparent total tract digestibility (ATTD) of nutrients (p<0.05). The ATTD of gross energy, crude protein (CP) and dry matter (DM) in the wheat shorts were greater than that in the wheat bran. Addition of wheat bran or wheat shorts had no effect on total heat production and fasting heat production. The NE of wheat bran was negatively correlated with neutral detergent fiber (r = -0.84; p<0.05) and acid detergent fiber (r = -0.83; p<0.05), while it was positively correlated with CP (r = 0.92; p<0.01). The NE values of wheat bran ranged from 6.79 to 8.15 MJ/kg DM, and the NE value of wheat shorts was 12.47 MJ/kg DM. The ratio of NE to metabolizable energy for wheat bran fed to growing pigs was from 66.0% to 71.7%, whereas the value for wheat shorts was 83.7%. Conclusion: The NE values of wheat bran ranged from 6.79 to 8.15 MJ/kg DM, and the NE value of wheat shorts was 12.47 MJ/kg DM. The NE value of wheat bran can be well predicted based on energy content and proximate analysis.

The comparisons of Lycii Radicis Cortex and Corni Fructus water extract effects on streptozotocin-induced diabetes in rats (지골피, 산수유의 streptozotocin 유발 당뇨흰쥐에서의 효과 비교 연구)

  • Han, Yunkyung;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.28 no.6
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    • pp.71-77
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    • 2013
  • Objectives : This study aimed to compare the anti-diabetic efficacy of Lycii Radicis Cortex (Lycium chinense Mill.) and Corni Fructus (Cornus officinalis) on streptozotocin (STZ)-induced diabetes in rats. Methods : Male Sprague-Dawley rats were divided into four groups; normal, STZ-control, Lycii Radicis Cortex extract-administrated group (LRC) and Corni Fructus extract-administrated group(CF). Diabetes in rats was induced by intraperitonal injection with streptozotocin (STZ) at doses of, 30 mg/kg (body weight) for 5 days (once per a day). STZ-induced diabetic rats were orally administrated LRC and CF extract daily for 4 weeks at doses of 300 mg/kg. Fasting blood glucose, total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN) and creatinine were measured in sera of rats. Histopathological changes of kidney, liver and lung tissues were observed by microscope after H&E staining. Results : There were no differences in body and kidney weights, food intake and water intake in LRC- and CF-administrated groups compared with STZ control group. However, glucose, TC and TG levels in serum were significantly decreased in LRC-administrated groups compared with STZ-control group. In histopathological analysis of kidney, liver and lung, both LRC- and CF-administrated groups showed the inhibition of morphological damage. Conclusions : These results suggest that LRC and CF have a biological action on STZ-induced diabetes in rats via decreasing the serum TG and TG levels and may protect the morphological changes of kidney, liver and lung.

Effects of feed intake and water hardness on fluralaner pharmacokinetics in layer chickens

  • Sari, Ataman Bilge;Gunes, Yigit;Anlas, Ceren;Alkan, Fulya Ustun;Guncum, Enes;Ustuner, Oya;Bakirel, Tulay
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.64.1-64.9
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    • 2022
  • Background: Fluralaner is a novel drug belonging to the isoxazoline class that acts on external parasites of domestic animals. It is used systemically via drinking water, especially against red poultry mite in layer chickens. Fluralaner is frequently used in layers infected with D. gallinae. However, no study to date has investigated the effects of feed intake and water hardness. Objectives: This study aimed to investigate the effects of variable water hardness and feed intake on the pharmacokinetic profile of fluralaner. Methods: Layer chickens were divided into four groups (n = 8): fed + purified water (Group 1), feed restricted + purified water (Group 2), feed restricted + hard water (Group 3), and feed restricted + soft water (Group 4). After administering a single dose of the drug with drinking water, the blood samples were collected for 21 days. Fluralaner concentrations in plasma samples were determined by liquid chromatography/tandem mass spectrometry. The maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), area under the concentration-time curve values (AUC0-21d), half-life (t1/2), and other pharmacokinetic parameters were calculated. Results: Although the highest maximum plasma concentration (Cmax) was determined in Group 1 (fed + purified water), no statistically significant difference was found in the Cmax, tmax, t1/2, MRT0-inf_obs, Vz/Fobs, and Cl/F_obs parameters between the experimental groups. Conclusions: It was concluded that the feed intake or water hardness did not change the pharmacokinetic profile of fluralaner in layer chickens. Therefore, fluralaner could be used before or after feeding with the varying water hardness in poultry industry.

A plant-based multivitamin, multimineral, and phytonutrient supplementation enhances the DNA repair response to metabolic challenges

  • Yeo, Eunji;Hong, Jina;Kang, Seunghee;Lee, Wonyoung;Kwon, Oran;Park, Eunmi
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.450-461
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    • 2022
  • Purpose: DNA damage and repair responses are induced by metabolic diseases and environmental stress. The balance of DNA repair response and the antioxidant system play a role in modulating the entire body's health. This study uses a high-fat and high-calorie (HFC) drink to examine the new roles of a plant-based multivitamin/mineral supplement with phytonutrients (PMP) for regulating the antioxidant system and cellular DNA repair signaling in the body resulting from metabolic stress. Methods: In a double-blind, randomized, parallel-arm, and placebo-controlled trial, healthy adults received a capsule containing either a PMP supplement (n = 12) or a placebo control (n = 12) for 8 weeks. Fasting blood samples were collected at 0, 1, and 3 hours after consuming a HFC drink (900 kcal). The blood samples were analyzed for the following oxidative stress makers: areas under the curve reactive oxygen species (ROS) levels, plasma malondialdehyde (MDA), erythrocytes MDA, urinary MDA, oxidized low-density lipoprotein, and the glutathione:oxidized glutathione ratio at the time points. We further examined the related protein levels of DNA repair signaling (pCHK1 (Serine 345), p-P53 (Serine 15), and 𝛄H2AX expression) in the plasma of subjects to evaluate the time-dependent effects of a HFC drink. Results: In a previous study, we showed that PMP supplementation for eight weeks reduces the ROS and endogenous DNA damage in human blood plasma. Results of the current study further show that PMP supplementation is significantly correlated with antioxidant defense. Compared to the placebo samples, the blood plasma obtained after PMP supplementation showed enhanced DNA damage response genes such as pCHK1(Serine 345) (a transducer of DNA response) and 𝛄H2AX (a hallmark of DNA damage) during the 8 weeks trial on metabolic challenges. Conclusion: Our results indicate that PMP supplementation for 8 weeks enhances the antioxidant system against oxidative stress and prevents DNA damage signaling in humans.

Association between metabolic syndrome components and cardiac autonomic modulation in southern Indian adults with pre-metabolic syndrome: hyperglycemia is the major contributing factor

  • Endukuru Chiranjeevi Kumar;Girwar Singh Gaur;Dhanalakshmi Yerrabelli;Jayaprakash Sahoo;Balasubramaniyan Vairappan;Alladi Charanraj Goud
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.49-59
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    • 2023
  • Metabolic syndrome (MetS) involves multi-factorial conditions linked to an elevated risk of type 2 diabetes mellitus and cardiovascular disease. Pre-metabolic syndrome (pre-MetS) possesses two MetS components but does not meet the MetS diagnostic criteria. Although cardiac autonomic derangements are evident in MetS, there is little information on their status in pre-MetS subjects. In this study, we sought to examine cardiac autonomic functions in pre-MetS and to determine which MetS component is more responsible for impaired cardiac autonomic functions. A total of 182 subjects were recruited and divided into healthy controls (n=89) and pre-MetS subjects (n=93) based on inclusion and exclusion criteria. We performed biochemical profiles on fasting blood samples to detect pre-MetS. Using standardized protocols, we evaluated anthropometric data, body composition, baroreflex sensitivity (BRS), heart rate variability (HRV), and autonomic function tests (AFTs). We further examined these parameters in pre-MetS subjects for each MetS component. Compared to healthy controls, we observed a significant cardiac autonomic dysfunction (CAD) through reduced BRS, lower overall HRV, and altered AFT parameters in pre-MetS subjects, accompanied by markedly varied anthropometric, clinical and biochemical parameters. Furthermore, all examined BRS, HRV, and AFT parameters exhibited an abnormal trend and significant correlation toward hyperglycemia. This study demonstrates CAD in pre-MetS subjects with reduced BRS, lower overall HRV, and altered AFT parameters. Hyperglycemia was considered an independent determinant of alterations in all the examined BRS, HRV, and AFT parameters. Thus, hyperglycemia may contribute to CAD in pre-MetS subjects before progressing to MetS.

Hyperbaric oxygenation applied before or after mild or hard stress: effects on the redox state in the muscle tissue

  • Claudia Carolina Perez-Castro;Alexandre Kormanovski;Gustavo Guevara-Balcazar;Maria del Carmen Castillo-Hernandez;Jose Ruben Garcia-Sanchez;Ivonne Maria Olivares-Corichi;Pedro Lopez-Sanchez;Ivan Rubio-Gayosso
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.9-20
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    • 2023
  • The mechanism is unclear for the reported protective effect of hyperbaric oxygen preconditioning against oxidative stress in tissues, and the distinct effects of hyperbaric oxygen applied after stress. The trained mice were divided into three groups: the control, hyperbaric oxygenation preconditioning, and hyperbaric oxygenation applied after mild (fasting) or hard (prolonged exercise) stress. After preconditioning, we observed a decrease in basal levels of nitric oxide, tetrahydrobiopterin, and catalase despite the drastic increase in inducible and endothelial nitric oxide synthases. Moreover, the basal levels of glutathione, related enzymes, and nitrosative stress only increased in the preconditioning group. The control and preconditioning groups showed a similar mild stress response of the endothelial and neuronal nitric oxide synthases. At the same time, the activity of all nitric oxide synthase, glutathione (GSH) in muscle, declined in the experimental groups but increased in control during hard stress. The results suggested that hyperbaric oxygen preconditioning provoked uncoupling of nitric oxide synthases and the elevated levels of GSH in muscle during this study, while hyperbaric oxygen applied after stress showed a lower level of GSH but higher recovery post-exercise levels in the majority of antioxidant enzymes. We discuss the possible mechanisms of the redox response and the role of the nitric oxide in this process.

Association between Dietary Quality Based on the Korean Healthy Eating Index and Nonalcoholic Fatty Liver Disease in Korean Adult Women: Using Data from the Sixth (2013-2015) Korea National Health and Nutrition Examination Survey (중년여성에서 식생활평가지수에 의한 식사의 질과 비알코올 지방간질환 발생과의 연관성: 제6기(2013-2015) 국민건강영양조사 자료 이용)

  • Mi Hyun Kim
    • Journal of the Korean Society of Food Culture
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    • v.38 no.4
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    • pp.270-282
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    • 2023
  • We performed a study to examine the association between diet quality and nonalcoholic fatty liver disease (NAFLD). Our study included 3,586 women aged 40-64 years who participated in the sixth Korea National Health and Nutrition Examination Survey. The study subjects were classified into the NAFLD group (n=816) and the normal group (n=2,770) using the hepatic steatosis index. The anthropometric indices, blood profiles, and dietary intake data of the subjects were obtained. The waist circumference, body mass index, and the serum levels of triglycerides, fasting blood sugar, HbA1c, and systolic and diastolic blood pressures were higher in the NAFLD compared to the normal groups (p<0.001, respectively). The intakes of protein (g/kg body weight, p<0.001), potassium (p<0.001), and vitamin A (p=0.006) were significantly lower in the NAFLD group. It was observed that the higher the total Korean Healthy Eating Index score, the lower the risk of NAFLD. A reverse relationship was shown between the NAFLD risk and the intakes of total fruits, total vegetables, vegetables excluding Kimchi and pickled vegetables, meat, fish, eggs and beans. Therefore, it is recommended that middle-aged women in Korea increase their intakes of fruits, vegetables, and foods high in protein for the proper management of NAFLD.

Increased prevalence of periodontitis with hypouricemic status: findings from the Korean National Health and Nutrition Examination Survey, 2016-2018

  • Ji-Young Joo;Hae Ryoun Park;Youngseuk Cho;Yunhwan Noh;Chang Hun Lee;Seung-Geun Lee
    • Journal of Periodontal and Implant Science
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    • v.53 no.4
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    • pp.283-294
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    • 2023
  • Purpose: The aim of this study was to investigate the relationship between serum uric acid (SUA) levels and the risk of periodontitis in Korean adults using data from the Korean National Health and Nutrition Examination Survey (KNHANES). Methods: This cross-sectional study used data from the KNHANES 2016-2018 and analysed 12,735 Korean adults aged ≥19 years who underwent oral examinations. Hypouricemia was defined as SUA <3 mg/dL in men and <2 mg/dL in women, and hyperuricemia was defined as SUA ≥7 mg/dL in men and ≥6 mg/dL in women. Results: The weighted prevalence of hypouricemia and hyperuricemia was 0.6% and 12.9%, respectively. The overall weighted periodontitis rate was 30.5%. The frequency of periodontitis in subjects with hypouricemia, normouricemia, and hyperuricemia were 51.1%, 30.3%, and 30.6%, respectively. Study participants with hypouricemia were significantly older, had significantly fasting blood glucose levels, and had better kidney function than non-hypouricemic participants. In univariate logistic regression analyses, hypouricemia was associated with periodontitis, but hyperuricemia was not. The fully adjusted model revealed that the adjusted odds ratio of hypouricemia for periodontitis was 1.62 (95% confidence interval, 1.13-2.33), while the relationship between hyperuricemia and periodontitis in the multivariable logistic regression model was not significant. Conclusions: The results of this study suggest that hypouricemia is associated with an increased risk of periodontitis.