Kg-1 Groups Research Articles

The Effect of Acetamiprid Administration on Bcl-2 Immunoreactivity in the Liver

This study aimed to show the effect of acetamiprid, a neonicotinoid insecticide, on B-cell lymphoma 2 (Bcl-2) gene expression, which plays an important role in apoptotic mechanisms in liver tissue. The study consisted of four groups in total, in which three doses of acetamiprid (5, 10, and 15 mg kg-1) were administered, together with the negative group, in which no substance was administered. Liver tissues resected from mice sacrificed by cervical dislocation after 14 days of acetamiprid administration by gavage were fixed in a 10% formaldehyde solution for histological and immunohistochemical analyses and blocked in paraffin after routine tissue follow-up, and sections were stained with haematoxylin-eosin and immunostaining. Histological analysis revealed normal liver tissue in the control group; whereas, sinusoidal dilatation, vasodilatation, and necrosis and steatosis in the parenchyma were found in the acetamiprid-treated group at an increasing rate depending on the dose amount. The immunoreactivity of Bcl-2 in liver tissue was observed in the sinusoidal epithelium. Bcl-2 immunoreactivity was observed severely in the control and 5 mg kg-1 groups and moderately in the 10 mg kg-1 and 15 mg kg-1 acetamiprid-treated groups. Bcl-2 immunoreactivity was observed homogenously in the region from the central vein to the Kiernan’s space. It was observed that acetamiprid used in the study showed a toxic effect on liver tissue, affected bcl-2 expression, an important biomarker in apoptotic pathways, and induced a dose-dependent decrease in bcl-2 immunoreactivity.

Effect of a novel alkaline protease from Bacillus licheniformis on growth performance, carcass characteristics, meat quality, antioxidant capacity, and intestinal morphology of white feather broilers.

The present study was conducted to investigate the effects of dietary novel alkaline protease from Bacillus licheniformis on the growth performance, meat quality, antioxidant status and intestinal morphology of broilers. In total, 4000 broilers were randomly assigned into five groups and treated with normal control, normal control + 100 mg kg-1 protease, normal control + 200 mg kg-1 protease, normal control + 300 mg kg-1 protease and normal control + 400 mg kg-1 protease. Supplementing protease impacted final body weight (linear, P = 0.003; quadratic, P = 0.006) and decreased feed conversion rate (linear, P = 0.036) in broilers. Moreover, dietary protease significantly increased breast muscle rate (linear, P = 0.005; quadratic, P = 0.021) and decreased drip loss (linear, P < 0.001; quadratic, P < 0.001). In addition, dietary protease notably increased protein digestibility (linear, P = 0.001; quadratic, P = 0.006) and trypsin activity (linear, P = 0.002; quadratic, P = 0.009) in jejunum. Light microscopy revealed that the jejunum villi in the 300 mg kg-1 and 400 mg kg-1 groups exhibited greater height and a denser arrangement compared to those in the control group. The addition of protease decreased malondialdehyde content (linear, P < 0.001; quadratic, P < 0.001) and increased total antioxidant capacity (linear, P = 0.001; quadratic, P < 0.001) in pectoral muscles. The results of the present study suggest that dietary novel alkaline protease from B. licheniformis improved growth performance by affecting trypsin activity, protein digestibility, antioxidant capacity and intestinal health. © 2024 Society of Chemical Industry.

Assessing the impact of different heparin dosing regimens for cardiopulmonary bypass on anticoagulation: the HepDOSE pilot study.

It has been suggested that a larger heparin dose during cardiopulmonary bypass (CPB) is associated with reduced perioperative coagulopathy and thromboembolic complications. We investigated the effect of different heparin doses during routine elective cardiac surgery. Our primary outcomes include blood loss and transfusion and secondary outcomes investigate the effects on coagulation biomarkers. In this prospective pilot trial, we allocated 60 patients undergoing cardiac surgery on CPB in a single tertiary cardiac centre into three groups to receive an initial dose of 300, 400, or 500 units (U) per kilogram of intravenous heparin prior to the commencement of CPB. Blood was sampled after induction of anesthesia, at 30 and 60min of CPB, and three minutes after heparin reversal with protamine. Samples were analyzed for fibrinopeptide A (FPA), fibrinopeptide B (FPB), D-dimer, and thrombin-antithrombin (TAT) complexes. Postoperative blood loss and transfusion was measured for the first 24-hr period after surgery. The total mean (95% CI) administered heparin dose in the 300U·kg-1, 400U·kg-1, and 500U·kg-1 groups were 39,975 (36,528 to 43,421) U, 43,195 (36,940 to 49,449) U and 47,900 (44,807 to 50,992) U, respectively. There were no statistically significant differences in FPA, FPB or D-dimer levels at the measured time intervals. There was a trend towards lower TAT levels while on CPB with greater heparin dosing, which was statistically significant after the administration of protamine. The clinical significance appears to be negligible, as there is no difference in overall blood loss and amount of packed red blood cell transfusion or other blood product transfusion. This pilot study indicates that, while larger heparin dosing for routine cardiac surgery results in subtle biochemical changes in coagulation, there is no demonstrable benefit in postoperative blood loss or transfusion requirements.

The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin.

Alpha cypermethrin (α-CYP) is an insecticide, a member of the group of synthetic pyrethroid pesticides. This study aims to assess the histopathological and biochemical subacute effects of α-CYP on the renal tissues of 48 male Spraque-Dawley adult rats. In this study, the rats were divided into six groups: control, α-CYP (10 mg kg-1), α-CYP (20 mg kg-1), caffeic acid phenethyl ester (CAPE) (10 µmol kg-1), α-CYP + CAPE (10 mg kg-1), and α-CYP + CAPE (20 mg kg-1) groups. The percentage of weight gain was found to be dose-dependent on α-CYP in all groups. As a result of exposure, the normal histological structure of renal tissue was also observed in the control and CAPE groups, while glomerular atrophy and haemorrhage, enlargement of Bowman capsule, glomerular lobulation, and degeneration in distal and proximal tubules were noted in the α-CYP-treated groups with an increased frequency and severity in parallel with the dose increase. Although the severity and intensity of lesions decreased in the α-CYP + CAPE groups, they were statistically insignificant (p > 0.05). A decrease in the antioxidant parameter levels and an increase in oxidant parameters were observed in parallel with the negative effects of the antioxidant system in the α-CYP-treated groups. The groups exposed to CAPE in combination with α-CYP exhibited a therapeutic trend towards normalization in biochemical parameters due to the antioxidant character of CAPE. However, considering the statistical difference between the groups treated with α-CYP alone and CAPE alone, it was observed that the therapeutic features of those chemicals were not robust.

Dietary Supplementation of Silybum marianum Seeds Improved Growth Performance and Upregulated Associated Gene Expression of Muscovy Ducklings (Cairina moschata).

The effect of feeding on diets supplemented with Silybum marianum L. dry seeds (SMS) on growth performance, mortality percentage, biochemical parameters, the expression profile of related genes, and genotoxic effect in Muscovy ducklings was evaluated during a brooding period of 4 weeks. Two hundred and forty one-day-old Muscovy ducks were randomly assigned to four treatment groups (60 ducklings/group), the first group fed on basal diet with no additives (control), and the second (4 g kg-1), third (8 g kg-1), and fourth (12 g kg-1) groups fed the basal diet supplemented with 0, 4, 8, and 12 g kg-1 diet SMS, respectively. A substantial improvement in live body weight (LBW), body weight gain (BWG), and growth rate (GR), and a decrease in feed conversion ratios (FCR) and mortality rate were shown in ducks fed a diet supplemented with either 8 g kg-1 or 12 g kg-1 SMS compared to the other groups. Relevant improvements in liver function, oxidative stress markers, purinergic cell energy, and brain appetite were recorded on ducklings fed diets supplemented with SMS. Moreover, diets which included 8 or 12 g kg-1 SMS positively upregulated the expression of growth hormone gene (GH) and antioxidant genes (SOD1, SOD2, and CAT). These results are consistent with the increase in liver activity SOD and CAT enzymes, resulting in less DNA fragmentation. Consequently, all the aforementioned improvements in biochemical parameters and gene expression profiling may explain the superiority of the treated ducklings compared with the control group. Conclusively, the SMS could be used as a natural feed additive to promote health status and improve the growth performance of small grower ducks during the brooding period.

Post-treatment with metformin improves random skin flap survival through promoting angiogenesis in rats.

Skin flap necrosis has been remained as an unsolved problem in plastic and reconstructive surgeries. Here, we explored the effects of metformin post-treatment on random skin flap survival in rats. An 8.00 × 2.00 cm dorsal skin flap was created in 24 rats and they were then divided into three groups (n = 8) including Control, metformin (Met) 50.00 mg kg-1 and Met 100 mg kg-1. All animals were administrated orally until seven days after flap surgery. Flap survival, the number of blood vessels and mast cells in the flap tissues were analyzed. Vascular endothelial growth factor (VEGF) expression levels in flap tissues was also determined using immunohistochemical methods. The percentage of survival area in Met 50.00 mg kg-1 and Met 100 mg kg-1 groups were significantly higher compared to control. The blood vessel density and the VEGF positive cells in the viable areas of flaps showed a significant increase in Met 50.00 mg kg-1 group compared to control group. The results of this study suggested that treatment with metformin, especially with low dose following skin flap surgery was effective in improving the flap survival and increasing the neovascularization in the flaps tissues of rats.

In-vivo sub-chronic toxicological evaluation of extract of Vernonia glaberrima leaves in experimental rats

The toxicological profile of a plant is an important ethnomedicinal parameter considered in drug discovery, ethno-therapeutics and safety management in vital organs. The study evaluated the 28-day repeated-dose toxicological profile of moderately polar extract of Vernonia glaberrima being investigated as a therapeutic for sleeping sickness and other parasitic infections in experimental rats. Albino rats were divided into four groups (n=10) and the fraction was administered orally once daily at doses of 0 (control), 40, 250 and 1000 mg kg-1 day-1. Food intake, body weight, organ-to-body weight, biochemical, hematological, plasma blood chemistry, serum hormone levels and histopathological examinations were evaluated on the 29th day. There was no difference in the clinical signs between the treated and untreated rats. The mean body weight of female rats treated with 250 mg kg-1 dose increased significantly (p &lt; 0.05) on the 20th day with no difference in the food intake. All the changes in the blood chemistry, hematology and serum hormone levels cannot be considered to be of toxicological importance. A statistically significant elevation (p &lt; 0.05) was observed in the liver-to-body weight (3.21 to 3.89 g 100g-1) of male rats and in the kidney- (0.67 to 0.98 g 100g-1) and brain-to-body (0.58 to 0.72 g 100g-1) weights of female rats in the 1000 mg kg-1 groups. The histopathological examination showed that there was no definitive association between the lesions in the liver and the treatments. The present data, in addition to folklore, has further demonstrated its safety and the need for the isolation of non-toxic bioactive constituents, especially from the dichloromethane fraction.

Neuroprotective and memory enhancing effects of Zataria multiflora in lipopolysaccharide-treated rats.

The study was aimed to evaluate the effects of hydro-ethanol extract Zataria multiflora on the brain tissue oxidative damage, and hippocampal interleukin-6 (IL-6) as well as learning and memory capacity in lipopolysaccharide (LPS) - challenged rats. The rats were randomized into five groups as follow: Control group: Rats were treated with saline, LPS group: Rats were treated with LPS 1.00 mg kg-1, ZM50, ZM100 and ZM200 groups in which the rats were treated with Z. multiflora extract (50.00, 100 or 200 mg kg-1 per day, respectively). The treatments including extract or vehicle were administered intraperitoneally ‎and given three days before the behavioral tests and were continued within a6-day behavioral experiment. Injection of LPS was daily done before the behavioral tests. Finally, the brains were collected for biochemical evaluations. Although LPS administration prolonged the latency in Morris water maze and shortened the latency to enter the dark chamber in passive avoidance test, ZM extract restored these changes to approach control group values. Also, LPS increased IL-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites levels and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) levels in the brain, however, Z. multiflora extract reduced IL-6, MDA and NO metabolites concentrations, but increased thiol content, SOD, and CAT levels. The results of this study showed that Z. multiflora ameliorated learning and memory dysfunction in LPS - challenged rats by alleviating of inflammatory responses and brain tissue oxidative damage.

Influence of Strength Level on Performance Enhancement Using Resistance Priming.

Nishioka, T and Okada, J. Influence of strength level on performance enhancement using resistance priming. J Strength Cond Res 36(1): 37-46, 2022-The current study aimed to investigate (a) whether resistance priming was effective in enhancing jump performance for both stronger and weaker individuals and (b) how resistance priming influences the lower-body force-velocity profile. A total of 20 resistance-trained men performed priming and control conditions 72-144 hours apart in a randomized and counterbalanced order. Jump performances (0 and 40% 1 repetition maximum [1RM] squat jump, 0 and 40% 1RM countermovement jump [CMJ] and drop jump) were assessed before and 24 hours after the priming session, and before and 24 hours after rest (control). Priming session-induced percentage change in 0% 1RM CMJ height was positively correlated with the individual's relative half squat 1RM (r = 0.612, p ≤ 0.05). Using the median split method, subjects were divided into stronger (relative half squat 1RM = 1.93-2.67 kg·kg-1) and weaker (relative half squat 1RM = 1.37-1.92 kg·kg-1) groups and subsequently analyzed. The stronger group showed specific improvement in 0% 1RM CMJ performance 24 hours after the priming session (p ≤ 0.05), whereas the weaker group showed no improvement in any of their jump performances. Moreover, the priming session enhanced the theoretical maximum velocity (p ≤ 0.05), but not the theoretical maximum force during CMJ in the stronger group; whereas none of the force-velocity profile variables were enhanced in the weaker group. These results suggest that stronger individuals are more likely to experience performance enhancement using resistance priming, which may be movement- and velocity-specific.

Prenatal dexamethasone exposure and developmental programming of the ovary of the offspring: a structural study in the rat.

Overexposure to glucocorticoids during fetal development alters fetal organ growth and maturation patterns, which can result in adverse programming outcomes in adulthood. The aim of this study was to determine whether exposure to dexamethasone (Dx) during the fetal period programmed ovary development and function in infant (16-day-old) and peripubertal (38-day-old) female offspring. Pregnant Wistar rats were separated into control and Dx-treated (0.5mg kg-1) groups and were injected with Dx or an equivalent volume of vehicle on Days 16, 17 and 18 of gestation. Ovaries from 16- and 38-day-old female offspring were prepared for histological and stereological examination. The volume of the ovary and the number of primordial and primary follicles were significantly reduced in prenatally Dx-exposed infant and peripubertal female offspring compared with control offspring. The number of multilaminar follicles was decreased in infant female offspring. In peripubertal females, prenatal exposure to Dx increased the number of multilaminar and large follicles of all classes. Because vaginal opening did not occur up to Day 38 postpartum in the Dx-exposed offspring, the absence of ovulation and corpora lutea is confirmation that the onset of puberty had been delayed. We can conclude that overexposure to glucocorticoids early in life programs ovary development, which may affect fertility in adulthood.

Effects of dietary κ-carrageenan on growth and resistance to acute salinity stress in the black tiger shrimp Penaeus monodon post larvae

Acute salinity stress happens unnoticed in shrimp ponds and there is a need to protect the animals by providing dietary functional ingredients that will elicit resistance to this stress. k-Carrageenan, a sulfated polysaccharide from red seaweed, is reported to trigger innate immunity in vitro and in vivo in shrimps. The present study aims to evaluate its potential as growth-promoter and its immune-enhancement effects against salinity stress. Three separate experiments were done: (a) an attractability test; (b) a 30-day feeding trial to determine optimal inclusion of k-carrageenan, and (3) acute salinity stress test. Results of the attractability tests showed that all the experimental diets did not differ in their attractability to the shrimps. In the feeding trial, 5 groups of post larval shrimp were fed with 5 experimental diets containing various inclusion levels of k-carrageenan, namely, 0.0, 0.15, 0.30, 0.45, and 0.60 g kg-1. Results showed that the final average body weight (FABW), weight gain (WG), and specific growth rate (SGR) and feed conversion efficiency (FCE) values of shrimps in the 0.15 and 0.3 g kg-1 were significantly higher than that of the control group; the values of those in 0.45 and 0.60 g kg-1 groups were not significantly different from those of the control group. Protein efficiency ratio (PER) values, in contrast, were not significantly different from each group. Optimal inclusion level in the diet of k-carrageenan was 0.29 g kg-1. In the acute salinity stress test, 5 groups of shrimps were fed with the same 5 experimental diets as those in the feeding experiment for 2 weeks, transferred them from 21 ppt salinity media to 4 ppt. Results showed that the control group exhibited significantly highest mortality rate while in the 0.6 g kg-1 group the lowest; each group were significantly different from each other. Mortality rate decreased with increased dietary k-carrageenan level in a linear fashion. In conclusion, the study demonstrated that the the diets containing dietary k-carrageenan was equally as attractive as the basal/control diet and that k-carrageenan showed both growth-promoting and immune-stimulating effects against acute salinity stress in the black tiger shrimp P. monodon post larvae.

The anti-tussive, anti-inflammatory effects and sub-chronic toxicological evaluation of perilla seed oil.

Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Furthermore, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity studies inferred that the 'no-observed adverse effect level' (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of PSO. © 2020 Society of Chemical Industry.

Effects of Different Doses of Eucalyptus Oil From Eucalyptus globulus Labill on Respiratory Tract Immunity and Immune Function in Healthy Rats

Eucalyptol (1,8-cineole), the major constituent of eucalyptus oil (EO), was used in traditional medicine as a remedy for colds and bronchitis. This study aimed at clarifying the effect of eucalyptol on respiratory immune function of CD8 and CD4 cells, and alveolar macrophages (AM). Thirty male Sprague-Dawley rats were divided into experimental and control groups. The drug was given once a day for 3 weeks and the experimental group was divided according to the eucalyptol dose into: 30, 100, and 300 mg·kg-1 groups. Flow cytometry was used to detect the phagocytic function of CD4, CD8 cells, and AM in the bronchopulmonary lavage fluid. The 30 and 100 mg·kg-1 groups had an up-regulation effect on CD8 (p < 0.05), with no significant effect on macrophage phagocytosis. The 300 mg·kg-1 group had an inhibitory effect on CD8 and macrophage phagocytosis (p < 0.05), with no significant difference in CD4 between groups. Further investigation was conducted to evaluate the effect of EO on immune function in rats by detecting blood T, B, and NK cells using flow cytometry, and blood IgA, IgG, IgM, and IFN-γ levels by ELISA. High dosage of eucalyptol significantly reduced the proportion of blood B and NK cells (p < 0.05). IgA was decreased in the 100 and 300 mg·kg-1 groups (p < 0.05). There are no significant differences between the number of T cells and the IgG, IgM, and IFN-γ levels between experimental and control groups. Rational use of EO containing eucalyptol can improve the immune function of the respiratory tract and the body immunity, while high dose could have damaging effects, through modifying the phagocytic function of CD8 cells and reducing the proportion of blood B cells, NK cells, and IgA.

Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway.

We investigated the liver protective activity of dandelion polyphenols (DP) against acetaminophen (APAP; Paracetamol)-induced hepatotoxicity. Mice were acclimated for 1 week and randomly divided into the following groups (n = 9 per group): Control, APAP, APAP + DP (100 mg·kg-1), APAP + DP (200 mg·kg-1), and APAP + DP (400 mg·kg-1) groups. Mice were pretreated with DP (100, 200, and 400 mg·kg-1) by oral gavage for 7 d before being treated with 350 mg·kg-1 APAP for 24 h to induced hepatotoxicity. Severe liver injury was observed, and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers, protein expressions levels, and liver histopathology. Pretreatment with DP was able to restore serum liver characteristics (aspartate transaminase, AST; alanine aminotransferase, ALT; alkaline phosphatase, AKP), improve redox imbalance (superoxide dismutase, SOD; glutathione, GSH; malondialdehyde, MDA), and decrease inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β). Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein. DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1. The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration, congestion, and necrosis. Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

Acute and 30-day oral toxicity studies of a novel coccidiostat - ethanamizuril.

Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg-1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg-1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg-1 groups. Histopathological observations revealed that 60 and 120 mg kg-1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg-1 feed.

Diuretic effect and material basis of Clematidis Armandii Caulis in rats

To search for the active diuretic fractions of Clematidis Armandii Caulis( CAC) and determine its main active chemical components by using liquid chromatography-mass spectrometry( LC-MS) and diuretic activity evaluation. CAC 75% ethanol extracts and extracts from different polar solvents were orally administered to saline-loaded rats at different doses. 6 h urinary volume,p H and contents of electrolyte Na+,K+and Cl-were measured. The chemical components of the active fractions were separated and identified by ultra performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry( UPLC-ESI-Q-TOF-MS/MS) method. As compared with the control group,the urine volume was increased by 44%( P< 0. 01) and 34%( P < 0. 05) in CAC75% ethanol extract 57. 74 and 28. 8 mg·kg-1 groups respectively; the Na+excretion was increased by 52%( P< 0. 01) and 45%( P<0. 05),respectively; while the Cl-excretion was increased by 101%( P<0. 01) and 85%( P<0. 05),respectively. The urine volume,Na+excretion and Cl-excretion were increased by 50%( P< 0. 01),58%( P< 0. 05),and 65%( P< 0. 05) respectively in petroleum ether extract 70. 98 mg·kg-1 group as compared with the control group. While for the n-butanol extract 194. 18 mg·kg-1 group,the urine volume,Na+and Cl-excretion were increased by 42%( P<0. 01),41%( P<0. 05) and 97%( P<0. 01),respectively. The diuretic activity of other fractions was not obvious. There was no statistical difference in K+excretion in all groups. The results of LC-MS analysis showed that six compounds,including two sterols,one chromogen and three fatty acids,were identified from petroleum ether extract.Fourteen compounds,including six triterpenoid saponins,six lignin glycosides,one sterol glycoside and one phenolic glycoside,were identified from the n-butanol extract. All the results suggested that the ethanol extract of CAC had remarkable diuretic activity and its main effective components included sterol,triterpenoid saponin and lignin glycosides.

Determination of the median effective dose of propofol in combination with different doses of ketamine during gastro-duodenoscopy in children: a randomised controlled trial

Propofol is used to induce deep sedation or general anaesthesia for procedures in children. Adjuvants, such as ketamine, are routinely added to reduce the dose of propofol required and propofol-related adverse events. We conducted a randomised controlled trial to determine the effective bolus dose of propofol in combination with ketamine that induces adequate depth of anaesthesia in 50% of children (ED50) undergoing gastro-duodenoscopy. Children were randomised to one of four doses of ketamine: 0 (control), 0.25, 0.5, and 1 mg kg-1, followed by a dose of propofol according to Dixon's up-and-down methodology. Excessive movement, coughing, gagging, or airway obstruction that prevented endoscope insertion was considered a failure. The ED50 of propofol (median, 95% CI) was greater in the ketamine 0, 0.25, and 0.5 mg kg-1 groups compared with the ketamine 1 mg kg-1 group (6.1, 4.1-8.1; 4.5, 2.9-6; 4.7, 3.1-6.2 mg kg-1vs 1.1, 0.5-1.8 mg kg-1, respectively, P<0.008). Total dose of propofol administered during the procedure was reduced with ketamine 1 mg kg-1. The mean arterial pressure was lower in the ketamine 0 mg kg-1 group compared with the 1 mg kg-1 group during and immediately after the procedure. The ketamine 1 mg kg-1 group experienced a higher incidence of nausea and visual disturbances. Ketamine at 0.5-1 mg kg-1 reduces the dose of propofol required to provide general anaesthesia for gastro-duodenoscopy in children and may reduce the incidence of propofol-related changes in haemodynamics. NCT 02295553.

Protective effect of Ginkgo biloba extract on paracetamol-induced acute hepatic injury in mice

To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism. Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg-1)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1. Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(P<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(P<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(P<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(P<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). The high-dose of GBE possessed the most obvious treatment effect among them. GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.

Protective effect of hydroxysafflor yellow A on bleomycin- induced pulmonary inflammation and fibrosis in rats.

To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats. Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone (DXM) group. Three doses of HSYA (35.6, 53.3, and 80.0 mg•kg-1•day-1) were intraperitoneally (i.p.) injected in rats for 3 weeks after BLM administration and DXM was used as the positive control (n=8 or 12). Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin (α-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure (PaO2) increased (HSYA 80.0 mg•kg-1, P<0.01) and CO2 partial pressure (PaCO2) decreased (HSYA 53.3, 80.0 mg•kg-1, P<0.05). Moreover, the mRNA expression of TNF-α, IL-1β, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg•kg-1 groups than those in the model group (all P<0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 (HSYA 53.3, 80.0 mg•kg-1, P<0.01), and decreased PaCO2 (53.3 and 80.0 mg•kg-1, P<0.05). Further, the mRNA expression of TGF-β1, α-SMA, and collagen I as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes (53.3, 80.0 mg•kg-1, P<0.05). Hematoxylin and eosin and Masson's trichrome staining indicated that the fibrosis and collagen deposition were ameliorated in HSYA groups (53.3, 80.0 mg•kg-1, P<0.05). HSYA could alleviate acute lung inflflammation and chronic pulmonary fibrosis induced by BLM in rats.

Pharmacokinetics and analgesic effectiveness of intravenous parecoxib for tonsillectomy ± adenoidectomy.

Few pharmacokinetic (PK) and pharmacodynamic (PD) data exist for COX-2 selective inhibitors in children. We wished to characterize the PKPD of parecoxib and its active metabolite, valdecoxib, in this population. Children (n = 59) were randomized to parecoxib 0.25 mg·kg-1 , 1 mg·kg-1 , and 2 mg·kg-1 during tonsillectomy ± adenoidectomy. Samples (4-6 per child) were obtained from indwelling cannula over 6 h. A second group of inpatient children (n = 15) given 1 mg·kg-1 contributed PK data from 6 to 24 h. Pain scores and rescue medication for the first group were recorded postoperatively for up to 24 h. PK data were pooled with those (10 samples/24 h) from a published study of children (n = 38) who underwent surgery. A three-compartment parent and one-compartment metabolite model with first-order elimination was used to describe data using nonlinear mixed effects models. An EMAX model described the relationship between dose and rescue morphine equivalents during recovery. Parecoxib PK parameter estimates were CLPARECOXIB 19.1 L·h-1 ·70 kg-1 , V1PARECOXIB 4.2 L·70 kg-1 , Q2PARECOXIB 6.29 L·h-1 ·70 kg-1 , V2PARECOXIB 130 L·70 kg-1 , Q3PARECOXIB 6.02 L·h-1 ·70 kg-1 , and V3PARECOXIB 2.03 L·70 kg-1 . We assumed all parecoxib was metabolized to valdecoxib with CLVALDECOXIB 9.53 L·h-1 ·70 kg-1 and VVALDECOXIB 51 L·70 kg-1 . There was no maturation of clearance over the age span studied. There were no differences in pain scores between groups on waking, discharge, 12 h, or 24 h. There were no differences in analgesia consumption over 24 h between groups for tramadol, fentanyl, and morphine rescue use. Fentanyl and morphine consumption, expressed as morphine equivalents (0.13 mg·kg-1 ) in the 0.25 mg·kg-1 group, was greater than that observed in the 1 or 2 mg·kg-1 groups (0.095 mg·kg-1 ) in PACU. Parecoxib 0.9 mg·kg-1 in a 2-year-old, 0.75 mg·kg-1 in a 7-year-old, and 0.65 mg·kg-1 in a 12-year-old child achieves dose equivalence of 40 mg in a standard 70 kg person. Clearance maturation may occur in infants younger than the current cohort. Parecoxib doses above 1 mg·kg-1 add no additional analgesia.