Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic (ANT) application and affect gene expression. In this study, we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate (GLY), two ANTs, and one anticoccidial drug (AD). A total of 260 Ross 308 broilers aged 1‍-‍40 d were divided into the following four groups of 65 birds each: control group, which was fed the main diet (MD), and three experimental groups, which were fed MD supplemented with GLY, GLY+ANTs (enrofloxacin and colistin methanesulfonate), and GLY+AD (ammonium maduramicin), respectively. The results showed that the addition of GLY, GLY+ANTs, and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance. In particular, genes related to inflammation and apoptosis (interleukin 6 (IL6), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 6 (CASP6)) were downregulated by up to 99.1%, and those related to antioxidant protection (catalase (CAT), superoxide dismutase 1 (SOD1) and peroxiredoxin 6 (PRDX6)) by up to 98.6%, compared to controls. There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups, and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood. The changes revealed in gene expression and blood indices in response to GLY, ANTs, and AD provide insights into the possible mechanisms of action of these agents at the molecular level. Specifically, these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY, GLY+ANTs, and GLY+AD in broilers.
Animals ; Glyphosate ; Glycine/administration & dosage* ; Chickens/blood* ; Pancreas/metabolism* ; Anti-Bacterial Agents/pharmacology* ; Animal Feed ; Gene Expression/drug effects* ; Herbicides

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.
Administration, Intranasal ; Animals ; Anxiety ; Arm ; Brain ; Central Nervous System ; Isoniazid ; Mice ; Picrotoxin ; Receptors, Glycine ; Seizures ; Strychnine ; Taurine ; Yohimbine

Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.
Administration, Oral* ; Animals ; Dipeptides* ; Elasticity* ; Glycine* ; Humans ; Hyaluronic Acid ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Keratinocytes ; Leucine* ; Mice ; Mice, Hairless* ; Minerals ; Miners ; Pancreatic Elastase ; Peptides ; Placenta ; RNA, Messenger ; Skin* ; Up-Regulation

OBJECTIVETo observe and study the effects of sivelestat on acute lung injury in dogs with severe burn-blast combined injury.

METHODSThirty-two male beagle dogs of clean grade were divided into 4 groups: uninjured group (U), combined injury control group (CIC), combined injury+low dose of sivelestat group (CI+LS), combined injury+high dose of sivelestat group (CI+HS), with 8 dogs in each group. Except for the dogs in group U which were not injured, the dogs in the other 3 groups were inflicted with severe burn-blast combined injury. According to the Parkland formula, the dogs in groups U and CIC were infused with physiological saline, and the dogs in groups CI+LS and CI+HS received sivelestat with the dosage of 0.5 and 2.0 mg·kg(-1)·h(-1) respectively in addition. The 24 h continuous intravenous infusion was carried out for 2 days. At post injury hour (PIH) 6, CT scanning was conducted to observe the lung damage. At PIH 2, 6, 12, 24, and 48, mean arterial pressure (MAP), respiratory rate (RR), extra vascular lung water (EVLW), pulmonary vascular permeability index (PVPI), PaO2, and PaCO2 were measured; the contents of neutrophil elastase (NE), IL-8, and TNF-α were determined by ELISA. At PIH 48, all the dogs were sacrificed, and the lung tissues were harvested to measure the wet to dry lung weight ratio. The same examination was carried out in the dogs of the group U at the same time points. Data were processed with analysis of variance of repeated measurement and LSD test.

RESULTS(1) CT images showed some exudative lesions in the dogs of groups CIC and CI+LS but not in the dogs of groups U and CI+HS. (2) No statistically significant differences were observed in MAP at each time point between every two groups (with P values above 0.05). The RR values in group U were significantly different from those of the other 3 groups at all time points (with P values below 0.05). The values of EVLW and PVPI in 3 combined injury groups were significantly different from those in group U at PIH 6, 12, 24, and 48 (with P values below 0.05). The values of RR and EVLW in group CI+LS were significantly different from those in group CI+HS at PIH 12, 24, and 48 (with P values below 0.05). The values of PVPI in group CI+LS were significantly different from those in group CI+HS at PIH 24 and 48 (with P values below 0.05). (3) The levels of PaO2 and PaCO2 showed significant differences between group U and the other 3 groups at each time point (with P values below 0.05). The levels of PaO2 in group CI+LS were significantly different from those in CI+HS group at PIH 12, 24, and 48 (with P values below 0.05). The level of PaCO2 showed significant differences between group CI+LS and group CI+HS at PIH 24 and 48 (with P values below 0.05). (4) The contents of NE (except for PIH 2), TNF-α, and IL-8 showed significant differences between group U and the other 3 groups at each time point (P < 0.05 or P < 0.01). At PIH 2, 6, 12, 24, and 48, the contents of NE in groups U, CIC, CI+LS, and CI+HS were respectively (69 ± 21), (83 ± 24), (80 ± 20), (75 ± 17), (72 ± 27) pg/mL; (66 ± 24), (196 ± 20), (231 ± 26), (252 ± 25), (266 ± 22) pg/mL ; (71 ± 22), (180 ± 27), (214 ± 21), (194 ± 24), (218 ± 20) pg/mL; (68 ± 22), (136 ± 24), (153 ± 22), (146 ± 26), (150 ± 28) pg/mL. NE values in group CI+HS were statistically different from those in groups CIC and CI+LS at PIH 6, 12, 24, and 48 (with P values below 0.05). The contents of TNF-α in group CI+LS were statistically different from those in groups CIC and CI+HS at PIH 24 and 48 (with P values below 0.05). The contents of IL-8 in group CI+LS were statistically different from those in group CI+HS at PIH 24 and 48 (with P values below 0.05). (5) At PIH 48, the wet to dry lung weight ratio of group CIC was statistically different from that in group CI+LS or group CI+HS (with P values below 0.05); there was also difference between group CI+LS and group CI+HS (P < 0.05).

CONCLUSIONSSivelestat, especially in a high dose, exerts a protective effect in acute lung injury after burn-blast combined injury through improving the index of blood gas analysis, ameliorating pulmonary edema, and lowering the production of pro-inflammatory mediators.

Acute Lung Injury ; complications ; drug therapy ; Animals ; Blood Gas Analysis ; Burns ; complications ; Capillary Permeability ; Dogs ; Extravascular Lung Water ; Glycine ; administration & dosage ; analogs & derivatives ; Infusions, Intravenous ; Interleukin-8 ; Male ; Pulmonary Edema ; etiology ; Serine Proteinase Inhibitors ; administration & dosage ; Sulfonamides ; administration & dosage ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the effect of different doses of glyphosate on apoptosis and expressions of androgen-binding protein (ABP) and vimentin mRNA in mouse Sertoli cells.

METHODSPrimarily cultured mouse Sertoli cells incubated with different doses of glyphosate (60, 90, 120, 150 and 180 mg/L) for 24 h. The growth and morphological alterations in the cells were observed under inverted microscope, and the cell proliferation rate was evaluated withMTT assay. Hoechst 33342 staining was used to detect cell apoptosis after the treatment, and RT-PCR was performed to examine the changes in the expression of ABP and vimentin mRNAs.

RESULTSSertoli cells exposed to glyphosate showed a reduced cell volume, cell dissociation with occasional cell disruption. The proliferation of the exposed was suppressed with an increased rate of cell apoptosis and lowered expressions of ABP and vimentin mRNAs (P<0.05).

CONCLUSIONGLY can cause cellular damages, inhibit cell proliferation, induce cell apoptosis, and decrease expression of ABP and vimentin mRNAs in mouse Sertoli cells in vitro.

Androgen-Binding Protein ; genetics ; metabolism ; Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Glycine ; administration & dosage ; analogs & derivatives ; toxicity ; Herbicides ; administration & dosage ; toxicity ; Male ; Mice ; RNA, Messenger ; metabolism ; Sertoli Cells ; cytology ; drug effects ; metabolism ; Vimentin ; genetics ; metabolism

OBJECTIVETo evaluate the effect of decoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C on the indices of hepatic fibrosis in chronic hepatitis B.

METHODThe 94 cases of chronic viral hepatitis B patients were randomly divided into two groups. The treatment group was treated with stronger neo-minophagen C 100 mL dissolved in 10% dextrose 250 ml once a day intravenously, combined with decoction of turtle shell for anti-fibrosis one powder daily. And the control group was treated with stronger neo-minophagen C alone, 3 months as a course. Liver fibrosis indexes and liver function index were tested for two groups of patients before and after the treatment.

RESULTBoth the difference of liver fibrosis indexes between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01). Both the difference of liver function index between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01). The basic cure rate and total effective rate were 40% and 84.0% in the treatment group and 27.27% and 86.18% in the control group respectively with significant difference. The treatment group was superior to control group in the mean size of diameter of portal vein and the thickness of spleen (P < 0.01).

CONCLUSIONDecoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C could significantly improve the clinical efficacy and the liver fibrosis indexes and liver function index in chronic hepatitis B.

Adult ; Aged ; Alanine Transaminase ; blood ; Animal Shells ; chemistry ; Animals ; Aspartate Aminotransferases ; blood ; Cysteine ; administration & dosage ; therapeutic use ; Drug Combinations ; Drug Therapy, Combination ; Female ; Glycine ; administration & dosage ; therapeutic use ; Glycyrrhetinic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; blood ; drug therapy ; etiology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Tissue Extracts ; therapeutic use ; Treatment Outcome ; Turtles ; gamma-Glutamyltransferase ; blood

OBJECTIVETo research the content changes of excitatory neurotransmitter and inhibitory neurotransmitter in corpus striatum of rats after single-used borneol and combining it with diazepam in hope of comprehending the activity of borneol on central nervous system and to observe whether borneol could increase the penetration of other drugs into the brain.

METHODThe content of four amino acids neurotransmitters in corpus striatum of rats were sampled by brain microdialysis technology at different time after administration and were determined by RP-HPLC which involved pre-column derivation with orthophthaladehyde (OPA), using phosphate gradient elution and fluorescence detection to detect the content of excitatory neurotransmitter aspartate (Asp), glutamate (Glu) and inhibitory neurotransmitter glycine (Gly), gamma-aminobutyric acid (GABA) in standards and samples and carry on statistical analysis.

RESULTThe content of both Gly and GABA in corpus striatum of rats with borneol increased significantly, compared with diazepam group (P < 0.05), while Asp and Glu showed no significant difference.

CONCLUSIONBorneol can improve permeability of diazepam through BBB.

Animals ; Aspartic Acid ; analysis ; Blood-Brain Barrier ; Bornanes ; administration & dosage ; pharmacology ; Corpus Striatum ; chemistry ; drug effects ; Diazepam ; administration & dosage ; pharmacology ; Glutamic Acid ; analysis ; Glycine ; analysis ; Male ; Neurotransmitter Agents ; analysis ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; analysis

Glycine and gamma-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are well known, little is known about the effect of GABA in strychnine-induced hyperalgesia. To investigate the effect of GABA and the role of the glycine receptor in thermal hyperalgesia, we designed an experiment involving the injection of muscimol (a GABAA receptor agonist), baclofen (a GABAB receptor agonist) or glycine with strychnine (strychnine sensitive glycine receptor antagonist). Glycine, muscimol, or baclofen with strychnine was injected into the cisterna magna or lumbar subarachnoidal spaces of mice. The effects of treatment on strychnine-induced heat hyperalgesia were observed using the pain threshold index via the hot plate test. The dosages of experimental drugs and strychnine we chose had no effects on motor behavior in conscious mice. Intracisternal or intrathecal administration of strychnine produced thermal hyperalgesia in mice. Glycine antagonize the effects of strychnine, whereas, muscimol or baclofen does not. Our results indicate that glycine has anti-thermal hyperalgesic properties in vivo; and GABA receptor agonists may lack the binding abilities of glycine receptor antagonists with their sites in the central nervous system.
Animals ; Baclofen/*administration & dosage/pharmacology ; Drug Delivery Systems ; GABA Agonists/administration & dosage/pharmacology ; GABA Antagonists/administration & dosage/pharmacology ; Glycine/*administration & dosage/pharmacology ; Hot Temperature ; Hyperalgesia/chemically induced/*drug therapy ; Injections, Spinal ; Male ; Mice ; Mice, Inbred ICR ; Muscimol/*administration & dosage/pharmacology ; Pain Threshold ; Random Allocation ; Strychnine ; gamma-Aminobutyric Acid/metabolism

OBJECTIVETo investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora.

METHODSampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection.

RESULTGABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P < 0.01). GABA content of zolpidem group and Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P < 0.05). GABA content of Calculus Bovis group was higher than combination group (P < 0.05). GABA content of zolpidem group was not significantly different from combination group. Gly content of Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P < 0.05).

CONCLUSIONContents of two inhibitive neurotransmitters in rat striatum corpora were all significantly increased in Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

Animals ; Calculi ; chemistry ; Cattle ; Chromatography, High Pressure Liquid ; Corpus Striatum ; drug effects ; metabolism ; Glycine ; metabolism ; Male ; Medicine, Chinese Traditional ; Neurotransmitter Agents ; metabolism ; Pyridines ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo evaluate the effect of intrathecal administration of glycine on the minimum alveolar concentration (MAC) of isoflurane in rats.

METHODSIntrathecal catheters were implanted in 40 adult male rats anesthetized with isoflurane. Baseline MAC of isoflurane was measured during the infusion of artificial cerebrospinal fluid (CSF) alone. Subsequently, 10, 40, 80, 160, and 300 mmol/L of glycine dissolved in artificial CSF were infused for two hours at the same rate as under control conditions, and MAC for isoflurane was re-determined.

RESULTSIntrathecal administration of glycine produced a significant, dose-dependent decrease in MAC for isoflurane (up to -65.2% +/- 16.2%).

CONCLUSIONSIntrathecal administration of glycine decreases anesthetic requirement This result supports the idea that glycine receptors may be important to the immobilizing effect of anesthetics that enhance glycine receptor function such as isoflurane.

Anesthetics, Inhalation ; metabolism ; Animals ; Glycine ; administration & dosage ; pharmacology ; Injections, Spinal ; Isoflurane ; metabolism ; Male ; Pulmonary Alveoli ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley