OBJECTIVETo explore the effect and mechanism of cinnabaris and realgar in promoting awake effect of endotoxin- induced brain injury rat applied with Angong Niuhuang Wan.

METHODNormal rats implanted cortical electrode in advance were divided into 6 groups: control, model, the Angong Niuhuang Wan (AGNH, 0.4, 0.2 g · kg(-1)), the Angong Niuhuang Wan without cinnabaris and realgar (QZX-AGNH, 0.32, 0.16 g · kg(-1)). Rats in the control and model groups were given distilled water. After three days of intragastric administration, the brain injury model was injected with endotoxin through tail vein. Then trace electro-corticogram (EcoG) 1-6 h after LPS injection, and compare the power and relative power of beta (β) and delta-waves (δ) at 6 h of these groups. The content of acetylcholine (Ach) and the affinity of M-receptor (M-R) in cortex and brainstem were detected by alkaline hydroxylamine colorimetric method and radioactive ligand binding assay, respectively.

RESULTAGNH (0.4, 0.2 g · kg(-1)) could increase the power and relative power of β and AGNH (0.4 g · kg(-1)) showed better action on brain electrical activation. QZX-AGNH showed weak effect on it. AGNH (0.4 g · kg(-1)) could increase the affinity of M-R in cortex and the content of Ach in brainstem. The action of QZX-AGNH was not obvious.

CONCLUSIONIn endotoxin-induced brain injury rats, AGNH can raise the cholinergic system function of cortex, and strengthen the uplink of cortex activation of brainstem cholinergic system, improve the level of cortical activity and enhance the activation of EcoG to promote the body's awakening. QZX-AGNH show weak effect. Cinnabaris and realgar play an important role in promoting awake effect in endotoxin-induced brain injury applied with Angong Niuhuang Wan. The mechanism may be related to cortical and brainstem cholinergic system function.

Animals ; Brain Injuries ; chemically induced ; drug therapy ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; Endotoxins ; adverse effects ; Humans ; Male ; Rats ; Rats, Sprague-Dawley

The protective effect of erythropoietin (EPO) on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing endotoxin-induced organ damage. Rat model of multiple organ failure (MOF) was established by tail vein injection of 10 mg/kg lipopolysaccharide (LPS). Recombinant human EPO treatment (5000 U/kg) was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN) and creatinine (Cr), were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α) were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ultrastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein expression levels were detected by using Western blotting. EPO treatment showed a modest effect in preventing LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-α levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase (AKT) and increased nuclear factor-κB (NF-κB) activation in the lung, liver, and kidney (P<0.05 vs. control). However, EPO treatment significantly decreased the LPS-induced pAKT up-regulation in these tissues (P<0.05 vs. LPS treatment alone). The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Blotting, Western ; Creatinine ; blood ; Endotoxins ; Erythropoietin ; administration & dosage ; genetics ; pharmacology ; Injections, Intravenous ; Kidney ; drug effects ; metabolism ; ultrastructure ; Lipopolysaccharides ; Liver ; drug effects ; metabolism ; ultrastructure ; Lung ; drug effects ; metabolism ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Multiple Organ Failure ; blood ; chemically induced ; prevention & control ; NF-kappa B ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Recombinant Proteins ; administration & dosage ; pharmacology ; Tumor Necrosis Factor-alpha ; blood

In order to discover the mechanism of Xuebijing oral effervescent tablet (XBJOET) to treat infectious diseases, the effect of XBJOET on endotoxin induced rabbit fever and disseminated intravascular coagulation (DIC) was investigated. Auricle microcirculation in rabbit was detected by laser speckle blood perfusion imager system; coagulation function was measured by coagulation analyzer, fibrinolytic system was quantified by Elisa assay and micro thrombosis in tissues was observed with HE staining under light microscope. The results demonstrated that the body temperature of rabbit decreased significantly at 1-3 h after administration with 4.8, 2.4 and 1.2 g x kg(-1) XBJOET to endotoxin induced DIC rabbit model, the auricle microcirculation blood flow in model group (54.45 +/- 14.53) PU was lower than that in control group (77.18 +/- 12.32) PU. The auricle microcirculation blood flow increased markedly and there was significant difference between model group and 1.2 g x kg(-1) XBJOET group. There was significant difference between model group and control group in the content of PAI1 and FIB. The PAI1 levels in model and control groups were (30.48 +/- 2.46) ng x mL(-1) and (20.93 +/- 3.25) ng x mL(-1), respectively. The FIB levels in model and control group were (3.34 +/- 1.09) g x L(-1) and (4.84 +/- 1.10) g x L(-1), respectively. The content of PAI1 in rabbit plasma decreased notably, there were significant differences between model group and 4.8, 2.4 g x kg(-1) XBJOET groups. On the contrary the content of FIB increased. XBJOET possessed pharmacological activities of curing infectious fever and DIC, the mechanism of which is related to amelioration of microcirculation disturbance, inhibition of fibrinolytic system activation and coagulation and micro thrombosis elimination.
Administration, Oral ; Animals ; Blood Coagulation ; drug effects ; Body Temperature ; drug effects ; Disseminated Intravascular Coagulation ; blood ; chemically induced ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ear Auricle ; blood supply ; Endotoxins ; Female ; Fever ; chemically induced ; drug therapy ; physiopathology ; Fibrinogen ; metabolism ; Male ; Microcirculation ; Partial Thromboplastin Time ; Plasminogen Activator Inhibitor 1 ; blood ; Prothrombin Time ; Rabbits ; Tablets ; Thrombosis ; pathology

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.
Animals ; Antitrichomonal Agents ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; methods ; Endotoxins ; Gingival Crevicular Fluid ; metabolism ; Injections ; Periodontal Pocket ; metabolism ; Periodontitis ; chemically induced ; metabolism ; Polyesters ; chemical synthesis ; pharmacokinetics ; Polyethylene Glycols ; chemical synthesis ; pharmacokinetics ; Rabbits ; Random Allocation ; Rheology ; Tinidazole ; administration & dosage ; pharmacokinetics

OBJECTIVETo study the change of intestinal mucosa barrier in chronic severe hepatitis B patients and clinical intervention.

METHOD(1) 30 normal healthy controls and 60 chronic severe hepatitis B patients were enrolled in this study. The change of intestinal permeability was determined by urine lactulose/ mannitol ratio (L/M), and the serum diamine oxidase (DAO) was measured. (2) 60 chronic severe hepatitis B patients were randomly divided into two groups: the control group and the treated group, each group has 30 cases. Patients in the control group received standard treatment for 2 weeks, however, in addition to standard treatment, patients in the treated group also received glutamine 10g tid. Endotoxin (ET), DAO and L/M were compared between the two group.

RESULTS(1) Compared to healthy controls, the level of L/M and DAO was significantly increased in chronic severe hepatitis B patients (t = 2.762, P less than 0.01 or t = 6.326, P less than 0.01). (2) Compared to the control group, ET, DAO and L/M were significantly lower 2 weeks after treatment (F = 11.662, P less than 0.01; F = 12.699, P less than 0.01; F = 19.981, P less than 0.01).

CONCLUSION(1) There is an early intestinal mucosa barrier damage in chronic severe hepatitis B patients. (2) Compared to standard treatment, adding glutamine can reverse intestinal mucosa barrier damage.

Administration, Oral ; Adolescent ; Adult ; Amine Oxidase (Copper-Containing) ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; Child ; Endotoxins ; blood ; Female ; Glutamine ; pharmacology ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; metabolism ; physiopathology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; physiopathology ; Intestine, Small ; Lactulose ; urine ; Male ; Mannitol ; urine ; Middle Aged ; Permeability ; Treatment Outcome ; Young Adult

Alanine Transaminase ; blood ; Animals ; Bilirubin ; blood ; Disease Models, Animal ; Endotoxemia ; etiology ; Endotoxins ; blood ; Gastrointestinal Hormones ; blood ; Gastrointestinal Motility ; physiology ; Intestine, Small ; physiopathology ; Liver ; pathology ; Liver Failure, Acute ; blood ; etiology ; physiopathology ; Liver Function Tests ; Rats ; Thioacetamide ; administration & dosage

PURPOSE: This study was undertaken to determine the effects of intratracheal administration of endotoxin on hyperoxia-induced lung injury in neonatal rats. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were divided into four experimental groups: normoxia control (NC), normoxia with endotoxin treatment (NE), hyperoxia control (HC), and hyperoxia with endotoxin treatment (HE) groups. In HC and HE, rat pups were subjected to 14 days of hyperoxia (> 95% oxygen) within 12 hours after birth. In endotoxin treated group (NE and HE), Escherichia coli endotoxin (0.5microgram in 0.03mL of saline) was given intratracheally at the 1st, 3rd and 5th postnatal day. Radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratios, and degree of fibrosis were measured to assess the changes in lung morphology. RESULTS: During the research period, survival rates in both HC and HE were notably reduced 7 days after endotoxin was administered, but body weight gain was considerably reduced only in HC. On day 14, significant arrest in alveolarization, as evidenced by the decrease of RAC and RAC/MLI ratio and increase of MLI as well as increased fibrosis, were noted in HC. Although slight but significant arrest in alveolarization and increased fibrosis score were observed in NE compared to NC, the hyperoxia-induced lung damage observed in HC was significantly improved in HE. CONCLUSION: This study suggests that intratracheal administration of endotoxin significantly attenuated hyperoxia-induced lung injury in neonatal rats.
Animals ; Animals, Newborn ; Body Weight ; Drug Administration Routes ; Endotoxins/*administration & dosage ; Hyperoxia/*complications ; Lung Diseases/*chemically induced/*etiology/pathology ; *Lung Injury ; Rats ; Rats, Sprague-Dawley

OBJECTIVEBronchopulmonary displasia (BPD) is characterized by decreased alveolar development resulting in large saccular airspaces that are thought to result from the superposition of injury on the developing lung. Inflammation and hyperoxia appear to be the common factors. Preterm delivery is frequently preceded by chorioamnionitis, resulting in exposure of the fetal lung to inflammation. Subsequently, resuscitation with positive-pressure ventilation or supplemental O2 can continue to injure the lungs. Although mechanisms that impair lung growth in BPD are poorly understood, recent studies have shown that disruption of vascular endothelial growth factor (VEGF) function plays a pivotal role in the pathogenesis of BPD. The purpose of this study was to investigate the expression of VEGF and its receptors in premature lungs of rats with intra-amniotic endotoxin priming and/or exposed to 60% O2 and to elucidate the relationship between intrauterine inflammatory/chronic high O2 exposure and the pathogenesis of BPD.

METHODSTimed pregnant Sprague Dawley (SD) rats were randomly divided into two groups: lipopolysaccharide (LPS) group and saline solution group. LPS or saline solution was intra-amniotically injected into the sacs on gestational age day 15 (70% of term). Six days after intra-amniotic injection, the preterm rats of each group were delivered and further randomized to put in 60% O2 exposure or in room air. On days 1, 7 and 14 after birth, the lungs of the rats from both groups were removed and dissected from the main bronchi for analysis. Left lungs of each group were used to assess lung histological changes after hematoxylin and eosin (HE) staining. Total RNA and protein were extracted from the right frozen lung tissues. Lung VEGF and its receptors mRNA and protein levels were measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and polypeptides analysis (Western blot).

RESULTS(1) Lung histology revealed striking differences in lung structure in the four experimental groups. Compared with control rat lungs, endotoxin and/or hyperoxia treated groups showed a histological pattern of alveolar simplification characterized by the presence of larger and fewer distal air spaces. To quantify the apparent decreases in alveolar number, radial alveolar counts (RAC) were measured in the four experimental groups: RAC increased along with the lung development from d 1 to d 14 in both control and endotoxin alone groups. However, in endotoxin alone group, RAC was significantly lower than that of controls from d 1 to d 14. In hyeroxia alone group, RAC began to decrease on day 7, and became significantly lower than that of the control group on day 14 (P < 0.05). In endotoxin plus hyperoxia groups, RAC significantly decreased as compared to controls on days 1 and 7, and became significantly lower than those of the other three groups on day 14. (2) Western blotting showed changes in protein content of VEGF164 and its receptor Flk-1 increased from day 1 to day 14 in both control group and endotoxin alone group. However, In endotoxin alone group, they were significantly lower than those of controls from d 1 to d 7 (P < 0.05). Conversely, they decreased from day 1 to day 14 in the other two groups, and were significantly lower than those of the control group on days 7 and 14 in both hyperoxia alone group and endotoxin plus hyperoxia groups. Importantly, the expression of VEGF and its receptor in endotoxin plus hyperoxia group was lower than those of both the hyperoxia alone group and the endotoxin alone group with significant difference. The levels of Flt-1 had obviously an age-dependent increase from day 1 to day 14 in the four experimental groups. (3) The changes of mRNA expression of VEGF and its receptors were basically consistent with the changes on protein expression.

CONCLUSIONSThese results suggest that the intra-amniotic endotoxin and/or hyperoxia can down-regulate expression of VEGF and Flk-1, which may contribute to the pathogenesis of BPD.

Amnion ; chemistry ; Animals ; Animals, Newborn ; Drug Administration Routes ; Endotoxins ; metabolism ; pharmacology ; Female ; Lung ; drug effects ; metabolism ; Oxygen ; metabolism ; Pregnancy ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Vascular Endothelial Growth Factor ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1degrees C. There was a significant reduction in the elimination halflife by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasmaconcentration- time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.
Animals ; Anti-Bacterial Agents/*administration&dosage/blood/*pharmacokinetics ; Area Under Curve ; Cephalosporins/*administration&dosage/blood/*pharmacokinetics ; Endotoxins/pharmacology ; Escherichia coli Infections/drug therapy/physiopathology ; Fever/chemically induced/*physiopathology ; Half-Life ; Injections, Intramuscular ; Male ; Rabbits

AIMTo investigate the effects of L-arginine and nitric oxide synthase (NOS) inhibitor Aminoguanidine (AG) on endotoxin induced lung injury in rats.

METHODSForty eight healthy male SD rats weighing (300 +/- 20) g were used. The animals were anesthetized with 20% urethane 1 g x kg(-1). Common carotid artery (CAA) and common carotid vein (CAV) were exposed through a median incision in the neck. Mean arterial pressure (MAP) was measured through a pressure transducer connected with intubation of CAA. The animals were randomly divided into six groups: group 1: control: group 2: LPS (5 mg x kg(-1) intravenous injection, i.v.); group 3: AG (50 mg x kg(-1) intraperitoneal injection, IP); group 4: high dose L-arginine (500 mg x kg(-1), IP); group 5: low dose L-arginine (250 mg x kg(-1) IP). Group 6: L-arginine + AG (250 mg x kg(-1), 50 mg x kg(-1), IP). Group 1: The animals were killed 6 h after 0.9% saline solution was given. Group 2: 0.9% saline solution was given 3 h after LPS i.v. and the animals were killed 3 h after medication. Group 3, 4, 5 and 6: AG, L-arginine and L-arginine+ AG were given 3 h after LPS i.v. respectively and the animals were killed 3 h after medication respectively. The pulmonary was removed immediately. The pulmonary coefficient and water content in pulmonary tissue were calculated (%). The NO content in plasma, MDA content and NOS, SOD activity in the pulmonary tissue were measured.

RESULTSL-arginine, AG and L-arginine + AG significantly decreased pulmonary coefficient and water content in pulmonary tissue and ameliorated endotoxin induced lung injury. AG and L-arginine + AG significantly decreased NO content in plasma, decreased MDA content and inhibited NOS activity and enhanced SOD activity in the pulmonary tissue.

CONCLUSIONIt may be concluded that L-arginine, AG and L-arginine + AG have beneficial effects on lung injury induced by LPS.

Animals ; Arginine ; administration & dosage ; therapeutic use ; Endotoxins ; adverse effects ; Guanidines ; administration & dosage ; therapeutic use ; Lung Injury ; chemically induced ; drug therapy ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism