Objective To evaluate the effect of sedation with midazolam combined with propofol on delirium in mechanically ventilated patients in the intensive care unit (ICU).Methods Five hundred and twenty-two patients who required sedation and analgesia,endotracheal intubation and mechanical ventilation used to assist respiration,aged 28-64 yr,weighing 41-82 kg,were randomized into 2 groups according to the sedation protocols during therapy:sedation with midazolam group (group M,n =240) and sedation with midazolam + propofol group (group MP,n=232).In M and MP groups,sedation was induced with midazolam infusion 0.03-0.17 mg/min,and analgesia was induced with sufentanil infusion 0.07-0.14 μg/min.In group MP,when hemodynamics was stable,pressure support was 8-10 cmH2O,tidal volume＞400 ml,RR ＜25 bpm,and FiO2＜45％,sedation was induced with propofol infusion 0.8-2.0 mg/min instead,lasting for 12-24 h.Richmond Agitation Sedation Scale score was maintained at-1 to-2 during vcntilation.The development and duration of delirium were recorded.Delirium was divided into hyperactive delirium,hypoactive delirium and mixed delirium 3 subtypes,and the development and duration of the 3 subtypes of delirium were also recorded.Results There was no significant difference between the two groups in the incidence and duration of delirium.Compared to group M,the incidence of hyperactive delirium was significantly decreased,and no significant change was found in the incidence of hypoactive delirium and mixed delirium and the duration of the 3 subtypes of delirium in group MP.Conclusion Sedation with midazolam and propofol can decrease the development of hyperactive delirium,but can not shorten the duration of delirium in mechanically ventilated patients in the ICU.

Objective To investigate the incidence of hearing disorder and analyse the high-risk factors with hearing injury in newborns with hyperbilirubinemia.Methods The newborns with hyperbilirubinemia who admitted to the department of neonate,were received the distortion product otoacoustic emission(DPOAE)test when they recovered from hyperbilirubinemia;those babies who didn′t pass the first test received screening again in 42 days after birth.Those babies who didn′t pass the second test received auditory brain stem response(ABR)test.Results Fifty-eight(33.2%)newborns didn′t pass the first DPOAE test among 235 newborns with hyperbilirubinemia;11(18.9%)infants didn′t pass the second DPOAE test among 58 infants;5 infants failed to pass the ABR test,the ratio of hea-ring disorder in newborns with hyperbilirubinemia was 2.13%;18(9.9%)newborns didn′t pass the first DPOAE test among 182 normal newborns,and those infants all passed the second DPOAE test.Conclusions Hyperbilirubinemia is high-risk population of hearing disorder.The congenital cytomegalovirus infection,neonatal septicemia and hemolytic disease of newborn are the high risk factors responsible for hearing disorder.All high risk newborns should recieve hearing examination regularly.

OBJECTIVETo investigate changes in synaptic and extrasynaptic N-methyl-D-aspartate receptors (NMDAR) during the development of cultured rat hippocampal neurons.

METHODSSynaptic and extrasynaptic NMDAR channel currents were recorded from 1-day-old rat hippocampal neurons cultured for 1 and 2 weeks with patch-clamp technique in whole-cell configuration and outside-out configuration, respectively.

RESULTSThe amplitude of NMDAR-mediated miniature excited postsynaptic current (Meps(CNMDA)) decreased in neurons cultured for 2 weeks as compared with that recorded in neurons cultured for 1 week, and the 2-week neurons showed also much lowered sensitivity to selective NR2B blocker ifenprodil. The amplitude and open probability of extrasynaptic NMDAR in the 2-week neurons were significantly higher than those in the 1-week neurons, but the neurons differred little in conduction and reverse potential. Ifenprodil decreased the high conductance and open probability in both neurons, but the effect was more potent in the 2-week ones.

CONCLUSIONSThere can be developmental changes in synaptic and extrasynaptic NMDAR channel currents in cultured rat hippocampal neurons, indicating that different NMDAR subtypes are expressed in the synaptic and extrasynaptic regions during the development of the hippocampal neurons. In 1-week neurons, NR2B are predominant both in synaptic and extrasynaptic regions, and at 2 weeks, synaptic NR2B are replaced by NR2A but NR2B still remains the predominant subtypes outside the synapses.

Animals ; Animals, Newborn ; Cells, Cultured ; Excitatory Amino Acid Antagonists ; pharmacology ; Excitatory Postsynaptic Potentials ; drug effects ; physiology ; Hippocampus ; cytology ; Neurons ; cytology ; physiology ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; physiology ; Synapses ; physiology ; Synaptic Transmission ; physiology ; Time Factors

BACKGROUNDRecent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.

METHODSForty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.

RESULTSIn the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).

CONCLUSIONSOur results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.

Alzheimer Disease ; physiopathology ; therapy ; Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; methods ; Entorhinal Cortex ; physiology ; Fornix, Brain ; physiology ; Male ; Memory ; physiology ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; physiology

Activation of N-methyl-d-aspartic acid (NMDA) receptor plays an important role in neuronal apoptosis induced by cerebral ischemia but the underlying mechanisms are still unclear. The present study examined the neuroprotection of three chloride blockers in an in vitro cell model of cerebral ischemia established by treatment of cultured rat hippocampal neurons with NMDA. Hoechst 33258 staining and MTT assay were used to detect neuronal apoptosis and cell viability, respectively. The neuroprotective effects of chloride channel blockers on the cell viability and neuronal apoptosis were only observed when the blockers were applied before NMDA exposure. In comparison with DIDS, SITS showed more potent protective effect in a dose-dependent manner, whereas NPPB showed no significant neuroprotective effect. The results demonstrate that pretreatment with both SITS and DIDS have protective effect against neuronal apoptosis, which is achieved by blocking both NMDA receptor and chloride channel.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ; pharmacology ; 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid ; pharmacology ; Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Bisbenzimidazole ; chemistry ; Cell Survival ; drug effects ; Cells, Cultured ; Chloride Channels ; antagonists & inhibitors ; Hippocampus ; cytology ; Microscopy, Fluorescence ; N-Methylaspartate ; pharmacology ; Neurons ; chemistry ; cytology ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.
Antioxidants ; chemistry ; Apoptosis ; drug effects ; Hep G2 Cells ; Humans ; Nitrates ; chemical synthesis ; chemistry ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; Oleanolic Acid ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Ursodeoxycholic Acid ; analogs & derivatives ; pharmacology

The study aims to elucidate the characteristics of pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in healthy Beagle dogs. Chromatographic separation was performed on a C18 column (100 mm x 3.0 mm, 3.5 microm) with methanol - 2 mmol x L(-1) ammonium formate (25 : 75) as the mobile phase. A trip-quadrupole tandem mass spectrum with the electrospray ionization (ESI) source was applied and positive ion multiple reaction monitoring mode was operated. Six Beagle dogs were randomly devided into two groups. They received oral single dose of scopolamine hydrobromide oral disintegrative microencapsule tablets 0.6 mg (test tablet) or scopolamine hydrobromide normal tablets (reference tablet). Plasma samples were collected at designed time. Plasma concentration of scopolamine hydrobromide was determined by LC-MS/MS and pharmacokinetic parameters were calculated. The pharmacokinetic parameters of test tablet vs reference tablet were as follows: C(max): (8.16 +/- 0.67) ng x mL(-1) vs (3.54 +/- 0.64) ng x mL(-1); t1/2: (2.83 +/- 0.45) h vs (3.85 +/- 0.82) h; t(max): (1.25 +/- 0.27) h vs (0.42 +/- 0.09) h; AUC(0-12h): (25.06 +/- 3.75) h x ng x mL(-1) vs (9.59 +/- 1.02) h x ng x mL(-1); AUC(0-infinity): (26.30 +/- 3.92) h x ng x mL(-1) vs (10.80 +/- 1.45) h x ng x mL(-1); MRT(0-12h): (3.38 +/- 0.34) h vs (3.86 +/- 0.26) h; MRT(0-infinity): (3.98 +/- 0.63) h vs (5.37 +/- 1.00) h. The absorption rate and AUC of test tablet is different from that of reference tablet. The bioavailability of test tablet is better than those of reference tablet.
Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Capsules ; Chromatography, Liquid ; Dogs ; Drug Stability ; Female ; Male ; Muscarinic Antagonists ; administration & dosage ; blood ; pharmacokinetics ; Random Allocation ; Scopolamine Hydrobromide ; administration & dosage ; blood ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry

OBJECTIVETo explore the pathological characteristics and the dynamic change regularity of the testis induced by high power microwave (HPM) radiation.

METHODSOne hundred and sixty-five male Wistar rats were exposed to 0, 3, 10, 30 and 100 mW/cm2 HPM radiation for five minutes, and changes of testicular morphology and teratogenic ratio of epididymal spermatozoa were observed through light microscope and electron microscope at 6 h, 1, 3, 7, 14, 28 and 90 d after radiation.

RESULTSInjury of testicular spermatogenic cells in rats might be induced by 3 to approximately 100 mW/cm2 HPM radiation, and the main pathological changes were degeneration, necrosis, shedding of spermatogenic cells, formation of multinuclear giant cells, decrease or loss of sperm and interstitial edema. Injury of spermatogenic cells underwent such phases as death and shedding, cavitation, regeneration and repair, characterized by being focalized, inhomogenous and phased. And the severity of pathological changes of the testis increased with power density. There was only scattered degeneration, necrosis, shedding of spermatogenic cells in the seminiferous tubule one day after 3 mW/cm2 radiation, and the pathological changes six hours after 10 mW/cm2 radiation was similar to those one day after 3 mW/cm2 radiation, but with the formation of multinuclear giant cells, and the above-mentioned pathological changes aggravated from one day to seven days after radiation. There was a significant increase in degeneration, necrosis, shedding of spermatogenic cells, as well as a significant decrease in spermatozoa and focal necrosis in simple seminiferous tubules six hours after 30 and 100 mW/cm2 radiation, and the subsequent changes were similar to those of 10 mW/cm2 radiation. There was a significant increase in teratogenic ratio of epididymal spermatozoa at 3 d, 1 to approximately 7 d, 6 h to approximately 7 d after 3, 10, 30 and 100 mW/cm2 microwave radiation respectively (P < 0.01 or P < 0.05).

CONCLUSIONHPM radiation may cause injury of testicular spermatogenic cells in rats, which has a positive correlation to radiation dosage and time.

Animals ; Dose-Response Relationship, Radiation ; Male ; Microwaves ; Rats ; Rats, Wistar ; Spermatozoa ; pathology ; radiation effects ; Testis ; pathology ; radiation effects

BACKGROUND: Acetabular defect is one of the typical characteristics of adult developmental dysplasia of the hip. The acetabular defect caused an insufficient coverage to the femoral head, which means the contact area between them decreased and the pressure increased. Stress concentration could quicken hip wear and lead to arthritis or dislocation of the hip. Till now, there is no accepted objective criterion about what degree defect could lead to biomechanics changes in the hip. OBJECTIVE: To analyze the influence of different degrees of acetabular defect on the stress distribution of hip joint by using three-dimensional finite element method, and provide theoretical guidance for clinical treatment of hip dysplasia. METHODS: CT thin layer scanning data of normal adult hip were selected. Hip dysplasia models with varying degrees of bone defect were built by using Mimics15.0 and Hypermesh software. Von Mises stress distribution on the subchondral bone of the hip was analyzed by using Ansys10.0 software in the case of single foot touchdown. RESULTS AND CONCLUSION: Each model result was consistent with the actual situation. The maximum Von Mises stress value appeared at the top of the acetabulum dome and medial posterior femoral neck. When simulating one leg standing, the smaller the CE angle, the greater the maximum Von Mises stress on femoral head was; and acetabulum increased from 2.768 MPa and 3.029 MPa with 30° CE angle to 11.075 MPa and 15.322 MPa with 5° CE angle. This change was more obvious when CE angle was less than 15°. These findings confirmed that acetabular defect increases the peak stress of the hip joint, and the greater the defect, the greater the stress was. It is suggested that clinical intervention should be done as early as possible in patients with acetabular defect.

BACKGROUNDNanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects.

METHODSTwenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation.

RESULTSThe tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed.

CONCLUSIONSThe hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capability than that of nanobone putty only.

Absorbable Implants ; Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; analysis ; genetics ; Female ; Male ; Mice ; Osteogenesis ; physiology ; Rabbits ; Transforming Growth Factor beta ; analysis ; genetics