Clinical characteristics and prognosis of serous body cavity effusions in patients with sepsis: a retrospective observational study.

BACKGROUND: Cavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients. METHODS: From January 2010 to January 2015, a total of 214 patients with severe sepsis and septic shock were enrolled in this retrospective observational study. Thoracentesis or abdominal paracentesis was performed in 45 septic patients because of massive pleural effusions or ascites. The serum concentrations of VEGF, VEGFR, Ang, sICAM-1, sVCAM-1, E-selectin, Serpine1 and VE-cadherin in 45 septic patients underwent paracentesis were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 214 septic patients, 155 (72.4%) had SCE according to imaging or ultrasound manifestations. 45 subjects with SCE underwent therapeutic thoracentesis or abdominal paracentesis. Effusion laboratory analysis showed that exudates were predominant when compared with transudates (95.6% vs. 4.4%), and 16 (35.6%) patients suffered bloody effusions. Compared with patients with non-bloody effusions, those with bloody effusions showed higher critical illness scores (13 vs. 17 for APACHE II; 7 vs. 9 for SOFA), and higher mortality (6.9% vs. 62.5%). Moreover, patients with bloody effusions had delayed TT and APTT, increased D-dimer concentration, and higher serum levels of CRP and PCT (P < 0.05). In addition, the serum levels of Ang2, sVCAM-1 and E-selectin were significantly higher in patients with bloody effusions than in those with non-bloody effusions (P < 0.05). However, the serum level of VEGFR2 was lower in patients with bloody fluids (P = 0.025). CONCLUSIONS: The incidence of serous cavity effusion is high in patients with sepsis. The septic patients with bloody effusions suffer a more inflammatory burden and a worse prognosis compared to septic patients with non-bloody effusions.

Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats.

The effect of hypercapnia on outwardly rectifying currents was examined in locus coeruleus (LC) neurons in slices from neonatal rats [postnatal day 3 (P3)-P15]. Two outwardly rectifying currents [4-aminopyridine (4-AP)-sensitive transient current and tetraethyl ammonium (TEA)-sensitive sustained current] were found in LC neurons. 4-AP induced a membrane depolarization of 3.6 ± 0.6 mV (n = 4), while TEA induced a smaller membrane depolarization of 1.2 ± 0.3 mV (n = 4). Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the TEA-sensitive current was reduced by 52.1 ± 4.5% (n = 5) in 15% CO2 [extracellular pH (pHo) 7.00, intracellular pH (pHi) 6.96]. The maximal amplitude of the 4-AP-sensitive current was reduced by 34.5 ± 3.0% (n = 6) in 15% CO2 (pHo 7.00, pHi 6.96), by 29.4 ± 6.8% (n = 6) in 10% CO2 (pHo 7.15, pHi 7.14), and increased by 29.0 ± 6.4% (n = 6) in 2.5% CO2 (pHo 7.75, pHi 7.35). 4-AP completely blocked hypercapnia-induced increased firing rate, but TEA did not affect it. When LC neurons were exposed to HA with either pHo or pHi constant, the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive current (likely an A current) is inhibited by decreases in either pHo or pHi. The change of the A current by various levels of CO2 is correlated with the change in firing rate induced by CO2, implicating the 4-AP-sensitive current in chemosensitive signaling in LC neurons.

Parylene-based implantable platinum-black coated wire microelectrode for orbicularis oculi muscle electrical stimulation.

A novel and simple process was proposed to fabricate a parylene-based platinum-black coated wire microelectrode for orbicularis oculi muscle electrical stimulation. Compared with conventional microelectrodes, wire microelectrodes would enable smaller wounds, increased ease of implantation, and improved cosmesis. Meanwhile, the circumferential electrode sites of this wire microelectrode fabricated by lift-off process would contribute to fully contact with tissue and reduction of electrode-tissue interface impedance. The width and the amount of electrode sites could be decided by the thickness and the amount of sacrificial layer, respectively. The platinum-black coatings were electroplated on electrode sites by applying a current pulse train in chloroplatinic acid solution with ultrasonic bath for further electrode-tissue interface impedance reduction and good mechanical stability of coatings. Electrode impedance at 1 kHz has been significantly reduced by 90%, and the cathodic charge storage capacity (CSCc) has been increased by 13 times. In addition, hematoxylin-eosin (HE) staining section of muscle demonstrated the good biocompatibility of this electroplated platinum-black. By applying a charge imbalanced biphasic stimulation waveform for orbicularis oculi muscle stimulation, the rabbits with facial paralysis rehabilitated the function of closing eyes. This kind of microelectrode will be promising for neuromuscular applications.

[Toxic effect of neonatal exposure to 2,2',4,4',5,5'-hexa-chlorobiphenyl on spermatogenesis in rats].

OBJECTIVE: To determine the long-term testicular effect after neonatal exposure to 2,2', 4,4',5,5'-hexa-chlorobiphenyl (PCB153). METHODS: On birth day (Postnatal day 0, PNDO), the Sprague-Dawley (SD) male rats were mixed together and divided into 12 pups/litter. At PND1, the rats were grouped randomly into control and treatment groups according to different litters, 24 pups/group. They were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, 0.250 and 2.500 mg/kg BW-day from PNDI to PND7. The rats were sacrificed at PND8 and PND90 by anesthesia. The testes were collected and weighed for histological examination and daily sperm production at PND8 or/and PND90. The epididymidis and the epididymidis cauda also were collected and weighed for determination the sperm counts at PND90. RESULTS: The body weight of 2.500 mg/kg dose group was decreased significantly from PND3 to PND8 compared with that of control (P < 0.05). At PND8, the loose structure in seminiferous cord and the spermatogonia with enlarged volume and detached from the cord were observed in 2.500 mg/kg dose group by light microscope and electronic microscopy. With the increase of exposure doses, the testicular daily sperm production (DSP) and the sperm counts of epididymidis cauda were decreased in dose-dependent manner at PND90. The DSP in 0.250 mg/kg [30 x 10(6)/testis(g)] and 2.500 mg/kg [18 x l0(6)/testis(g)] dose groups were significantly reduced compared with that of control [36 x 10(6)/testis(g)] (P < 0.05). And there was a significant reduction in the sperm counts of epididymidis cauda in 0.250 mg/kg [42 x 10(7)/epididymidis cauda (g)] and 2.500 mg/kg [18 x 10(7)/epididymidis cauda (g)] dose groups compared with that of control [51 x 10(7)/epididymidis cauda (g)] (P < 0.05). CONCLUSIONS: The spermatogenesis of adult testis is disturbed, which causes the decrease in the testicular DSP and the sperm counts of epididymidis cauda after neonatal exposure to PCB153. The long-term damage in male reproductive function is caused by neonatal exposure to chemicals.

Clinical characteristics and prognosis of community-acquired pneumonia in autoimmune disease-induced immunocompromised host: A retrospective observational study.

BACKGROUND: Community-acquired pneumonia (CAP) in autoimmune diseases (AID)-induced immunocompromised host (ICH) had a high incidence and poor prognosis. However, only a few studies had determined the clinical characteristics of these patients. Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH. METHODS: From 2013 to 2018, a total of 94 CAP patients accompanied with AID-induced ICH, admitted to Emergency Department of Zhongshan Hospital, Fudan University, were enrolled in this study. Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations (GEEs) analysis. An open-cohort approach was used to classify patient's outcomes into the survival or non-survival group. RESULTS: The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%. No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups, while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients (P<0.05). Both noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) were performed more frequently in non-survival group (P< 0.05). By the multivariate GEEs analysis, the repeated measured longitudinal indices of neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]=1.055, 95% confidence interval [95%CI] 1.025-1.086), lactate dehydrogenase (LDH) (OR=1.004, 95%CI 1.002-1.006) and serum creatinine (sCr) (OR=1.018, 95%CI 1.008-1.028), were associated with a higher risk of mortality. CONCLUSION: The CAP patients in AID-induced ICH had a high mortality. A significant relationship was demonstrated between the factors of NLR, LDH, sCr and mortality risk in these patients.

Brain-derived neurotrophic factor facilitates maturation of mesenchymal stem cell-derived dopamine progenitors to functional neurons.

The generation of dopamine (DA) neurons from stem cells holds great promise in the treatment of Parkinson's disease and other neural disease associated with dysfunction of DA neurons. Mesenchymal stem cells (MSCs) derived from the adult bone marrow show plasticity with regards to generating cells of other germ layers. In addition to reduced ethical concerns, MSCs could be transplanted across allogeneic barriers, making them desirable stem cells for clinical applications. We have reported on the generation of DA cells from human MSCs using sonic hedgehog (SHH), fibroblast growth factor 8 and basic fibroblast growth factor. Despite the secretion of DA, the cells did not show evidence of functional neurons, and were therefore designated DA progenitors. Here, we report on the role of brain-derived neurotrophic factor (BDNF) in the maturation of the MSC-derived DA progenitors. 9-day induced MSCs show significant tropomyosin-receptor-kinase B expression, which correlate with its ligand, BDNF, being able to induce functional maturation. The latter was based on Ca2+ imaging analyses and electrophysiology. BDNF-treated cells showed the following: increases in intracellular Ca2+ upon depolarization and after stimulation with the neurotransmitters acetylcholine and GABA and, post-synaptic currents by electrophysiological analyses. In addition, BDNF induced increased DA release upon depolarization. Taken together, these results demonstrate the crucial role for BDNF in the functional maturation of MSC-derived DA progenitors.

Vascular endothelial growth factor acutely reduces calcium influx via inhibition of the Ca2+ channels in rat hippocampal neurons.

Vascular endothelial growth factor (VEGF) protects neurons against ischemic injury. An overload of intracellular calcium ions (Ca(2+)) caused by the excessive release of glutamate is widely considered to be one of the molecular mechanisms of ischemic neuronal death. In the present study, we investigated whether VEGF could modulate the activity of Ca(2+) channels on the neuronal membrane. We used the Fluo-3 image method assisted by confocal laser scan microscopy to detect any Ca(2+) influx in primary cultured hippocampal neurons. Whole-cell patch-clamp techniques were used to record the activity of the high-voltage-activated (HVA) Ca(2+) currents in the CA1 pyramidal neurons of hippocampal slices that were freshly prepared from neonatal brains of rats. The results obtained from the Fluo-3 image experiments showed that VEGF pretreatment of cultured neurons at a final concentration of 50, 100, or 200 ng/ml acutely and dose dependently attenuated the Ca(2+) influx induced by application of KCl (60 mM) or glutamate (50 microM). This effect was blocked by SU1498, an antagonist of Flk-1 VEGF receptor. The influx of Ca(2+) returned to basal levels after removal of VEGF. Furthermore, electrophysiological recording data showed that VEGF could acutely reduce the amplitudes of the HVA Ca(2+) currents in a dose- and voltage-dependent manner. The HVA Ca(2+) currents also returned to the levels of the control after removal of VEGF from the system. Taken together, the results obtained from the present study demonstrated that VEGF specifically reduced the influx of Ca(2+) via the inhibitory activity of the HVA Ca(2+) channels in hippocampal neurons.

Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors.

BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and absence of strychnine (a glycine receptor antagonist), GABAzine (a gamma-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and gamma-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. RESULTS: Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. In addition, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. CONCLUSION: Strychnine, the glycine receptor antagonist, dose-dependently reduced propofol-induced LORR in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.

Loss of RE-1 silencing factor in mesenchymal stem cell-derived dopamine progenitors induces functional maturity.

Stem cell-derived dopamine (DA) neurons hold great promise for Parkinson's disease (PD). Mesenchymal stem cells (MSCs) have great potential for clinical applications. The generation of DA cells from MSCs using sonic hedgehog (SHH) and fibroblast growth factors (FGF8 and bFGF) has been reported. However, the DA cells showed weak electrical properties, representing DA neuron progenitors. Since RE-1 Silencing Factor (REST), suppresses mature neuronal genes in neuronal progenitors, we studied its role in the maturation of MSC-derived DA cells. REST expression did not change during the induction process, thus we knocked down REST and subjected MSCs to the same neural induction cocktail. We observed increases in the protein level of the Na(+) voltage-gated channel and tyrosine hydroxylase (TH). Electrophysiological analyses showed spontaneous firings and spontaneous postsynaptic currents, similar to native DA neurons. Taken together, these results show REST as the limiting gene in the generation of functional mature neurons from MSCs.

[Effect of neonatal exposure to environmental pollutants on the DNA methylation of rat testis].

OBJECTIVE: To investigate the effects of neonatal exposure of DNA methylation inhibitor, Cadmium and PCB153 on DNA methylation, apoptosis and spermatogenesis in SD rats. METHODS: Neonatal SD rats were randomly divided into 10 groups and received oral administrations of PCB153 (0.025, 0. 250, 2.500 mg/kg), or Cadmium (1, 2, 4 mg/kg), or positive control 5-Aza-CdR (0.025, 0.250 mg/kg), or vehicle control for five days from PND3. Half of the rats were killed 24 h after the last administration. The remains were fed until 12 weeks. Sperm numbers, apoptosis and DNA methylation levels in testis were investigated. RESULTS: The daily sperm production was significantly decreased in each neonatal exposed group (P < 0.05). Neonatal rats exposed to 5-Aza-CdR and Cadmium reduced the global DNA methylation level, increased apoptosis, while PCB153 exposure did not significantly change DNA methylation and apoptosis. CONCLUSION: Neonatal rats exposed to chemicals could reduce spermatogenesis via multiple pathways. Lower DNA methylation and increased neonatal apoptosis were suggested as one of the causes.

Nanomolar propofol stimulates glutamate transmission to dopamine neurons: a possible mechanism of abuse potential?

Anesthesiologists among physicians are on the top of the drug abuse list, and the mechanism is unclear. Recent studies suggest occupation-related second-hand exposure to i.v. drugs, including propofol, may play a role. Growing evidence indicates that propofol is one of the choices of drugs being abused. In this study, we show that propofol at minute concentrations increases glutamatergic excitatory synaptic transmission and discharges of dopamine neurons in the ventral tegmental area (VTA). We found that acute application of propofol (0.1-10 nM) to the VTA in midbrain slices of rats increased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. We observed that propofol increased the amplitude but decreased the paired-pulse ratio of EPSCs evoked by stimulation in the absence and the presence of gabazine (SR 95531), a GABA(A) receptor antagonist. Moreover, the propofol-induced facilitation of EPSCs was mimicked by 6-phenyl-4-azabicyclo[5.4.0]undeca-7,9,11-triene-9,10-diol (SKF38393), an agonist of dopamine D(1) receptor, and by 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12935), a dopamine reuptake inhibitor, but blocked by (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrochloride (SKF83566), a D(1) antagonist, or by depleting dopamine stores with reserpine. Finally, 1 nM propofol increased the spontaneous discharge rate of dopamine neurons. These findings suggest that propofol at minute concentrations enhances presynaptic D(1) receptor-mediated facilitation of glutamatergic synaptic transmission and the excitability of VTA dopamine neurons, probably by increasing extracellular dopamine levels. These changes in synaptic plasticity in the VTA, an addiction-related brain area might contribute to the development of propofol abuse and the increased susceptibility to addiction of other drugs.

[Establishment of pharyngeal 3-dimensional finite element model of patients with isolated cleft palate].

PURPOSE: The aim of this study was to provide basis for future design and selection of cleft palate surgery through establishing finite element model of pharyngeal cavity which was suitable for biomechanical analysis. METHODS: One patient with isolated cleft palate and 1 normal child underwent multilayer head CT examination. The scanned data of pharyngeal cavity were imported into Mimics software for a 3-D geometric model reconstruction. The model was divided into a grid, so it can be further processed for subsequent finite element analysis. RESULTS: After applying 5cm water column pressure load of 0.0005 MPa at the back edge of the soft palate in the two models respectively, the results showed that the maximum stress of the abnormal nasopharyngeal cavity model was 0.025 MPa, greater than the normal model (0.017 MPa). The same pressure loading was applied to different parts of the two models, the stress change area in the posterior margin of the soft palate and the middle of the palate was the same, and the stress in the front of the hard palate was smaller. CONCLUSIONS: Finite element model has good biomechanical characteristics and geometric similarity. It can be used in isolated cleft palate with preoperative biomechanical analysis, for repairing and functional reconstructive surgery to provide ideal biomechanical model predicts.

The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats.

The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an "accelerator" whereby hypercapnic acidosis causes an inhibition of K+ channels or activation of Na+ and Ca+2 channels to depolarize CO2-sensitive neurons. Nevertheless, it is still unknown if this "accelerator" mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca2+ channels and large conductance Ca-activated K+ (BK) channels, which function as a "brake" on the chemosensitive response of LC neurons. Our findings indicate that both Ca2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses.

[Mandibular swing procedure for surgical resection of advanced oropharyngeal carcinoma].

OBJECTIVE: To explore a better approach to resect the advanced oropharyngeal carcinoma. METHODS: From 1995 to 2005, 17 patients underwent mandibular swing procedure for excision of advanced oropharyngeal carcinoma including: 13 tonsillar cancers, 2 soft palate carcinomas and 2 lingual root cancers. Surgical procedure was selected according to the lesion. All tumors were resected through the mandibular swing approach or its combined approaches. Immediate reconstruction of the surgical defect was done using tongue flap, pectoralis major myocutaneous flap, sternohyoid myofascial flap, temporalis myofascial flap and forehead flap, respectively. After surgical resection of the tumors, all patients received postoperative radiotherapy. RESULTS: All patients' advanced oropharyngeal carcinoma were successfully resected as planned through the mandibular swing procedure or its combined procedures without severe complications. Functions of deglutition, respiration and speech were well restored. The 3- and 5-year survival rate was 54. 5% and 40%, respectively. CONCLUSION: The mandibular swing procedure and its combined approach is safe and effective in the surgical resection of the advanced oropharyngeal carcinoma, which can provide a good exposure for the oropharynx, supraglottic region, hypopharynx, the parapharyngeal space and the base of the skull.

Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia.

Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO2/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O2 (Control) or 60% O2 (Hyperoxia) until studied at 4, 6-7, or 13-14days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO2 at all ages; CO2 sensitivity recovered within 7days after return to room air. Hypercapnic responses of CO2-sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS.

Microglial Acid Sensing Regulates Carbon Dioxide-Evoked Fear.

BACKGROUND: Carbon dioxide (CO2) inhalation, a biological challenge and pathologic marker in panic disorder, evokes intense fear and panic attacks in susceptible individuals. The molecular identity and anatomic location of CO2-sensing systems that translate CO2-evoked fear remain unclear. We investigated contributions of microglial acid sensor T cell death-associated gene-8 (TDAG8) and microglial proinflammatory responses in CO2-evoked behavioral and physiological responses. METHODS: CO2-evoked freezing, autonomic, and respiratory responses were assessed in TDAG8-deficient ((-/-)) and wild-type ((+/+)) mice. Involvement of TDAG8-dependent microglial activation and proinflammatory cytokine interleukin (IL)-1ß with CO2-evoked responses was investigated using microglial blocker, minocycline, and IL-1ß antagonist IL-1RA. CO2-chemosensitive firing responses using single-cell patch clamping were measured in TDAG8(-/-) and TDAG8(+/+) mice to gain functional insights. RESULTS: TDAG8 expression was localized in microglia enriched within the sensory circumventricular organs. TDAG8(-/-) mice displayed attenuated CO2-evoked freezing and sympathetic responses. TDAG8 deficiency was associated with reduced microglial activation and proinflammatory cytokine IL-1ß within the subfornical organ. Central infusion of microglial activation blocker minocycline and IL-1ß antagonist IL-1RA attenuated CO2-evoked freezing. Finally, CO2-evoked neuronal firing in patch-clamped subfornical organ neurons was dependent on acid sensor TDAG8 and IL-1ß. CONCLUSIONS: Our data identify TDAG8-dependent microglial acid sensing as a unique chemosensor for detecting and translating hypercapnia to fear-associated behavioral and physiological responses, providing a novel mechanism for homeostatic threat detection of relevance to psychiatric conditions such as panic disorder.

GABAergic neurons innervating the preganglionic cardiac vagal neurons in the dorsal motor nucleus receive tonic glutamatergic control.

The glutamatergic innervations and the GABAergic innervations are respectively the major excitatory and inhibitory inputs of preganglionic cardiac vagal neurons (CVNs). Whether and how these two kinds of innervations interact in the regulation of CVNs is unknown. Using retrograde fluorescent labeling of CVNs and voltage patch-clamp technique, we demonstrated that mixed global application of glutamatergic NMDA and non-NMDA antagonists AP(5) and CNQX, while had no effect on the GABAergic synaptic events of the CVNs in the nucleus ambiguus (NA), significantly decreased the GABAergic synaptic events of the CVNs in the dorsal motor nucleus of the vagus (DMNX). These results suggest that the GABAergic neurons preceding the CVNs in the DMNX receive tonic glutamatergic control, whereas the GABAergic neurons preceding the CVNs in the NA receive little, if any, glutamatergic innervations. This differential central regulation of the CVNs in the DMNX from those in the NA might be a possible mechanism that enables the CVNs in the DMNX play different roles from those in the NA in the parasympathetic control of heart rate and cardiac functions.

Streptomycin ototoxicity in rat cochlear organotypic cultures.

The purpose of this study is to investigate the ototoxic effect of streptomycin on cochlear hair cells, spiral ganglion cells, and nerve fibers in cochlear organ cultures. The cochlear basilar membrane of three- or four-day-old F344 rats was cultured and treated with various doses of streptomycin for 24 h. Cochlear hair cells and the spiral ganglion neurons were stained with immunofluorescence and were observed under confocal microscope. The increase in hair cell loss was concomitant with the increase in streptomycin sulfate concentrations. Streptomycin impaired both the inner and outer hair cells at a similar degree. The damage to hair cells was more severe at basal turn than apical turn. In contrast, the spiral ganglion neurons and auditory nerve fibers were intact. Streptomycin primarily caused hair cell loss, but not significant impairment in the neural structure in vitro. Streptomycin-induced cochlear hair cell lesion was initiated at the basal turn and extended towards the apical turn. Streptomycin ototoxicity was dose-dependent under in vitro conditions.

[Clinical observation on treatment of chronic suppurative otitis media caused large tympanic membranes perforation by ear-dropping with combined Chinese and Western drugs].

OBJECTIVE: To observe the therapeutic effect of the self-prepared ear dropping made by combined Chinese and Western drugs in treating chronic suppurative otitis media caused large tympanic membrane perforation. METHODS: Sixty-four patients were randomly divided into two groups, the treated group treated with the self-prepared ear-dropping and the control group treated with ear-dropping made by placebo, to observe the therapeutic effect and adverse reaction. RESULTS: In the 32 patients of the treated group, 15 patients were cured, the cured tympanic membrane was normal in shape and thickness in 11, scarred in 3, and thin and transparent in 1. The hearing was improved in all patients with cured tympanic membrane. But no one was cured in the control group. CONCLUSION: The self-prepared ear-dropping had good effect in treating tympanic membrane perforation, it is simple, cheap and no need of further operation.

[The effect of tripterygium wilfordii polyglycosidium on the compound action potential of skeletal muscle in experimental animals with myasthenia gravis].

OBJECTIVE: To observe and analyze the direct effect of tripterygium wilfordii polyglycosidium (TWP) on the activity of skeletal muscle in experimental animals with myasthenia gravis (EAMG). METHODS: C57BL/6 mice were used. After sieving EAMG animals, we observed and compared the variation of the attenuation percentage of compound action potential of gastrocnemius muscle and pronator teres muscle of EAMG before and after the muscle specimens being immersed in the breeding ground of TWP solution. Such variation of attenuation percentage was taken as an indicator of the direct effect of TWP on skeletal muscle. RESULTS: 1. Evident influence of TWP on the attenuation percentage of compound action potential of gastrocnemius muscle was observed (P < 0.05), and apparent decrease of the attenuation percentage could be seen one and a half hours after the muscle was immersed [(14 +/- 36)% before treatment, (-40 +/- 24)% after treatment]; 2. The influence of TWP on the attenuation percentage of compound action potential of pronator teres muscle was noted (P < 0.05), and an apparent decline of the attenuation percentage could be observed one and a half hours after the muscle was immersed[(17 +/- 25)% before treatment, (-17 +/- 10)% after treatment]; 3. There was no distinctive difference between the gastrocnemius muscle and pronator teres muscle in respect of their attenuation percentages of compound action potential. CONCLUSION: TWP has direct remedial effect on the activity of skeletal muscle of EAMG.