Traditional Chinese medicine for gastric cancer: An evidence mapping.

As a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual systematic reviews have not been comprehensively summarized, and the relationship between certain interventions and outcomes are ill-defined. This study aimed to analyze the advantages of TCM interventions for gastric cancer by the method of evidence mapping. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Database for systematic reviews of TCM treating gastric cancer up to December 31, 2023. We used Excel, Endnote 20, and Python software for the analysis of incorporated studies. We assessed the quality of included SRs by AMSTAR-2 and performed evidence mapping including 89 SRs, 1648 RCTs and 122,902 patients, identifying 47 types of interventions and 39 types of outcomes. From a visual overview, we displayed that most SRs reported beneficial effects in improving short- and long-term survival, myelosuppression, and immune function, even though the quality of evidence was generally low. The benefits of Brucea javanica Oil Emulsion Injection, ShenQiFuZheng Injection, XiaoAiPing, Astragalus-Containing TCM and Guben Xiaoji Therapy were found the most solid in corresponding aspects. Our findings suggest that although more rigorous clinical trials and SRs are needed to identify the precise effectiveness, integrating such evidence into clinical care of gastric cancer is expected to be beneficial.

Stereoselective bioaccumulation and degradation of chiral pesticide hexythiazox in earthworm-soil microcosm.

The chiral pesticide hexythiazox was extensively employed in agricultural activities and has garnered growing concern for its harmful impact on the ecosystem. This study investigates the toxicodynamic earthworm at the enantiomeric level of hexythiazox. Earthworms exhibited notable enantioselectivity during the accumulation stage. Furthermore, the presence of earthworms can impact the rate of degradation and enantioselectivity of hexythiazox in soil. The accumulation of the two hexythiazox enantiomers in the earthworm adhered to the one-compartment model, whereas the elimination phase was governed by the first-order kinetics equation. Furthermore, it was discovered that there was no notable enantioselectivity observed during the elimination phase.

Association of changes in frailty status with the risk of all-cause mortality and cardiovascular death in older people: results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

BACKGROUND: Few studies have investigated the association between changes in frailty status and all-cause mortality, inconsistent results were reported. What's more, studies that evaluated the effect of changes of frailty on cardiovascular death in older population are scanty. Therefore, the present study aims to investigate the association of such changes with the risk of all-cause mortality and cardiovascular death in older people, using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHODS: A total of 2805 older participants from two consecutive waves (i.e. 2011 and 2014) of the CLHLS were included for analysis. Based on the changes in frailty status from wave 2011 to wave 2014, participants were categorized into 4 subgroups, including sustained pre/frailty, robustness to pre/frailty, pre/frailty to robustness and sustained robustness. Study outcomes were all-cause mortality and cardiovascular death, and Cox regression analysis examined the association of changes in frailty status with outcomes. RESULTS: From wave 2011 to wave 2014, 33.2% of the participants had frailty transitions. From wave 2014 to wave 2018, there were 952 all-cause mortalities and 170 cardiovascular deaths during a follow-up of 9530.1 person-years, and Kaplan-Meier analysis demonstrated that cumulative incidences of the two outcomes were significantly lower in more robust participants (all log-rank p < 0.001). Compared with the subgroup of sustained pre/frailty, the fully adjusted HRs of all-cause mortality were 0.61 (95% CI: 0.51-0.73, p < 0.001), 0.51 (95% CI: 0.42-0.63, p < 0.001) and 0.41 (0.34-0.49, p < 0.001) in the subgroup of robustness to pre/frailty, the subgroup of pre/frailty to robustness, and the subgroup of sustained robustness, respectively. The fully adjusted HRs of cardiovascular death were 0.79 (95% CI: 0.52-1.19, p = 0.256) in the subgroup of robustness to pre/frailty, 0.45 (95% CI: 0.26-0.76, p = 0.003) in the subgroup of pre/frailty to robustness and 0.51 (0.33-0.78, p = 0.002) in the subgroup of sustained robustness when comparing to the subgroup of sustained pre/frailty, respectively. Stratified analysis and extensive sensitivity analyses revealed similar results. CONCLUSIONS: Frailty is a dynamic process, and improved frailty and remaining robust are significantly associated with lower risk of all-cause mortality and cardiovascular death in older people.

Clinical Observation and Analysis of Thyroglossal Duct Cyst Carcinoma: A Report of 5 Cases.

Thyroglossal duct cyst carcinoma (TGDCCa) is a rare condition with only approximately 300 cases reported to date. There is a lack of comprehensive reporting on its clinical manifestations, ultrasound, contrast-enhanced computed tomography, magnetic resonance imaging (MRI) features, immunophenotyping, procedure, and prognosis following modified Sistrunk's procedure. This study aimed to address these gaps by analyzing and summarizing the clinical features of 5 cases of papillary carcinoma arising in thyroglossal duct cysts (TGDC).Five patients with papillary carcinoma in TGDC treated by modified Sistrunk's procedure were included. Their clinical manifestation, physical examination findings, iconography, pathological findings, treatment, and outcomes were analyzed in aiding the diagnosis and treatment of TGDCCa. Immunohistochemistry was used to confirm the papillary carcinoma subtype. The BRAFV600E mutation was detected in 2 patients. No evidence of cancer recurrence, distant metastases, and malignant changes in the thyroid was found after a mean follow-up of 29.8 months.The management of TGDCCa with papillary carcinoma in low-risk patients can be accomplished by performing a modified Sistrunk's procedure along with a regular follow-up imaging of the thyroid and neck. Although postoperative pathological diagnosis is the gold standard for diagnosis, it is equally crucial to comprehend the clinical manifestations and auxiliary diagnostic techniques before surgical intervention.

Syringe purification with UPLC-MS/MS for detection of antibiotics in tea garden soil after long-term application of manure.

The residue of antibiotics in the soil is becoming more and more common, which may affect the normal growth of plants and organisms. The aim of this study was to investigate the residues of antibiotics in tea gardens' soil after a long-term application of manure. An ultra-high performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously determine the residues of 32 antibiotics in the soil of tea gardens after fertilization. The samples were extracted with methanol-acetonitrile and purified with C18 at the same time. Then, mixed dispersive sorbents dispersed in a syringe were used for the second purification. The results showed that the antibiotics have a good linear relationship within the range. The recovery rate is 70.1-120.3%. The applicability of the method was demonstrated by analyzing 30 real samples (with a detection rate of 43.3%). The method is a simple and environmentally friendly method for the analysis of multiple antibiotics in soils, and it could provide a basis for the risk assessment of antibiotics in agricultural environments and the standard application of organic fertilizers in tea gardens.

Intraoperative Repair of Cerebrospinal Fluid Rhinorrhea in Skull Base Tumor Resection: A Retrospective Study of Acellular Dermal Matrix Versus Turbinate Flap.

BACKGROUND: The acellular dermal matrix (ADM) and turbinate flap (TF) have been widely used in the reconstruction of skull base defects. However, owing to the lack of reported data, the therapeutic effects have been controversial. The purpose of the present study was to compare the effect of the ADM and TF on cerebrospinal fluid (CSF) rhinorrhea after nasal endoscopic resection of a skull base tumor. METHODS: The data from 46 patients who had undergone nasal endoscopic resection of a skull base tumor and repair of CSF rhinorrhea were retrospectively analyzed. The patients were divided into ADM and TF groups according to the difference in repair materials used. We compared and analyzed the intraoperative information and postoperative outcomes. RESULTS: The operation time, blood loss, defect area, and need for blood transfusion were not significantly different between the ALT and TF groups. The postoperative length of hospital stay (14.33 ± 3.66 vs. 16.76 ± 5.51 days; P = 0.669) and the incidence of complications, including wound infection (1 vs. 0; P = 0.270), intracranial infection (1 vs. 1; P = 0.900), hemorrhage (2 vs. 3; P = 0.788), 15-day CSF leak (1 vs. 2; P = 0.658), and respiratory infection (2 vs. 1; P = 0.450) were comparable between the 2 groups. The 6-month (0 vs. 0; P = 1.000) and 12-month (0 vs. 0; P = 1.000) incidence of recurrence also showed no significant differences. CONCLUSION: The use of the ADM for patients with CSF rhinorrhea showed comparable results in terms of postoperative outcomes compared with the use of TF. ADM could serve as a safe and feasible alternative for endoscopic repair of CSF rhinorrhea after nasal endoscopic resection of skull base tumors.

Acute ST-segment elevation myocardial infarction due to extrinsic compression of left coronary artery from pulmonary epithelioid hemangioendothelioma: A case report.

RATIONALE: Acute myocardial infarction is usually caused by coronary atherosclerotic plaque disruption (rupture or erosion), also including other uncommon etiologies. Pulmonary epithelioid hemangioendothelioma (PEH) is a rare low to intermediate malignant vascular tumor originating from vascular endothelial cells. Here, we report a rare case of acute ST-segment elevation myocardial infarction (STEMI) due to extrinsic compression of left coronary artery from PEH. PATIENT CONCERNS: A 63-year-old woman with pulmonary nodules received left pulmonary nodulectomy, and the pathological examination indicated PEH. Five months after the pulmonary nodulectomy, the patient was admitted due to progressive dyspnea. DIAGNOSIS: Electrocardiography showed the obvious ST-segment elevation in the leads I, aVL, and V1-3, and laboratory tests revealed the elevated level of cardiac troponin T. Emergent coronary angiography and the contrast-enhanced computed tomography scan conformed STEMI due to extrinsic compression of left coronary artery from PEH. INTERVENTIONS: The patient did not undergo further therapy after the pulmonary nodulectomy. During the present hospitalization, she received basic life support and nutritional support treatment. OUTCOMES: The patient deteriorated rapidly into multi-organ failure and eventually died. LESSONS: Acute STEMI could be caused by extrinsic compression of the coronary artery from the mass effects of PEH, and active therapy and close follow-up should be considered for patients with PEH.

Bilirubin augments Ca2+ load of developing bushy neurons by targeting specific subtype of voltage-gated calcium channels.

Neonatal brain is particularly vulnerable to pathological levels of bilirubin which elevates and overloads intracellular Ca2+, leading to neurotoxicity. However, how voltage-gated calcium channels (VGCCs) are functionally involved in excess calcium influx remains unknown. By performing voltage-clamp recordings from bushy cells in the ventral cochlear nucleus (VCN) in postnatal rat pups (P4-17), we found the total calcium current density was more than doubled over P4-17, but the relative weight of VGCC subtypes changed dramatically, being relatively equal among T, L, N, P/Q and R-type at P4-6 to predominantly L, N, R over T and P/Q at P15-17. Surprisingly, acute administration of bilirubin augmented the VGCC currents specifically mediated by high voltage-activated (HVA) P/Q-type calcium currents. This augment was attenuated by intracellular loading of Ca2+ buffer EGTA or calmodulin inhibitory peptide. Our findings indicate that acute exposure to bilirubin increases VGCC currents, primarily by targeting P/Q-type calcium channels via Ca2+ and calmodulin dependent mechanisms to overwhelm neurons with excessive Ca2+. Since P/Q-subtype calcium channels are more prominent in neonatal neurons (e.g. P4-6) than later stages, we suggest this subtype-specific enhancement of P/Q-type Ca2+ currents likely contributes to the early neuronal vulnerability to hyperbilirubinemia in auditory and other brain regions.

NAD+ Attenuates Bilirubin-Induced Hyperexcitation in the Ventral Cochlear Nucleus by Inhibiting Excitatory Neurotransmission and Neuronal Excitability.

Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity. We found that NAD+ effectively decreased the size of evoked excitatory postsynaptic currents (eEPSCs), increased paired-pulse ratio (PPR) and reversed the effect of bilirubin on eEPSCs, implicating its inhibitory effects on the presynaptic release probability (Pr). Moreover, NAD+ not only decreased the basal frequency of miniature EPSCs (mEPSCs), but also reversed bilirubin-induced increases in the frequency of mEPSCs without affecting their amplitude under either condition. Furthermore, we found that NAD+ decreased the frequency of spontaneous firing of VCN neurons as well as bilirubin-induced increases in firing frequency. Whole-cell current-clamp recordings showed that NAD+ could directly decrease the intrinsic excitability of VCN neurons in the presence of synaptic blockers, suggesting NAD+ exerts its actions in both presynaptic and postsynaptic loci. Consistent with these observations, we found that the latency of the first postsynaptic spike triggered by high-frequency train stimulation of presynaptic afferents (i.e., the auditory nerve) was prolonged by NAD+. These results collectively indicate that NAD+ suppresses presynaptic transmitter release and postsynaptic excitability, jointly weakening excitatory neurotransmission. Our findings provide a basis for the exploration of NAD+ for the prevention and treatment of bilirubin encephalopathy and excitotoxicity associated with other neurological disorders.

Taurine protects against bilirubin-induced hyperexcitation in rat anteroventral cochlear nucleus neurons.

No effective medication for hyperbilirubinemia yet exists. Taurine is believed to exert a neuroprotective action. The aim of the present study was to determine whether taurine protected neurons of the rat anteroventral cochlear nucleus (AVCN) against bilirubin-induced neuronal hyperexcitation. AVCN neurons were isolated from 13 to 15-day-old Sprague-Dawley rats. The effects of bilirubin on the spontaneous excitatory postsynaptic currents (sEPSCs) and action potential currents were compared with those exerted by bilirubin and taurine together. Bilirubin dramatically increased the frequencies of sEPSCs and action potential currents, but not sEPSC amplitude. Taurine suppressed the enhanced frequency of action potentials induced by bilirubin, in a dose-dependent manner. In addition, taurine decreased the amplitude of voltage-dependent calcium channel currents that were enhanced upon addition of bilirubin. We explored the mechanism of the protective effects exerted by taurine using GABAA and glycine receptor antagonists, bicuculline and strychnine, respectively. Addition of bicuculline and strychnine eliminated the protective effects of taurine. Neither bilirubin nor taurine affected the sensitivity of the glutamate receptor. Our findings thus indicate that taurine protected AVCN neurons against bilirubin-induced neuronal hyperexcitation by activating the GABAA and glycine receptors and inhibiting calcium flow through voltage-gated channels. Thus, taurine may be effective in treatment of neonatal hyperbilirubinemia.

Delayed diagnosis and treatment of benign paroxysmal positional vertigo associated with current practice.

The purposes of this study were to demonstrate the current status of benign paroxysmal positional vertigo (BPPV) management and the advantages of repositioning maneuvers as well as to facilitate the accurate and efficient diagnosis and management of BPPV. Of 131 participants with severe dizziness/vertigo who were examined and treated, 31 (23.7%) fulfilled the diagnostic criteria for BPPV. All patients in the study had a diagnosis of BPPV confirmed by their history, typical subjective symptom reports, and characteristic positional nystagmus during the Dix-Hallpike test and/or roll test. All participants were comprehensively interviewed regarding their medical history, characteristics of the first attack of vertigo, associated symptoms, previous financial costs, and number of hospital visits. The average duration from the appearance of the first symptoms until a final diagnostic positional maneuver was >70 months. On average, patients visited hospitals more than eight times before the final diagnosis due to initial visits to inappropriate departments, including neurology, emergency, orthopaedic surgery, and Traditional Chinese Medicine, with a corresponding average financial cost of more than 5,000 RMB. The canalith repositioning procedure (CRP) was effective in 80.65% of patients after the first repositioning maneuver. Our data demonstrated that despite the significant prevalence of BPPV, delays in diagnosis and treatment frequently occur, which have both cost and quality-of-life impacts on both patients and their caregivers. The CRP is very effective for patients with BPPV. It is important for patients to pay more attention to the impact of BPPV on their lives and recognize its nature to ensure compliant follow-up in otolaryngology.

Application of distortion product otoacoustic emissions to inflation of the eustachian tube in low frequency tinnitus with normal hearing.

OBJECTIVE: This study was designed to investigate the applications of distortion product otoacoustic emissions to assess the efficacy of eustachian tube inflation on low frequency tinnitus with normal hearing. METHODS: Ninety-four patients (155 ears) suffering from subjective tinnitus with normal hearing sensitivity participated in this study. Control group consists of fifty volunteers (100 ears) without tinnitus. They were subjected to full history taking, otoscopy, basic audiologic evaluation and distortion product otoacoustic emissions (DPOAE). As for the patients with decreased DPOAE amplitude over a limited frequency range from 0.5 to 1kHz, we offered nose dropping and tubal inflation for a week and DPOAE was preformed again. The patients were followed up for a month. RESULTS: 34.8% DPOAE-gram showed decreased amplitude at the frequencies from 0.5 to 1kHz in tinnitus group and "the ring" is mostly lower in pitch. Among the patients accepted the treatment of eustachian tube inflation, 16.7% the tinnitus disappeared, no recurrence within one month; 66.67% the tinnitus reduced within one month. 95.5% the amplitude of DPOAE showed improved over the limited frequency. 16.7% the tinnitus still existed. CONCLUSION: The changes of the mechanical properties of ossicular chain or the tympanic membrane influenced by tympanum pressure may cause tinnitus, which is sub-clinical prior to the changes of audiometry and tympanometry. The low frequency tinnitus may gain transitory relief from ringing with the tubal inflation. DPOAE was proved to be a useful tool in the evaluation of the efficacy of tubal inflation on low frequency tinnitus with normal hearing.

Interaction between taurine and GABA(A)/glycine receptors in neurons of the rat anteroventral cochlear nucleus.

Taurine, one of the most abundant endogenous amino acids in the mammalian central nervous system (CNS), is involved in neural development and many physiological functions. In this study, the interaction between taurine and GABA(A)/glycine receptors was investigated in young rat (P13-P15) anteroventral cochlear nucleus (AVCN) neurons using the whole-cell patch-clamp method. We found that taurine at low (0.1mM) and high (1mM) concentrations activated both GABA(A) and glycine receptors, but not AMPA and NMDA receptors. The reversal potentials of taurine-, GABA- or glycine-evoked currents were close to the expected chloride equilibrium potential, indicating that receptors activated by these agonists were mediating chloride conductance. Moreover, our results showed that the currents activated by co-application of GABA and glycine were cross-inhibitive. Sequential application of GABA and glycine or vice versa also reduced the glycine or GABA evoked currents. There was no cross-inhibition when taurine and GABA or taurine and glycine were applied simultaneously, but the response was larger than that evoked by GABA or glycine alone. These results suggest that taurine can serve as a neuromodulator to strengthen GABAergic and glycinergic neurotransmission in the rat AVCN.

Minocycline cannot protect neurons against bilirubin-induced hyperexcitation in the ventral cochlear nucleus.

Excitotoxicity has been suggested to play an important role in many central nervous system diseases, particularly in bilirubin encephalopathy. Minocycline treatment has been proposed to be one of the most promising potential therapies for excitotoxicity-induced neurological disorders. However, some key questions, such as the electrophysiological effect of minocycline on neuronal excitability and hyperexcitation in pathological conditions, require clarification. In this study, using patch-clamp techniques, we showed that bilirubin increased the frequency of both spontaneous excitatory postsynaptic currents (sEPSCs) and neuronal firing in isolated ventral cochlear nucleus (VCN) neurons at postnatal days 11-14 (P11-14) in rats but it did not affect the amplitude of sEPSCs or glutamate-activated (I(Glu)) currents. However, minocycline had no effect on sEPSC frequency or I(Glu) amplitude. Furthermore, minocycline pretreatment did not abolish bilirubin-induced sEPSC potentiation or neuron firing. These data suggest that minocycline does not affect excitatory synaptic transmission or hyperexcitation induced by bilirubin in VCN neurons. From these results, we propose that the neuroprotective efficacy of minocycline, if it can protect neurons against neurotoxicity induced by substances like bilirubin, is mediated by either an alternative mechanism or downstream events post neuronal hyperexcitation. Certainly, additional investigation of the neuroprotective effects of minocycline is required before embarking on further clinical trials.

Differences in developmental changes in GABAergic response between bushy and stellate cells in the rat anteroventral cochlear nucleus.

Many mammalian central nervous system neuron responses mediated by GABA(A) receptors undergo a developmental transition from excitation to inhibition, but little is known about the time of this switch in specific cell types in the developing anteroventral cochlear nucleus (AVCN). In the present study, bushy and stellate cells, two major cell types in the AVCN, were identified according to their morphology and electrophysiology. The equilibrium potential of GABA-evoked currents (E(GABA)) was examined using the gramicidin-perforated patch-clamp technique. We found that the action of GABA in bushy and stellate cells switched from predominantly depolarizing to predominantly hyperpolarizing with respect to their resting membrane potential (V(rest)) at different postnatal ages. Such a switch in the GABA response of bushy cells occurred before the first postnatal week, whereas that in stellate cells happened at the end of the second postnatal week. Furthermore, we discovered that bushy cells had a more depolarized V(rest) than did stellate cells before the second postnatal week; however, the E(GABA) of bushy and stellate cells was not significantly different. Thus, the discrepancy in the timing of the developmental shift from depolarizing to hyperpolarizing GABA responses between bushy and stellate cells may be due to the difference in their V(rest), but not due to E(GABA) itself. These results suggest that GABAergic inhibition functions earlier in bushy than in stellate cells. In contrast, the longer excitatory action of GABA on stellate cells possibly renders them more vulnerable than bushy cells to excitotoxic substances during early development.

Bilirubin facilitates depolarizing GABA/glycinergic synaptic transmission in the ventral cochlear nucleus of rats.

Excitotoxicity contributes to bilirubin-induced central nervous system injury; however, the mechanisms involved remain controversial. Previous studies from our lab have demonstrated that in juvenile rats bilirubin facilitates γ-aminobutyric acid (GABA)/glycinergic synaptic transmission through activation of presynaptic protein kinase A (PKA) in isolated neurons of the ventral cochlear nucleus (VCN). However, the descending mechanism and physiological effects of bilirubin-induced potentiation remain unclear. Here, whole-cell recordings show that 3×10(-6) M bilirubin increased the frequency of both spontaneous (sPSCs) and miniature (mPSCs) GABA/glycinergic postsynaptic currents in VCN neurons of postnatal day 12-14 (P12-14) rats. This action was dependent on the concentration and duration of exposure to bilirubin and was only partially suppressed by 10(-5) M bicuculline. The potentiation effect on mPSCs persisted in a Ca2+-free solution, but was fully occluded by pretreatment with 1,2 bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), an intracellular Ca2+ chelator. Following pretreatment of the neurons with BAPTA-AM, forskolin, a PKA activator, had no effect on the frequency or amplitude of mPSCs. This suggests that Ca2+ release from presynaptic stores is part of the descending pathway of PKA activation and is responsible for biliurbin-induced potentiation of cell activity. Using gramicidin-perforated patch recordings, the reversal potential of GABA-evoked currents (EGABA) was also investigated. The GABA response resulted in depolarization of 12 of 20 recorded VCN neurons from P12-14 rats. Therefore, potentiation of depolarizing GABA/glycinergic transmission by bilirubin may underlie bilirubin excitotoxicity, which may play a role in the hearing impairment observed among hyperbilirubinemic neonates.

Bilirubin enhances neuronal excitability by increasing glutamatergic transmission in the rat lateral superior olive.

Hyperbilirubinemia is one of the most common clinical phenomena observed in human newborns. To achieve effective therapeutic treatment, numerous studies have been done to determine the molecular mechanisms of bilirubin-induced neuronal excitotoxicity. However, there is no conclusive evidence for the involvement of glutamatergic synaptic transmission in bilirubin-induced neuronal hyperexcitation and excitotoxicity. In the present study, using gramicidin-perforated patch-clamp techniques, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded from lateral superior olive (LSO) neurons isolated from postnatal 11-14-day-old (P11-14) rats. The application of 3 µM bilirubin increased the frequency, but not the amplitude, of sEPSCs. The action of bilirubin was tetrodotoxin (TTX)-insensitive, as bilirubin also increased the frequency, but not the amplitude, of mEPSCs. The amplitudes of GABA-activated (I(GABA)) and glutamate-activated (I(glu)) currents were not affected by bilirubin. Under current-clamp conditions, no spontaneous action potentials were observed in control solution. However, the application of 3 µM bilirubin for 4-6 min evoked a considerable rate of action-potential firing. The evoked firing was partially occluded by D,L-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, but completely inhibited by a combination of APV and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), an AMPA receptor antagonist. These results indicate that bilirubin facilitates presynaptic glutamate release, enhances glutamatergic synaptic transmission by activating postsynaptic AMPA and NMDA receptors, and leads to neuronal hyperexcitation. This study provides a better understanding of the mechanism of bilirubin-induced excitotoxicity and determines for the first time that both AMPA and NMDA receptors are likely involved in the excitotoxicity produced by bilirubin.