The purpose of this study was to investigate the effect of glutamate and its ionotropic receptor agonists on the response to acute hypoxia in rat carotid body in vitro. Briefly, after SD rats were anesthetized and decapitated, the bilateral carotid bifurcations were rapidly isolated. Then bifurcation was placed into a recording chamber perfused with 95% O₂-5% CO₂ saturated Kreb's solution. The carotid body-sinus nerve complex was dissected, and the carotid sinus nerve discharge was recorded using a suction electrode. To detect the response of carotid body to acute hypoxia, the chamber was perfused with 5% O₂-5% CO₂-90% N₂ saturated Kreb's solution for a period of 100 s at an interval of 15 min. To observe the effect of glutamate, ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonist AMPA or N-methyl-D-aspartate (NMDA) receptor agonist NMDA on the response to acute hypoxia in rat carotid body, the chamber was perfused with 5% O₂-5% CO₂-90% N₂ saturated Kreb's solution containing the corresponding reagent. The results showed that glutamate (20 μmol/L), AMPA (5 μmol/L) or NMDA (10 μmol/L) inhibited the acute hypoxia-induced enhancement of carotid sinus nerve activity, and these inhibitory effects were dose-dependent. In summary, the activation of glutamate ionotropic receptors appears to exert an inhibitory effect on the response to acute hypoxia in carotid body of rats.
Rats ; Animals ; Glutamic Acid/pharmacology* ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology* ; N-Methylaspartate/pharmacology* ; Carotid Body ; Rats, Sprague-Dawley ; Carbon Dioxide ; Receptors, N-Methyl-D-Aspartate ; Receptors, AMPA ; Hypoxia

Objectives: This study aimed to describe the clinical outcomes related to theintroduction of Paliperidone Palmitate in a specialty hospital in the Philippines. Methodology: Cross-sectional study among patients with Schizophrenia seen at thepsychiatry service of a specialty hospital catering to war veterans who were initiated onPaliperidone Palmitate. We reviewed and abstracted baseline patient data from themedical record of eligible patients. Outcome of treatment was collected through a one-time objective assessment of the patient by a third-party psychiatrist using theStructured Clinical Interview for Symptoms of Remission (SCI-SR) tool. Results: A total of 30 patients were recruited for the study from August 2020 and June2021, the majority of whom were males (80%), residents of the National Capital Region(50%) and single (20%). The median duration from schizophrenia diagnosis to initiation of Paliperidone treatment was 19.50 years (IQR: 16.60 – 33.50). In eight patients (22.67%),other antipsychotic drugs were discontinued following initiation of Paliperidonetreatment; in the remaining 22 participants (73.33%), Paliperidone was taken concurrentlywith other antipsychotic drugs. The median duration from the initiation of Paliperidonetreatment to follow-up assessment was 27.20 months (IQR: 24.73 – 30.50), with allparticipants having at least 6 months of treatment. At follow-up assessment, allparticipants were classified to be in remission. Conclusion In this study among patients with schizophrenia seen in a specialtyhospital in the Philippines, we found evidence that clinical outcomes with PaliperidonePalmitate were comparable to those given a combination of oral and long- actingantipsychotics.
Paliperidone Palmitate ; Schizophrenia

The Community Mental Health Program (CMHP) of the Center for Health Development Calabarzon is an initiative that aims to integrate mental health into primary care to facilitate person-centered and holistic services. At the core of CMHP is a referral pathway between health centers and tertiary-level mental health services for the diagnosis and continuing management of persons with mental health conditions, as well as the use of an innovative medication (specifically for schizophrenia). This commentary presents lessons learned from a one-year implementation of CMHP in four pilot sites in the provinces of Rizal and Laguna, which stakeholders in mental health may consider in the design of community-based mental health programs to further the mandate of the Mental Health Act.
Schizophrenia ; Mental Health Services ; Program Evaluation ; Paliperidone Palmitate

OBJECTIVE: To investigate the effect of parecoxib sodium preemptive analgesia on pain and stress response after surgery in elderly hip fracture patients. METHODS: The clinical data of 70 elderly patients with hip fracture treated in our hospital from October 2017 to October 2019 were prospectively analyzed. According to different analgesic patterns, 35 cases were randomly divided into experimental group, aged 65 to 86(78.5±9.1) years, 21 males and 14 females, including 18 femoral neck fractures and 17 femoral intertrochanteric fractures. There were 35 cases in control group, aged 66 to 88 (80.6±8.1) years, 18 males, and 17 females, including 20 cases of femoral neck fractures and 15 cases of intertrochantericfractures. The visual analogue scale (VAS) at 4 h, 12 h, 24 h, 48 h, and 72 h after surgery, the incidence of delirium and stress indicators of malondialdehyde (MDA), superoxide dismutase (SOD), cortisol (COR), and epinephrise (E) postoperatively in the two groups were observed. RESULTS: At 4 h, 12 h, 24 h, 48 h after surgery, the VAS score of experimental group was lower than that of the control group, and the difference was statistically significant ( CONCLUSION The advanced analgesic application of parecoxib sodium can significantly reduce the postoperative stress response of elderly hip fracture patients, enhance the postoperative analgesic effect, reduce the incidence of postoperative delirium, and improve the quality of rehabilitation of patients.
Aged ; Analgesia ; Female ; Hip Fractures/surgery* ; Humans ; Isoxazoles ; Male ; Pain ; Prospective Studies ; Treatment Outcome

Symptomatic relapse is observed frequently and often associated with social and/or occupational decline that can be difficult to reverse in patients with schizophrenia. Several atypical antipsychotics, including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting injectable antipsychotics (LAIs), and new evidence has been accumulating. LAIs appear to have a significant role in at least a group of schizophrenia patients. Improving the adherence, continuous availability, managing changes in receptor sensitivity, and lowering the requirement of cumulative doses are some of the major advantages of LAIs. Patients with first episode psychosis, dopamine super-sensitivity syndromes, and comorbid substance abuse might particularly benefit. Delaying the initiation of LAI until the establishment of non-adherence is not recommended. The results of clinical trials comparing LAIs with oral antipsychotics (OAPs) are inconsistent because they are influenced considerably by the study design. On the other hand, several barriers to LAIs use in current practice include clinical lack of knowledge, and negative attitudes about LAIs. This article tries to help clinicians better characterize the role of LAIs in the treatment of schizophrenia.
Antipsychotic Agents ; Aripiprazole ; Dopamine ; Hand ; Humans ; Medication Adherence ; Paliperidone Palmitate ; Psychotic Disorders ; Recurrence ; Risperidone ; Schizophrenia ; Substance-Related Disorders

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A₁ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A₁R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.
Action Potentials ; Adenosine ; Alzheimer Disease ; Fires ; Ibotenic Acid ; Membranes ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Patch-Clamp Techniques ; Pyramidal Cells

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018) with other recently published guidelines for treating bipolar disorder. We reviewed a total of five recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2018 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2018 did not prefer monotherapy with MS or AAP for psychotic mania. Quetiapine, olanzapine and aripiprazole were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Most guidelines advocated newer AAPs as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs (such as asenapine, cariprazine, paliperidone, lurasidine, long-acting injectable risperidone and aripiprazole once monthly) became prominent. KMAP-BP 2018 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2018, predominantly in the treatment of psychotic mania and severe depression. Further studies were needed to address several issues identified in our review.
Aripiprazole ; Bipolar Disorder ; Depression ; Drug Therapy ; Lithium ; Paliperidone Palmitate ; Prescriptions ; Quetiapine Fumarate ; Risperidone ; Valproic Acid

Aripiprazole is an atypical antipsychotic that acts as a partial agonist of dopamine type 2 receptors as well as 5-HT1A receptors. It is used in the treatment of schizophrenia and in type 1 bipolar disorder for mania. Because aripiprazole is well tolerated with few side effects it is used off-label in other psychotic disorders. The prevalence of abnormal liver function tests with antipsychotic use is 32%, with clinically significant effects in 4% of cases. No cases of aripiprazole-induced liver injury have been published. We report a 28-year-old female who presented with non-affective first-episode psychosis and who was treated with aripiprazole. Initially she was medicated with 10 mg per day, with an increase to 20 mg per day on the 12th day of hospitalization. Nine days after she became icteric, with nausea and had a vomiting episode. Laboratory analysis revealed a very high level of alanine aminotransferase, and minor to moderately high levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Aripiprazole was tapered and paliperidone was started with the improvement of clinical and laboratory findings.
Adult ; Alanine Transaminase ; Alkaline Phosphatase ; Aripiprazole ; Aspartate Aminotransferases ; Bilirubin ; Bipolar Disorder ; Dopamine ; Female ; Hepatitis ; Hospitalization ; Humans ; Liver ; Liver Function Tests ; Nausea ; Paliperidone Palmitate ; Prevalence ; Psychotic Disorders ; Receptor, Serotonin, 5-HT1A ; Schizophrenia ; Transaminases ; Transferases ; Vomiting

OBJECTIVE: Whether long-acting injectable antipsychotics (LAI) are superior to oral antipsychotics remains a controversial question, and results vary depending on the study design. Our study was performed to compare outcomes of oral anti-psychotics and paliperidone palmitate (PP) in clinical practice by investigating the numbers of admissions and bed days. METHODS: We performed a retrospective observational mirror-image study at a single medical center, reviewing medical charts to obtain the clinical data. Forty-six patients with a diagnosis of schizophrenia or schizoaffective disorder who had received at least two doses of PP were included in the analysis. The Wilcoxon signed-rank test was used to compare the numbers of bed days and admissions 1 year before starting PP with those numbers at 1 year after. RESULTS: The mean number of admissions fell from 0.83 to 0.17 per patient (p < 0.0002), and the median fell from 1 to 0. The mean number of bed days decreased significantly, from 24.85 to 8.74 days (p < 0.006). The outcomes remained similar in sensitivity analyses set up with different mirror points. CONCLUSION: Our results indicate that initiating PP reduced the mean numbers of hospital admissions and bed days compared with prior oral medication. LAIs may thus be cost effective in practice; its use bringing about cost reductions greater than its purchase cost.
Antipsychotic Agents ; Diagnosis ; Hospitalization ; Humans ; Paliperidone Palmitate ; Psychotic Disorders ; Retrospective Studies ; Schizophrenia

The neuronal activity-dependent change in the manner in which light is absorbed or scattered in brain tissue is called the intrinsic optical signal (IOS), and provides label-free, minimally invasive, and high spatial (~100 µm) resolution imaging for visualizing neuronal activity patterns. IOS imaging in isolated brain slices measured at an infrared wavelength (>700 nm) has recently been attributed to the changes in light scattering and transmittance due to aquaporin-4 (AQP4)-dependent astrocytic swelling. The complexity of functional interactions between neurons and astrocytes, however, has prevented the elucidation of the series of molecular mechanisms leading to the generation of IOS. Here, we pharmacologically dissected the IOS in the acutely prepared brain slices of the stratum radiatum of the hippocampus, induced by 1 s/20 Hz electrical stimulation of Schaffer-collateral pathway with simultaneous measurement of the activity of the neuronal population by field potential recordings. We found that 55% of IOSs peak upon stimulation and originate from postsynaptic AMPA and NMDA receptors. The remaining originated from presynaptic action potentials and vesicle fusion. Mechanistically, the elevated extracellular glutamate and K⁺ during synaptic transmission were taken up by astrocytes via a glutamate transporter and quinine-sensitive K2P channel, followed by an influx of water via AQP-4. We also found that the decay of IOS is mediated by the DCPIB- and NPPB-sensitive anion channels in astrocytes. Altogether, our results demonstrate that the functional coupling between synaptic activity and astrocytic transient volume change during excitatory synaptic transmission is the major source of IOS.
Action Potentials ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Amino Acid Transport System X-AG ; Astrocytes ; Brain ; Electric Stimulation ; Glutamic Acid ; Hippocampus ; Jupiter ; Neurons ; Receptors, N-Methyl-D-Aspartate ; Synaptic Transmission ; Water