Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that leads to a progressive muscle wasting and paralysis. The pathological phenotypes are featured by severe motor neuron death and glial activation in the lumbar spinal cord. Proposed ALS pathogenic mechanisms include glutamate cytotoxicity, inflammatory pathway, oxidative stress, and protein aggregation. However, the exact mechanisms of ALS pathogenesis are not fully understood yet. Recently, a growing body of evidence provides a novel insight on the importance of glial cells in relation to the motor neuronal damage via the non-cell autonomous pathway. Accordingly, the aim of the current paper is to overview the role of astrocytes and microglia in the pathogenesis of ALS and to better understand the disease mechanism of ALS.
Amyotrophic Lateral Sclerosis ; Astrocytes* ; Glutamic Acid ; Microglia* ; Motor Neurons ; Neurodegenerative Diseases ; Neuroglia ; Oxidative Stress ; Paralysis ; Phenotype ; Spinal Cord

alpha2 adrenoceptor agonists have been used successfully to treat patients with hypertension and patients withdrawing from long-term abuse of drugs or alcohol. alpha2 adrenoceptor agonists have also proved to be a clinically useful adjunct in clinical anesthetic practice as well as in chronic pain therapy because they have both anesthetic and analgesic-sparing activity. In addition, they have a role in providing hemodynamic stability in patients who are at risk of perioperative ischemia. Dexmedetomidine, a novel selective alpha2 adrenoceptor agonist, has been registered for use as a sedative-analgeic in a variety of clinical setting including monitored anesthesia care and intensive care unit. However, the side-effects of hypotension and bradycardia have limited the routine use of alpha2 adrenoceptor agonists perioporeatively. In this review, we discuss the pharmacology of alpha2 adrenoceptor agonists and their useful applications in anesthesia and intensive care unit.
Anesthesia ; Bradycardia ; Chronic Pain ; Dexmedetomidine ; Hemodynamics ; Humans ; Hypertension ; Hypotension ; Intensive Care Units ; Ischemia

BACKGROUND: Remifentanil has gained wide clinical acceptance during anesthesia due to its short context-sensitive half time and organ-independent metabolism. However, its mechanism as an anesthetic remains unclear. Glutamate transporters may be important targets for anesthetic action in the central nervous system, and we tested whether remifentanil affected the activity of the primary neuronal glutamate transporter, EAAC1 (excitatory amino acid carrier 1). METHODS: EAAC1 was expressed in Xenopus oocytes by mRNA injection. By using two-electrode voltage clamping, membrane currents were recorded before, during, and after application of L-glutamate (30microM) in the presence or absence of remifentanil. Oocytes were exposed to a protein kinase C (PKC) activator and inhibitor to study the role of PKC on EAAC1 activity. RESULTS: L-Glutamate induced an inward current in EAAC1-expressing oocytes. This response increased in a bell-shaped manner in the presence of 0.1microM to 1 mM remifentanil. Remifentanil significantly increased Vmax (3.1 +/- 0.2microC for controls vs. 4.9 +/- 0.3 microC for remifentanil treatment; n = 12-15; P < 0.05). However, remifentanil did not significantly change Km. Treatment of the oocytes with phorbol-12-myristate-13-acetate (PMA), a PKC activator, caused a significant increase in transporter current (1.00 +/- 0.03 to 1.35 +/- 0.03microC; P < 0.05). Oocytes pretreated with the PKC inhibitor alone (staurosporine) abolished remifentanilenhanced EAAC1 activity. CONCLUSIONS: Our data suggests that remifentanil enhances EAAC1 activity and that PKC is involved in mediating this effect.
Amino Acid Transport System X-AG ; Anesthesia ; Central Nervous System ; Constriction ; Glutamic Acid ; Membranes ; Negotiating ; Neurons ; Oocytes ; Piperidines ; Protein Kinase C ; RNA, Messenger ; Xenopus

Guillain-Barre syndrome is an acute inflammatory demyelinating polyradiculopathy characterized by progressive motor weakness, areflexia, and ascending paralysis. Guillain-Barre syndrome is extremely rare in pregnant patients, and there are no established guidelines for delivery or safest anesthetic methods. We report a Cesarean delivery in the case of a 32-year old woman who was diagnosed with Guillain-Barre syndrome 18 weeks into gestation. Tracheostomy was performed due to progressive respiratory muscle weakness and respiratory failure, and ventilator support was required in the intensive care unit. The respiratory difficulty was exacerbated by the growth of the fetus, necessitating emergency Cesarean delivery. The delivery was successfully performed under general anesthesia, and the patient recovered without neurological sequelae.
Anesthesia, General ; Cesarean Section ; Emergencies ; Female ; Fetus ; Guillain-Barre Syndrome ; Humans ; Intensive Care Units ; Paralysis ; Polyradiculopathy ; Pregnancy ; Respiratory Insufficiency ; Respiratory Muscles ; Tracheostomy ; Ventilators, Mechanical

Retrobulbar block is commonly performed under monitored anesthesia prior to cataract surgery. Known complications associated with retrobulbar block include cranial nerve palsies, seizures, and cardiorespiratory arrest. We report a case of severe shivering following a retrobulbar block. Two minutes after the block was administered, the patient experienced severe shivering, which subsided after injection of pethidine 25 mg. The likely etiology of the shivering was inadvertent dural puncture of the optic nerve sheath and local anesthetic spread into the cerebrospinal fluid space. Shivering may be a warning sign of brain stem anesthesia, and in such a scenario the clinician should direct special attention to possible life-threatening complications.
Anesthesia ; Brain Stem ; Cataract ; Cranial Nerve Diseases ; Humans ; Meperidine ; Nerve Block ; Optic Nerve ; Punctures ; Seizures ; Shivering

BACKGROUND: Epidural analgesia provides effective pain control during labor. However, its influence on the course of delivery is controversial. The aim of this study was to assess the effect of epidural analgesia on the course of delivery and the perinatal outcome and to examine the changes of the cesarean delivery rates that are associated with epidural analgesia. METHODS: Among 1,200 parturients who delivered in our hospital from 2003 to 2005, we obtained the demographic and obstetric data for 240 primiparous deliveries (120 women in the epidural group [group E] and 120 women in the nonepidural group [group N]). The duration of the active phase and the second and third stages of labor, the perinatal outcome and the incidence of emergency cesarean delivery were analyzed. RESULTS: The duration of the second stage of labor was longer in group E (41 +/-23 min in group N vs. 49 +/-28 min in group E, P = 0.02). The incidences of cesarean delivery were similar between the two groups [15 (12.5%) in group N vs. 18 (15%) in group E, P = 0.6]. The incidences of fetal distress during the active phase of labor did not differ in both groups (48% vs. 41%, respectively, P = 0.4). The neonatal outcomes, including the birth weight, fetal heart rate deceleration or bradycardia during labor and the Apgar score, were similar between the two groups. CONCLUSIONS: We conclude that epidural labor analgesia does not seem to be associated with an increased incidence of cesarean delivery. In addition, epidural labor analgesia seems to have no adverse effect on the perinatal outcomes of primiparous women.
Analgesia ; Analgesia, Epidural ; Apgar Score ; Birth Weight ; Bradycardia ; Deceleration ; Emergencies ; Female ; Fetal Distress ; Heart Rate, Fetal ; Humans ; Incidence ; Pregnancy ; Retrospective Studies