Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the presence of extracellular β-amyloid in the senile plaques, intracellular aggregates of abnormal phosphorylation of tau protein in the neurofibrillary tangles, neuronal loss and cerebrovascular amyloidosis. The manifestations of clinical symptoms include memory impairment, cognitive decline, altered behavior and language deficit. Currently available drugs in AD therapy consist of acetylcholinesterase inhibitors, NMDA receptor antagonists, non-steroidal anti-inflammatory drugs, etc. These drugs can only alleviate the symptoms of AD. Gene therapy is achieved by vector-mediated gene transfer technology, which can delivery DNA or RNA into target cells to promote the expression of a protective or therapeutic protein and silence certain virulence genes.
Alzheimer Disease ; therapy ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Cholinesterase Inhibitors ; therapeutic use ; Genetic Therapy ; Humans ; Phosphorylation ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; tau Proteins ; metabolism

Although ophthalmoplegia following snake bites is not indicative of a serious neurotoxic complication, symptoms of diplopia, dizziness and ocular discomfort can be emotionally devastating for patients. The authors experienced two cases of ophthalmoplegia following snake bites in Korea. The patients complained of diplopia that had developed several hours after the snake bites. The diplopia did not improve with antivenom treatment, but resolved completely after several injections of neostigmine.
Adolescent ; Animals ; Child ; Cholinesterase Inhibitors/*therapeutic use ; Diplopia/drug therapy/etiology ; Female ; Humans ; Male ; Neostigmine/therapeutic use ; Ophthalmoplegia/*drug therapy/*etiology ; Snake Bites/*complications

To evaluate the impact of galantamine treatment on the function, caregiver time, and resource used in the treatment of patients with mild to moderate Alzheimer's disease (AD), costs and outcomes were evaluated during a 52-week prospective, randomized, double-blind, community-controlled trial of galantamine. Patients received either galantamine treatment (n=72) or no treatment (n=66). The analysis was performed from a societal perspective. Galantamine treatment reduced time spent caring for the patients and maintained improved functional capacity, whereas, when no treatments were given, a great increase in caregiver time and progressive functional deteriorations were observed. Saved caregiver time was equivalent to 113 working days per year. After 52 weeks, mean total annual costs per patient were 14,735,000 Korea Won (KRW) (USD 12,315) for patients with galantamine treatment and 25,325,000 KRW (USD 21,166) for patients without treatment. Adjusted annual cost saving of galantamine treatment was 6,428,000 KRW (USD 5,372) when compared to no treatment (p=0.0089). Galantamine had a beneficial effect not only to slow functional decline in patients with mild to moderate AD, but also to save a substantial amount of costs, closely related to reduction in caregiver burden and decrease in caregiver time.
Aged ; Alzheimer Disease/*drug therapy ; Cholinesterase Inhibitors/*therapeutic use ; Cost of Illness ; Double-Blind Method ; Female ; Galantamine/economics/*therapeutic use ; Health Care Costs ; Humans ; Male ; Prospective Studies

BACKGROUNDThe nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine.

METHODSRat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-alpha were determined in every group.

RESULTSThe level of circulating TNF-alpha was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-alpha level at all the three tested doses. Galanthamine obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with vagotomy.

CONCLUSIONCholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.

Animals ; Cholinesterase Inhibitors ; therapeutic use ; Galantamine ; therapeutic use ; Lipopolysaccharides ; toxicity ; Male ; Peritonitis ; blood ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEThe present study investigated the inhibitory effects of Chinese herb component sinapine on activity of acetylcholinesterase (AChE) in cerebral homogenate and blood serum of rats.

METHODAChE was prepared from cerebral homogenate and blood serum of rats, respectively. Acetylcholinesterase activity assay kit and Chromatometry were used to detect the AChE activity.

RESULTSinapine significantly inhibited AChE activity in vitro, with more effective on cerebral homogenate (IC50 3.66 micromol x L(-1)) than blood serum (IC50 22.1 micromol x L(-1)).

CONCLUSIONSinapine could significantly inhibit the cerebral AChE activity and may be a promising drug used for prevention and cure of Alzheimer's disease as a cholinesterase inhibitor.

Acetylcholinesterase ; blood ; metabolism ; Alzheimer Disease ; drug therapy ; prevention & control ; Animals ; Brain ; cytology ; enzymology ; Choline ; analogs & derivatives ; pharmacology ; therapeutic use ; Cholinesterase Inhibitors ; pharmacology ; therapeutic use ; Rats

OBJECTIVETo investigate the therapeutic and prophylactic efficiency of HupA in mice with acute isocarbophos poisoning, and the protective effects of the HupA on AChE inhibited by isocarbophos.

METHODSMice were randomizedly divided into the non-treatment group, the atropine control group, the HupA treatment group and the atropine and HupA combined treatment group. Toxic signs and survival rates were observed and compared among these groups. The AChE activity was monitored in the whole blood, the red cells and brain tissue exposed to isocarbophos in the either treated with HupA or non-treated groups.

RESULTSIn HupA treatment group compared with the non-treatment group, toxic signs were significantly decreased and the survival rate was increased. The therapeutic efficiency in the atropine and HupA combined treatment group was better than other groups. After isocarbophos was administered, the AChE activity in the HupA treatment group and the non-treatment group was decreased. However, the AChE activity in the whole blood (1.096 +/- 0.111), (1.262 +/- 0.146), (1.181 +/- 0.353) U/ml, the red cells (0.798 +/- 0.063), (1.000 +/- 0.176), (0.837 +/- 0.331) and the brain tissue (13.739 +/- 2.970), (18.507 +/- 3.466), (10.764 +/- 2.212) U/g in HupA treatment group 0.5, 1 and 2 hours after isocarbophos was administered was significantly higher than those in the non-treatment group (P < 0.05 or P < 0.01).

CONCLUSIONHupA has therapeutic effect on mice with acute isocarbophos poisoning. The protective effect of HupA on blood and brain AChE inhibited by isocarbophos may be one of the mechanisms of the therapeutic effect of HupA in acute Isocarbophos poisoning.

Acetylcholinesterase ; blood ; metabolism ; Alkaloids ; Animals ; Brain ; enzymology ; Cholinesterase Inhibitors ; therapeutic use ; Insecticides ; poisoning ; Malathion ; poisoning ; Male ; Mice ; Mice, Inbred Strains ; Poisoning ; drug therapy ; Random Allocation ; Sesquiterpenes ; therapeutic use

Acute Disease ; Adult ; Antidotes ; therapeutic use ; Antiparkinson Agents ; therapeutic use ; Benserazide ; Cholinesterase Inhibitors ; poisoning ; Humans ; Insecticides ; poisoning ; Levodopa ; therapeutic use ; Male ; Organophosphate Poisoning ; Parkinson Disease ; drug therapy ; pathology ; Pralidoxime Compounds ; therapeutic use ; Trihexyphenidyl ; therapeutic use

Adrenergic alpha-Antagonists ; therapeutic use ; Cholinesterase Inhibitors ; therapeutic use ; Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Glomerulonephritis, IGA ; diagnosis ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Phytotherapy

Activities of Daily Living ; Alzheimer Disease ; diagnosis ; drug therapy ; psychology ; therapy ; Caregivers ; psychology ; Cholinesterase Inhibitors ; therapeutic use ; Clinical Trials as Topic ; Cognition ; Endpoint Determination ; Humans ; Memantine ; therapeutic use ; Neuropsychological Tests ; Patient-Centered Care ; Quality of Life ; Singapore ; Stress, Psychological ; prevention & control ; Treatment Outcome

OBJECTIVETo study the clinical characteristics of myasthenia gravis (MG) in children and the changes in AchR-Ab-seronegative (SNMG) MG and AchR-Ab-seropositive MG (SPMG) patients.

METHODSThe study was done on 77 MG patients who were diagnosed at The Pediatric Hospital, Fudan University from 1992 to 2002. This clinical trial was a non-randomized, controlled open study.

RESULTS(1) The age of onset ranged from 3 months to 16 years, and the most common ages of onset were before 3 years; 32 cases were males and 45 females. The extraocular muscles were more frequently involved. According to the modified Osserman's criteria, 54 patients (70%) were classified as type I, 21 cases (27%) as type II and 2 cases (3%) as type III. (2) Eighteen of 55 cases (35%) were positive for anti-acetylcholine receptor antibodies (AchRab) and 16 of 55 cases (31%) were positive for acetylcholine premembrane receptor antibody (PremRab) on the initial examination. The clinical state of the patient during the examination did not show any clear correlation with the level of these antibodies. There was no significant difference between clinical type and AchRab positive rate among the three groups. Two of 18 patients (11%) were positive for thymoma associated antibody (Tintinab). The serological test on follow-up showed that 6 of 10 SNMG cases (60%) turned to be SPMG. In 85% of the cases the results of CD cells examination was abnormal, most of them showed reduced levels of CD4(+) or CD3(+) and CD8(+). (3) The thymus proliferation was found in 22 patients (42%) by CT and changes of thymoma were found in 2 cases (4%) and were confirmed by operation. (4) In 50% of the cases the electromyography (EMG) was abnormal. (5) After anticholinesterase drugs and steroids treatment the prognosis of patients with MG was usually good.

CONCLUSIONSMG in our children's hospital has increased, the age of onset became younger, and type II MG cases increased. Seronegative patients could turn positive, so monitoring the patient's serology is helpful for finding more SPMG cases. Steroids have been proven effective and safe in treatment of MG in children. Patients in methylprednisolone group experienced less side effects of steroid therapy than group treated with oral prednisone.

Adolescent ; Antibodies ; blood ; Child ; Child, Preschool ; Cholinesterase Inhibitors ; therapeutic use ; Female ; Follow-Up Studies ; Hospitals, University ; Humans ; Infant ; Male ; Myasthenia Gravis ; blood ; classification ; drug therapy ; Prognosis ; Receptors, Cholinergic ; immunology ; Steroids ; therapeutic use ; Treatment Outcome