OBJECTIVEInhibition of acetylcholinesterase (AChE) in human brain caused by phoxim or phoxim oxon, their reactivation with oxime and aging of phosphorylated AChE were studied and compared in vitro.

METHODSMicro-colorispectrophotometric assay was used to determine the activity of AChE.

RESULTSThe pI(50) of inhibition of AChE in human brain by phoxim and phoxim oxon were 5.39 and 5.77, respectively, whereas the pI(90) were 4.60 and 5.00, respectively. The reactivation rate of 0.1 mmol/L of pralidoxime (2-PAM), obidoxime (LüH(6)), trimedoxime (TMB-4) and pyramidoxime (HI-6) for phoxim-inhibited AChE in human brain was 65%, 97%, 91% and 56%, respectively, and their reactivation rate for phoxim oxon-inhibited AChE in human brain was 97%, 87%, 99% and 89%, respectively. The optimal reactivator for phoxim and phoxim oxon-inhibited AChEs was LüH(6) and TMB-4, respectively. The half aging time of phoxim and phoxim oxon inhibited phosphorylated AChEs were 39 and 28 hours, respectively, and the 99% aging time were 256 and 186 hours, respectively.

CONCLUSIONSLüH(6) or TMB-4 should be used at the earlier as possible after poisoning with phoxim and phoxim oxon, and the reactivator should be consecutively used for more than seven days, even after their acute symptoms have been well controlled.

Acetylcholinesterase ; metabolism ; Brain ; drug effects ; enzymology ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterase Reactivators ; pharmacology ; Enzyme Stability ; Humans ; In Vitro Techniques ; Obidoxime Chloride ; pharmacology ; Organothiophosphorus Compounds ; pharmacology ; Oximes ; pharmacology ; Paraoxon ; pharmacology ; Pralidoxime Compounds ; pharmacology ; Time Factors ; Trimedoxime ; pharmacology

PURPOSE: In cases of patients who underwent bipolar hemiarthroplasty (BPHA) for treatment of a pertrochanteric fracture, we compared and analyzed the amount of blood loss and complications between a group using the cemented stem and a group using the cementless stem. MATERIALS AND METHODS: A total of 104 patients who underwent BPHA for treatment of a pertrochanteric fracture in our hospital for three years and 10 months (From January 2008 to October 2011) were included in this study. Among the 104 patients, 64 patients with a cemented stem were categorized into group 1, and the other 40 patients with an uncemented stem were categorized into group 2. Before surgery, the type of stem was determined by the bone quality of the proximal femur, which had been evaluated with a simple X-ray. Then, after surgery, the amount of blood loss and complications were compared between the two groups. RESULTS: Expected blood loss during the operation was 389.8 cc in group 1, and 395.3 cc in group 2(P=0.88). Postoperatively, average drained blood loss was 219.6 cc in group 1, and 338.1 cc in group 2. Cemented stem was associated with significantly less blood loss (P=0.004). The average operation time in group 1 and in group 2 was 96 minutes and 72 minutes. There was no significant difference in operating time (P=0.85). In addition, there was no difference in INR (International Normalized Ratio) and BMI (Body Mass Index) (P=0.28 and 0.08) regarding total amount of postoperatively drained blood loss. There was no occurrence of hypotensive shock or fatal pulmonary embolism in either group. Three cases of periprosthetic fracture occurred in group 2. CONCLUSION: Fewer occurrences of postoperative blood loss and fewer complications were observed in the cemented stem group than in the cementless stem group. Preoperative evaluation of bone quality and use of the cement stem for patients with poor bone quality may be a good treatment method that can help to reduce complications.
Femur ; Hemiarthroplasty ; Hemorrhage ; Humans ; Hydroxylamines ; International Normalized Ratio ; Periprosthetic Fractures ; Postoperative Hemorrhage ; Pulmonary Embolism ; Shock

Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD , CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.
Azacitidine ; Cell Transformation, Neoplastic ; Epigenomics ; Gene Expression ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; Histones ; Humans ; Hydroxylamines ; Leukemia ; Oligonucleotide Array Sequence Analysis ; Quinolines

OBJECTIVETo study the effect of HDAC inhibitor Scriptaid on multiple myeloma IM9 cells and preliminarily clarify the mechanism of Scriptaid-induced cell apoptosis.

METHODSThe cell viability, cell cycle and cell apoptosis were measured by CCK8 assay and flow cytometry respectively, the relative target gene expression levels were detected by RT-PCR, the effect of Scriptaid on p21 promoter activity was detected by using luciferase reporter assay.

RESULTSScriptaid inhibited IM9 cell viability in a dose-dependent manner. Scriptaid induced IM9 cell cycle arrest at G/M phase in a dose-dependent manner. Scriptaid triggered IM9 cell apoptosis was obviously, the mRNA levels of apoptosis-related proteins Caspase 9, Caspase 3 and PARP1 were also activated. The apoptosis-associated factors BAD, PTEN and p21 increased following treatment with different dose of Scriptaid, meanwhile, p21 promoter activity was also activated significantly.

CONCLUSIONHDAC inhibitor Scriptaid can promote IM9 cell apoptosis by transcriptional activation of p21 promoter in concentration-dependent manner.

Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxylamines ; pharmacology ; Quinolines ; pharmacology

PURPOSE: The optimal dose of oximes for use in the treatment of organophosphorus pesticide poisoning has not been conclusively established. In this retrospective study, we assessed the effectiveness of the use of high-dose pralidoxime infusion in treating organophosphorus pesticide poisoning. METHODS: From January 1998 to December 2009, 71 patients visited the hospital Emergency Department (ED) as a result of organophosphate pesticide intoxication. All of these patients received an initial bolus of 2 g of pralidoxime as the first step of treatment. Patients who then received continuous infusion of pralidoxime at a dose of 500 mg/hr were entered into study group 1 (low dose), and those treated by continuous infusion of pralidoxime at a dose of 1000 mg/hr were entered into study group 2 (high-dose). Plasma cholinesterase activities for each patient were evaluated at ED arrival and re-evaluated 24 hours after pralidoxime infusion. The effectiveness of the two treatment modalities was gauged by comparing the required duration of mechanical ventilation, time spent in the intensive care unit (ICU) and total time spent in the hospital. RESULTS: The mean duration of mechanical ventilation was 9.98+/-6.47 days for group 1 and 4.39+/-6.44 days for group 2. The respective mean duration of time spent in ICU and the total number of days in the hospital were 16.38+/-18.84 days and 21.87+/-20.16 days for group 1, and 7.83+/-9.99 days and 11.71+/-13.53 days for group 2. High-dose pralidoxime treatment was associated with shorter required durations for mechanical ventilation, ICU and hospital stay. In addition, plasma cholinesterase reactivation rates were higher for those patients receiving high-dose pralidoxime treatment. CONCLUSION: The results suggest that high-dose pralidoxime treatment has greater efficacy for patients suffering from organophosphorus pesticide poisoning.
Cholinesterases ; Emergencies ; Humans ; Intensive Care Units ; Length of Stay ; Organophosphates ; Oximes ; Plasma ; Pralidoxime Compounds ; Resin Cements ; Respiration, Artificial ; Retrospective Studies ; Stress, Psychological

OBJECTIVETo observe the relaxant effect of Aike Mixture (AKM) on isolated bladder and prostatic urethral smooth muscle of rabbits.

METHODSThe isolated bladder and prostatic urethral smooth muscle from male rabbits were placed in a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing.

RESULTSAKM dose-dependently reduced contractile tension of bladder trigone smooth muscle (r=0.831, P<0.05), reduced contractile wave amplitude (r=0.837, P<0.05) and decreased contractile frequency (r=-0.917, P<0.01). AKM significantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2.

CONCLUSIONAKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing α1-adrenergic receptors and M-cholinergic receptors.

Animals ; Calcium Chloride ; pharmacology ; Carbachol ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Hydroxylamines ; pharmacology ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Neuromuscular Agents ; pharmacology ; Prostate ; drug effects ; physiology ; Rabbits ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Muscarinic ; metabolism ; Urethra ; drug effects ; physiology ; Urinary Bladder ; drug effects ; physiology

OBJECTIVE: To investigate the effects of aminooxyacetic acid (AOAA) on learning and memory ability and possible mechanisms in rats with chronic alcoholism. METHODS: Sixty SD male rats were randomly divided into three groups on average.The model group rats and the remedy group rats were fed with the water containing (v/v) 6% alcohol for 28 days.After 14 days, the remedy group rats were treated with AOAA (5 mg/kg·d) by intraperitoneal injection once a day for 14 days and the other two group rats were treated with the equal amount of saline by intraperitoneal injection every day.Five days before the end of the experiment, the water maze test was carried out to test the learning and memory ability of rats for 5 days.Subsequently, the content of HS, the activity of ATP enzyme and the expression of 5-HT in hippocampus were measured. RESULTS: Compared with the rats in the control group, the latency and the swimming distance of the 2nd to the 4th day, the content of HS in hippocampus of rats in the model group were all increased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were decreased (<0.01).Compared with the rats in the model group, the latency and the swimming distance of the 2nd to the 4th day, the content of HS in hippocampus of the rats in the remedy group were decreased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were increased (<0.01). CONCLUSIONS AOAA could alleviate the symptoms of chronic alcoholism rats, which may be related to the effects of AOAA on the content of HS, the mitochondrial enzyme activity and the expression of 5-HT in hippocampus.
Alcoholism ; Aminooxyacetic Acid ; Animals ; Hippocampus ; Learning ; Male ; Maze Learning ; Memory ; Rats ; Rats, Sprague-Dawley

In healthy Korean adult males, 6 hour-MED was 51 2+22.6mJ/cm,24 hour-MED was 67. 5+26. 7mJ/cm, and MMD was 86. 5 t21. 3mJ/cm for UVB irradiation respectively. UVB-MED and UVB-MMD was increased by desoxymethasone, hydrocortisone, and bufexama.c creams. Hydrophilic ointment base increased only 24 hour-MED. For 1 MED of UVB, all test agents inhibited erytherna for 48 hours, For 2 MEDs of UVB, desoxymethasone, bufexamac; and hydrocortisone creams inhibited erythema at 6 hours, while desoxymethasone and hydrophilic ointment base could suppress erythema at: 24. hours after irradiation. However, desoxymethasone was the most effective. Hydrophilic ointment base was efficacious only at 24 hours after irradiation. For 1 MMD of UVB, desoxymethasone, hydrocortisone, and bufexamac creams could reduced the delayed tanning (DT) reaction.
Adult ; Anti-Inflammatory Agents* ; Bufexamac ; Desoximetasone ; Emollients* ; Erythema* ; Humans ; Hydrocortisone ; Male* ; Pigmentation* ; Tanning ; Triacetoneamine-N-Oxyl

PURPOSE: Organophosphorus (OP) pesticides are differentiated into 3 groups according to their toxicity. The differences in chemical composition of each OP pesticide determines its toxicokinetic characteristics. There are few human studies that address the clinical results of poisoning according to the OP pesticide. In this study, we aimed to examine the differences in clinical features among self-poisoning from 4 highly toxic OP pesticides. METHODS: The 4 kinds of OP poisonings included 17 cases of Dichlorvos, 17 cases of EPN, 17 cases of methidathion, and 13 cases of phosphamidon. We set primary outcomes as GCS, atropine dose required, duration of patient need for atropine, proportion who required ventilation, duration on ventilation, and the interval from ingestion to ventilation. Secondary outcomes were the proportion of OP-induced delayed neuropathy, duration of ICU stay, and proportion who required additional infusion of pralidoxime chloride (PAM). RESULTS: The EPN group required the largest amount of atropine, the longest duration of atropine use, the longest duration for support of mechanical ventilation, and the longest ICU stay. Furthermore the proportion who required additional PAM and neuropathy were in the EPN group. However, the EPN group had the longest interval from ingestion to ventilatory support. Meanwhile, the Dichlorvos group exhibited comparatively mild clinical features. CONCLUSION: Throughout this study, we found different clinical features to each OP pesticide poisoning. It can be explained by differences in chemical composition, which determined the speed of aging, the reactivation rate of OPenzyme, the metabolism, the fat solubility, and other characteristics of the pesticides.
Aging ; Atropine ; Dichlorvos ; Eating ; Humans ; Organophosphorus Compounds ; Organothiophosphorus Compounds ; Pesticides ; Phosphamidon ; Pralidoxime Compounds ; Respiration, Artificial ; Solubility ; Ventilation

Organophosphate fungicides include edifenphos, iprobenfos and tolclofos-methyl. Edifenphos inhibits cell wall synthesis by reduction in chitin synthase activity and inhibits the action of acetylcholinesterase. Thus, exposure to this chemical results in excessive salivation, lacrimation, urination, defecation, gastrointestinal motility and emesis symptoms, just like other organophosphate insecticides. Although edifenphos is an organophosphate fungicide, it is the only agricultural chemical which inhibits the action of pralidoxime and atropine, an activity which in turn, inhibits treatment. Thus, we have to treat these cases as soon as possible with atropine and pralidoxime, using the same approach as used for exposure to other organophosphate insecticides. In this report we evaluate the results of treatment of 4 patients who were intoxicated by fungicides (3 cases with edifenphos and 1 case with iprobenfos).
Acetylcholinesterase ; Atropine ; Cell Wall ; Chitin Synthase ; Defecation ; Gastrointestinal Motility ; Humans ; Insecticides ; Organothiophosphorus Compounds ; Pralidoxime Compounds ; Salivation ; Urination ; Vomiting