Effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats / 中华麻醉学杂志

Objective To evaluate the effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats.Methods Ninety-six clean-grade male infantile Sprague-Dawley rats,weighing 40-50 g,aged 14 days,were allocated into 4 groups (n =24 each) using a random number table method:control group (C group),penehyclidine hydrochloride group (P group),hyperoxia group (HO group) and hyperoxia plus penehyclidine hydrochloride group (HP group).Infantile rats were intravenously injected with penehyclidine hydrochloride (0.3 mg/kg) at the same time point every day for 3 consecutive days in P and HP groups.Infantile rats were injected with the equal volume of normal saline instead of penehyclidine hydrochloride in C and H groups.Acute lung injury was induced by inhaling oxygen at concentration greater than 90％ for 72 h starting from 4th day after administration.Infantile rats were sacrificed at the end of inhaling,and lungs were removed for examination of the pathological changes and for determination of weight to dry weight ratio (W/D ratio),index of quantitative evaluation for alveolar damage (IQA),pneumonocyte apoptosis (using TUNEL),expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) protein and mRNA in lung tissues (by Western blot or using reverse transcription-polymerase chain reaction).The mitochondrial injury score was assessed,and apoptotic index (AI) was determined.Results Compared with C group,the W/D ratio,IQA,AI and mitochondrial injury score were significantly increased,and the expression of GRP78 and CHOP protein and mRNA was up-regulated in HO and HP groups (P＜0.05),and no significant change was found in the parameters mentioned above in group P (P＞0.05).Compared with HO group,the W/D ratio,IQA,AI and mitochondrial injury score were significantly decreased,the expression of GRP78 and CHOP protein and mRNA was downregulated (P ＜ 0.05),and the pathological changes of lung tissues were significantly attenuated in HP group.Conclusion Penehyclidine hydrochloride can mitigate hyperoxia-induced acute lung injury,and the mechanism may be related to inhibiting endoplasmic reticulum stress-dependent apoptosis in infantile rats.

Effect of penehyclidine hydrochloride on level of angiopoietin-1 and tyrosine kinase receptor-2 during endotoxin-induced acute lung injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the level of angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) during endotoxin-induced acute lung injury (ALI) in rats.Methods Forty adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups using a random number table (n =10 each):control group (group C),ALI group,low-dose PHC group (group L-PHC) and high-dose PHC group (group H-PHC).ALI was induced with iv injection of lipopolysaccharide 5.0 mg/kg via the tail vein.In L-PHC and H-PHC groups,PHC 0.6 and 2 mg/kg were injected,respectively,via the tail vein at 1 and 24 h after lipopolysaccharide injection.The rats were sacrificed at 48 h after the initial injection of PHC to measure the lung water content,protein concentration in bronchoalveolar lavage fluid (BALF),and the expression of Ang-1,Tie-2 and phosphorylated Tie-2 in lung tissues.The morphological changes of lung tissues were observed under light microscope and the ultrastructural changes of alveolar epithelial barrier under transmission electron microscope.Results Compared with group C,the lung water content and protein concentrations in BALF were significantly increased,and the expression of Ang-1 and phosphorylated Tie-2 was down-regulated in the other three groups (P ＜ 0.05).Compared with group ALI,the lung water content and protein concentrations in BALF were significantly decreased,and the expression of Ang-1 and phosphorylated Tie-2 was up-regulated in H-PHC group (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in group L-PHC (P ＞0.05).The damage to lung tissues was significantly reduced in group H-PHC as compared with group ALI.Conclusion PHC can improve the permeability of pulmonary microvascular and reduce injury to alveolar epithelial barrier,thus ameliorating endotoxin-induced ALI in rats,and the effect is dose-related and up-regulation of Ang-1 expression and inhancement of Tie-2 activity are involved in the mechanism.

Abuso de anticolinérgicos en pacientes con esquizofrenia: reportes de caso y breve revisión de la literatura / Abuse of anticholinergic drugsin schizophrenic patients: case reports and brief literature review

Introducción: El abuso de fármacos anticolinérgicos es un problema que ocasionalmente se ha reportado en la literatura médica aunque al parecer su frecuencia puede ser mayor a lo considerado usualmente; sobre todo en pacientes con esquizofrenia, donde se indica anticolinérgicos para contrarrestar los síntomas extrapiramidales secundarios al uso de antipsicóticos, es donde se detectan la mayoría de casos. Método: reportamos cuatro casos de pacientes con esquizofrenia que abusaban de anticolinérgicos y revisamos la literatura pertinente. Resultados: El uso excesivo de anticolinérgicos por pacientes con esquizofrenia ha sido atribuido a su intento de controlar síntomas depresivos o negativos o la disforia inducida por antipsicóticos sin embargo no hay usualmente correlación entre el uso de antipsicóticos y el abuso de anticolinérgicos; por tanto, es menester considerar el potencial de abuso de los anticolinérgicos. Conclusión: Se impone revisar la indiscriminada prescripción de fármacos anticolinérgicos a los usuarios de antipsicóticos de modo tal que el riesgo de abuso se detecte tempranamente.

Introduction: The abuse of anticholinergic drugs is a problem occasionally reported in the medical literature although it has been suggested that its frequency is higher than usually considered. Since the main indication of anticholinergics today is to alleviate extrapyramidal symptoms in patients using antipsychotics, several cases of excessive use of anticholinergic drugs in schizophrenic patients are detected in psychiatric practice. Method: We report four schizophrenic patients who used anticholinergic drugs in excessive doses and we review the respective bibliography. Results: The excessive use of anticholinergic drugs by schizophrenic patients has been attributed to their attempt to counteract their negative symptoms, depressive symptoms or the dysphoria induced by antipsychotics, however, there is not usually correlation between the use of neuroleptics and anticholinergics abuse; therefore it is necessary to take into account the addictive potential of antiparkinson drugs. Conclusion: We advise to review the extensive prescription of anticholinergic drugs to antipsychotic users so the risk of anticholinergic drug abuse can be detected early.

Effects of penehyclidine hydrochloride on blood-brain barrier in a rat model of cardiopulmonary bypass / 中华麻醉学杂志

Objective To investigate the effects of penehyclidine hydrochloride on blood-brain barrier in a rat model of cardiopulmonary bypass ( CPB) . Methods Sixty adult male SD rats, aged 4-6 months, weighing 320- 370 g, were randomly divided into 5 groups ( n = 12 each) : sham operation group (group S), CPB group, and low-, median- and high-dose penehyclidine hydrochloride groups (groups LP, MP and HP). The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg, intubated and mechanically ventilated. The femoral and jugular arteries and jugular vein were cannulated. CPB was performed for 60 min. Penehyclidine hydrochloride 0.2, 0.6 and 2.0 mg/kg were added to the priming solution in groups LP, MP and HP respectively, while the equal volume of normal saline was added in group CPB. Evans blue was injected via femoral vein at 1 h before the animals were sacrificed. Six rats in each group were sacrificed, their brains immediately removed and the hippocampi isolated for determination of Evans blue content. The other rats were sacrificed and the hippocampi isolated to determine the water content and observe the ultrastructure of blood-brain barrier. Results Compared with group S, the Evans blue content and water content were significantly increased in the other groups ( P ＜ 0.05) . Compared with groups CPB and LP, the Evans blue content and water content were significantly decreased in groups MP and HP ( P ＜ 0.05) . The Evans blue content was significantly lower in group HP than in group MP ( P ＜ 0.05). The CPB-induced changes were significantly attenuated in groups MP and HP compared with groups CPB and LP. Conclusion Penehyclidine hydrochloride can protect blood-brain barrier against the CPB-induced injury and the effect is related to the dose.

Experience of Combination Therapy with Alpha Adrenergic Receptor Antagonist and Anticholinergic Agent in Patients with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: 12 Month Follow-up / 대한남성과학회지

PURPOSE: Through more than 12 months of follow-up, the efficacy and safety of combination therapy with alpha adrenergic receptor antagonist and anticholinergic agent was investigated retrospectively. MATERIALS AND METHODS: This study retrospectively analyzed the data of 84 patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) who were managed with an alpha adrenergic receptor antagonist and anticholinergic agent for at least 12 months between Jan 2007 and Dec 2010. On patients' first visit to our department, we obtained the patients' demographic data and information about the prostate total volume, serum prostate specific antigen (sPSA), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR) of each patient. After 12 months, changes in the above factors and the side-effects of anticholinergic agents were investigated. RESULTS: The mean age of the patients was 66.1 years and the total observation period after drug administration was an average 20 months; the total sPSA and prostatic volume of patients was 1.8+/-0.8 ng/dl and 37.3+/-9.5 g, respectively. Qmax in uroflowmetry was improved after 12 months of medication (changed from 9.0+/-3.4 to 13.8+/-4.5 ml/sec; p<0.001). PVR was increased from 35+/-22.2 ml to 49.3+/-37 ml (p<0.001), but the change was not clinically significant, and no acute urinary retention occurred. The total IPSS score decreased from 21.4+/-5.1 to 13.3+/-4.6 (p<0.001), the storage score of IPSS decreased from 9.8+/-2.4 to 5.6+/-2 (p<0.001), and the voiding score was decreased from 11.6+/-3.7 to 7.7+/-3.2 (p<0.001). The QoL with IPSS was improved from 4.2+/-0.8 to 2.8+/-0.7 (p<0.001). During the 12 months there were 34 patients (56 cases) of adverse events. However, no serious adverse events were reported. CONCLUSIONS: Combination therapy with alpha adrenergic receptor antagonist and anticholinergic agent was safe and made an improvement in LUTS in patients with BPH and storage symptoms.