This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

Objective To investigate the serum concentrations of protein-bound uremic toxins of hippuric acid ( HA) , indoxyl sulfate ( IS ) , p-cresyl sulfate ( PCS ) and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid ( CMPF ) in patients with chronic kidney disease(CKD) 3-5 stages(CKD3-5) and to assess the correlation between renal function and pro-tein-bound uremic toxin concentrations in CKD3-5 patients.Methods Serum concentrations of HA, IS, PCS, and CMPF from 60 healthy volunteers and 112 CKD3 -5 patients were measured by liquid chromatography mass spectrometry/mass spectrometry ( HPLC-MS/MS ) .Correlation analysis was conducted between the levels of HA, IS, PCS, CMPF and the estimated glomerular filtration rate( eGFR) .Results Compared with healthy subjects, serum concentrations of these four solutes were significantly increased in CKD3-5 patients (all P<0.01).The serum levels of HA,IS and PCS in CKD3-5 patients were significantly increased (all P<0.05),while those of CMPF did not significantly change (P>0.05).Linear correlation analysis showed that HA, IS, PCS and CMPF were in significantly negative correlation with eGFR.The curve regression analysis showed that the curvilinear regression fitting equation was Y=-46.171lnX+209.464(R2 =0.601,P<0.01)for HA and eGFR, Y=-62.570 lnX+279.537(R2 =0.633,P<0.01)for IS and eGFR, Y=-84.297 lnX+383.172(R2 =0.529,P<0.01)for PCS and eGFR, and was Y=-7.648 lnX+53.546(R2 =0.172,P<0.01)for CMPF and eGFR .Conclusion The levels of the four types of protein-bound toxins in CKD3-5 patients increase significantly compared to healthy subjects.The serum levels of HA,IS and PCS are increased when the renal function decreases, but the level of CMPF changes little.Renal dysfunction can lead to significantly elevated levels of HA,IS and PCS in CKD3-5 patients, but has little effect on CMPF.

Objective To explore the rehabilitation for dysphagia in young patient after tracheotomy and cricopharyngeal achalasia with-out cough reflex. Methods A child was reviewed, who accepted tracheotomy after resection of cerebellar pilocytic astrocytoma for dyspha-gia. The features characterized as severe silent aspiration and failure of cricopharyngeus muscle relaxation. Therapies included Passy-Muir valve placement, breathing exercises, balloon dilatation, surface electromyography biofeedback, and electrical stimulation. Results The aspi-ration was observed when she drank thin liquid with weak cough reflex, and disappeared as eating thick liquid and paste food, with complete cricopharyngeus muscle opening, 7 weeks after treatment. She was removed the tracheotomy tube and nasal feeding tube 11 weeks after treatment, and got sufficient nutrition by fully oral intake. Conclusion The application of Passy-Muir valve and comprehensive swallowing training is helpful for patient post tracheotomy with silent aspiration in decreasing the risk of aspiration, improving cough reflex and prompt-ing swallowing function.

Objective To observe the application of dysphagia ventilation swallowing and speaking valve inchildren with swallowing disorder after tracheostomy.Methods Four children with tracheostomy done and swallowing disorders(3 with brainstem encephalitis caused by hand,foot and mouth disease and 1 post-surgery case of cerebellar astrocytoma)were observed.Videofluoroscopic swallowing studies(VFSS)showed cricopharyngeal achalasia and silent aspiration.After VFSS assessments,ventilation swallowing and speaking valves(Passy-Muir,USA,PMVs)were applied to the 4 children.After that they received comprehensive swallowing trainings including balloon dilatation,breathing exercises,sensory stimulation and electrical stimulation.Results Four children could pronounce with PMVs immediately.After(36.50 ± 35.63)d of comprehensive intervention,all of them could live without tracheostomy tube or nasal feeding tube,their swallowing function improved obviously and could take food per os.Conclusions The application of PMVs combining with swallowing training is effective for children with swallowing disorder and dysphonia after tracheostomy.It is helpful to decrease the risk of aspiration,to open the cricopharyngeus muscle and to restore pronunciation.

This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

Objective To investigate the effects of using a catheter balloon to treat crieopharyngeal achala-sia in patients with brainstem lesions. Methods Thirty cases of dysphagia caused by brainstem lesions were diag-nosed as crieopharyngeal achalasia through videofluoroscopy of swallowing.The cases were divided into a treatment group and a control group randomly.The treatment group was treated with balloon dilatation and routine dysphagia re-habilitation training once daily,while the control group was treated with routine dysphagia rehabilitation training only.The treatment end point was either the patient resuming an oral diet or after 4 weeks of treatment.All eases were evaluated videofluoroscopically with a drinking test pre-and pest-treatment.Results After 10 to 24 balloon dilata-tions,10 of the 15 patients in the treatment group regained the ability to take solid food and water orally,thoush 2 of them could take pasty food only.Only 2 of the 15 patients in the control group regained the ability to take common food by mouth,though 5 of them could take pasty food.The other patients had no improvement.There wag a signifi-cant difference between the two groups.The cricopharyngeal aehalasia of 12 patients in the ffeatment group improved from incomplete relaxation/opening to complete relaxation/opening.Pooling and residue in the pyriform sinus or val-leculae was reduced and no misaspiration was observed.In the control group only 7 patients had some improvement.The mesn time for the bolus passing the pharynx after treatment was significantly shortened from 0.23 s to 0.15 s in the treatment group,but not significantly in the control group.Conclusions Catheter balloon dilatation is effective for cricopharyngeal achalasia caused by brainstem injury and is helpful for relieving the symptoms in the pharynx phase and the esophagus phase of dysphagia.

Objective To compare 76% meglucamine diatrizoate solution with 60%barium sulphate suspen-sion for use in videofluoroscopic swallowing studies(VFSSs).Methods Forty-nine cases of dysphagia caused by brain injury.brainstem lesion ir nasopharyngeal carcinoma(NPC)were recruited for this study.They were divided into a meglucamine diatrizoate group of 22 patients who were administered 76% meglucamine diatrizoate solution as a contrast agent,and a barium sulphate group of 27 patients with whom 70%barium sulphate suspension was used.All the Datients were treated by balloon dilatation and other routine dysphagia rehabilitation procedures.The treatment end point was either the patient's resuming an oral diet or after 4 weeks of treatment. All cases were evaluated by VFSS pre-and post-treatment.Results The patients in the meglucamine diatrizoate group showed significant pre-and post-treatment differences in terms of the pharynx transit times of brain injury and brainstem lesion victims.NPC patients showed no significant differences.In the barium sulphate group there were significant pre-and post-treatment differences in Dharynx transit time for patients with all three conditions. Conclusions Using 76%meglucamine di-atrizoate solution as a contrast agent decreases the sensitivity of VFSS. Using 60% barium sulphate suspension in VFSS is recommended.

ObjectiveTo study the effects and feasibility of balloon dilatation on cricopharyngeal achalasia in children with dysphagia. MethodsOne 21-month-old child was reported. ResultsAfter 14 times dilatation therapy, the video fluoroscopic swallowing study showed that the bolus can pass the cricopharyngeus. The residuals in the epiglottis and piriform sinuses reduced. No bucking and aspiration happened and the cricopharygeus muscle relaxed normally. The gastric tube can be removed and the child got full per-oral nutrition. ConclusionBalloon dilatation is effective to relax the cricopharygeus muscle and improve the swallowing function of children with dysphagia because of cricopharyngeal achalasia.

Objective To observe the effect of surface electromyographic biofeedback (sEMG-BFB) combined with routine swallow training on dysphagic patients with cerebral infarction at recovery stage.Methods Fiftyone dysphagic patients with cerebral infarction were randomly divided into two groups:control group (26 cases) and biofeedback training group (25 cases).The control group was given routine training including orofacial function training,balloon dilatation and behavioral swallowing training,while the biofeedback training group was given behavioral swallowing training was conducted with the guidance of sEMG-BFB in addition to the routine training.Before and after the treatment,videofluoroscopy swallowing study (VFSS) was performed to observe the opening of upper esophageal sphincter (UES).Functional oral intake scale (FOIS) was used to evaluate swallow function.Results Before treatment,there were no significant difference between the two groups in terms of FOIS score and UES opening (P ＞0.05).The FOIS score increased in both groups after treatment (P ＜ 0.05),and the FOIS score was higher in the biofeedback training group than that of the control group (P ＜ 0.05).After treatment,the number of UES complete opening and incomplete opening was 18 and 8,respectively,in the control group,versus 20 and 5,respectively,in the biofeedback training group.UES opening improved in both groups after treatment (P ＜ 0.05).Conclusion Routine swallowing training combined with sEMG-BFB can benefit the dysphagic patients with cerebral infarction for their UES opening and swallowing ability at recovery stage.

Objective To develop a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of forsklin in rat plasma.Methods After extraction with methyl tert-butyl ether,chromatographic separation was performed on a C18 column with the mobile phase consisting of water ( 0.1％ formic acid)-acetonitrile in a gradient elution mode.A tandem mass spectrometer equipped with electrospray ionization (ESI) source was used as detector in the positive ion mode.Quantification was performed using multiple reaction monitoring (MRM) with the precursor product combination ions of m/z 411→375.3 and 285→193 for forsklin and diazepam.Results Good linearity was obtained in the 0.5-1000 ng/ml range for the analyte and the analytical method was validated in terms of specificity,precision,accuracy,recovery,stability and matrix effect.These assays gave RSD values always lower than 14.4％ and RE values between -3.5 ％ and 3.8％.In addition,the specificity,extraction recovery,stability and matrix effect were satisfactory.Conclusion Due to its high sensitivity,specificity and simplicity,the method could be used for pharmacokinetic studies of forsklin.