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BACKGROUND: The causes of post-stroke depression (PSD) were complex, and it is hard to identify the consistent risk factors because the correlation may change along with time. AIM: To study the prevalence and multiple correlation factors of PSD in acute stroke patients. PATIENTS AND METHODS: The patients within over 2-6 weeks after stroke were collected and divided into depression group, depressive symptom group, and control group according to the Hamilton Depression Rating Scale for Depression. The NIH (National Institute of Health) Stroke Scale, the Barthel index (BI), the Instrumental Activities of Daily Living (IADL), and the Mini-Mental State Examination (MMSE) were respectively used to evaluate the neurologic impairment, Ability of Daily Life, and cognitive function of patients. RESULTS: PSD was associated with lower incomes (p < 0.05), but not associated with education level, medical insurance, and nature of the acute stroke (p > 0.05). The lesion location in the left hemisphere of the brain had a higher morbidity than that in the right hemisphere or both sides. There was a significant difference in the incidence of PSD between multifocal lesions and single lesion (p < 0.01). CONCLUSIONS: Lower income, cognitive dysfunctions, poor activities of daily life, poor social support, and history of hypertension and previous stroke were risk factors for the acute stroke patients to get depression. Stroke survivors with left hemisphere of the brain and more lesions (≥ 2) have more chance to get the PSD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality ( P< 0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P< 0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period ( P =0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR =0.62, 95% CI 0.55-0.69, P <0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P< 0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.

Objective: To evaluate the value of the diaphragmatic thickening fraction (DTF) combined with the maximum inspiratory pressure (MIP) for the prediction of weaning success in mechanically ventilated patients. Methods: Patients admitted to the intensive care unit (ICU) of Yijishan Hospital of Wannan Medical College and on mechanical ventilation for 24 hours from June 2018 to April 2019 were selected as the study subjects. A low-level pressure support ventilation (PSV) method was applied to conduct a spontaneous breathing test (SBT) for 30 minutes after the patients met the screening conditions for clinical weaning; and the patients were weaned when they met the clinical weaning criteria. Before weaning, the patient's MIP was measured. The right hemidiaphragmatic excursion (DE) and the thickness of the diaphragm at the end of inspiration and at the end of exhalation were measured by ultrasound, and the DTF was calculated. The statistical relationship between the DTF, DE and MIP was analyzed. The predictive value for the success of weaning was calculated with the DTF, DE and MIP and was evaluated by the area under the receiver operating characteristic curve (AUC). Results: A total of 73 patients were included in this study, including 57 patients who were successfully weaned, and 16 patients who experienced failure. The DTF of the successful weaning group (35%, 8%) was significantly higher than that of the failed weaning group (25%±5%), and the difference was statistically significant ( t= 6.401, P< 0.01). The MIP (34±9 cmH(2)O) in the successful weaning group was significantly higher than that in the failed weaning group (23±3 cmH(2)O), and the difference was statistically significant ( t= 7.186, P< 0.01). The ROCs for the DTF, MIP, and diaphragmatic displacement were 0.907, 0.896, and 0.749, respectively. A DTF ≥ 27.78%, with a sensitivity of 92.98%, a specificity of 81.25%, and an AUC of 0.907 (95% CI: 0.816-0.963), was used as the standard to predict the success of weaning. An MIP > 26.5 cmH(2)O, with a sensitivity of 80.7%, a specificity of 93.75%, and an AUC of 0.896 (95% CI: 0.803-0.955), was used as the standard to predict the success of weaning. The AUC of DTF ≥ 27.78% and MIP ≥ 26.5 cmH(2)O was 0.920 (95% CI: 0.832-0.971), and the specificity increased to 87.7%, but the sensitivity was slightly reduced to 87.5%. Conclusions: The DTF and MIP play a crucial role in determining the appropriate time and predicting the outcome of weaning of mechanical ventilation patients. Compared with the DTF and MIP alone, the DTF combined with MIP greatly improved the accuracy of predicting successful weaning.

The complex reactions of typical medical waste materials pyrolysis and the evolution of different volatile species can be well represented by a Distributed Activation Energy Model (DAEM). In this study, A thermogravimetric analyser (TGA), coupled with Fourier transform infrared analysis of evolving products (TG-FTIR), were used to perform kinetic analysis of typical medical waste materials pyrolysis. A simple direct search method was used for the determination of DAEM kinetic parameters and the yield of individual pyrolysis products under any given heating condition. The agreement between the model prediction and the experimental data was generally good. The results can be used as inputs to a pyrolysis model based on first-order kinetic expression with a Gaussian Distribution of Activation Energies as a sub-model to CFD code.

Pyrolysis of certain medical waste materials was studied using thermogravimetric analyzer coupled with Fourier transform infrared spectroscopy (TG-FTIR). Pyrolysis characteristics of three common materials were discussed. The pyrolysis of absorbent cotton turned out to be the most concentrative, followed by medical respirator and bamboo stick. From TG and DTG curves, pyrolysis of these three materials occurred in single, two and three stages respectively. Evolved volatile products from all these three materials included 2-butanone, benzaldehyde, formic acid, acetic acid, hydrocarbon, carbon dioxide, carbon monoxide, and water; whereas no sulphur dioxide, ammonia and hydrogen cyanide was detected. There are several differences in yield among them. However, the study in this paper is essential for medical waste pyrolysis model, the TG-FTIR approach is potential to provide valuable inputs for predictive modeling of medical waste pyrolysis. More studied are needed to get the kinetic parameters and pyrolysis models that can predict yields and evolution patterns of selected volatile products for CFD applications.

Rizatriptan nasal spray was developed to achieve fast a high effectiveness and to overcome limitations associated with oral formulation. The objective of this study was to investigate the pharmacokinetics and tolerability of a rizatriptan nasal spray compared with an oral formulation in a two treatments, two periods, randomized crossover design. At each phase, each subject received 5 mg rizatriptan as a nasal spray or an oral tablet. Plasma concentrations of rizatriptan were determined by HPLC. Rizatriptan was absorbed more rapidly following nasal spray with detectable plasma concentrations 5 min after dosing. There was no statistically significant difference for AUC or Cmax values between the nasal spray and the oral tablet. The relative bioavailability of nasal formulation to oral formulation was 96%+/-16%. All the formulations were well tolerated and adverse events were generally of short duration and of mild intensity. Thus, rizatriptan nasal spray offers more rapidly absorption compared to the oral route, which may be particularly beneficial to those patients who have gastrointestinal disturbances during their migraine attack or who have difficulty in swallowing a tablet.

Objective: The methodology of corpus cavernosum electromyography (CC-EMG) was revisited, in order to overcome current methodological difficulties that hinder its clinical application., Materials and Methods: Using an 8-channel device, CC-EMG was performed in 12 healthy volunteers. Surface electrodes were placed bilaterally on the penile shaft and the kneecap (reference electrode), the pubis region and the anterior superior iliac spine (ASIS). A band pass filter with cut-off frequencies of 0.1 and 20 Hz was used. At least 2 sessions of recordings were performed in each subject., Results: Thirty-five of 46 recordings were interpretable. Significant time delays between potentials recorded from different sites of the CC were detected. Clear spatial voltage gradients related to CC-potentials were observed on the pubis region. No voltage changes related to CC-potentials, but electrical activity from other sources were recorded from the ASIS. In contrast to frequency, a clear correlation could be demonstrated between amplitude, duration and polyphasity of CC-potentials recorded in 2 different sessions in the same individual., Conclusions: Multichannel monopolar recording of CC-EMG with surface electrodes is practical and has several advantages compared with bipolar recording. The results provide evidence that the recorded signals indeed reflect electrical activity of the CC and therefore offer a basis to pursue further clinical validation studies.

A liquid chromatographic-mass spectrometric (LC-MS) assay was developed and validated for the determination of loratadine in human plasma using reversed-phase HPLC combined with electrospray ionization (ESI) mass spectrometry. The analysis involved a simple liquid-liquid extraction. The organic extract was then evaporated and the residue was reconstituted in mobile phase. The reconstituted solution was injected into an HPLC system and was subjected to reverse-phase HPLC on a 5-microm ODS-3 column at a flow-rate of 0.2 ml/min. The mobile phase comprised of acetonitrile-ammonium acetate (pH 4.0; 0.02 M, using formic acid to adjust) using gradient elution. Loratadine was detected in the single ion monitoring (SIM) mode. Standard curves were linear over the concentration range of 0.2-100 ng/ml. The mean predicted concentrations of the quality control (QC) samples deviated by less than 10% from the corresponding nominal values; the intra-assay and inter-assay precision of the assay were within 12% relative standard deviation. The extraction recovery of loratadine was more than 80%. The validated assay was applied to a pharmacokinetic study of loratadine in human plasma following the administration of a single loratadine tablet (40 mg).

In the last decade, several investigators have tried to develop corpus cavernosum electromyography (CC-EMG) as a direct clinical method to evaluate the state of the penile autonomic innervation and the cavernous smooth muscle. Both basic and clinical studies have shown promising results. However, its application as a diagnostic tool with clinical relevance was hindered by insufficient knowledge of cavernous smooth muscle electrophysiology, lack of standardization, technical and practical difficulties and problems in the interpretation of the results. Recently, the European Commission created the so-called COST Action B18 (corpus cavernosum EMG in erectile dysfunction), aiming to strengthen the coordination of the European research groups and give the development of CC-EMG a new impetus. This review presents an overview of the physiological background, the current status of CC-EMG, and discusses possibilities for further developments., (Copyright 2003 Elsevier Science B.V.)

Aim: To evaluate the nasal absorption enhancement of insulin by sodium deoxycholate (SDC) in combination with cyclodextrins (CD)., Methods: The concentration of glucose in blood was measured. Scanning electron microscopy technique was used to investigate the effect of enhancers on the nasal mucocilia. The effect of SDC in combination with CD on the leucine aminopeptidase (LAP) activity in the nasal mucosa was observed., Results: Intranasal administration of insulin (4 U/kg) along with 0.75 % SDC/beta-CD at a molar ratio of 1 : 2 slowly decreased the blood glucose levels of rats. The minimal blood glucose level was (72.6 +/- 2.1) % of baseline, and which was lasted for 3 h. Though the decrement of blood glucose in 0.75 % SDC/beta-CD (1 : 2) treated group was less than that in 0.75 % SDC treated group, there was no significant difference between the two groups in AOC0- t values (P > 0.05). SDC (0.01 %) solution did not have any absorption prompting effect. Scanning electron microscopy investigation showed that 0.75 % SDC/beta-CD (1 : 2) solution had no marked damage on rat nasal mucosa 4 h after nasal administration, while 0.01 % SDC still had some damage on the rat nasal mucosa. The inhibitory effect of SDC on the LAP activity was decreased from 89.2 % to 69.2 %, 71.5 %, 60.4 %, and 61.3 % in 0.75 % SDC/beta-CD (1 : 1), 0.75 % SDC/beta-CD (1 : 2), 0.75 % SDC/DM-beta-CD (1 : 1), and 0.75 % SDC/DM-beta-CD (1 : 2) treated group, respectively., Conclusion: Combining beta-CD with SDC lowered the serious nasal ciliotoxicity of SDC and had a marked absorption promoting effect, which was not due to low concentration of SDC but was related with the inhibition of LAP activity.

Aim: To lower the nasal ciliotoxicity of sodium deoxycholate (SDC) in combination with cyclodextrins (CD)., Methods: The erythrocyte hemolysis test was carried out to evaluate the damaging effect of SDC on the erythrocyte membrane. The in situ toad palate model and scanning electron microscope technique were used to investigate the nasal ciliotoxicity of SDC solution in combination with CD. The inclusion effect between SDC and beta-cyclodextrin (beta-CD) was studied by differential thermal analysis (DTA) and X-ray diffractometry., Results: The hemolysis test showed that beta-CD and dimethyl-beta-cyclodextrin (DM-beta-CD) could effectively protect the erythrocyte membrane against damage by SDC at the molar ratios of 1:1 and 2:1. When SDC combined with beta-CD or DM-beta-CD at a molar ratio of 1:2 or 1:3, the ciliotoxicity of SDC was greatly alleviated and the percent lasting time of the ciliary movement increased to 50 % or above. Scanning electron microscope investigations showed that SDC combined with beta-CD at a molar ratio 1:2 had no marked damage on the rat nasal mucosa after nasal administration thrice a day for a week. DTA and X-ray diffractometry investigations showed that SDC formed an inclusion with beta-CD., Conclusion: Combining beta-CD or DM-beta-CD with SDC can greatly lower the hemolytic effect and ciliotoxicity of SDC and the optimal molar ratio of SDC to CD is 1:2. Such protection provided by CD is due to the inclusion effect between SDC and CD.

Aim: To explore the kinetic changes in plasma D(-)-lactate and lipopolysaccharide (LPS) levels, and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/reperfusion, burn, and acute necrotizing pancreatitis (ANP)., Methods: Three models were developed in rats: (1)gut ischemia/reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion; (2)severe burn injury created by 30% of total body surface area (TBSA) full-thickness scald burn; and (3)ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic-spectrophotometric method and limulus amebocyte lysate (LAL) test kit, respectively. Tissue samples of intestine were taken for histological analysis., Results: One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)-lactate and LPS levels, and there was a significant correlation between the plasma D(-)-lactate and LPS (r = 0.719, P<0.05). The plasma concentrations of D(-)-lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r=0.877 P<0.01). D(-)-lactate and LPS levels elevated significantly at 2h after ANP, with a similar significant correlation between the two levels (r = 0.798, P < 0.01). The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups., Conclusion: The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood. The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.

Helicobacter pylori, an organism recently described in association with gastritis and peptic lesions. The degree of relationship between these micro-organisms was studied on molecular level using SDS-PAGE protein profiles and immunoblot patterns. Study on a total of 112 lysates of H. pylori showed some differences in protein patterns of different H. pylori strains. However, the difference became more apparent when studied by immunoblot analysis. According to SDS-PAGE protein, strains isolated from gastric mucous of the patients were identified as types I-IV, while type IV can be further classified as sub-type IV-1 to IV-5 analysis of SDS-PAGE protein patterns proved to be an excellent method of characterizing those H. pylori, different from traditional methods.

In order to find out the quantitative relationship between physicochemical properties of drugs and their nasal absorption, diltiazem hydrochloride and paracetamol were selected as model drugs and their octanol-water partition coefficient was determined. In situ nasal recirculation method at different pH values was used to estimate the rate constant of nasal drug absorption in rats. Results showed that quantitative relationship existed between partition coefficient and nasal absorption constant, with correlation coefficient being 0.9761(n = 9). Besides methods of partition coefficient determination, the in situ nasal recirculation manipulation was also improved.

A new HPLC method for the determination of a metabolite of analgin, MAA (4-methylaminoantipyrine), in plasma and its application to determine the bioavailabilities of analgin nasal drops in human volunteers is reported in this paper. A Waters Model 481 instrument was used throughout the experiment. IAA (isopropylaminoantipyrine) was shown to be the most suitable internal standard at absorption wavelength of 254 nm. A mixture of phosphate buffer (pH 5.5) and methanol (68:32) was used as the mobile phase with a flow rate of 2 ml.min-1, and YWG-C18H37 as stationary phase. Calibration curve was linear (gamma = 0.9998) in the concentration range of 0.1-5 micrograms.ml-1. The within day and day-to-day precision (RSD) of this method were 2.35% and 2.61%, respectively, with average recoveries of 99.3%-103.9%. No interference was found in the body fluid. The plasma samples of healthy volunteers were treated with acid and extracted with ether. The system of mobile phase and the process of blood sample treatment were simpler than those reported in literature. So, the method is suitable for the study of pharmacokinetics and clinical determination of blood level of analgin. The studies on bioavailabilities of analgin nasal drops were carried out in 8 men relative to intramuscular injection and 6 men relative to oral tablets, respectively, at the dose of 250 mg analgin in different preparations administered by cross-over method. The main pharmacokinetic parameters were shown in Table 3. The results indicate that analgin nasal drops exhibited a higher bioavailability (relative to injection) and faster absorption (relative to tablet). So, analgin is suitable to be developed as a nasal preparation.

A useful assay for epidemiological survey of H. pylori infection was reported, using the urease antigen of H. pylori to detect the anti-urease antibody in sera from 676 patients suffered from gastropathy with ELISA technique, and compared with whole cell antigen. Results showed that the purified urease antigen was better than whole cell antigen. The partially purified urease antigens rapid diagnostic reagent of H. pylori was examined in hospital/institution and compared with whole-cell antigens. Results of sera from 676 H. pylori-positive gastritis and non-ulcer dyspepsia patients being tested showed that specificity and sensitivity of ELISA were 96% and 98% respectively. It seemed to be very useful for epidemiological studies on H. pylori infection. The use of ELISA in the detection of IgG antibodies against H. pylori was also sensitive, specific and rapid in assessing the improvement of both acute and chronic inflammation, cleaning of bacteria and the antibody titers after treatment, so as recognized an ideal diagnostic method.

Effect of solutions or suspensions of eight drugs including analgin, paracetamol, propafenone hydrochloride, propranolol hydrochloride, ephedrine hydrochloride, gentamycin sulfate, sodium deoxycholate and hydrocortisone on ciliary movement were evaluated with in vitro or in situ toad palate model and scanning electron microscope. In vitro toad palate model: 0.2 ml of test drug solution or suspension was applied to a piece of freshly dissected upper palate of toad. The mucocilia were examined with an optical microscope and the lasting time of ciliary movement was recorded after drug application. The upper palate was rinsed with physiological saline when the ciliary movement stopped. The lasting time of ciliary movement after rinsing was then recorded again. In situ palate model: 0.5 ml of test drug solution or suspension was applied to the upper palate of toad for 30 min, and rinsed with physiological saline. The palate was dissected out and the operation was carried out in a similar manner. The results showed that the in situ toad palate model is a satisfactory method for studying the ciliotoxicity of drugs. The in vitro toad palate model is unsuitable for suspension and gel. The results of the eight drugs revealed that ciliary movement is frequently affected by many drugs and, therefore, care must be taken in developing any nasal dosage form to ensure its least ciliotoxicity.

The systematic and local concentrations of piroxicam after oral and transdermal administration were determined and compared. Mice were randomly grouped, and oral suspensions (0.72 mg.ml-1) or transdermal gels 1 mg.ml-1 were given. Systematic concentration (Cs) and local concentration (C1) of the drug in each mouse were determined by HPLC method. After transdermal administration of 0.25 mg of piroxicam gels Cmax(s) = 8.06 micrograms.ml-1 and AUC(s)0-24(s) = 58.36 micrograms.h.ml-1 were obtained, whereas after oral administration of 0.026 mg.10 g-1 body weight of piroxicam suspensions Cmax(s) was 36.82 micrograms.ml-1 and AUC(s)0-24 was 155.59 micrograms.h.ml-1. The C1/Cs ratio (0.01) through oral route was far lower than the C1/Cs ratio (0.13) through transdermal route. The area under local concentration-time curve (15.85 micrograms.h.ml-1) calculated from transdermal administration was much higher than that from oral administration (1.93 micrograms.h.ml-1). So, it seems to be unreasonable that only serum concentration is taken as a criterion for bioavailability test of piroxicam for local dosage forms, the local drug concentration should also be investigated and evaluated.

Tretinoin (Tre) and its active stereo isomer isotretinoin (Iso) were simultaneously determined by reversed-phase high pressure liquid chromatographic method with a uv detector adjusted to 348 nm. Separation was accomplished on YWG-C18 column by using a MeOH:NH4Ac buffer (pH 6.0) 85:15 (vol:vol), chlorpromazine (Chl) being chosen as internal standard. Minimal detectable amount of Tre was 0.5 ng. Calibration curve was linear (r = 0.9999) in the concentration range of 25-2500 ng.ml-1. This method was used to determinate the transdermal amounts of Tre from three different preparations in Franz diffusion cell in vitro. The results showed that the proposed method could distinguish the transdermal differences from various formulations or different skin samples. In addition, it is able to be used in quantitative analysis of Tre and Iso.

Minimal detectable concentration of serum piroxicam by using HPLC reported in literature was mostly around 50 ng.ml-1 serum. Though the sensitivity was enough for pharmacokinetics study, it could not meet the needs of drug formulation screen study in developing precision drug delivery system (DDS) such as transdermal delivery system. A new HPLC method providing a detection limit of 0.75 ng, sensitive enough to quantify low concentrations of serum piroxicam down to 5 ng.ml-1 was reported in this paper. A Waters Model 481 instrument was used throughout the experiment. Isoxicam was proved to be the most suitable internal standard at maximum absorption wave length of 360 nm. A mixture of methanol and ammonium acetate 0.1 mol.L-1 (1:0.9 vol.vol-1) was selected as mobile phase with a flow rate of 1 ml.min-1. 0.025% tetramethyl ethylene diamine was added to ammonium acetate solution and adjusted to pH 4.5 with citric acid before mixing. Calibration curve was linear (r = 0.9999) in the concentration range of 10-5,000 ng.ml-1. The within-day and day-to-day precisions (CV) of this method were 2.88% and 2.89% respectively, with average recoveries of 96.0-102.4% (10-5,000 ng.ml-1). No interference was found in the body fluids of subjects who took piroxicam concomitantly with other commonly used non-steroidal anti-inflammatory medicines such as indomethacin, ibuprofen, naproxen, phenylbutazone and acetylsalicylic acid.

Enhancing effects on the permeation of piroxicam (Pir) through excised hairless mouse (inbred HRS mice) skin were investigated by measuring flux. Azone 1% was found to be the most effective enhancer studied, increasing the flux about 21 times. The effect of Azone was enhanced by the presence of propylene glycol. Oleic acid, ethylacetate, and ethanol promoted the diffusion of Pir. Other enhancers, such as DMSO, PEG 400, acetone, urea and salicylic acid, showed little or no effect. Pir-beta-cyclodextrin inclusion compound increased the flux about 3 times. The results revealed that lipophilic enhancers were more effective than lipophobic ones.