Reference Intervals of Serum Iodine Concentration in Chinese Pregnant Women.

The study aims to establish trimester-specific reference ranges for serum iodine (SI) in Chinese pregnant women and explore its associations with maternal and infantile thyroid function. Apparently healthy pregnant women were enrolled during their first antenatal visit. Fasting venous and spot urine samples were collected for determining serum and urinary iodine (UI) levels by a validated inductively coupled plasma mass spectrometry. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), and neonatal TSH levels were tested by electro-chemiluminescent assay. The reference ranges of SI were established by percentile method and reported as 2.5-97.5%. ROC analysis was applied to compare the discriminative ability of SI, UI, and UI to urinary creatine ratio (UI /UCr) in early pregnancy for various thyroid conditions. The trimester-specific reference ranges of SI for Chinese pregnant women were 60.91-114.53 µg/L for the first trimester (T1, n = 1029), 54.57-103.42 µg/L for the second trimester (T2, n = 379), and 52.03-110.40 µg/L for the third trimester (T3, n = 455). Maternal SI at T1 but not UI and UI/UCr was significantly correlated with FT3 (r = 0.393, P < 0.001), FT4 (r = 0.637, P < 0.001), and TSH (r = -0.299, P<0.001). Maternal SI change% from T1 to T2 (but not SI change% from T1 to T3) had marginal correlation with neonatal TSH (r=-0.106, P=0.046). ROC analysis showed that maternal SI at T1 had better predictability for several thyroid conditions than UIC and UI/UCr.

Associations of Maternal Serum Iodine Concentration with Obstetric Complications and Birth Outcomes-Longitudinal Analysis Based on the Huizhou Mother-Infant Cohort, South China.

This study aimed to explore the temporal associations between maternal serum iodine concentration (SIC) and common pregnancy outcomes in Chinese women. Eligible singleton pregnant women aged 20-34 years were selected, and their fasting blood samples were collected during early (T1, n = 1101) and mid-pregnancy (T2, n = 403) for SIC testing by inductively coupled plasma mass spectrometry. Multivariable linear regression indicated that log10SIC at T1 (ß = -0.082), T2 (ß = -0.198), and their % change (ß = -0.131) were inversely associated with gestational weight gain (GWG, all p < 0.05). Maternal log10SIC at both T1 (ß = 0.077) and T2 (ß = 0.105) were positively associated with the Apgar score at 1 min (both p < 0.05). Women in the third quartile (Q3) of SIC at T1 had a lower risk of small for gestational age (SGA, OR = 0.405, 95% CI: 0.198-0.829) compared with those in Q4. Restricted cubic spline regression suggested a U-shaped association between SIC and SGA risk, and SIC above 94 µg/L at T1 was the starting point for an increased risk of SGA. The risk of premature rupture of membrane (PROM) increased by 96% (OR = 1.960, 95% CI: 1.010-3.804) in Q4 compared to that in Q1. Our longitudinal data from an iodine-replete region of China indicated that high maternal SIC could restrict GWG and improve Apgar scores at delivery, but might increase the risk of SGA and PROM.

Increased Dietary Intakes of Total Protein, Animal Protein and White Meat Protein Were Associated with Reduced Bone Loss-A Prospective Analysis Based on Guangzhou Health and Nutrition Cohort, South China.

In this study, we aimed to prospectively investigate the relationships between different types of dietary protein and changes in bone mass in Chinese middle-aged and elderly people. Dietary intakes were evaluated by means of a validated food frequency questionnaire. Bone mineral density (BMD) was measured using a dual-energy bone densitometer at multiple bone sites. Multivariable regression models were applied to investigate the associations of the participants' dietary intakes of total protein, intakes of protein from various sources, and amino acid intakes with the annualized changes in BMD during a 3-year follow-up. A total of 1987 participants aged 60.3 ± 4.9 years were included in the analyses. Multivariable linear regression results showed that dietary intakes of total protein, animal protein, and protein from white meat were positively correlated with BMD changes, with standardized coefficients (ß) of 0.104, 0.073, and 0.074 at the femur neck (p < 0.01) and 0.118, 0.067, and 0.067 at the trochanter (p < 0.01), respectively. With each increase of 0.1g·kg-1·d-1 in animal protein and white meat protein intakes, the BMD losses were reduced by 5.40 and 9.24 mg/cm2 at the femur neck (p < 0.05) and 1.11 and 1.84 mg/cm2 at the trochanter (p < 0.01), respectively. Our prospective data, obtained from Chinese adults, showed that dietary total and animal protein, especially protein from white meat, could significantly reduce bone loss at the femur neck and trochanter.

Comparison of Electrocardiogram and QT Interval between Viral Hepatitis Cirrhosis and Alcoholic Cirrhosis.

Objective: This study aims to compare the electrocardiogram (ECG) abnormalities and QT interval prolongation in 2,886 patients with viral hepatitis cirrhosis and 643 patients with alcoholic cirrhosis in order to understand the characteristics of ECG in patients with cirrhosis and provide information and evidence for clinical diagnosis and treatment. Methods: The ECG data of patients with viral hepatitis cirrhosis and alcoholic liver cirrhosis in the outpatients and inpatients of our hospital from August 2012 to July 2018 were reviewed. The ECG data were recorded, and the ECG report was issued by ECG experts to analyze the abnormal ECG and QT interval of patients in these two groups. Results: In the present study, 1,132 (39.22%) of the 2,886 patients with viral liver cirrhosis and 322 (50.08%) of the 643 patients with alcoholic liver cirrhosis had an abnormal ECG (P < 0.001). Among patients with QT prolongation, 388 patients had viral liver cirrhosis (13.44%) and 170 patients had alcoholic liver cirrhosis (26.44%, P < 0.001). Conclusion: The hemodynamics and electrophysiology of the myocardium are often changed in patients with cirrhosis, and ECG changes may also occur. QT interval prolongation is one of the most common electrophysiological abnormalities in patients with cirrhosis, and QT prolongation is more common in patients with alcoholic liver cirrhosis. Prolonged QT is associated with severe arrhythmia and sudden death and can warn of malignant arrhythmia and sudden death. Therefore, the routine detection of abnormal ECG and QT interval in patients with liver cirrhosis is of significant importance for preventing malignant events.

Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

Objectives: This study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH). Methods: This work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level. Results: A total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928-2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005-3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021-2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose-response manner. Conclusion: The longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

Analysis of indications for pulmonary peripheral lesions diagnosed using radial endobronchial ultrasound-guided transbronchial lung biopsy.

The aim of the present study was to determine the indications for radial endobronchial ultrasound-guided transbronchial lung biopsy (rEBUS-D-TBLB) for the diagnosis of peripheral pulmonary lesions (PPL) located at the bronchopulmonary segments and subsegments. Data collected from 774 patients who underwent rEBUS-D-TBLB for suspected PPL, including clinical information, distribution of lesions, diagnostic spectrum and diagnostic rate, were collected and retrospectively reviewed. Additionally, the Wilcoxon signed-rank test was performed to analyze the diagnostic yield of lesions in bronchopulmonary subsegments under the lesion diameter limit of 3 cm. In total, 802 lesions were found in 774 patients. The diagnostic yield of rEBUS-D-TBLB for all lesions was 67.18%. Overall, 362 cases of malignant disease and 158 cases of benign disease were diagnosed, with sensitivities of 70.98 and 79.00% respectively. Lesions were distributed throughout the 18 bronchopulmonary segments of the lungs. The bronchopulmonary segments with >5% of the majority of the discovered lesions were LB1+2, LB3, LB6, LB10, RB1-4 and RB9. The diagnostic yield of rEBUS-D-TBLB was found to be >65% for lesions located at LB3, RB1-3 and RB9. Further rEBUS-D-TBLB examinations of the LB1+2a, LB6a and RB4b segments produced diagnostic yields of 81.25, 66.67 and 71.43% respectively. Finally, at segment RB4a, rEBUS-D-TBLB examination was more effective for lesions with diameters >3 cm compared with lesions with diameters <3 cm. The diagnostic yields for PPL distributed at LB1+2a, LB3, LB6a, RB1-3, RB4a (diameter >3 cm), RB4b, and RB9 using rEBUS-D-TBLB were higher compared with for other segments, providing a theoretical basis for the clinical application of rEBUS-D-TBLB for the diagnosis of PPL in patients.

Effects of adjuvant chemotherapy on survival of patients with stage IB non-small cell lung cancer with visceral pleural invasion.

BACKGROUND: Adjuvant chemotherapy could improve the prognosis of stage II-III non-small cell lung cancer (NSCLC). However, its influences on stage IB were controversial. The purpose of this study was to investigate whether patients with stage IB NSCLC could benefit from adjuvant chemotherapy. METHODS: Stage IB NSCLC in 2010-2015 was selected from the surveillance, epidemiology, and end result database. Chi square test was used to compare the clinical characteristics of patients with different adjuvant chemotherapy status. Kaplan-Meier survival curves were plotted by the log-rank test. Cox proportional hazard regression was used to perform multivariate analysis on overall survival (OS), and the life table method was employed to calculate 1-, 3-, and 5-year survival rates. RESULTS: A total of 2915 patients were included in this study, and the number of patients with visceral pleural invasion (VPI) was 1096 (37.6%), of which 145 (13.2%) received adjuvant chemotherapy. There was no statistical difference in OS among the total population with or without chemotherapy (p = 0.295), nor in patients with VPI (p = 0.216). In patients with VPI, the 1-, 3-, 5-year survival curves of patients who are receiving adjuvant chemotherapy showed an upward trend compared with patients who did not. Additionally, female, high differentiated, adenocarcinoma, and tumor size ≤ 3 cm were also independent prognostic factors for improving the prognosis of patients with VPI. CONCLUSION: In our study, stage IB NSCLC did not benefit from adjuvant chemotherapy, even in patients with VPI. However, the significance of adjuvant chemotherapy in patients with VPI is still worth further exploration.

MicroRNA­4500 suppresses tumor progression in non­small cell lung cancer by regulating STAT3.

Research has revealed that microRNA (miR)­4500 is downregulated in non­small cell lung cancer (NSCLC), and miR­4500 suppresses tumor growth by targeting lin­28 homolog B and NRAS proto­oncogene, GTPase. In the present study, it was reported that signal transducer and activator of transcription 3 (STAT3) may function as a novel target gene for miR­4500 in NSCLC. The experiments conducted in the present study confirmed that the miR­4500 expression was decreased in NSCLC tissues and cells compared with adjacent normal tissues and a normal lung cell line. miR­4500 suppressed the cell proliferation, migration, invasion and promoted apoptosis of the human NSCLC cell lines A549 and H1975. Expression of STAT3 was negatively correlated with miR­4500 expression in vivo. A luciferase reporter assay suggested that miR­4500 directly targeted the 3' untranslated region of STAT3. The tumor inhibition effect of small interfering RNA STAT3 in A549 and H1975 lines may be partially impaired by a miR­4500 inhibitor. The results of the present study suggests that miR­4500 may be a tumor suppressor and a potential therapeutic target in NSCLC.

Upregulated microRNA­671­3p promotes tumor progression by suppressing forkhead box P2 expression in non­small­cell lung cancer.

In the present study, the expression of microRNA (miR)­671­3p in non­small­cell lung cancer (NSCLC) was detected via reverse transcription­quantitative polymerase chain reaction analysis, and its role in cell proliferation, apoptosis, migration and invasion was investigated via Cell Counting Kit­8, colony formation, flow cytometry, Transwell and scratch assays, respectively. It was observed that the expression of miR­671­3p was upregulated in NSCLC tissues and cell lines (A549 and H1975). Treatment with miR­671­3p inhibitors suppressed cell proliferation, migration and invasion, and increased apoptosis in vitro, suggesting that miR­671­3p functions as an oncogene in NSCLC. In addition, forkhead box P2 (FOXP2) has been reported to be a tumor suppressor that is downregulated in several types of cancer, and its low expression was confirmed in NSCLC tissues and cell lines in the current study via western blotting. The results of the luciferase reporter assay also demonstrated that miR­671­3p targeted directly the 3'­untranslated region of FOXP2. Furthermore, overexpression of FOXP2 in A549 and H1975 cell lines suppressed the growth, migration and invasion, and promoted apoptosis, whereas these effects were reversed by transfection with miR­671­3p mimics, suggesting that miR­671­3p promoted tumor progression via regulating FOXP2. Taken together, the results reported in the present study implied that miR­671­3p may be a potential therapeutic target in NSCLC.

The effect of ellagic acid on photodynamic therapy in leukemia cells.

Ellagic acid (EA) is a naturally phenolic acid presented in different foods. It has a variety of biological activities including antioxidant, anti-inflammatory, anti-microbiological and anti-cancer properties. On account of its antioxidant activity, EA might protect cancer cells from free radical damage in photodynamic therapy (PDT) during which reactive oxygen species (ROS) production was stimulated leading to irreversible tumor cell injury. In this study, the influence of EA on K562 cells in 5-aminolevulinic acid (ALA)-based PDT is demonstrated. Cell apoptosis was assayed by flow cytometry. Oxidative damage induced by PDT was investigated by measurement of malondialdehyde (MDA). Comet assay was used to evaluate the potential genotoxic effect induced by PDT on the cells. The results showed that EA supplementation alone did not affect the lipid peroxidation, DNA damage and apoptosis in K562 cells. It increases the lipid peroxidation, DNA damage, apoptosis and decreases the survival rate in K562 cells induced by ALA-PDT. The singlet oxygen quencher sodium azide suppresses apoptosis, lipid peroxidation and DNA damage induced by EA in PDT. In conclusion, EA consumption during PDT did not decrease the effectiveness of cancer therapy on malignant cells. The effect of antioxidants on PDT maybe was determined by its sensitization ability to singlet oxygen.

Radial endobronchial ultrasonography with distance measurement through a thin bronchoscope for the diagnosis of malignant peripheral pulmonary lesions.

BACKGROUND: Peripheral pulmonary lesions (PPLs) are being discovered more frequently. We investigated efficiency, safety, and influencing factors in radial probe endobronchial ultrasound with distance measurement (rEBUS-D) using a thin bronchoscope during transbronchial biopsy (TBB) for the diagnosis of malignant PPLs. METHODS: Patients with PPLs who underwent rEBUS were retrospectively analyzed. Cases with rEBUS-D and a gold-standard final diagnosis were considered. RESULTS: rEBUS was completed in 589 cases; 328 were analyzed. The lesion discovery rate was 85.06%; the overall rEBUS-D-TBB diagnostic rate was 54.88%. There were 193 cases of malignant tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of rEBUS-D-TBB in the diagnosis of malignant PPLs were 63.73%, 100%, 100%, 65.85%, and 78.40%, respectively. Single- and multi-factor analyses showed that lesion size, ultrasound probe position, and a positive bronchus sign on thoracic computed tomography (CT) were significant factors influencing diagnosis (all P=0.000); probe position and the bronchus sign were independent influencing factors. The effect of lesion distribution on diagnosis was not significant. In seven cases, postoperative pathology showed mixed tumors. Two cases of malignant tumors were combined with benign pathology; rEBUS-D-TBB did not suggest two pathologies. Thirteen cases had 50-100 mL of blood loss (3.96%); no pneumothorax or infection was observed. CONCLUSIONS: rEBUS-D-TBB had high sensitivity, 100% specificity, excellent safety, and a lower cost than rEBUS-GS-TBB in the diagnosis of malignant PPLs. Larger lesions, a positive bronchus sign on CT, and ultrasound probe position at the lesion's center yielded higher diagnostic rates.

Research on the effect of formononetin on photodynamic therapy in K562 cells.

At the present time, many cancer patients combine some forms of complementary and alternative medicine therapies with their conventional therapies. The most common choice of these therapies is the use of antioxidants. Formononetin is presented in different foods. It has a variety of biological activities including antioxidant and anti-cancer properties. On account of its antioxidant activity, formononetin might protect cancer cells from free radical damage in photodynamic therapy (PDT) during which reactive oxygen species (ROS) production was stimulated leading to irreversible tumor cell injury. In this study, the influence of formononetin on K562 cells in PDT was demonstrated. The results showed that formononetin supplementation alone did not affect the lipid peroxidation, DNA damage and apoptosis in K562 cells. It increases the lipid peroxidation, DNA damage and apoptosis in K562 cells induced by PDT. The singlet oxygen quencher sodium azide suppresses the apoptosis induced by PDT with formononetin. In conclusion, formononetin consumption during PDT increases the effectiveness of cancer therapy on malignant cells. The effect of antioxidants on PDT maybe was determined by its sensitization ability to singlet oxygen.

Comparison of radial endobronchial ultrasound with a guide sheath and with distance by thin bronchoscopy for the diagnosis of peripheral pulmonary lesions: a prospective randomized crossover trial.

BACKGROUND: Transbronchial biopsy (TBB) using radial endobronchial ultrasound with a guide sheath (REBUS-GS) has improved the diagnosis of peripheral pulmonary lesions (PPLs). Because of the high cost of the GS, REBUS with distance (REBUS-D) has certain advantages. The aim of this study was to compare the diagnostic yield of the REBUS-GS and REBUS-D by thin bronchoscopy for PPLs. METHODS: Patients with PPLs were enrolled in a prospective randomized crossover study from August 2014 and July 2015. Once the lesion was localized, TBB using REBUS-GS and TBB using REBUS-D were performed sequentially in a randomized order in each patient. Each patient received four to five transbronchial biopsies with REBUS-GS as well as four to five transbronchial biopsies with REBUS-D. All brushing was performed through GS. RESULTS: A total of 54 patients were enrolled in this study. After excluding seven participants with PPLs that were not detected by REBUS, a total of 47 subjects underwent REBUS-TBB. The diagnostic yield of REBUS-GS-TBB and REBUS-D-TBB was 72.2% (39/54) and 75.9% (41/54) respectively (P=0.625). Moreover, there was no statistically significant difference in diagnostic yield between REBUS-GS and REBUS-D in different lobe lesions and lesion sizes. Two cases of adenocarcinoma were only diagnosed with REBUS-GS-TBB. Two cases of tuberculosis, one case of mucosa-associated lymphoid tissue lymphoma (MALT) and one case of adenocarcinoma were only diagnosed by REBUS-D-TBB. The mean biopsy time after visualization of PPLs for REBUS-GS-TBB and REBUS-D-TBB were 5.17±2.34 and 7.36±3.18 min (P=0.00053). CONCLUSIONS: Using thin bronchoscopy, the diagnostic yield for PPLs with REBUS-D-TBB is not inferior to the yield with REBUS-GS-TBB. The diagnosis rate of small subpleural lesions with REBUS-D is lower than the rate with REBUS-GS. Although it is associated with shorter operation time and less bleeding, REBUS-GS has a higher cost and sometimes leads to check failure due to small specimens and the impact of the bronchoscope curvature.

In vivo microdialysis for the evaluation of transfersomes as a novel transdermal delivery vehicle for cinnamic acid.

In this study, cinnamic acid-loaded transfersomes were prepared and dermal microdialysis sampling was used in Sprague-Dawley rats to compare the amount of drug released into the skin using transfersomes as transdermal carriers with that released on using conventional liposomes. The formulation of cinnamic acid-loaded transfersomes was optimized by a uniform design through in vitro transdermal permeation studies. Hydration time was confirmed as a significant factor influencing the entrapment efficiency of transfersomes, further affecting their transdermal flux in vitro. The fluxes of cinnamic acid from transfersomes were all higher than those from conventional liposomes, and the flux from the optimal transfersome formulation was 3.01-fold higher than that from the conventional liposomes (p < 0.05). An in vivo microdialysis sampling method revealed that the dermal drug concentrations from transfersomes applied on various skin regions were much lower than those required with conventional liposomes. After the administration of drug-containing transfersomes and liposomes on abdominal skin regions of rats for a period of 10 h, the Cmax of cinnamic acid from the compared liposomes was 3.21 ± 0.25 µg/mL and that from the transfersomes was merely 0.59 ± 0.02 µg/mL. The results suggest that transfersomes can be used as carriers to enhance the transdermal delivery of cinnamic acid, and that these vehicles may penetrate the skin in the complete form, given their significant deformability.

Preparation and in vitro anti-tumor properties of toad venom extract-loaded solid lipid nanoparticles.

In this study, we prepared solid lipid nanoparticles (TV-SLNs) loaded with toad venom extract and investigated their anti-tumor effects in vitro in HeLa and SKOV-3 cells. TV-SLNs were prepared using a cold homogenization technique, and the formulation was optimized by central composite design and response surface methods. The anti-tumor activities of TV-SLNs were evaluated by analyzing cell division and cell cycle distribution by using the MTT assay and flow cytometry. After incubation with TV-SLNs, the growth of both HeLa and SKOV-3 cells was inhibited significantly. The percentage of HeLa cells in G0/G1 phase decreased, whereas that in the S and G2/M phases increased. Thus, the S and G2/M phases were blocked after the incubation of HeLa cells with TV-SLNs for 24 h. In contrast, the percentage of SKOV-3 cells in G0/G1 phase increased and then decreased in S and G2/M phases, with the G0/G1 phase being blocked after incubation with TV-SLNs for 24 h. Our results demonstrate that TV-SLNs inhibited the fissiparism of HeLa and SKOV-3 cells in a time-and dose-dependent manner. TV-SLNs may be effective as a novel TV vaginal delivery system for the treatment of cervical and ovarian cancers.

Duration of viral shedding of influenza A (H1N1) virus infection treated with oseltamivir and/or traditional Chinese medicine in China: a retrospective analysis.

OBJECTIVE: H1N1 was a new and potentially serious infectious disease, in human, the severity of influenza can vary from mild to severe, thus to find an effective and safety way to control the influenza pandemic is of crucial importance. This retrospective study describes the duration of viral shedding in H1N1 patients that were hospitalized and treated in China. METHODS: Clinical data were collected from May to July, 2009 in China for 963 patients with influenza A (H1N1) virus infection. Patients were treated based on the guidelines issued by the Chinese Ministry of Health. The primary outcome was duration of viral shedding and statistical comparisons were performed. RESULTS: In the patients with body temperature greater than 38.0 degrees C, there were no differences in virus shedding duration among the patients taking oseltamivir within two days, patients undergoing Traditional Chinese Medicine (TCM) therapy or those receiving no drug therapy. In patients with body temperature > or =38.1 degrees C, TCM therapy reduced the viral shedding duration (P < 0.05, vs. oseltamivir therapy). Furthermore, taking oseltamivir two days after onset of symptoms might prolong the virus shedding duration (P < 0.05, vs. taking oseltamivir less than 2 days of onset). CONCLUSION: TCM therapy is effective for reducing the length of virus shedding in patients with body temperature > or =38.0 degrees C. Oseltamivir used for reducing virus shedding duration should be taken within two days of onset.

In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion.

OBJECTIVE: To investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures. MATERIALS AND METHODS: A microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity. RESULTS: The maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed. CONCLUSION: The lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.

The effect of dietary soyabean isoflavones on photodynamic therapy in K562 leukemia cells.

The soyabean isoflavones genistein (GEN) and daidzein (DA) are popular presented in diet. Isoflavones have a variety of biological activities including antioxidant and anticancer properties. On account of its antioxidant activity, isoflavones might protect cancer cells from free radical damage in photodynamic (PDT) during which reactive oxygen species (ROS) production was stimulated leading to irreversible tumor cell injury. In this study, the influence of GEN and DA on K562 cells in 5-aminolevulinic acid (ALA)-based PDT was demonstrated. The results showed that GEN inhibited cell proliferation and enhance cell apoptosis, lipid peroxidation, and DNA damage in ALA-PDT on K562 cells. However, DA did not enhance cell apoptosis, lipid peroxidation, and DNA damage in ALA-PDT. In conclusion, the results suggested that soy consumption during PDT did not decrease the effectiveness of cancer therapy on malignant cells.

Enhanced transdermal delivery of evodiamine and rutaecarpine using microemulsion.

OBJECTIVE: The purpose of this study was to improve skin permeation of evodiamine and rutaecarpine for transdermal delivery with microemulsion as vehicle and investigate real-time cutaneous absorption of the drugs via in vivo microdialysis. METHODS: Pseudoternary phase diagrams were constructed to evaluate microemulsion regions with various surfactants and cosurfactants. Nine formulations of oil in water microemulsions were selected as vehicles for assessing skin permeation of evodiamine and rutaecarpine in ex vivo transdermal experiments. With a microdialysis hollow fiber membrane implanted in the skin beneath the site of topical drug administration, dialysis sampling was maintained for 10 hours and the samples were detected directly by high performance liquid chromatography. Real-time concentrations of the drugs in rat skin were investigated and compared with those of conventional formulations, such as ointment and tincture. Furthermore, the drugs were applied to various regions of the skin using microemulsion as vehicle. RESULTS: In ex vivo transdermal experiments, cutaneous fluxes of evodiamine and rutaecarpine microemulsions were 2.55-fold to 11.36-fold and 1.17-fold to 6.33-fold higher, respectively, than those of aqueous suspensions. Different drug loadings, microemulsion water content, and transdermal enhancers markedly influenced the permeation of evodiamine and rutaecarpine. In microemulsion application with in vivo microdialysis, the maximum concentration of the drugs (evodiamine: 18.23 ± 1.54 ng/mL; rutaecarpine: 16.04 ± 0.69 ng/mL) were the highest, and the area under the curve(0-t) of evodiamine and rutaecarpine was 1.52-fold and 2.27-fold higher than ointment and 3.06-fold and 4.23-fold higher than tincture, respectively. A greater amount of drugs penetrated through and was absorbed by rat abdominal skin than shoulder and chest, and a reservoir in the skin was found to supply drugs even after the microemulsion was withdrawn. CONCLUSION: Compared to conventional formulations, higher cutaneous fluxes of evodiamine and rutaecarpine were achieved with microemulsion. Based on this novel transdermal delivery, the transdermal route was effective for the administration of the two active alkaloids.

Influences of sodium carbonate on physicochemical properties of lansoprazole in designed multiple coating pellets.

Lansoprazole (LSP), a proton-pump inhibitor, belongs to class II drug. It is especially instable to heat, light, and acidic media, indicating that fabrication of a formulation stabilizing the drug is difficult. The addition of alkaline stabilizer is the most powerful method to protect the drug in solid formulations under detrimental environment. The purpose of the study was to characterize the designed multiple coating pellets of LSP containing an alkaline stabilizer (sodium carbonate) and assess the effect of the stabilizer on the physicochemical properties of the drug. The coated pellets were prepared by layer-layer film coating with a fluid-bed coater. In vitro release and acid-resistance studies were carried out in simulated gastric fluid and simulated intestinal fluid, respectively. Furthermore, the moisture-uptake test was performed to evaluate the influence of sodium carbonate on the drug stability. The results indicate that the drug exists in the amorphous state or small (nanometer size) particles without crystallization even after storage at 40°C/75% for 5 months. The addition of sodium carbonate to the pellet protects the drug from degradation in simulated gastric fluid in a dose-dependent manner. The moisture absorbed into the pellets has a detrimental effect on the drug stability. The extent of drug degradation is directly correlated with the content of moisture absorption. In conclusion, these results suggest that the presence of sodium carbonate influence the physicochemical properties of LSP, and the designed multiple coating pellets enhance the drug stability.