Iridoid glycosides from Eremostachys glabra

Reversed-phase preparative HPLC of a methanol extract of the rhizomes of Eremostachys glabra yielded three new iridoid glycosides, namely, 6,9-epi-8-O-acetylshanziside methyl ester, 5,9-epi-penstemoside, and 5,9-epi-7,8-didehydropenstemoside. Their structures were elucidated on the basis of spectroscopic data interpretation. The free-radical scavenging activity of these compounds was assessed using the DPPH assay.     

Synthesis and antihypertensive activity of 1-(2-thiazolyl)-3, 5-disubstituted -2-pyrazolines

Several substituted 3-aryl-1-(4-aryl-2-thiazolyl)-5-(3-pyridyl)-2-pyrazolines were synthesized by reacting substituted 3-aryl-5-(3-pyridyl)-1-thiocarbamoyl-2-pyrazolines with phenacyl bromide in ethanol. The structures of all compounds were confirmed by IR, (1)H-NMR, mass spectral data and elemental analyses. The antihypertensive activity of compounds was examined by the tail-cuff method and compared with clonidine. Compounds 24-28 showed significant antihypertensive activity.     

Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs?

Recently, a series of case reports and small studies has suggested that births involving assisted reproductive technology (ART) may have an increased risk of imprinting disorders such as Beckwith-Wiedemann syndrome and Angelman syndrome. Herein, the significance and implications of these findings are discussed. It is speculated that, although such imprinting disorders may be shown to be only rare complications of ART, epigenetic errors might account for a much wider spectrum of ART-related complications than is recognized currently. Addressing these questions should be a priority for research on cohorts of ART children.     

The apoptotic profile of human cumulus cells changes with patient age and after exposure to sperm but not in relation to oocyte maturity

OBJECTIVE: To determine the expression of apoptosis-associated molecules on cumulus cells removed from individual oocytes of different maturity, inseminated oocytes and to investigate the possibility of an age-dependent expression. DESIGN: Analysis of apoptosis in cumulus cells isolated from oocytes of different stages of maturity. SETTING: Assisted reproductive technology program of the Birmingham Women's Hospital, Birmingham, UK. PATIENT(S): Patients undergoing intracytoplasmic sperm injection or IVF cycles. MAIN OUTCOME MEASURE(S): Percentage of positive cumulus cells when assessed for nuclear DNA damage using the terminal deoxyuridine nucleotide end-labeling assay or stained with antibodies [Fas, Fas ligand, the antiapoptotic protein Bcl-xl, and the RNA-binding protein (TIAR)]. RESULT(S): Cumulus cells collected from mature oocytes showed no significant difference in the percentage of apoptotic markers compared to those recovered from immature oocytes, whereas those from patients >/=38 years differed significantly. When cumulus cells were exposed to sperm the levels of apoptotic markers altered significantly from those not exposed to sperm. CONCLUSION(S): The results show that the cumulus cells of human oocytes are equipped with a mechanism to undergo apoptosis and that patient age and the exposure of cumulus cells to sperm can alter their profiles of apoptotic markers.     

Low Helicobacter pylori eradication rates with 4- and 7-day regimens in an Iranian population

BACKGROUND: In Iran, there is insufficient information on the efficacy of Helicobacter pylori eradication regimens shorter than 10 days. This study aims at assessing the efficacy of 4- and 7-day H. pylori eradication regimens in a high-incidence area of gastric cancer in Iran. METHODS: Subjects with an endoscopic diagnosis of gastritis, positive urease test, and a histological diagnosis of chronic gastritis were enrolled. Patients were randomly assigned to one of three groups: AOC7 (1000 mg amoxicillin, 20 mg omeprazole, and 500 mg clarithromycin twice daily for 7 days), FOT4 (200 mg furazolidone, 20 mg omeprazole, and 500 mg tetracycline twice daily for 4 days) and FOT7 (the same treatment as the FOT4 group but for 7 days). Sensitivity to these antibiotics was determined in all isolates recovered from culture. The efficacy of eradication was assessed 8 weeks after the end-of-treatment by the 14C-urea breath test. RESULTS: One hundred and twenty-eight patients were enrolled in the study. Culture was positive for 84 patients and none of these were resistant to amoxicillin, tetracycline or furazolidone, 1.2% were resistant to clarithromycin and 32.1% to metronidazole. Forty-five, 41 and 42 patients were randomly allocated to the AOC7, FOT4, and FOT7 groups, respectively. The intention-to-treat eradication rates were 35.5, 17.1, and 23.8% for the AOC7, FOT4, and FOT7 groups, respectively. CONCLUSION: Treatment regimens of 4 or 7 days are unacceptable for H. pylori infection in Iran, even in the presence of a favorable sensitivity profile.     

Antituberculosis agents II. Evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole derivatives

Using the radiometric BACTEC 460-TB methodology, the minimum inhibitory concentration (MIC) of a series of 2-(1-methyl-5-nitro-2-imidazolyl-1,3,4-thiadiazole-5-alkylsulfides, alkylsulfoxides and alkylsulfones which had been reported previously as antifungal agents, were determined. Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. The results indicate that compounds bearing a primary alkylthio substitution displayed good antituberculosis activity (MIC = 3.13-6.25 microg/ml). Oxidation to sulfone abolished the antituberculosis activity in methyl and propyl derivatives while the ethylsulfonyl analogue was active (MIC = 1.56 microg/ml). The cytotoxic effects indicate that 2-(1-methyl-5-nitro-2-imidazolyl)-5-methylthio-1,3,4-thiadiazole was the least toxic compound (IC50 > 10 microg/ml). Generally, all compounds showed a low selectivity index.     

Vascular Pattern and Spectral Parameters of Power Doppler Ultrasound as Predictors of Malignancy Risk in Thyroid Nodules

Introduction: Determination whether spectral Doppler ultrasound parameters, including resistance index (RI) and pulsatility index (PI), or vascular pattern can be used to distinguish malignant from benign thyroid nodules. Materials and Methods: We prospectively examined 85 thyroid nodules in patients undergoing surgery. The flow pattern seen via power Doppler examination was ranked for each nodule on a scale of 0 to 4 as follows: absent, perinodular alone, mixed with perinodular prominency, mixed with intranodular prominency, and exclusively intranodular, respectively. For each nodule, the RI and PI values were recorded as the average of the recordings obtained. Pathological examination were used as a proof of final diagnosis to categorize all nodules as benign or malignant. Results: The malignant nodules had a mean RI of 0.72 ± 0.13. These values were significantly higher than those associated with benign nodules (0.60 ± 0.08) (P = .000). Malignant nodules had a mean PI of 1.15 ± 0.33 that were also significantly different from those associated with benign nodules (0.91 ± 0.19) (P = .000). Shifting to intranodular vascularization had a significant correlation with malignancy (P = .001). Conclusion: Spectral parameter and vascular pattern are useful to distinguish malignant from benign thyroid nodules, especially for those with suspicious or undetermined fine‐needle aspiration biopsy.     

玻璃体腔注射曲安奈德治疗视网膜静脉阻塞黄斑水肿(英文)

目的:比较玻璃体腔注射曲安奈德和传统方法治疗视网膜静脉阻塞黄斑水肿的疗效。方法:共有21例因视网膜静脉阻塞导致黄斑水肿的患者纳入此项临床研究。接受治疗前所有的患者均进行了全面的眼科检查,并随机分为两组。实验组9例患者进行玻璃体腔注射4mg曲安奈德治疗;对照组12例患者接受传统方法治疗。结果:治疗前,对照组视力(logMAR)为1.20±0.38,而实验组为1.64±0.31。治疗后1mo,对照组的视力改善到0.98±0.54(logMAR),而曲安奈德治疗组改善到0.87±0.61(logMAR)。实验组和对照组之间视力改善有显著差异(P<0.01)。结论:研究结果显示,尽管实验组和对照组的患者视力均有改善,但治疗视网膜静脉阻塞黄斑水肿,玻璃体腔注射曲安奈德比传统方法更有效。     

Evaluation of the potential of ion pair formation to improve the oral absorption of two potent antiviral compounds, AMD3100 and PMPA.

9-(2-phosphonyomethoxypropyl)adenine (PMPA) and AMD3100 are highly potent and selective antiretroviral agents. Since PMPA is negatively charged and AMD3100 positively charged at physiological pH, their transepithelial transport and their potential for oral drug delivery is very low. In this study, ion pair formation was evaluated as a possible strategy to enhance transepithelial transport of PMPA and AMD3100. Positively charged counter ions such as t-hexyl-, t-heptyl-, t-octylammonium bromide and dodecyl-, tetradecyl-, hexadecyltrimethylammonium bromide were used to form ion pairs with PMPA, while sodium taurodeoxycholate (in vitro experiments) and sodium taurocholate (in vivo experiments) were used as counter ions for AMD3100. The effect of counter ions on transepithelial transport of PMPA (1 mM) and AMD3100 (1 mM) was investigated by measuring the flux across Caco-2 monolayers. An enhancement in drug transport could be observed at a concentration of 2 mM of hexadecyltrimethylammonium bromide (counter ion for PMPA) and 10 mM of sodium taurodeoxycholate (counter ion for AMD3100), but at the concentrations used, the absorption enhancing effect could be attributed to a reduction of the integrity of the monolayers. When AMD3100 transport was tested at a concentration of 200 microM, no flux was observed, even in the presence of relatively high concentrations of counter ion (20 times the concentration of AMD3100). Results obtained from partitioning studies of the drugs in the presence or absence of counter ion revealed that competition by other ions was responsible for the absence of an effect: when pure water was used as the aqueous phase, a reduction up to 24.4+/-1.4% and 17.0+/-1.3% of the initial aqueous concentration was observed for PMPA and AMD3100, respectively; however, as soon as other ions were present in the aqueous phase, the effect of the counter ion was diminished (25-50 mOsm) or completely abolished (270-305 mOsm). The absorption enhancing effect of counter ions was also studied in vivo: pharmacokinetic studies in rabbits showed that the oral bioavailability of AMD3100 in the presence of 4 equivalents of taurocholic acid remained very low and was only 3.2-fold better (i.e. 3.6%) in comparison to pure AMD3100. In view of the results obtained in the Caco-2 system, this absorption enhancement can be attributed to an effect on monolayer integrity rather than to the potential to form ion pairs. We can conclude that the formation of ion pairs may not be very efficient as a strategy to enhance transepithelial transport of charged hydrophilic compounds, as competition by other ions may abolish the beneficial effect of counter ions.     

Synthesis and docking studies of new 1,4-dihydropyridines containing 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent as novel calcium channel agonist

1,4-Dihydropyridines have been recognized as calcium channel agonist. Three new analogues of Bay K8644 in which the ortho trifluromethyl phenyl group at position 4 is replaced by the 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent, were designed and synthesized as calcium channel agonist. For this propose, the structures of designed compounds were drawn by HYPERCHEM program. Conformations of the compounds were optimized through semi-empirical method followed by PM3 calculation. Then the crystalin stucture of L-type calcium channel was obtained from the Protein Data Bank (PDB) server. Docking calculations were carried out using Auto-Dock.4 program. The good interaction of our 1,4-DHP derivatives showed that they can be as possible calcium channel agonist agents. Finally compounds were synthesized according to a modified Hantzsch condensation procedure.