Unexpected presence of estrogens in culture medium supplements: subsequent metabolism by the yeast Sacchromyces cerevisiae

We have previously shown the presence of 17 beta-estradiol in extracts of commercially prepared Saccharomyces cerevisiae ss well as the production of estradiol by yeast grown in the laboratory. In our current study, yeast grown in a chemically defined medium synthesized estradiol in only small amounts, (less than 500 pg/liter). We have analyzed a variety of media commonly used for growing yeast and found that substantial estradiol production (greater than 5 ng/liter) was obtained when yeast were grown in medium supplemented with Bacto-peptone. The peptone was shown to contain significant amounts of estrone, and the results of the experiments establish a precursor-product relationship where estrone from the medium is metabolized to estradiol by S. cerevisiae. Studies with added [3H]estrone demonstrated rapid conversion into [3H]estradiol and a 3H-labeled nonpolar estrogen derivative. The commercially obtained yeast used previously had been grown in a molasses medium. We demonstrate here that the molasses medium contains substantial amounts of estrone and estradiol. We conclude that the conversion of estrone in a culture medium to estradiol in laboratory grown yeast and estrone and estradiol present in the commercially grown yeast medium account for the majority of estradiol found in yeast.     

Guide to Drug Regulatory Affairs.

Ohne Zusammenfassung     

A novel anticholinesterase THB013: Biochemical and behavioural studies

Summary Clinical trials with tacrine (THA) have resulted in elevations of liver enzymes in Alzheimer patients that showed improvement. In an effort to minimize these side effects several THA analogues were synthesized. These analogues were compared to THA in biochemical as well as behavioural studies. In this study, the biochemical effects of THA and one of these analogs, THB 013, on plasma cholinesterase activity, cholinergic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. THB 013 was, at lower concentration, more efficacious in inhibiting plasma cholinesterase as well as blocking the scopolamine induced disruption of spatial learning when administered 10 min before the scopolamine injection. It is possible that THB 013 with more potent cholinergic effects than THA might be useful in the treatment of Alzheimer's disease.     

Right ventricular function and its relationship with grade of hepatosteatosis in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognised as the most common cause of chronic liver disease worldwide.1 NAFLD encompasses a spectrum of disorders, including variable degrees of simple hepatic steatosis (HS, fatty liver), non-alcoholic steatohepatitis (NASH) and cirrhosis.This disease is a common clinicopathological condition characterised by significant lipid deposition in the hepatocytes of the liver parenchyma in the absence of alcohol abuse, contributing medications and viral hepatitis. It is strongly associated with several cardiovascular risk factors such as obesity, insulin resistance, hypertension, hyperlipidaemia, coronary artery disease, obstructive sleep apnoea syndrome, oxidative stress, endothelial dysfunction and the metabolic syndrome.2-5 There are recent data suggesting that NAFLD is linked to increased cardiovascular risk independent from the broad spectrum of metabolic syndrome (MS) risk factors.6,7Multiple mechanisms contribute to left ventricular dysfunction in obesity, including lipotoxicity associated with cardiac steatosis and lipo-apoptosis, alterations in fatty acid metabolism, overproduction of cardio-inhibitory cytokines, up-regulation of some neurohormones (especially angiotensin II), myocardial fibrosis and chronic overload with left ventricular dilatation and hypertrophy, and increased oxygen consumption.8Evaluating the possible influence and correlation of metabolic, cardiovascular and liver biopsy parameters on cardiac left ventricular dysfunction, we found a positive correlation between left ventricular parameters and severity of liver damage (NAS score).9 Cardiac dysfunction determined by echocardiographic measurements in patients with NAFLD was also studied.10 Determination of myocardial velocity using tissue Doppler imaging (TDI) is a new technique that has recently been developed to analyse right ventricular function.11-14This study aimed to investigate the association between right ventricular function and grade of hepatosteatosis (HS grade) in NAFLD patients using transthoracic and tissue Doppler echocardiography.     

Serum Pentraxin-3 Level in Patients Who Underwent Coronary Angiography and Relationship with Coronary Atherosclerosis

Objectives

To evaluate the role of pentraxin-3 (PTX-3) in determining the presence and severity of coronary atherosclerosis in patients with coronary artery disease (CAD).

Subjects and Methods

Ninety-five patients (77 males and 18 females) who underwent elective coronary angiography were enrolled in this study. Patients with heart failure, renal failure, diabetes and thyroid disease were excluded. The study population was divided into 3 groups: individuals with normal coronary arteries, patients with critical CAD (n = 35) and patients with noncritical CAD (n = 36). The association of PTX-3 levels with the presence and severity of CAD and the number of involved vessels were analyzed.

Results

The mean age was 53.40 ± 10.25 years. The PTX-3 levels were significantly higher in patients with CAD than without CAD (146.48 ± 48.52 vs. 109.83 ± 49.06 pg/ml, p < 0.001). A statistically significant difference was found among the 3 groups regarding the severity of CAD (165.66 ± 49.10, 127.83 ± 40.51 and 109.83 ± 49.06 pg/ml, p < 0.001, respectively). The serum PTX-3 levels in normal arteries were 110.4 ± 48.11 pg/ml, in single-vessel disease 132.35 ± 32.96 pg/ml, in 2-vessel disease 142.57 ± 55.88 pg/ml, in 3-vessel disease 156.07 ± 50.53 pg/ml, and in 3-vessel disease 160.50 ± 30.41 pg/ml. After adjusting for baseline confounders, older age (OR = 1.107, 95% CI = 1.027-1.193, p = 0.008) and higher PTX-3 levels (OR = 1.017, 95% CI = 1.003-1.032, p = 0.021) were detected as significant predictors for the presence of CAD.

Conclusions

Higher PTX-3 levels were associated with the presence of CAD and its increased severity in clinically stable patients. Higher PTX-3 levels may be regarded as a novel diagnostic predictor and may offer therapeutic options in the clinic.Key Words: Coronary angiography, Coronary artery disease, Pentraxin-3     

Relaxivity enhancement of aquated Tris(β‐diketonate)gadolinium(III) chelates by confinement within ultrashort single‐walled carbon nanotubes

Ultrashort single‐walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T₁‐weighted relaxivities (>100 mm ^?1 s^?1). To further examine the effect of nanoconfinement on the relaxivity of gadolinium‐based contrast agents for magnetic resonance imaging, a series of ultrashort single‐walled carbon nanotube (US‐tube) materials internally loaded with gadolinium chelates have been prepared and studied. US‐tubes were loaded with Gd(acac)₃ · 2H₂O, Gd(hfac)₃ · 2H₂O, and Gd(thd)₃ (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm ^?1 s^?1 for Gd(acac)₃ · 2H₂O@US‐tubes, 105 mm ^?1 s^?1 for Gd(hfac)₃ · 2H₂O@US‐tubes and 26 mm ^?1 s^?1 for Gd(thd)₃@US‐tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm ^?1 s^?1) as well as accounting for the T₁ reduction observed for the empty US‐tubes, the boost in relaxivity for chelate‐loaded US‐tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.     

Assessment of left-atrial strain parameters in patients with frequent ventricular ectopic beats without structural heart disease

Ventricular ectopic beats (VEBs) are often encountered in daily clinical practice. Clinical significance of VEBs seen in patients without structural cardiovascular diseases is controversial. We aimed to investigate the effects of VEBs on left atrium (LA) function using speckle tracking echocardiography with LA strain parameters. Patients with frequent VEBs (more than 30 times in 1 h, according to the Lown classification) were identified. Identified patients were evaluated by speckle tracking methods. There were 40 patients with frequent VEBs and 40 controls in our study. The general characteristics were similar of the study population. The LA global longitudinal strain parameters were significantly different. Global Peak atrial longitudinal strain (PALS) (38.39 ± 7.93 vs. 44.15 ± 6.71, p = 0.001) and peak atrial contraction strain (PACS) (16.37 ± 4.58 vs. 20.49 ± 3.65, p = 0.000) were revealed significantly lower in the VEBs group. Time to peak longitudinal strain (TPLS) was found significantly longer in the VEBs group [485.5 (352–641) vs. 435 (339–516.5) p = 0.000]. Number of VEBS was correlated with TPLS (r = 0.499, p = 0.000). PALS and PACS were negatively correlated with number of VEBs (r = ?0.348, p = 0.002 and r = ?0.444, p = 0.000, respectively). We described that in this study, The LA functions are affected by VEBs adversely. This deterioration is increasing as the number of VEBs.     

Videolaparoscopic treatment of hepatic hydatid cyst

BACKGROUND/AIMS: Unroofing, cystopericystectomy, or cystic evaluation and omentoplasty have been used in videolaparoscopic treatment in hepatic hydatidosis since 1992. Currently it is shown that videolaparoscopic treatment has been carried out successfully in selected cases. METHODOLOGY: Fifteen hepatic hydatid cysts in 12 cases were treated by videolaparoscopic methods. Formerly in the 5 cases, the cysts were aspirated with a needle designed for a 5-mm trocar, leaving a cystic cavity that was tension-free, then scolicidal solution was injected and aspirated. In the last 7 patients an aspirator-grinder apparatus was used. Intraoperative ultrasonography was applied in all patients. RESULTS: All the cysts were treated by drainage and omentoplasty. In one case cystic cavity infection was diagnosed in the 2nd postoperative month (morbidity rate 8.33%). Another patient died due to cerebral hydatid cyst and multiple organ failure after the postoperative first month (mortality rate 8.33%). Operative mortality was not seen. CONCLUSIONS: Videolaparoscopic treatments of hepatic hydatid cysts may be carried out successfully in selected cases.