Development of apple wine from Golden Delicious cultivar using a local yeast isolate.

The present study was conducted to optimize fermentation parameters for apple wine production using Golden Delicious apples. Physicochemical analysis of the cultivar revealed a °Brix-acid ratio of 24.61 with ample amount of total and reducing sugars (9.6 and 6.03% w/v); making it a suitable substrate to produce ethanol. Microbiological analysis lead to isolation of a yeast strain (namely A2) which was molecularly identified and accessed at GenBank as S. cerevisiae KY069279. Ethanol fermentation optimization using response surface methodology revealed that a temperature of 20 °C, an inoculum size of 7.08 (%v/v) and diammonium hydrogen phosphate supplementation @ 154.4 mg/100 mL as optimum for apple wine production which lead to 10.73% (v/v) ethanol production with a desirability of 86.9%. Fresh wine having malic acid content of 1.87 (mg/100 mL) was subjected to malolactic fermentation (MLF) for 8 days using Leuconostoc oenos NCIM 2219 resulting in apple wine having 0.4 (mg/100 mL) malic acid. Sensory analysis of MLF and non-MLF apple wines categorised them as superior quality with average scores of 69.5 and 74.5, respectively. Gas chromatography-mass spectrometric analysis of apple wine revealed the presence of 38 volatile compounds including higher alcohols, acids, esters etc. The study thus revealed a process for apple wine preparation using an indigenous yeast and also optimized and compared malolactic and non-malolactic fermented ciders.

Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.

Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.

Production of tea vinegar by batch and semicontinuous fermentation.

The fermented tea vinegar combines the beneficial properties of tea and vinegar. The complete fermentation takes 4 to 5 weeks in a batch culture and thus can be shortened by semi continuous/ continuous fermentation using immobilized bacterial cells. In the present study, alcoholic fermentation of 1.0 and 1.5% tea infusions using Saccharomyces cerevisae G was carried out that resulted in 84.3 and 84.8% fermentation efficiency (FE) respectively. The batch vinegar fermentation of these wines with Acetobacter aceti NRRL 746 at the initial 1% acidity yielded 4.5 and 4.7% volatile acidity with 71.4 and 73% FE in 24 days. The semi continuous fermentation using sugarcane bagasse adsorbeded A.aceti cells produced 4.4% of volatile acidity from 1.5% tea wine (8.9% ethanol and 1.0% acidity), in 9 flow cycles, each of 4 h duration in a fermentation column at 50 ml/h. In the scale up process, 600 ml 1.5% tea wine produced 4.3% volatile acidity at 42.7% FE in 9 flow cycles of 12 h duration each.

[Effectiveness of zopiclone in disorders of initiating and maintaining sleep. Results of a drug monitoring study in 811 general practices]. / Die Effektivität von Zopiclon bei Ein- und Durchschlafstörungen. Ergebnisse einer Anwendungsbeobachtung in 811 Hausarztpraxen.

BACKGROUND AND METHOD: In a drug monitoring study with 811 participating general practitioners, safety and tolerability of zopiclone were studied in 2416 patients with disorders of initiating and maintaining sleep. RESULTS: In general, zopiclone was efficient in all forms of insomnia; the subjective sleep duration was prolonged for 2 hours on average. Patients without somatic complaints or comorbidity showed the greatest benefit. Daytime well-being and vigilance were in general not impaired. Drug related adverse events occurred rarely; the great majority of the participating physicians rated the treatment with zopiclone as efficient and acceptable. CONCLUSION: In this drug monitoring study, zopiclone proved an efficient hypnotic for the treatment of disorders of initiating and maintaining sleep.

Progressive visual loss, diabetes mellitus, and associated abnormalities (DIDMOAD syndrome).

A syndrome including juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and high-frequency sensorineural hearing loss, expressed completely or partially, is being identified with greater frequency. Visual loss may be progressive and accompanied by primary optic atrophy. Concurrent diabetic retinopathy has only rarely been reported. Visual acuity may deteriorate to less than 20/400. The etiology is unknown. However, histopathologic studies indicate that the diabetes insipidus, optic atrophy, and neurosensory hearing loss represent progressive degenerative conditions. Inheritance appears to be autosomal recessive with incomplete penetrance. The syndrome is rare; therefore, a complete neuroophthalmologic and neuroradiologic evaluation is imperative to rule out a mass lesion. This syndrome should be considered in young people with visual loss and optic atrophy of unknown etiology even if they are not known juvenile diabetics.

Aspergillosis presenting as a corticosteroid-responsive optic neuropathy.

A case of orbital aspergillosis presenting as a steroid response of optic neuropathy is presented. The invasive and aggressive nature of this infection in the presence of systemic corticosteroids is documented by serial CT scans and necropsy examination. The authors urge inclusion of aspergilloma in the differential diagnosis of a steroid responsive optic neuropathy.

Mutagenicity of 8-ethoxycaffeine in vitro. Induction of point mutations in the Salmonella/microsome test and of sister-chromatid exchanges as well as chromosomal aberrations in Chinese hamster ovary cells (CHO line).

The caffeine derivative 8-ethoxycaffeine (EOC) was tested in 3 different test systems in vitro. Each experiment was carried out with and without S9 mix. Incubation temperatures were 20 and 37 degrees C. (1) In the Salmonella/microsome test, EOC behaved as a pro-mutagen in the Salmonella typhimurium strain TA1535. No mutagenic activity was found in experiments without S9 mix. The influence of temperature was negligible. The mutagenic activity of EOC depended mainly on the mammals used to prepare the S9 fraction and on the agents given to them to induce liver enzymes. (2) EOC did not induce sister-chromatid exchanges in cell cultures, either at 20 or at 37 degrees C. (3) On the other hand, EOC induced chromosomal aberrations when the cells were incubated at 37 degrees C without S9 mix.

Effects of caffeine on sister-chromatid exchanges (SCE) in vivo.

Chinese hamsters were twice treated with caffeine via stomach tube. The single doses were either 20, 100, 200 or 400 mg per kg body weight. A dose-dependent increase was observed in the frequencies of SCE induced in vivo in bone-marrow cells. Two intraperitoneal injections of the chemical mutagens, cyclophosphamide or benzo[a]pyrene, led to a pronounced increase of the frequency of SCE. Simultaneous applications of the chemical mutagens and caffeine decreased the rate of SCE. The effect of caffeine per se to induce SCE, and the mechanisms by which caffeine reduces the level of SCE induced by chemical mutagens are discussed.

Mutagenicity of polycyclic hydrocarbons. V. Induction of sister-chromatid exchanges in vivo.

The potency of polycyclic hydrocarbons to induce SCEs in vivo was analysed. The most potent SCE-inducing compound was benzo[a]pyrene. Benzanthracene, benzo[b]fluoranthene, benzo[e]pyrene, phenanthrene, chrysene and dibenzanthracene enhanced the SCE frequency to a smaller extent. The number of anthracene-induced SCEs per metaphase was not increased as compared with the controls.

Effects of various cyclophosphamide concentrations in vivo on sister chromatid exchanges (SCE) and chromosome aberrations of Chinese hamster bone marrow cells: comparison of two methods measuring the mutagenicity of a test compound.

The in vivo SCE formation and the induction of chromosome aberrations in the bone marrow of Chinese hamsters (Cricetulus griseus) were studied after various concentrations of cyclophosphamide, and the sensitivity of the two test methods was compared. The administraiton of 1.0, 5.0, 13.3, 25.0, and 40.0 mg/kg body weight induced a dose-dependent increase in SCE. The frequency of chromosome aberration, however, was not increased significantly with doses of 1.0 and 5.0 mg/kg body weight. Only with doses of more than 13.3 mg is a significant induction of chromosome aberrations seen. Therefore the SCE test system seems to be 10 times more sensitive than the induction of chromosome aberrations in the same cell type.