Abstract  Objectives: To investigate the effects of terazosin and melatonin on isolated rabbit bladder strips after partial bladder outlet obstruction and determine responses to agonist-induced contractility and changes in oxidant-antioxidant system. Methods: We created partial bladder outlet obstruction in 5 groups of rabbits, each containing 8. Rabbits with sham operation (group 1) received no drug treatment. Similarly, animals in group 2 underwent partial bladder outlet obstruction and received no drug treatment. Rabbits in groups 3 were administered 5 mg/day oral terazosin, and rabbits in group 4 received 10 mg/kg/day melatonin intraperitoneally. Animals in group 5 received both terazosin and melatonin. We removed their bladders and performed histopathological and biochemical measurements. We assessed tissue malondialdehyde and antioxidant enzyme activity levels and recorded in vitro contractility response to KCl in isolated organ baths. Results: The thickness of muscularis propria was significantly increased in group 2 compared with all other groups. KCl-evoked contractions after partial outlet obstruction were significantly impaired in group 3 and 4 animals receiving terazosin and melatonin, respectively. However, combined use of melatonin and terazosin in group 5 showed contractility responses similar to sham-operated animals (P <0.05). Melatonin administration to groups 4 and 5 showed decreased levels of lipid peroxidation. Similarly, animals receiving melatonin and melatonin plus terazosin showed statistically significant increase in antioxidant enzyme activities. Conclusions: In the present study, we showed that oxidative stress induced by partial bladder outlet obstruction can be successfully antagonized by the potent antioxidant melatonin, and its combined use with an alpha-antagonist such as terazosin may restore in vitro contractility. [Copyright 2008 Elsevier] Copyright of Urology is the property of Excerpta Medica Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Abstract  49 substances permitted for use in food in the United States was tested for mutagenicity in the Ames Salmonella typhimurium assay and in Escherichia coli strain WP2. Four of these substances caused increases in revertant counts in S. typhimurium. Two of these four (papain and pepsin) were found to contain histidine, and therefore the results of the tests on these two substances could not be taken as demonstrating mutagenicity. The other two substances causing increases in revertant counts (hydrogen peroxide and potassium nitrite) were mutagenic. The results on one chemical, beta-carotene, were evaluated as inconclusive or questionable. The remaining 44 substances were nonmutagenic in the test systems used. It is concluded that, for those generally physiologically innocuous chemicals tested, there are very few 'false positives' in the bacterial test systems used.

Abstract  Breflate is a water soluble prodrug developed to facilitate parenteral administration of the investigational antineoplastic agent brefeldin A (BFA). Previously, using analytical methods based upon reversed-phase high performance liquid chromatography (HPLC) with low wavelength UV detection or gas chromatography (GC) with electron capture detection following derivatization with heptafluorobutyrylimidazole, it was demonstrated that breflate undergoes rapid and efficient conversion to BFA following bolus i.v. injection in mice and dogs. However, plasma concentrations of the drug and prodrug achieved during the administration of nontoxic doses of breflate to beagle dogs as a 72 h continuous i.v. infusion were undetectable (< 0.1 microgram ml-1) by these methods. The sensitivity and specificity required for therapeutic drug level monitoring were achieved by GC with selected-ion mass spectrometry (MS) detection. Breflate, BFA and 1-eicosanol, the latter added to the sample as an internal standard (IS), were extracted from plasma into tert-butyl methyl ether (TBME) and esterified with trifluoroacetic anhydride. Methanol was added to the reaction mixture to effect the convenient removal of excess reagent as the volatile methyl ester during evaporation of the solvent. The residual material was analyzed directly upon reconstitution by capillary GC with automated splitless injection. Electron-ionization (70 eV) MS detection was performed by sequentially scanning ions at m/z 58, 202 and 325. The lowest concentration of either analyte quantified with acceptable reproducibility, as defined by an inter-day R.S.D. of about 20%, was near 10 ng ml-1 in plasma using a sample volume of 100 microliters. The assay has proven to be sufficiently sensitive, specific and reproducible for the routine analysis of pharmacokinetic specimens acquired during IND (investigational new drug)-directed toxicology studies in dogs.

Abstract  Primary alcohols, from methanol to eicosanol, were applied to water for control of larval stage mosquitoes. By applying the alkanols as soluble solutions rather than as insoluble monolayers, and by trapping larvae under glass in assays that isolated them from the surface phenomena believed to be responsible for death by suffocation, we have shown that the action of alkanols against mosquito larvae is biochemical in nature, not just physical. Primary alcohols are known to act as general anesthetics, with increasing potency correlated to increasing chain length until a point of cutoff is reached, usually at dodecanol (C12), after which activity disappears entirely. In mosquitoes, we found that activity levels off after undecanol (C11) but does not disappear until after pentadecanol (C15), that it is reversible, and that chain length plays a role not only in potency, but also in the time needed to manifest toxic effects. We used sonication, a surfactant, temperature, and the introduction of double bonds to manipulate activity around the cutoff, suggesting that it is at least partially a function of solubility. Mosquitoes appear to be the first animal for which cutoff has been demonstrated to occur at a chain length beyond C12, offering new insights into the molecular basis of anesthetic cutoff and suggesting the possibility that alkanols might be used for selective pest control. Alkanols are stable, colorless, inexpensive, biodegradable and essentially non-toxic to humans, making them promising candidates for pest management programs.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. The application of Salmonella/microsomal mammalian tests to column chromatography fractions isolated from river and marine sediments collected in the vicinity of Barcelona City, Spain, demonstrated a positive response (TA98+S9 mix) among the polar fractions. Chemical analysis by high resolution gas chromatography coupled to negative ion chemical ionization mass spectrometry (HRGC-NICI MS) provided sensitivity and selectivity to detect several mutagenic chemical classes. Among them, nitrated PAHs, azaarenes, aromatic amines, anhydrides, and ketones were identified. A total of 116 compounds were tentatively identified, 22 for the first time, of which 16 possessed mutagenic activity. However, a lack of correlation between chemical composition and fraction mutagenicity in the medium polarity fractions, especially in the river sediment, was evidenced. The occurrence of multiple interactions between components in spiked organic extracts is demonstrated.

Abstract  The rabbit external ear canal was used to define which chemicals caused comedone formation on topical application. Some of the tested ingredients are currently used in topically applied formulations. Certain raw materials have been shown to produce follicular hyperkeratosis in the rabbit ear assay. This study quantifies comedogenic potential of cosmetic materials, including: isopropyl palmitate, isopropyl myristate, butyl stearate, isopropyl isostearate, decyl oleate, isostearyl neopentanoate, isocetyl stearate, myristle myristate, cocoa butter, cetyl alcohol, paraffin, stearyl alcohol sodium lauryl sulfate (SLS), and petrolatum. The first nine were deemed positive. Factors aiding clinical relevance are listed.

Abstract  Structural analogues of phospholipidic platelet activating factor, (2-acetoxy-3-octadecyloxy)propyl-1-phosphonocholine and (2-methoxy-3-octadecyloxy)propyl-1-phosphonocholine, were synthesized. High efficiency of the polymer-bound dibenzo-18-crown-6-ether as the 0-alkylation catalyst was demonstrated. Reaction of allyl-octadecyl ether with methanol and iodine in the presence of zinc oxide was shown to give a mixture of 1-iodo-2-methoxy- and 1-methoxy-2-iodoprop-3-yl ethers of octadecanol in the 3 : 1 ratio.

Abstract  The antimicrobial activity of the n-hexane, chloroform, ethyl acetate and ethanol extracts of the aerial parts of C. drabifolia S.M. subsp. cappadocica (DC.) Wagenitz (Asteraceae) was evaluated against microorganisms including multi-antibiotic resistant bacteria using the paper disc diffusion method. The chemical composition of the chloroform extract of this plant was determined by gas chromatography and gas chromatography-mass spectrometry. The chloroform extract exhibited significant antibacterial activity against all the bacteria tested, except Stenotrophomonas maltophilia MU63. The major compounds of the chloroform extract were spathulenol (14.1%), caryophyllene oxide (12.5%), octadecanol (10.2%), ethyl palmitate (7.7%), [Z,Z]-10,12-hexadecadienal (6.0%), 3-hydroxy p-anisaldehyde (5.9%) and pentacosane (5.8%).

Abstract  OBJECTIVE: To study the chemical constituents of Wikstroemia indica.

METHODS: The constituents were isolated and purified by silica gel chromatography repeatedly, and the structures were determined by spectral data and chemical envidance.

RESULTS: Six compounds were isolated from its petroleum ether, dichloromethane, acetone and methanol extracts and identified as: daphnoretin-7-O-beta-D-glucoside (1), aloe-emodin (2), kaempferol (3), 29-nonacosanolide (4), 1-octadecanol (5), beta-sitosterol (6).

CONCLUSION: Compounds 2, 4, 5 are isolated from this plant for the first time.

Abstract  Structure-activity relationships between acute toxicities of 95 alcohols to rat and mouse (oral LD50) and four special substructure factors, hydroxyl number, carbon atom number were examined by means of expert system method. The results showed that the expert system based QSAR model was excellent for classification for miscellaneous alcohols (only 9 of them were wrong classified). It was also used to predict the toxicity of other 25 alcohols, and the false prediction rate was only 12%.

Abstract  Objectives. Pretreatment with oral tadenan (TAD) has been shown to possess a protective effect on bladder dysfunction-induced obstruction. We evaluated the functional influence of cotreatment and post-treatment with oral TAD on the frequency/volume characteristics of micturition of conscious rats stimulated with exogenous dihydrotestosterone (DHT) to induce experimental prostate growth.

Methods. Studies were done on 36 adult Sprague-Dawley male rats, treated daily for 6 weeks and grouped as follows: group 1, sesame oil during weeks 1 and 2, peanut oil during weeks 3 to 6; group 2, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle during weeks 1 and 2 and peanut oil during weeks 3 to 6; group 3, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle and TAD (100 mg/kg orally) in peanut oil during weeks I and 2 and TAD during weeks 3 to 6; and group 4, DHT in sesame oil during weeks 1 and 2 and TAD in peanut oil during weeks 3 to 6. The characteristics of frequency/volume were monitored biweekly and at the sixth week.

Results. Controls showed no significant changes from baseline values in volume or frequency during the entire study period. DHT treatment produced a significant increase in frequency (1.9 +/- 0.3 to 3.0 +/- 0.4/hr) and a significant decrease in volume (1.8 +/- 0.3 to 1.2 +/- 0.1 mL). In groups 3 and 4, no significant changes occurred in frequency or volume. By the sixth week of observation, the effects of DHT treatment decreased to control values in all groups. A significant increase in prostatic weight (1191 +/- 11 to 1434 +/- 17 mg/kg) was produced by DHT treatment and TAD cotreatment suppressed growth to 1390 +/- 8.4 mg/kg.

Conclusions. TAD cotreatment or post-treatment suppressed the effects of DHT on micturition, and TAD cotreatment regressed a developing increase in prostatic weight. Post-treatment TAD administration did not reduce already established growth.

Abstract  Mass spectrometry has become an indispensable tool for the global study of metabolites (metabolomics), primarily using electrospray ionization mass spectrometry (ESI-MS). However, many important classes of molecules such as neutral lipids do not ionize well by ESI and go undetected. Chemical derivatization of metabolites can enhance ionization for increased sensitivity and metabolomic coverage. Here we describe the use of tris(2,4,6,-trimethoxyphenyl)phosphonium acetic acid (TMPP-AA) to improve liquid chromatography (LC)/ESI-MS detection of hydroxylated metabolites (i.e. lipids) from serum extracts. Cholesterol which is not normally detected from serum using ESI is observed with attomole sensitivity. This approach was applied to identify four endogenous lipids (hexadecanoyl-sn-glycerol, dihydrotachysterol, octadecanol, and alpha-tocopherol) from human serum. Overall, this approach extends the types of metabolites which can be detected using standard ESI-MS instrumentation and demonstrates the potential for targeted metabolomics analysis.

Abstract  After patch testing of several groups of patients we analyzed the development of contact allergy to wool wax alcohols and emulsifying fatty alcohols in the last years. For identifying the allergens we used high purified n-alcanols of the chain length of C-8 to C20, lanosterol and aliphatic diols. We found no reaction to cetyl and stearyl alcohol at all - the main allergens in literature. Most of the patch test reactions were caused by n-alcanols of C10H21OH to C15H31OH, but also by lanosterol and aliphatic diols. Alcohols of the chain length C-12 and C-14 we found in all gaschromatographically analyzed samples. Therefore we like to propose allergenfree emulgators for patients on risk.

Abstract  The MCF-7 cell line (human breast epithelial cells) accumulates fatty alcohols. The fatty alcohols were identified as C16:0, C18:0, and C18:1 alcohols by thin-layer chromatography and gas chromatography/mass spectrometry. This accumulation of alcohols in MCF-7 was found in cultures of MCF-7 cells obtained from other laboratories but not in a variety of unrelated cell lines. The presence of the alcohols suggested an aberrant ether lipid metabolism in the MCF-7 cells. Therefore, the capacity for either lipid biosynthesis was evaluated using cells incubated with either [14C]stearyl alcohol or [14C]stearic acid. MCF-7 cells incorporated less than 0.4% of the [14C]alcohol into ether-linked phospholipids, whereas the AB589 breast epithelial cells, used as a "normal control" for comparisons, did not accumulate fatty alcohol and incorporated approximately 20% of the radiolabeled alcohol into phospholipids containing ether linkages. Although the MCF-7 cells were unable to effectively incorporate the fatty alcohol into ether linkages, the cells were able to oxidize the alcohol to fatty acid. When incubated with [14C]stearic acid, the conversion to radiolabeled fatty alcohol in MCF-7 cells was approximately four times higher than the alcohol levels found in AB589 cells. While deficient in the ability to synthesize ether linkages, the MCF-7 cells did incorporate radiolabeled hexadecylglycerol, a precursor containing an ether linkage, into phospholipids. Collectively, the data indicate that the MCF-7 cells possess a deficiency in the alkyl DHAP synthase activity. A near absence of ether-linked lipids in the MCF-7 cells was indicated by the radiolabeling studies, and this finding was corroborated by results from HPLC analysis. Analyses of the partial glycerides, obtained from the enzymatic hydrolysis of cellular phospholipids, found only trace levels of ether lipids in the MCF-7 cells. The aberration in ether lipid biosynthesis did not correlate with the expression of the multidrug resistance phenotype in a series multidrug resistant MCF-7 variants. The results are discussed relative to the use of the MCF-7 cells as a model for investigations of ether lipid biosynthesis and the cellular physiology of ether lipids.

Abstract  Bladder dysfunction secondary to benign prostatic hyperplasia (BPH) is a major affliction of aging men. BPH can initiate both irritative lower urinary tract symptoms (urgency, frequency, and nocturia), and obstructive symptoms (reduced flow rate, increased micturition pressure, increased duration of micturition, and incomplete emptying). Although these symptoms are related to the effect of the enlarging prostate and subsequent urethral obstruction, there appears to be no direct relationship between prostate size or composition and severity of symptoms.3,13,17,19,23 In addition, the results of standard urodynamic evaluations do not correlate well with the severity of patient symptoms; standard urodynamics cannot accurately predict either level of bladder pathology or potential for recovery following surgery.3,13,17,19,23 One major problem is that current methods of urodynamic analysis, including pressure measurements, are indirect assessments of detrusor power or contractile function.

Abstract  A new oxyneolignan (rel-(7 alpha,8 beta)-3-methoxy-4',7-epoxy-8,3'-oxyneolignan-4,9,9'-triol) with a scarce C(7)-O-C(4') and C(8)-O-C(3') epoxy linkage, along with eight known compounds, abieta-8,11,13-triene, sandaracopimara-8(14), 15-diene, 6,7-dehydroferruginol methyl ether, 18-hydroxydehydroabietane, sandaracopimara-8(14), 15-dien-18-ol, docosanol, sugiol and palmitic acid, were isolated from the chloroform-soluble fraction of the acetone extract from Juniperus brevifolia leaves. Their structures were established on the basis of the spectral evidences and direct comparison with values from literature data. (C) 2010 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.

Abstract  The ATPase activity of the (Ca2+-Mg2+)-ATPase purified from skeletal muscle sarcoplasmic reticulum and reconstituted into phosphatidylcholine bilayers of defined composition depends on the fatty acyl chain length of the surrounding phospholipid. The stoichiometry of Ca2+ binding to the ATPase is also sensitive to fatty acyl chain length, changing from the normal two Ca2+ ions bound per ATPase molecule to one Ca2+ ion bound for the ATPase reconstituted with phosphatidylcholines of chain lengths C12, C14, or C24. For the ATPase reconstituted with mixtures of phosphatidylcholines where one phosphatidylcholine supports a Ca2+ binding stoichiometry of two and the other a stoichiometry of one, a highly cooperative change in binding stoichiometry with change in phospholipid composition is observed, suggesting that the effects of phospholipids follow from binding to a large number of sites at the lipid-protein interface of the ATPase. For the ATPase reconstituted with either 1-myristoyl-2-oleoylphosphatidylcholine or 1-oleoyl-2-myristoylphosphatidylcholine, the stoichiometry of Ca2+ binding is the normal two per ATPase molecule. Effects of short-chain phosphatidylcholines on Ca2+ binding stoichiometry and on ATPase activity can be reversed by addition of androstenol, oleic acid, methyl oleate, or oleyl alcohol but these molecules have no effect on the ATPase reconstituted with dinervonylphosphatidylcholine (C24:1). For the ATPase reconstituted with phosphatidylcholines with chain lengths between C16 and C22, release of the two bound Ca2+ ions is sequential, with release of the second Ca2+ being inhibited by high concentrations of Ca2+ in the bathing medium. For the ATPase reconstituted with phosphatidylcholines of chain lengths C14 or C24, release of the single bound Ca2+ is only slightly inhibited by the presence of Ca2+ in the medium. For the ATPase reconstituted with phosphatidylcholines of chain lengths between C16 and C24, removal of bound Ca2+ results in a decrease in tryptophan fluorescence intensity, whereas for the ATPase reconstituted with phosphatidylcholines of chain lengths C12 or C14, removal of bound Ca2+ results in an increase in tryptophan fluorescence intensity. In mixtures of phosphatidylcholines, changes in the tryptophan response mirror changes in Ca2+ binding stoichiometry.

Abstract  Mitotic checkpoint impairment is present in human lung cancers with chromosomal instability (CIN). Spindle-checkpoint genes have been reported to be mutated in several human cancers; but these mutations are infrequent. Recent reports suggest that the hBUBR1 gene may play an important role in mitotic checkpoint control and in mitotic checkpoint impairment in human cancers. We analyzed the expression of hBUBR1 in lung cancer cell lines using real time quantitative RT-PCR. The expression of BUBR1 was found to be up-regulated in all of these cell lines. In addition, we cloned and characterized the promotor region of hBUBR1 and determined its genomic structure, which includes 23 exons. The open reading frame (ORF) of the hBUBR1 gene comprises exons 1 through 23. There are GC-rich regions located at the flanking region and about 150 bp upstream from exon 1. The promoter region (424 bp upstream from exon 1) showed promoter activity and includes multiple transcription factor consensus binding motifs, including those for Sp1, Nkx-2, CdxA, SRY, MyoD, Ik-2, HNF-3b, Staf, Oct-1, Nkx-2, v-Myb, and AML 1a. Multiple pathways leading to activation of those binding factors may contribute to hBUBR1 gene transcription. Knowledge of the genomic structure and the promoter region of the hBUBR1 gene will facilitate investigation of its role in mitotic checkpoint control and tumor progression in human cancers. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Abstract  The autumn gum moth, Mnesampela privata (Guenee) (Lepidoptera: Geometridae), is native to Australia and can be a pest of plantation eucalypts. Field-collected and laboratory-reared female autumn gum moths were dissected to remove glands likely to contain components of the sex pheromone. Using gas chromatography (GC) and combined gas chromatography-mass spectrometry (GC-MS), three compounds were identified from female extracts, namely (3Z,6Z,9Z)-3,6,9-nonadecatriene, 1-hexadecanol and 1-octadecanol (confirmed by comparison with synthetic samples). Nonadecatriene elicited an antennal response in male autumn gum moth during gas chromatographic analyses combined with electroantennographic detection (GC-EAD). In electroantennogram (EAG) recording male M. privata antennae responded to the nonadecatriene. Nonadecatriene was synthesised via Kolbe electrolysis, starting with (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid (linolenic acid) and propanoic acid or via an alternative four-step method also starting from linolenic acid. In field trials (3Z,6Z,9Z)-3,6,9-nonadecatriene proved attractive to male moths. Thus, we conclude that (3Z,6Z,9Z)-3,6,9-nonadecatriene is a sex pheromone component of autumn gum moth. This component has been identified in extracts from other geometrids in the same subfamily, Ennominae. However, to our knowledge this is the first example where (3Z,6Z,9Z)-3,6,9-nonadecatriene has been found in females and also proved attractive to male moths when presented on its own. Our results are discussed in relation to other geometrid pheromones.

Abstract  Sjogren-Larsson syndrome (SLS) is an inherited disorder associated with deficient oxidation of long-chain aliphatic alcohols. Previous studies have reported modest elevations in total (free + esterified) fatty alcohols in SLS, but free fatty alcohols have not been selectively measured, in part because of their low concentrations in most tissues and the presence of trace fatty alcohol contaminants in some solvents used for their analysis. We adapted methods to measure free fatty alcohols in cultured cells and plasma that minimize exogenous alcohol contamination. Fatty alcohols were analyzed as acetate derivatives, using capillary column gas chromatography. By this method, cultured skin fibroblasts from SLS patients were found to have 7- and 8-fold elevations in the mean content of hexadecanol (16:0-OH) and octadecanol (18:0-OH), respectively. The mean plasma 16:0-OH and 18:0-OH concentrations in SLS patients (n = 11) were 9- and 22-fold higher than in normal controls, respectively. In SLS fibroblasts, most of the fatty alcohol (59%) that accumulated was free rather than esterified alcohol, whereas free alcohol accounted for 23% of the total alcohol in normal cells. These results indicate that elevations in free fatty alcohols provide a sensitive marker for the enzymatic defect in SLS. The ability to measure free fatty alcohols in cultured cells and plasma should prove useful for investigations of normal fatty alcohol metabolism and the deranged metabolism in SLS.

Abstract  Human prostate was used as a source of 5 alpha reductase. Compounds were incubated with an enzyme preparation and [3H]testosterone. [3H]-dihydrotestosterone production was measured to calculate 5 alpha reductase activity. IC50 values (ng/ml) were finasteride = 1; Permixon = 5,600; Talso = 7,000; Strogen Forte = 31,000; Prostagutt = 40,000; and Tadenan = 63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5 alpha reductase, while Permixon and Bazoton have neither anti-androgen nor 5 alpha reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5 alpha reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 micrograms/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5 alpha reductase.

Abstract  The hydrogenation of methyl oleate (methyl 9Z-octadecenoate) into oleyl alcohol (9Z-octadecen-1-ol) is carried out in an autoclave at 8.0 MPa and 543 K with Ru-Sn catalysts. The activity and the selectivity of this catalytic system are linked to the preparation method, the nature of the support (alumina, silica, active carbon and zinc oxide) and to the tin content. Selectivities of 50 and 55% to unsaturated alcohol respectively were obtained with a Ru-Sn-B/alumina catalyst resulting from the co-reduction of metallic salts by sodium borohydride and a Ru-Sn/alumina catalyst prepared by a sol-gel method. Our work also showed that a previously unreported transesterification reaction between methyl oleate and oleyl alcohol occurred rapidly and led to a 'higher' ester (oleyl oleate). This side-reaction significantly decreases the selectivity to unsaturated alcohol. Nevertheless, at higher conversion the oleyl oleate is gradually hydrogenated into oleyl alcohol.

Abstract  The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5'-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5'-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing.

Abstract  Recovery of metabolites from fermentation broth by solvent extraction can be used to optimize fermentation processes. End-product reutilization, low product concentration and large volumes of fermentation broth and the requirements for large bioreactors, in addition to the high cost largely contributed to the decline in fermentative 2,3-butanediol production. Extraction can successfully be used for in-situ alcohol recovery in 2,3-butanediol fermentations to increase the substrate conversion. In the present work organic extraction of 2,3-butanediol produced by Klebsiella pneumoniae fermentation was studied to determine solvent effect on 2,3-butanediol production. The aim of this project was liquid-liquid extractive fermentation systems evaluation as an alternative to overcome the end product effect and to increase of 2,3-butanediol production by K. pneumoniae because Conventional fermentative production of 2,3-butanediol by K. pneumoniae has the disadvantage of product reutilization by the organism. Alternatives to overcome this problem have met with limited success. Extractive fermentation has been shown to solve this problem. An effort has been made in this study to use for the extractive fermentation of 2,3-butanediol using oleyl alcohol as extract-ant. Eighteen organic solvents were examined to determine their biocompatibility for in situ extraction of fermentation products from cultures of the K. pneumoniae. From 18 tested solvents, 13 of which were non-toxic to K. pneumoniae. The highest 2,3-butanediol production (23.01 g l(-1)) was achieved when oleyl alcohol was used. In situ removal of end products from K. pneumoniae resulted in increased productivity. In conclusion 2, 3-hutanediol productivity increased from 0.5 g l(-1)h(-1) to 0.66 g l(-1)h(-1) in extractive fermentation using oleyl alcohol as the extraction solvent.

Abstract  In this work, the potential of waxes for preparing with the ultrasonic spray congealing technique microparticles for controlling the in vitro release of verapamil HCl was investigated. The first part of the study encompassed the optimisation of the formulation to achieve an efficient drug incorporation together with a satisfactory in vitro drug release rate. In particular, microcrystalline wax, stearyl alcohol and mixtures of the two were used. Also a surfactant (soya lecithin) was added to the formulations. After the particle size analysis, the characterisation of the microparticles involved the study of the solid state of drug and carriers in the systems (DSC, HSM and XRD) and the morphological and chemical analyses of the microparticle surface (SEM and XPS). Finally, the drug release mechanism from these devices was evaluated using the statistical moment analysis. The results of this study show that by selecting the type and the amount of the carriers, microparticles with a spherical shape and a good encapsulation efficiency were observed. These particles showed a zero-order release for 8 h, without modifying the solid state properties of the drug. Therefore, waxy microparticles prepared by the ultrasonic spray congealing technique are promising solvent-free devices for controlling the release of verapamil HCl. (C) 2003 Elsevier Science B.V. All rights reserved.