Abstract  Analysis of the sex pheromone gland of virgin Synanthedon scoliaeformis females by gas chromatography/mass spectrometry revealed six compounds structurally related to sex pheromone components of other clearwing moths: (E,Z)-2,13-octadecadienyl acetate (E2,Z13-18:OAc), (E,Z)-2,13-octadecadienol, octadecanol acetate, octadecanol, (Z,Z)-3,13-octadecadienyl acetate (Z3,Z13-18:OAc), and (Z)-13-octadecenyl acetate. Trapping tests demonstrated that E2,Z13-18:OAc is the sex pheromone of S. scoliaeformis and is essential for attracting males; addition of the other compounds did not enhance catch. Synanthedon scoliaeformis and S. tipuliformis are the only Palearctic clearwing moths whose distribution range and seasonal flight periods overlap and that are known to use E2,Z13-18:OAc in sex pheromonal communication. Hourly monitoring of male catches in traps revealed that sex pheromone communication in S. scoliaeformis and S. tipuliformis species follows different diurnal patterns. Z3,Z13-18:OAc, found in S. scoliaeformis females, is a known behavioral antagonist against S. tipuliformis males, while (E,Z)-3,13-octadecadienyl acetate, a minor sex pheromone component of S. tipuliformis, is an antagonist against S. scoliaeformis males. The effect of sex pheromones and antagonists, combined with different diurnal mate searching times, contribute to the specificity of sex communication channels in these two clearwing moth species.

Abstract  A chemical analysis of the crude sex pheromone gland extracts of virgin calling Paranthrene tabaniformis females, obtained from the European, part of Kazakhstan, revealed the presence of five compounds: (3E,13Z)-octadeca-3,13-dien-1-ol (E3,Z13-18:OH), (3Z,13Z)octadeca-3,13-dien-l-ol (Z3,Z13-18:OH), (2E,13Z)-octadeca-2,13-dien-1-ol (E2,Z13-18:OH), (13Z)-octadec-13-en-1-ol (Z13-18:OH), and octadecan-1-ol (18:OH) at the ratios 64.0:32.4: 1.4:0.9:1.3, which are structurally related to sex pheromone components of clearwing moths. Our previous field tests showed synergistic effects of Z3,Z13-18:OH and E2,Z13-18:OH to attract P tabaniformis males, when these compounds were tested in binary mixtures with the known sex pheromone E3,Z13-18:OH. The three dienic alcohols should all be considered as sex pheromone components of the P tabaniformis species, while the role of Z13-18:OH and 18:011 remained unclear.

Abstract  Interest in pyruvic acid has been growing due to the increase in its potential areas of use and its importance in metabolic reactions. These reasons along with the limitations on recovery have prompted researchers to consider novel recovery techniques. Reactive extraction has been proposed as a promising approach to the recovery of carboxylic acids. In this study, equilibrium and kinetic data were obtained for reactive extraction of pyruvic acid using trioctylamine (TOA) or Alamine 336 in 1-octanol or oleyl alcohol. The results showed that, without pH adjustment in the aqueous phase, and without the use of an extractant, 1-octanol extracted more pyruvic acid than oleyl alcohol with a distribution coefficient (K(D)) of 0.30. This trend remained the same when tertiary amines were used as an extractant. The K(D) values did not significantly differ with TOA or Alamine 336. The recovery of pyruvic acid was observed to increase as a function of TOA concentration and the stoichiometry of the reaction was mainly 1:1. As tertiary amines react only with undissociated acids, an increase in the initial pH of the aqueous phase lowered the KD values. When the pH was 4.0, the effect of TOA concentration on pyruvic acid extraction disappeared and for all concentration levels a distribution coefficient of 0.10 was obtained. Kinetic measurements showed that the reaction between pyruvic acid and TOA in 1-octanol is first order with respect to the two reactants with a rate constant of 0.94 L mol(-1) s(-1). The enhancement factor was calculated as 25.

Abstract  The expression of Pax-5 gene is altered in human myeloma cells (malignant plasma cells). This altered expression is considered to be closely involved in oncogenesis of human myeloma. To investigate the possible mechanism(s) underlying this alteration, we first cloned the 1,050 bp fragment in the 5' upstream region of human Pax-5 gene by PCR-mediated gene walking method. The cloned fragment has predicted regulatory motifs for Lyf-1(Ik-1), IK-2, bHLH, E-47, Sox-5, Oct-1, GATA-1,-2, and -3, but it lacks a TATA box. By constructing deletion mutants of this fragment, its basal promoter activity was analyzed by transfecting these mutants to Cos 7 cells. The maximal promoter activity was recovered by the fragment that extends between -70 to -820 upstream of the transcription start site. Also, three DNA fragments from this cloned sequence were used as templates in gel shift assay; these fragments covered most of the predicted regulatory sites. Specific binding activities were found in each DNA fragment. Therefore, we could clone the functionally active fragment of 5' upstream region of human Pax-5 gene.

Abstract  Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILRα) in vitro. In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. The CHO-K1 cells stably expressing PILRα were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. The effector and target cells were co-cultured, and luminescence was measured when both cells were successfully fused. Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases.

Abstract  Ether lipids show high specific cytotoxicity in vitro on a wide variety of experimental tumors, but only moderate activity in vivo. One reason for this lack of activity in the whole animal might be a high degree of metabolic degradation. We therefore studied the biotransformation of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine ([H]ET18-OMe) labeled in position 9-10 of the 1-alkyl chain, in rat plasma and erythrocytes, HL60 and K562 leukemic cells. HT29 adenocarcinoma cells, and cultured hepatocytes at 37 degrees C, and in a system of isolated and perfused rat liver. ET18-OMe and its metabolites were identified and quantified after lipid extraction and TLC separation. In tumor cells, 98% of ET18-OMe remained almost unmodified in vitro after 24-hr incubation. Plasma and erythrocytes from rats metabolized only 4-5% of the original compound in 3 hr. In cultured hepatocytes, 35% and 58.3%, respectively, of ET18-OMe was present after 6 and 24 hr as the metabolites 1-O-alkyl-2-O-methylglycerol (AMG), 1-O-alkyl-2-O-methylphosphatidic acid (AMPA), and stearyl alcohol (SA) (products of direct hydrolysis by phospholipases C and D and alkylhydrolase); phospholipids (phosphatidylcholine and phosphatidylethanolamine); and neutral lipids (products of secondary metabolism). In perfused rat liver, similar to 15% of the total radioactivity incorporated after 3 hr was distributed in metabolites as follows: 5.9% of AMPA, 5.0% of AMG, and 3.1% of SA. We conclude that the metabolism of ET18-OMe in normal tissues occurring through the same enzymes that metabolize natural lipids may partly explain the lack of effect in vivo.

Abstract  Objective To systematically review the evidence for the clinical effects and safety of the rye-grass pollen extract (Cernilton) in men with symptomatic benign prostatic hyperplasia (BPH).

Methods Trials were identified by searching Medline, specialized databases (EMBASE, Cochrane Library, Phytodok), bibliographies, and contacting relevant trialists and manufacturers. Randomized or controlled clinical trials were included if: men with symptomatic BPH were treated with Cernilton; a control group received either placebo or pharmacological therapy; the treatment duration was greater than or equal to 30 days; and clinical outcomes were reported.

Results In all, 444 men were enrolled in two placebo-controlled and two comparative trials lasting 12-24 weeks. Three studies used a double-blind method although the concealment of treatment allocation was unclear in all. Cernilton improved 'self-rated urinary symptoms' (the proportion reporting satisfactory or improving symptoms) vs placebo and another plant product, Tadenan. The weighted mean (95% confidence interval) risk ratio (RR) for self-rated improvement vs placebo was 2.40 (1.21-4.75) and the weighted RR vs Tadenan was 1.42 (1.21-4.75). Cernilton reduced nocturia compared with placebo or Paraprost (a mixture of amino acids); against placebo, the weighted RR was 2.05 (1.41-3.00), and against Paraprost the weighted mean difference for nocturia was - 0.40 times per evening (-0.73 to 0.07). Cernilton did not improve urinary flow rates, residual volume or prostate size compared with placebo or the comparative study agents. Adverse events were rare and mild; the withdrawal rate for Cernilton was 4.8%, compared with 2.7% for placebo and 5.2% for Paraprost.

Conclusions The Cernilton trials analysed were limited by their short duration, limited number of enrolees, omissions in reported outcomes, and the unknown quality of the preparations used. The comparative trials had no confirmed active control. The available evidence suggests that Cernilton is well tolerated and modestly improves overall urological symptoms, including nocturia. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton.

Abstract  A goldfish (Carassius auratus) model of Parkinson's disease (PD) was constructed by a single dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to previously reported methods. Global metabolite changes in brain of the MPTP induced goldfish model of PD were investigated. (1)H NMR-based metabolomics combined with various statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) found significant increase of leucine, isoleucine, valine, alanine, alanylalanine, creatinine, myo-inositol, 18:2 fatty acid, total fatty acids, arachic alcohol, taurine and significant decrease of N-acetylaspartate, (phospho)creatine, (phospho)choline, betaine, glutamine, 3-hexenedioate, acetamide, malonate, isocitrate, scyllo-inositol, phosphatidylcholines, cholesterols, n-3 fatty acids, polyunsaturated fatty acids (PUFAs) in brain of MPTP induced PD goldfish. These disturbed metabolite levels were involved in oxidative stress, energy failure, neuronal cell injury and death, consistent with those observed in clinical PD patients, and rodents and primates model of PD, indicating that the acute MPTP model of goldfish was an ideal and valuable model for PD research. In addition, several unusual metabolites in brain were significantly changed between MPTP induced PD and control goldfish, which might also play an important role in the pathogenesis of PD. This study also demonstrated the applicability and potential of (1)H NMR-based metabolomics approach for evaluation of animal models of disease induced by chemicals, such as MPTP-induced PD goldfish.

Abstract  Purpose: Tadenan is a pharmaceutical agent used in the treatment of BPH. Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction following two weeks of partial outlet obstruction, The specific aim of the present study was to determine the effect of Tadenan pretreatment on the time course of the response to partial outlet obstruction and correlate the effect of Tadenan on the contractile responses to field stimulation, bethanechol, and KCl with both mitochondrial enzyme activity (citrate synthase) and sarcoplasmic reticular function (calcium-ATP'ase activity).

Materials and Methods: Sixty male New Zealands white rabbit (3 to 5 kg.) were separated into 12 groups of 5 rabbits each. Each rabbit in groups 1-6 received Tadenan orally at 100 mg./kg./day for three weeks; each rabbit in groups 7-12 received vehicle (peanut oil). Each rabbit in groups 2-6 and 8-12 received a partial outlet obstruction as described below. One group of Tadenan treated and one group of vehicle-treated rabbits were euthanized at 1, 3, 5, 7, and 14 days following partial outlet obstruction. The non-obstructed groups were studied after 4 weeks of drug or vehicle treatment. Each bladder was rapidly removed and weighed, and 3 longitudinal strips prepared and mounted in individual baths for contractile studies. The remainder of the bladder was frozen for biochemical analysis. The contractile responses to field stimulation, bethanechol, and KCl were determined; and the enzyme activities of citrate synthase (marker for mitochondrial function) and calcium-ATP'ase (marker for sarcoplasmic reticulum) were determined,

Results: 1) Tadenan did not reduce the effect of partial outlet obstruction on bladder mass. 2) Although the contractile responses to all forms of stimulation were reduced at 1 day following partial outlet obstruction, Tadenan pretreatment resulted in a significant protective effect on the contractile responses to field stimulation, bethanechol, and KCl at 3, 5, 7, and 14 days of obstruction. 3) The activities of both citrate synthase and calcium ATP'ase were reduced significantly at 1 day following obstruction for both Tadenan treated and vehicle treated groups. The activities of both enzymes returned to near normal levels at 7 and 14 days for the Tadenan groups whereas the activities of both enzymes remained significantly reduced in the vehicle treated groups.

Conclusions: These results clearly demonstrate that Tadenan pretreatment protected the bladder from both the contractile and metabolic dysfunctions induced by partial outlet obstruction.

Abstract  AIMS: To investigate the content of hydroxyproline (Hyp) and the expression of transforming growth factor beta1 (TGF beta1) and basic fibroblast growth factor (bFGF) in the bladder 8 weeks after diabetes induction.

METHODS: Thirty wistar rats were divided into three groups: control (n = 10), streptozotocin-induced diabetic group (n = 10), TAD group (n = 10; diabetic rats were fed with Tadenan 100 mg kg(-1) day(-1)). Eight weeks later, the bladders were dissected. RT-PCR, immunohistochemistry, and ELISA were used to detect the expression of TGF beta1 and bFGF in the bladder. Also hydroxyproline (Hyp) was measured using a method based on alkaline hydrolysis.

RESULTS: The content of hydroxyproline in the diabetic group was greater than that of control group (P < 0.05); we found significantly increased expression of TGF beta1 mRNA and bFGF mRNA in the bladder from the diabetic group compared with the control group; immunohistochemical and ELISA studies showed a statistically significant increased expression of TGF beta1 protein and bFGF protein in the bladder from the diabetic group compared with the control group (P < 0.05). The content of hydroxyproline in TAD group was less than that of diabetic group (P < 0.05); mRNA expression of TGF beta1 and bFGF greatly decreased in TAD group compared with that of the diabetic group; immunohistochemical and ELISA studies showed decreased levels of TGF beta1 protein and bFGF protein in the bladder from TAD group compared with the diabetic group (P < 0.05).

CONCLUSIONS: Rats with streptozoticin-induced diabetes mellitus showed significant increase in hydroxyproline, TGF beta1 and bFGF levels in their bladders, which may be an important mechanism inducing diabetic cystopathy. Tadenan could effectively reduce hydroxyproline, TGF beta1, and bFGF levels.

Abstract  The essential oils of two species of Sideritis growing spontaneously in Bulgaria and Macedonia are reported, Sideritis scardica and Sideritis raeseri. The oils of S. scardica from different locations differed significantly: in the Macedonian sample alpha-cadinol (20%) predominated, while in the oil of Bulgarian samples the main components were diterpenic compounds and octadecenol (over 20%). This is the first report of ditrpenoids in essential oil of S. scardica. The oil of S. raeseri demonstrated a distinct chemical profile with its high concentration of sesquiterpenes, main components being germacrone (25%) and elemol acetate (15.9%). The observed qualitative variability of the oil composition of S. scardica of different geographic origin could be a result of different ecologic conditions but might also reflect the well-known tendency of some Sideritis species to hybridize.

Abstract  Extractive citric acid fermentation with Aspergillus niger microoganism was investigated in the presence of corn oil and Hostarex A327 in oleyl alcohol. In the extractive fermentation, production and separation phases are achieved simultaneously. Before Response Surface Methodology (RSM) was applied,the effect of potassium ferrocyanide (K4Fe(CN)(6)) concentration on citric acid production and the prevention of solvent toxicity using corn oil were investigated. Citric acid concentration increased with increasing K4Fe(CN)(6) concentration. Solvent toxicity was reduced using corn oil in the extractive citric fermentation, In the RSM, the potassium ferrocyanide concentration, (0.02-0.10%, w/v), the ratio of organic phase volume to the aqueous phase volume, V-or/V-aq, (0.5-1.5), the corn oil concentration (0-20%, by volume) and the Hostarex A327 content in oleyl alcohol (10-50% by volume) were the critical components. Optimum citric acid concentration was obtained as 5.70 g/l with employing the following predicted optimum extraction conditions: K4Fe(CN)(6) of 0.06% (w/v), V-or/V-aq of 1.25. corn oil concentration of 13.7% (by volume) and Hostarex A327 content in oleyl alcohol of 33% (by volume). Citric acid production by extractive fermentation was increased approximately 40% with respect to the control run (4.10 g/l). (C) 2002 Elsevier Science Ltd. All rights reserved.

Abstract  We analyzed a single nucleotide polymorphism (SNP) at position -56 (T-->C) in the promoter region of the gene encoding the human interferon-gamma receptor ligand-binding chain I (IFN-gammaR1). The mutation was present at similar frequencies in Gabonese children with either mild or severe malaria. Functional investigations of the promoter in a transfected human B-cell line showed lower levels of luciferase reporter gene expression in the presence of the mutation, indicating the importance of this position for promoter activity, and suggesting that this SNP might negatively influence the expression level of IFN-gammaR1 at the cell surface. Further examinations of the DNA sequence at this polymorphic site showed a perfectly matched binding site for the transcription factor activator protein 4 (AP-4) on both strands. Binding sites for other important transcription factors involved in gene expression and regulation of the immune response against infections, including Ikaros 2 (Ik-2), nuclear factor kappaB (NFkappaB), and CETS1p54, are also situated in this region.

Abstract  The CTP:phosphocholine cytidylyltransferase (CT) gene from yeast and cDNA from rat liver were over-expressed 20-30-fold in COS cells. Most of the CT activities were found in the cytosolic fraction. The regulation of the yeast CT activity (Y-CT) by lipids was characterized for the first time in comparison with the regulation of the well-studied rat CT (R-CT). Sonicated vesicles composed of egg phosphatidylcholine (PC) or 1-stearoyl-2-oleoyl PC had no effect on Y-CT and only slightly stimulated R-CT activity. Both CTs were activated 10-50-fold by the anionic lipids cardiolipin, phosphatidylglycerol, phosphatidylinositol and oleic acid. The effects of varying the vesicle concentration and the mol% of anionic lipid in PC vesicles were tested. The concentration optima for the activation of Y-CT by oleic acid or anionic phospholipids were 5-10-fold lower than those for R-CT. For example, the stimulation of Y-CT activity by phosphatidylglycerol vesicles was optimal between 5 and 15-mu-m and declined at higher concentrations, but R-CT activation by these vesicles saturated at approximately 25 pm. The positively charged aminolipid sphingosine antagonized the stimulation by oleic acid of both Y-CT and R-CT. Y-CT activity was insensitive to PC vesicles containing the neutral lipids diacylglycerol, monoacylglycerol or oleyl alcohol. However, R-CT was stimulated 10-20-fold by vesicles containing these neutral lipids. Translocation of the CTs to microsomal membranes enriched with anionic or neutral lipids was compared. Oleic acid enrichment promoted translocation of Y-CT and R-CT, whereas diacylglycerol promoted only R-CT translocation. These data show that the activity of Y-CT is lipid-sensitive. Y-CT is affected only by charged lipids, whereas R-CT responds to charged and neutral lipid activators. The data are consistent with different modes of interaction of the two CTs with lipids.

Abstract  Stearyl and cetyl alcohols are the least irritating of the alcohols, and are present in many topical medicaments as vehicle ingredients. The commercial stearyl and cetyl alcohols used are not pure, but contain impurities, including other alcohols that may be potent sensitizers. We report here a case of contact dermititis due to impurities in stearyl and cetyl alcohols.

Abstract  The object of this study was to prepare rosiglitazone maleate (RM) sustained-release floating microspheres and investigate their pharmacokinetics. AM microspheres were prepared with ethyl cellulose (EC) and octadecyl alcohol as the carrier materials by an emulsion-solvent diffusion method, and the properties of morphology in vitro floating capability, drug loading (DL), entrapment efficiency (EE), in vitro release and in vivo pharmacokinetics were investigated. The prepared microspheres had a completely spherical shape. The percentage of microspheres floating after 12h was (91.45 +/- 1.62)%, and the DL and EE were (9.31 +/- 0.31)% and (89.55 +/- 1.65)% respectively. Pharmacokinetic studies demonstrated that the RM floating microspheres were superior to commercial tablets in terms of the decrease in peak plasma concentration and maintenance of AM concentration in plasma. The area under the curve of plasma concentration time (AUC) of the floating microspheres was equivalent to that of reference tablets. The results showed that floating microspheres are a feasible approach for the sustained-release preparation of drugs which have limited absorption sites in the upper small intestine.

Abstract  Stearyl heptanoate is an ester of stearyl alcohol and heptanoic acid that functions in cosmetics as a skin conditioning agent and is in the general class of chemicals called stearyl alkanoates. Stearyl caprylate, stearyl palmitate, stearyl stearate, stearyl behenate, and stearyl olivate are stearyl alkanoates with similar chemical structures, toxicokinetics, and functions in cosmetics. These water-insoluble stearyl alkanoates, when metabolized, yield stearyl alcohol and a corresponding fatty acid. The available information supports the safety of all of the related stearyl alkanoates. The Expert Panel concluded that stearyl heptanoate, stearyl caprylate, stearyl palmitate, stearyl stearate, stearyl behenate, and stearyl olivate are safe in the present practices of use and concentration.

Abstract  Two sex pheromone components of the gum leaf skeletonizer, Uraba lugens (Lepidoptera: Nolidae), recently established in New Zealand, were identified. Gas chromatography (GC) electroantennographic detection analyses of female pheromone gland extracts gave three compounds that consistently elicited antennal responses. Chemical analyses, using GC and GC-mass spectrometry, in conjunction with 4-methyl-1,2,4-triazoline-3,5-dione and dimethyldisulfide derivatizations, identified these compounds as (10E,12Z)-hexadecadien-1-yl acetate (E10,Z12-16:Ac), (10E,12Z)-hexadecadien-1-ol (E10,Z12-16:OH), and (Z)-11-hexadecen-1-yl acetate (Z11-16:Ac). A trapping trial in Queensland, Australia, in 2002, indicated that a blend of the two major components E10,Z12-16:Ac and E10,Z12-16:OH could attract gum leaf skeletonizer males. In the same trial, E10,Z12-16:Ac alone trapped large numbers of an unidentified nolid, Nola spp. Further trials in Auckland, New Zealand established that these two components were sufficient and necessary for trap catch of males; adding minor gland components, (10E,12E)-hexadecadien-1-yl acetate (E10,E12-16:Ac), Z11-16:Ac, or octadecan-1-ol (18:OH), to the two-component lure did not result in increased trap catches. Behavioral observations and gland analyses of the Auckland population revealed that female moths begin calling soon after emergence, with peak calling and pheromone production occurring 7 hr into the scotophase. Analysis of gland extract at two-hourly intervals during the first activity period showed that the ratio of E10,Z12-16:Ac to E10,Z12-16:OH (mean of 86: 14, respectively) and pheromone titer were fairly constant. No qualitative or quantitative differences in pheromone components were detected between gland extracts from Tasmanian univoltine and Auckland bivoltine populations of U. lugens.

Abstract  Immobilized Clostridium acetobutylicum was used to ferment glucose into acetone and butanol in a fluidized-bed bioreactor. A nontoxic immiscible solvent, oleyl alcohol, was added to, and removed directly from, the fermenting columnar reactor and extracted the majority of the inhibitory butanol from the aqueous broth. The extracting solvent had a distribution coefficient of near 3 for butanol. Nonfermenting system tests indicated that equilibrium between the phases could be reached in one pass through the column. Steady-state results are presented for the fermentation with and without the extractive solvent addition. One run, with a continuous aqueous feedstream containing 40 g/L glucose, was operated for 23 d. A steady state was established with just the aqueous feedstream. Approximately half of the glucose was consumed, and the pH fell to 4.5 from 6.5. Then, during multiple intervals, the flow of organic extractive solvent (oleyl alcohol) was begun into the fermenting columnar reactor. A new apparent steady state was reached in about 4 h. The final aqueous butanol concentration was lowered by more than half. The total butanol production rate increased by 50-90% during the solvent extraction, as the organic-to-aqueous ratio increased from 1 to 4, respectively. There was an observed maximum volumetric productivity of 1.8 g butanol h-1L-1 in this nonoptimized system. The butanol yield apparently improved because of the removal of the inhibition. More substrate is going to the desired product, butanol, and less to maintenance or acid production, resulting in 10-20% increases in the ratio of butanol relative to all products.

Abstract  PURPOSE: We examined the available data from clinical trials for certain botanicals used for lower urinary tract symptoms secondary to benign prostatic hyperplasia, including Serenoa repens (saw palmetto), Pygeum africanum (African plum), Secale cereale (rye pollen) and Hypoxis rooperi (South African star grass).

MATERIALS AND METHODS: MEDLINE and The Cochrane Library searches were done in June 2007 using the terms benign prostatic hyperplasia, lower urinary tract symptoms, phytotherapy, saw palmetto, Serenoa, Permixon, Pygeum africanum, Tadenan, Cernilton, Cernitin and Hypoxis. Search results were assessed for relevance and the inclusion of placebo controlled trials.

RESULTS: Two systematic reviews and 3 clinical trials were examined in the evaluation of Serenoa repens. Data from the systematic reviews showed an improvement in flow rates and symptoms. The results of 1 clinical trial were equivocal and the remaining 2 trials clearly showed equivalence to placebo. Systematic reviews were used in the evaluation of P. africanum, Secale cereale and Hypoxis rooperi. P. africanum and H. rooperi showed an improvement in flow rates and symptoms compared to placebo, while S. cereale showed an improvement in symptoms but not flow rates compared to placebo.

CONCLUSIONS: Most clinical trials of investigating the efficacy of botanicals suffer from well documented methodological flaws. Saw palmetto has been clearly shown as comparable to placebo in a trial of sound methodology. While preliminary results appear promising, to our knowledge the remaining botanicals have yet to be evaluated in a trial of similar quality.

Abstract  As long-chain alcohol dehydrogenases are not easily available and seldom reported enzymes, it is worthwhile to appraise the potential of well known dehydrogenases, like horse liver alcohol dehydrogenases (HLAD), for the oxidation of long-chain aliphatic alcohols. Oxidation of docosanol (C-22) and tetracosanol (C-24) is of technological relevance within an industrial platform for the fractionation and upgrading of tall-oil from the Kraft pulping process. Results are presented on the characterization of free and immobilized HLAD with respect to their potential for oxidizing long-chain aliphatic alcohols. Enzyme activity with respect to chain length and pH is presented. Activity for both free and immobilized HLAD increased with pH up to 8.8, but behavior with respect to chain length varied from one biocatalyst to the other. Even though both biocatalysts were less active towards very long-chain aliphatic alcohols, immobilized HLAD had an activity on docosanol and tetracosanol higher than 50% of the value obtained with ethanol, butanol and octanol, which is encouraging and has not been previously reported. Investigation on thermophilic sources and further immobilization strategies are underway to obtain more active and stable catalysts amenable for working at high temperatures which is quite relevant in this case due to the poor solubility of substrates. (C) 2008 Elsevier Inc. All rights reserved.

Abstract  A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.