Studies on the Reduction of Terpenes with Sodium in Aqueous-ammonia

On the reduction of (?)-carvone with sodium in aqueous-ammonia, the predominant product was found to be (?)-dihydrocarveol, a new stereoisomer. From this fact, it might be concluded that this reduction method is stereospecific for (?)-carvone, similary as in the case of (?)-menthone. By the catalytic hydrogenation of (?)-dihydrocarveol, a new stereoisomer of carvomenthol has also been prepared. It is noteworthy that (?)-dihydrocarveol has the same conformation (e, e, e) as that of (?)-menthol, which was also quantitatively obtained from (?)-menthone by application of our method of reduction reported previously.     

Studies on the Reduction of Terpenes with Sodium in Aqueous-ammonia

On reduction of (?)-menthone by various methods, generally, a mixture of (?)-menthol and (+)-neomenthol has been obtained. In the present work, it is found that (?)-menthol can be prepared almost quantitatively from (?)-menthone by treatment with sodium in aqueous-ammonia.     

Studies on the Reduction of Terpenes with Sodium in Aqueous Ammonia

The reduction of (?)-perillaldehyde (I) with sodium in aqueous ammonia afforded mainly trans- and cis-dihydroperillylalcohols (III_a and III_b). This fact indicates that this reduction method can surely be applied to α,β-unsaturated monoterpene aldehydes which are extremely sensitive to alkali and that the unconjugated carbon-carbon double bond is normally inert to this reducing condition.     

In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (−)-cubebin derivatives (−)-hinokinin and (−)-O-benzylcubebin

(?)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (?)-hinokinin (HK) and (?)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 – cyclooxygenase-2) interaction in comparison with CUB and HK.     

胡萝卜培养细胞的盐适应蛋白

近年来植物离体培养细胞盐适应蛋白的发现以及盐影响下植物信使 RNA 体外转译产物的研究,为耐盐分子机理的研究和耐盐基因的鉴定和克隆开辟了道路。烟草细胞在适应1—2.5%NaCl 之后,细胞蛋白质合成发生变化,特别是26kD 的蛋白质大量积累。体内标记实验表明,细胞从不加 NaCl 的培养基转到加有1%     

麻醉劑(巴比妥類)對於鹽酸引起胰液分泌的影響

本實驗比較急性實驗狗、慢性胰瘻狗和經過麻醉的慢性胰屢狗對於鹽酸注入小腸所引起的胰液分泌量和潛伏期,結果證明: (1)在急性實驗情况下,狗胰腺對鹽酸刺激小腸所引起的胰液分泌量遠較在慢性實驗時為少,且潛伏期較長。 (2)巴比妥類麻醉劑:硫賁妥鈉(sodium pentothal)和戊烷巴比妥鈉(sodiumpentobarbital)對鹽酸所引起的胰液分泌量及潛伏期影響極微。 (3)在急性實驗情况下,由鹽酸所引起的胰液分泌量的減少和潛伏期的加長,似乎不是由於巴比妥類麻醉劑的作用,而可能是由於手術創傷的影響。 (4)注射阿托平後,胰腺對於鹽酸刺激小腸所引起的反應顯著减小,故推测在鹽酸引起胰液分泌的機制中可能有神經反射作用的參與。本工作在进行過程中,承蘇聯專家同志親切地給予指導,并承沈(?)淇、劉曾復二教授关懷和支持,(?)此誌謝。     

Hawthorn special extract WS? 1442 increases red blood cell NO-formation without altering red blood cell deformability

WS(?) 1442 is a special extract of hawthorn leaves with flowers used for the treatment of mild cardiac failure. The activation of endothelial nitric oxide synthase (eNOS) has been shown to contribute to its vasodilating properties. Quite recently it has been demonstrated that red blood cells (RBCs) express a functional NO-synthase (rbcNOS) and rbcNOS activation has been associated with increased RBC deformability. The aim of the present study was to determine whether WS(?) 1442 is able to activate rbcNOS, to induce NO-formation in RBC and to alter RBC-deformability. Blood from healthy volunteers was incubated with WS(?) 1442 (25-100 μg/ml) for up to 30 min. RbcNOS activation was detected by immunohistochemical staining of phosphorylated rbcNOS and NO-formation was examined by diaminofluorescein (DAF) fluorescence. RBC deformability was measured by a laser assisted optical rotational cell analyzer. Serine 1177 of RbcNOS (rbcNOS Ser(1177)) was time- and concentration-dependently phosphorylated by WS(?) 1442. Rates of rbcNOS Ser(1177) phosphorylation were up to 149% higher in RBCs treated with WS(?) 1442 in comparison to control (DMSO 0.05%). WS(?) 1442 induced a time-dependent increase in NO-formation in RBCs which reached its maximum after 5 min. An increase in shear stress (0.3-50 Pa) caused an increase in RBC deformability. WS(?) 1442 did not change either basal or maximal RBC-deformability or shear stress sensitivity of RBC at normoxia. CONCLUSION: WS(?) 1442 activates rbcNOS and causes NO-formation in RBCs. WS(?) 1442-dependent NO-formation however does not affect RBC-deformability at normoxia.     

Properties of β-adrenergic receptors in untreated and butyrate-threated HeLa cells

HeLa cells contain receptors on their surface which are β-adrenergic in nature. The binding of (?)-[³H]dihydroalprenolol is rapid, reversible, stereo-specific and of relatively high affinity. The HeLa cells also contain an adenylate cyclase which is activated by (?)-isoproterenol > (?)-epinephrine > (?)-norepinephrine. The adenylate cyclase of HeLa is also activated by guanyl-5′-yl-imidodophosphate (Gpp(NH)p), a nonhydrolyzable analogue of GTP. Inclusion of both (?)-isoproterenol and Gpp(NH)p leads to approximately additive rathen than synergistic activation of adenylate cyclase. After treatment of HeLa cells with 5 mM sodium butyrate there is an increase in the number of β-adrenergic receptors, but not in their affinity, which is reflected in an increased ability of (?)-isoproterenol to activate adenylate cyclase. Other properties of the β-adrenergic receptor including association and dissociation rates, temperature optimum of adenylate cyclase and response to Gpp(NH)p are relatively unaffected by butyrate pretreatment of the cells.     

Highly enantioselective oxidation of racemic phenyl-1,2-ethanediol to optically pure (R)-(−)-mandelic acid by a newly isolated Brevibacterium lutescens CCZU12-1

Enantioselective oxidation of racemic phenyl-1,2-ethanediol into (R)-(?)-mandelic acid by a newly isolated Brevibacterium lutescens CCZU12-1 was demonstrated. It was found that optically active (R)-(?)-mandelic acid (e.e.p?>?99.9 %) is produced leaving the other enantiomer (S)-(+)-phenyl-1,2-ethanediol intact. Using fed-batch method, a total of 172.9 mM (R)-(?)-mandelic acid accumulated in the reaction mixture after the seventh feed. Moreover, oxidation of phenyl-1,2-ethanediol using calcium alginate-entrapped resting cells was carried out in the aqueous system, and efficient biocatalyst recycling was achieved as a result of cell immobilization in calcium alginate, with a product-to-biocatalyst ratio of 27.94 g (R)-(?)-mandelic acid g^?1 dry cell weight cell after 16 cycles of repeated use.     

Effect of sodium ascorbate on the chemiluminescent response of murine peritoneal exudate cells.

Vitamin C is an effective antioxidant that neutralizes reactive oxygen radicals. The purpose of this study was to determine if sodium ascorbate would neutralize the reactive oxygen products generated during the respiratory burst of thioglycollate-elicited murine peritoneal exudate cells (PEC). In vitro and in vivo studies were done. Cells treated in vitro showed a significant, dose-dependent reduction in chemiluminescence (CL) after activation with opsonized zymosan. Higher concentrations of sodium ascorbate (24.2 mM) produced a significantly greater reduction in CL than did lower concentrations (0.242 mM). This range of sodium ascorbate concentrations overlaps those found in normal leukocytes (1-4 mM). Sodium ascorbate at physiological plasma concentrations (0.09 mM) did not reduce CL. Cells incubated with 500 mM sodium ascorbate in vitro and then washed once prior to zymosan activation also showed a significant reduction in CL. In contrast, PEC harvested from mice treated in vivo with sodium ascorbate (one or five daily doses of 1.0 M sodium ascorbate, 0.01 ml/g body weight) did not show a reduction in CL. This concentration of sodium ascorbate represents a dose that is 2310 times greater than the Recommended Dietary Allowance (RDA). These studies show that physiological doses of sodium ascorbate can quench CL in vitro, but even large doses of sodium ascorbate administered in vivo do not affect the CL of harvested murine PEC.     

Stereoselectivity of the Enzymatic Reduction of Aldehydic and Ketonic Carbonyl Groups in Planar Chiral Organomanganese Complexes

(±)-Tricarbonyl(η⁵-1-formyl-2-methylcyclopentadienyl)manganese (1) was optically resolved with horse liver alcohol dehydrogenase (HLADH) and two species of yeasts, Saccharomyces sp. H-1 and Rhodotorula rubra IFO 889. Usually, (1R)-1 was preferentially reduced to give (?)-alcohol 2 of ≥ 97% e.e. ? 84% e.e. Ketone analogue (±)-tricarbonyl(η⁵-1-acetyl-2-methylcyclopentadienyl)-manganese (4) was reduced by the yeasts. The major product by S. sp. H-1 was the (1S,2R,1′S)-(+)-alcohol (5) (≥ 98% e.e.) and the minor product, the (1R,2S,1′S)-(?)-alcohol (6) (86% e.e.). R. rubra gave only the latter alcohol (≥ 99 % e.e.). The Stereodifferentiation mechanism for these bioreductions is discussed in terms of the Prelog rule. The mechanism for HLADH reduction was examined with computer graphics.     

High-sodium intake prevents pregnancy-induced decrease of blood pressure in the rat

Despite an increase of circulatory volume and of renin-angiotensin-aldosterone system (RAAS) activity, pregnancy is paradoxically accompanied by a decrease in blood pressure. We have reported that the decrease in blood pressure was maintained in pregnant rats despite overactivation of RAAS following reduction in sodium intake. The purpose of this study was to evaluate the impact of the opposite condition, e.g., decreased activation of RAAS during pregnancy in the rat. To do so, 0.9% or 1.8% NaCl in drinking water was given to nonpregnant and pregnant Sprague-Dawley rats for 7 days (last week of gestation). Increased sodium intakes (between 10- and 20-fold) produced reduction of plasma renin activity and aldosterone in both nonpregnant and pregnant rats. Systolic blood pressure was not affected in nonpregnant rats. However, in pregnant rats, 0.9% sodium supplement prevented the decreased blood pressure. Moreover, an increase of systolic blood pressure was obtained in pregnant rats receiving 1.8% NaCl. The 0.9% sodium supplement did not affect plasma and fetal parameters. However, 1.8% NaCl supplement has larger effects during gestation as shown by increased plasma sodium concentration, hematocrit level, negative water balance, proteinuria, and intrauterine growth restriction. With both sodium supplements, decreased AT1 mRNA levels in the kidney and in the placenta were observed. Our results showed that a high-sodium intake prevents the pregnancy-induced decrease of blood pressure in rats. Nonpregnant rats were able to maintain homeostasis but not the pregnant ones in response to sodium load. Furthermore, pregnant rats on a high-sodium intake (1.8% NaCl) showed some physiological responses that resemble manifestations observed in preeclampsia.     

Tolerability and effects of OROS® MPH (Concerta®) on functioning, severity of disease and quality of life in children and adolescents with ADHD: results from a prospective, non-interventional trial

Attention-deficit/hyperactivity disorder may have substantial impact on family life, peer interactions, and quality of life. Stimulants are recommended as first-line pharmacotherapy for ADHD. OROS(?) MPH (Concerta(?)) is a long-acting preparation with duration of effect for up to 12 h. In this 8-week, prospective, open-label, non-interventional trial the impact of therapy with OROS(?) MPH on functioning in four different areas of life (school, recreation, family life, and peer interaction), severity of disease, and quality of life (QoL) as well as tolerability were investigated under daily routine care. 306 patients, aged 10.2±2.3 years, were either transitioned to OROS(?) MPH from short-acting, immediate-release MPH (-IR) preparations (n=231; 75%), or treatment was initiated with OROS(?) MPH in MPH-na?ve patients (n =75; 25%). In both groups, therapy with OROS(?) MPH was associated with significant improvements in daily functioning, severity of disease, and QoL. Adverse events (AE) were documented in 160 patients (52.3%). In 95 patients (31.0%) a causal relationship was assessed as at least possible. Four serious AEs were reported in 2 patients and rated as doubtfully related to study medication. Most frequent AEs (≥5% of patients) were insomnia, anorexia, ineffectiveness of medication, and headache. In 12.1% of patients AE led to discontinuation of study participation. Considering the limitations of this non-interventional study, the results refer to the importance of a therapy that covers not only school-time, but also takes other areas of life into account. Initiating treatment with long-acting preparations, such as OROS(?) MPH in MPH-na?ve patients might be a feasible option.     

Stereoselective Synthesis of Ectocarpene and Its Antipode via Microbiological Asymmetric Hydrolysis

Biological asymmetric hydrolysis of ethyl (±)-cycloheptadienecarboxylate with Rhodotorula minuta var. texensis IFO 1102 and chemical resolution of the corresponding carboxylic acid with (?)-quinine provided (R)-(+)-ethyl 2,5-cycloheptadienecarboxylate (78% e.e.) and (S)-(+)-2,5-cycloheptadienecarboxylic acid (95% e.e.), respectively. The (R)-(+)-carboxylate was converted to (R)-(?)-2,5-cycloheptadienylcarbaldehyde and the (S)-(+)-carboxylic acid to (S)-(+)-2,5-cycloheptadienylcarbaldehyde. Ectocarpene (78% e.e.), male-gamete attractant of marine brown alga, and its antipode (95% e.e.) were synthesized by stereoselective Wittig reaction between the (R)-(?)- and (S)-(+)-aldehydes and propyltriphenylphosphonium bromide in a liquid-solid two phase system using 18-crown ether-t-BuOK, respectively.     

Studies on NO2-Tyr82and NH2-Tyr82 derivatives of adrenodoxin. Effects of chemical modification on electron transferring activity.

Bovine apoadrenodoxin was treated with tetranitromethane to introduce a nitro group into the tyrosyl residue at position 82 of this protein. The degrees of nitration under the best conditions were estimated to be 90% and nearly 100% on the basis of amino acid analysis and the spectrophotometric method, respectively. An amino derivative was prepared by reducing the nitro group with sodium dithionite. The apoadrenodoxin derivatives could be reconstituted to have an iron-sulfur chromophore similar to the native adrenodoxin which contains a 1:1 molar ratio of labile sulfur to iron content and displays absorption peaks at 414 and 450 nm. The enzymatic acitivies of these reconstituted nitro and amino derivatives toward cytochrome c reduction in the presence of adrenodoxin reductase and NADPH were 19 and 7% of native adrenodoxin, respectively. We studied the kinetics of the direct reduction of the reconstituted amino derivative in the presence of NADPH and adrenodoxin reductase under anaerobic conditons. The initial rate of reduction for the amino derivative was 7% of the native adrenodoxin, which is in good agreement with its activity toward cytochrome c reduction. From these results, it is concluded that by modifying the tyrosyl residue at position 82 of the adrenodoxin polypeptide, the electron-transferring activity of the molecule is largely diminished.     

Jasminum polyanthum Franch. as a natural source of (−)‐methyl jasmonate: an alternative to the use of the synthetic standard

Introduction – Methyl jasmonate (MJ) contains two chiral centres at C‐3 and C‐7 in its chemical structure, which implies that it can exist in four possible stereoisomeric forms, namely (+)‐MJ, (?)‐MJ, (+)‐epiMJ and (?)‐epiMJ. The absolute configuration of the two side chains of MJ affects the biological activity associated with this compound. Objective – To isolate pure (?)‐MJ from a natural source, Jasminum polyanthum Franch., with the intention of increasing the knowledge about its biological properties, including its effect on the biosynthesis of plant metabolites. Methodology – The method used was based on steam distillation extraction (SDE) as an extraction technique followed by high‐performance liquid chromatography (HPLC) as a purification procedure. The HPLC flow‐rate as well as the number of fractions accumulated were optimised to achieve the concentration and purity required. Results – The employment of 0.3 mL/min as HPLC flow‐rate and the accumulation of three HPLC fractions allowed the required enantiomeric purity (95%) and concentration (0.36 mg/L in each HPLC fraction) to efficiently obtain (?)‐methyl jasmonate from Jasminum polyanthum Franch. to be achieved. Conclusion – The approach proposed may enable the properties and effect of pure (?)‐MJ on plant responses to be studied. The use of a natural source to obtain (?)‐MJ is presented as an alternative to the enantioselective synthesis and enantiomeric resolution from the standard racaemic mixture. Copyright © 2009 John Wiley & Sons, Ltd.     

Decreased response with age of the cardiac catecholamine sensitive adenylate cyclase system

The cardiac β-adrenergic coupled adenylate cyclase system was examined in young and old male Wistar rats. The concentration of binding sites for (?) ³H-DHA in membranes prepared from cardiac ventricles was 21.1 ± 2.78 (SD) fmoles/mg protein in 3–4 month old rats (young rats) and 31.2 ± 2.20 fmoles/mg protein in 24 month old rats (old rats). The dissociation constant, K_D was 4.3 ± 1.8 nM and 6.7 ± 1.7 nM for young and old rats, respectively. Various compounds were used to study the characteristics of activation of adenylate cyclase in homogenates from cardiac ventricles. Basal adenylate cyclase was reduced 30% in old animals compared to young (6.1 pmoles/min/mg protein in 24 month vs. 8.6 pmoles/min/mg protein in 3–4 month). (?)Isoproterenol (10^?5M) alone stimulated adenylate cyclase greater than two-fold in young rats (10.6 pmoles/min/mg protein above basal) and this stimulation was 34% lower in old animals. GppNHp (100 μM), fluoride (10 mM), and forskolin (100 μM) activation of adenylate cyclase above basal was reduced 38, 37, and 34%, respectively, in the old animals. No significant changes between the two groups were noted in the apparent affinity of GppNHp either alone or in the presence of (?)isoproterenol nor in the affinities of catecholamine agonists for activation of cyclase. These results suggest a reduction in the amount of functional regulatory protein or possibly cyclase in 24 month old rat ventricular tissue compared to 3–4 month old tissue. However, this data does not rule out the possibility of altered molecular interactions of a full complement of regulatory protein (s) with β-adrenergic receptor and/or catalytic adenylate cyclase.     

Aggregation pheromone of the Oriental spruce engraver Pseudips orientalis

• 1 Volatiles from the hindgut extracts of males of the Oriental spruce engraver Pseudips orientalis (Wood & Yin) (Coleoptera: Curculionidae, Scolytinae) of different phases of gallery development were analyzed by gas chromatography‐mass spectrometry‐flame ionization detection (GC‐MS/FID) with both polar and enantioselective columns.
• 2 GC‐MS/FID analyses showed that unmated males or males mated with one female produced approximately 95%‐(?)‐ipsenol and (?)‐cis‐verbenol as major components, as well as (?)‐trans‐verbenol, myrtenol, approximately 70%‐(+)‐ipsdienol and (?)‐verbenone as minor or trace components. The release of these male‐produced compounds was confirmed by GC analysis of an aeration sample of a P. orientalis‐infested spruce log. Mating reduced production of the male‐specific hindgut volatiles.
• 3 A field‐trapping bioassay in Qinghai, China, showed that a ternary blend containing two major components, 97%‐(?)‐ipsenol (i.e. close to naturally produced enantiomeric ratio) and (?)‐cis‐verbenol, plus a minor component (?)‐trans‐verbenol, caught significantly more P. orientalis beetles (♂: ♀ = 1: 2.7) compared with the unbaited control. Subtraction of (?)‐trans‐verbenol from the active ternary blend had no significant effect on trap catches. The addition of (±)‐ipsdienol (at 0.2 mg/day release) to the active ternary or binary blends significantly interrupted their trap catches. Replacing 97%‐(?)‐ipsenol with (±)‐ipsenol in the ternary blend significantly reduced trap catches to a level that was no different from the blank control.
• 4 Pseudips species were sister to all other Ipini genera in a phylogeny reconstructed with mitochondrial cytochrome oxidase I DNA data for 51 Ipini and outgroup species.
• 5 The results obtained suggest that the two major components, 95%‐(?)‐ipsenol and (?)‐cis‐verbenol (at approximately 4–5 : 1), produced by unmated fed males, are probably the primary aggregation pheromone components for P. orientalis. In light of the phylogeny, the use of terpenoid semiochemicals as pheromones probably occurred early in the evolution of Ipini and these semiochemical blends were subsequently modified in the process of speciation.

     

Optimizing the attractiveness of pheromone baits used for trapping the four‐eyed spruce bark beetle Polygraphus poligraphus

Bark beetles have caused extensive damage to forests in central Sweden during the past decade, and the four‐eyed spruce bark beetle, Polygraphus poligraphus, seems to be involved. However, its role in these bark beetle outbreaks is still not clear. The purpose of this study was to develop an efficient pheromone bait for P. poligraphus, which would make it possible to study the species more carefully and thereby contribute to protect exposed forests in an environmentally friendly way. Three field studies were conducted in 2015, 2016 and 2018 in Medelpad, county of Västernorrland, Sweden. The pheromone of P. poligraphus, (?)‐terpinen‐4‐ol, was tested at different release rates and in different enantiomeric purities, to find the most attractive formulation for the beetles. It was also tested in combination with racemic frontalin, a compound which has previously been shown to produce a synergistic effect together with (?)‐terpinen‐4‐ol of low enantiomeric purity; 52% ee. Other compounds, chosen based on responses from electroantennographic studies, were also tested in an attempt to find additional attractants and repellents for P. poligraphus. The most attractive treatment tested was enantiomerically pure (?)‐terpinen‐4‐ol (99% ee). When the enantiomeric purity was lower (50% ee), the trap catches was lowered to levels comparable to the catches for unbaited control traps. A strong synergistic effect with frontalin was observed for (?)‐terpinen‐4‐ol of low enantiomeric purity (50% ee) but not for the enantiomerically pure compound (99% ee). The release rate of (?)‐terpinen‐4‐ol (99% ee) was shown to be an important factor. For the combination of frontalin and (?)‐terpinen‐4‐ol (50% ee), the attraction seemed strongest when (?)‐terpinen‐4‐ol was released at a higher rate than frontalin. An interesting and novel result was that a repellent compound, α‐terpineol, was identified in our studies. Our results from field studies and electroantennography recordings also indicate that (+)‐terpinen‐4‐ol is a repellent for P. poligraphus.     

Gold-deferrioxamine nanometric interface for selective recognition of Fe(III) using square wave voltammetry and electrochemical impedance spectroscopy methods

Deferrioxamine, a bacterial hydroxamic siderophore having high binding affinity for Fe(III), is used in its immobilized form, as self-assembled monolayer on Au, for accumulation and recognition of Fe(III) from the solution phase. The accumulated Fe(III) is detected via both active mode based on faradaic reduction current of Fe(III), and inactive mode based on impedimetric effect of accumulated Fe(III) against redox reaction of a suitable probe. Appropriate electrochemical techniques, square wave voltammetry and electrochemical impedance spectroscopy, are used for the transduction of analytical signals obtained by this sensor. Then, the parameters influencing the sensor response are optimized. In the best conditions, a linear response, from 1.0×10(-10) to 1.0×10(-7)M Fe(III) in logarithmic scale with a detection limit of 2.0×10(-11)M, and mean relative standard deviation of 1.7% for n=4 is observed. The results show that the sensor can be used for determination of Fe(III) in the presence of various inorganic ions and biological species. Validity of the method and applicability of the sensor are successfully tested by determination of Fe(III) in various real samples including plant tissue (corn leaves), industrial alloy (Ferrotitanium), and pharmaceutical samples (Venofer(?) ampoule, Ironorm(?) capsule, and V.M. Protein(?) powder).