Anti-inflammatory, analgesic and antipyretic activity of aqueous extract of fresh leaves of Coccinia indica

This study was aimed to evaluate both post- and pre-treatment anti-inflammatory activities of the aqueous extract of fresh leaves of Coccinia indica in rats using the carrageenan-induced paw oedema method at various dose levels. Analgesic and antipyretic properties were evaluated using tail flick model and yeast-induced hyperpyrexia, respectively. Ceiling effect of the extract was observed at 50 mg/kg in pre-treatment carrageenan test. In post-treatment studies, a dose-dependent anti-inflammatory effect was observed in the dose range of 25–300 mg/kg. The effect was equivalent to diclofenac (20 mg/kg) at 50 mg/kg but it was significantly pronounced at higher doses. Effectiveness of extract in the early phase of inflammation suggests the inhibition of histamine and serotonin release. The extract produced marked analgesic activity comparable to morphine at 300 mg/kg, which suggests the involvement of central mechanisms. A significant reduction in hyperpyrexia in rats was also produced by all doses of extract with maximum effect at 300 mg/kg comparable to paracetamol. In conclusion, this study has established the anti-inflammatory activity, analgesic and antipyretic activity of C. indica and, thus, justifies the ethnic uses of the plant.     

Potential anthelmintics: polyphenols from the tea plant <Emphasis Type="Italic">Camellia sinensis</Emphasis> L. are lethally toxic to <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

A novel gallate of tannin, (−)-epigallocatechin-(2β→O→7′,4β→8′)-epicatechin-3′-O-gallate (8), together with (−)-epicatechin-3-O-gallate (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4α→8′)-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (−)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 ≈ 6, 9, 4, 5, 1. The LC₅₀ (96 h) values of 8 and 9 were evaluated as 49 and 334 μmol L⁻¹, respectively. These data show that many green tea polyphenols may be potential anthelmintics.     

Attenuation of the effects of <Emphasis Type="Italic">d</Emphasis>-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion

Rationale  Interval timing in the free-operant psychophysical procedure is sensitive to the monoamine-releasing agent d-amphetamine, the D₂-like dopamine receptor agonist quinpirole, and the D₁-like agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzepine (SKF-81297). The effect of d-amphetamine can be antagonized by selective D₁-like and 5-HT_2A receptor antagonists. It is not known whether d-amphetamine’s effect requires an intact 5-hydroxytryptamine (5-HT) pathway. Objective  The objective of this study was to examine the effects of d-amphetamine, quinpirole, and SKF-81297 on timing in intact rats and rats whose 5-hydroxytryptaminergic (5-HTergic) pathways had been ablated. Materials and methods  Rats were trained under the free-operant psychophysical procedure to press levers A and B in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic functions were fitted to the data for derivation of timing indices (T ₅₀, time corresponding to %B = 50%; Weber fraction). The effects of d-amphetamine (0.4 mg kg⁻¹ i.p.), quinpirole (0.08 mg kg⁻¹ i.p.), and SKF-81297 (0.4 mg kg⁻¹ s.c.) were compared between intact rats and rats whose 5-HTergic pathways had been destroyed by intra-raphe injection of 5,7-dihydroxytryptamine. Results  Quinpirole and SKF-81297 reduced T ₅₀ in both groups; d-amphetamine reduced T ₅₀ only in the sham-lesioned group. The lesion reduced 5-HT levels by 80%; catecholamine levels were not affected. Conclusions   d-Amphetamine’s effect on performance in the free-operant psychophysical procedure requires an intact 5-HTergic system. 5-HT, possibly acting at 5-HT_2A receptors, may play a ‘permissive’ role in dopamine release.

Antimalarial activity of Gomphostemma crinitum leaf extracts

Abstract  Antimalarial efficacy of Gomphostemma crinitum leaf extracts were studied in vitro against the chloroquine-sensitive MRC-02 strain of Plasmodium falciparum. The CHCl₃ extract (IC₅₀ 37.28 μg/mL) was found to be better than the aqueous extract (IC₅₀ 111.4 μg/mL). The major compound present in CHCl₃ extract was coded as GC-7 (12,17-diacetoxy, 15-hydroxy, 2-oxo, 3, 13 E (14)-diene clerodane). Seasonal variation of GC-7 was studied and correlated to the antimalarial efficacy of the crude extracts of leaves collected in different months. GC-7 was found to be the only regular compound present in G. crinitum leaves throughout the year. A good correlation between antimalarial efficacy (IC₅₀ 9.3 μg/mL) and concentration of GC-7 in crude extracts was observed. The mode of action of GC-7 was found to be different from that of chloroquine. Graphical Abstract  Antimalarial activity of Gomphostemma crinitum leaf extracts B.N Acharya, Deepika Saraswat and M.P Kaushik^* Discovery Centre, Process Technology Development Division Defence R & D Establishment, Jhansi Road, Gwalior-474002 (MP) INDIA ^#Entomology division, Defence Research and Development Establishment,Gwalior-474002, India Antimalarial activity of chloroform extract of G. crinitum leaves and an isolated compound GC-7 (12,17-diacetoxy,15-hydroxy,2-oxo,3,13 E (14)-diene clerodane) against a chloroquine susceptible strain of Plasmodium falciparum is described.     

Cytotoxic activity of Perilla frutescens var. japonica leaf extract is due to high concentrations of oleanolic and ursolic acids

Three triterpene acids, ursolic acid (1), corosolic acid (2), and oleanolic acid (7), were isolated from the ethanol extract of leaves of Perilla frutescens (L.) Britton var. japonica Hara (Labiatae; Japanese name: Egoma). These acids are the active principles responsible for the cytotoxicity against three cultured human tumor cell lines, HL-60 (leukemia carcinoma), MCF-7 (breast carcinoma), and Hep-G2 (hepatic carcinoma), with half maximal inhibitory concentration (IC₅₀) values of 12–48 μM.     

β-secretase (BACE1) inhibitors from <Emphasis Type="Italic">Perilla frutescens</Emphasis> var. <Emphasis Type="Italic">acuta</Emphasis>

In the course of screening for anti-dementia agents from natural products, two β-secretase (BACE1) inhibitors were isolated from the methanolic extract of Perilla frutescens var. acuta and identified as luteolin (1) and rosmarinic acid (2) with IC₅₀ values of 5.0×10⁻⁷ M and 2.1×10⁻⁵ M, respectively. They inhibited BACE1 in a non-competitive manner with a substrate in Dixon plots, suggesting that they might bind to either β-secretase subsite or to another regulatory site. Ki values of 1 and 2 were 6.2×10⁻⁵ M and 3.9×10⁻⁵ M, respectively. They were less inhibitory against other enzymes such as α-secretase (TACE), acetylcholine esterase (AchE), chymotrypsin, and elastase, indicating that they were relatively specific inhibitors of BACE1.     

Protective effect of the ethanol extract of <Emphasis Type="Italic">Magnolia officinalis</Emphasis> and 4-<Emphasis Type="Italic">O</Emphasis>-methylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity

Magnolol, honokiol, and obovatol are well-known bioactive constituents of the bark of Magnolia officinalis and have been used as traditional Chinese medicines for the treatment of neurosis, anxiety, and stroke. We recently isolated novel active compound (named 4-O-methylhonokiol) from the ethanol extract of Magnolia officinalis. The present study aimed to test two different doses of ethanol extracts of Magnolia officinalis (5 and 10 mg/kg/mouse, p.o., 1 week) and 4-O-methylhonokiol (0.75 and 1.5 mg/kg/mouse, p.o., 1 week) administered for 7 days on memory impairment induced by scopolamine (1 mg/kg body weight i.p.) in mice. Memory and learning were evaluated using the Morris water maze and the step-down avoidance test. Both the ethanol extract of Magnolia officinalis and 4-O-methylhonokiol prevented memory impairment induced by scopolamine in a dose-dependent manner. The ethanol extract of Magnolia officinalis and 4-O-methylhonokiol also dose-dependently attenuated the scopolamine-induced increase of acetylcholinesterase (AChE) activity in the cortex and hippocampus of mice, and inhibited AChE activity in vitro with IC₅₀ (12 nM). This study, therefore, suggests that the ethanol extract of Magnolia officinalis and its major ingredient, 4-O-methylhonokiol, may be useful for the prevention of the development or progression of AD.     

Tolerance and accumulation of lead by species of <Emphasis Type="Italic">Iris</Emphasis> L.

Seedling development, accumulation and distribution of lead (Pb) in Iris lactea var. chinensis (Fisch.) Koidz. and I. tectorum Maxim. were studied using plants grown in sand culture and exposed to 0–10 mmol l⁻¹ concentrations of Pb supplied as Pb(NO₃)₂ for 28 days. A significant reduction in dry weight (dw) of shoots and roots of I. lactea var. chinensis was observed at 6 and 10 mmol l⁻¹, respectively, and a significant reduction in dw of shoots and roots of I. tectorum was observed at 6 mmol l⁻¹. Concentration of Pb in the shoots and roots of I. lacteal var. chinensis exposed to 4 mmol l⁻¹ Pb reached 1,109 μg g⁻¹ and 2,408 μg g⁻¹ dw, respectively. The index of tolerance (IT) of I. lactea var. chinensis among 0–8 mmol l⁻¹ Pb treatments were not significantly different, while those of I. tectorum at 6 mmol l⁻¹ Pb were significantly decreased. The results indicated that I. lactea var. chinensis was more tolerant to Pb than I. tectorum. Sub-cellular localization of Pb in root cells was evaluated using transmission electron microscopy (TEM) and Pb deposits were found along the plasma membrane of some root tip cells of I. lactea var. chinensis treated at 10 mmol l⁻¹ Pb. Deposits of Pd were also observed along the surface, in the root tip cell wall and in the cytoplasm of a few malformed cells of I. tectorum exposed at 10 mmol l⁻¹ Pb treatment. One possible mechanism to explain these observations may be that most cells can maintain normal activities in the plant by sacrificing a small number of cells that accumulate a large amount Pb and show toxicity. Future studies should be designed to test this hypothesis.     

Isolation and identification of antioxidants from Pedilanthus tithymaloides

A bioassay-guided methodology utilizing 2,2-diphenyl-1-picrylhydrazyl (DPPH), the trolox equivalent antioxidant capacity (TEAC), and reducing power assays, as well as an assessment of scavenging properties against O₂^·−, H₂O₂, HOCl, ROO·, ·NO, and ONOO⁻ were used to find the main antioxidant principles of Pedilanthus tithymaloides (Euphorbiaceae), a shrub used in traditional Cuban medicine. The principles were identified as kaempferol 3-O-β-D-glucopyranoside-6′′-(3-hydroxy-3-methylglutarate), quercitrin, isoquercitrin, and scopoletin. The contents of total phenolics and flavonoids were found to be 76.0 ± 4.8 mg of gallic acid equivalents/g extract and 9.8 ± 0.4 mg of rutin equivalents/g extract, respectively.     

Acute and chronic anti-inflammatory properties of the stem bark aqueous and methanol extracts of Sclerocarya birrea (Anacardiaceae)

Sclerocarya birrea is used in folk medicine for the treatment of inflammatory disorders. The effect of the stem bark aqueous and methanol extracts of S. birrea (150 or 300 mg/kg) was evaluated on carrageenan-, histamine- or serotonin-induced paw oedema in rats. The methanol extract of S. birrea (300 mg/kg) being the most active, exhibited a maximum inhibition of 75.45 and 55.31% on carrageenan- and histamine-induced inflammation, respectively. When administered at 300 mg/kg, the methanol extract of S. birrea also exhibited 80.68% inhibition on the 10th day and 54.43% inhibition on the 21st day in formalin- or complete Freund’s adjuvant (CFA)-induced paw oedema in rats. GSH level was significantly increased (75.14%), while MAD level was significantly decreased (31.22%) in the liver of CFA rats treated with S. birrea (300 mg/kg). The results suggest that the anti-inflammatory activity of the aqueous and methanol extracts of S. birrea is due to the inhibition of histamine and prostaglandin pathways and to its antioxidant activity.     

Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior

Rationale and objectives  The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs). Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, α-conotoxin MII (αCtxMII, α₃β₂*, β₃*, α₆*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-β-erythroidine (DHβE, α₄β₂*), and methyllycaconitine (MLA, α₇*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats. Methods  The effects of drugs were studied in rats trained for operant oral self-administration of ethanol (FR = 1). For ethanol deprivation, trained animals were subjected to a period of alcohol deprivation for 10 days. αCtxMII was given directly into the VTA through implanted permanent intracranial cannulae, whereas MEC, DHβE, and MLA were administered systemically. Results  αCtxMII reduced operant ethanol self-administration and blocked the deprivation-induced relapse-like ethanol consumption. MEC reduced operant ethanol self-administration and inhibited the deprivation-induced increase in alcohol consumption. DHβE did not alter ethanol self-administration in the lower-dose range but inhibited ethanol intake at a higher dose (4 mg/kg), although this effect might have been nonspecific. MLA failed to block self-administration of ethanol and relapse-like drinking after deprivation. Conclusions  Our results indicate that nAChRs are involved in the modulation of operant alcohol self-administration and relapse-like alcohol drinking behavior in rats. Our observations support the working hypothesis that systemically active selective ligands for nAChR α₃β₂*, β₃, and/or α₆* receptor subunits might be of therapeutic value for the treatment of alcoholism.     

Discriminative stimulus functions in rats of AM1346, a high-affinity CB1R selective anandamide analog

Objective  To characterize in vivo the high-affinity CB₁ cannabinoid receptor (CB₁R) selective anandamide analog AM1346 [alkoxyacid amide of N-eicosa-tetraenylamine] using drug discrimination. Substitution tests involved Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and R-(+)-methanandamide (mAEA), a metabolically stable analog of anandamide (AEA), as well as the CB₁R antagonist/inverse agonist rimonabant; d-amphetamine and morphine were also examined to assess pharmacological specificity. Materials and methods  Rats were initially trained to discriminate between i.p.-injected vehicle and 3 mg/kg AM1346 (group 3 mg/kg; t′ = 20 min); subsequently, the rats were retrained with 5.6 mg/kg AM1346 (group 5.6 mg/kg; t′ = 20 min). Results  Dose-generalization curves of AM1346, Δ⁹-THC, and mAEA suggested the following order of potency: Δ⁹-THC > AM1346 > mAEA both for rats discriminating between 3 and 5.6 mg/kg AM1346 from vehicle. In group 3 mg/kg, challenge by 1 mg/kg rimonabant resulted in parallel shifts to the right of the dose-generalization curves for Δ⁹-THC and AM1346, suggesting surmountable antagonism. Surmountable antagonism was not demonstrated with rimonabant–mAEA combinations. A long duration of effect was indicated when 3 mg/kg AM1346 was examined after different time intervals following i.p. administration (group 3 mg/kg). The in vivo half-life was close to 5 h. Neither d-amphetamine nor morphine generalized in either of groups 3 mg/kg and 5.6 mg/kg, suggesting pharmacological specificity. Conclusion  Unlike mAEA, the surmountable antagonism between rimonabant and AM1346 showed that the structural features of AEA can be modified to produce novel ligands that reduce the dissociation between the discriminative stimulus and rate decreasing effects of CB₁R agonists derived from an AEA template.     

Neolignans from North American Magnolia Species with Cyclooxygenase 2 Inhibitory Activity

Objectives:  Based upon reported ethnomedicinal use by Native Americans, extracts and pure isolates from leaves and seeds of Magnolia grandiflora, M. virginiana, M. acuminata and M. macrophylla, all native to the Southeastern United States, were investigated for their anti-inflammatory potential against cyclooxygenase 2 (COX-2). Material and methods:  The extracts and pure compounds from Magnolia species were tested for their production of prostaglandin E₂ (PGE₂) using a mouse macrophage (RAW 264.7) assay where cells were stimulated by lipopolysaccharide. Results:  Leaf extracts were moderately active (44–58% inhibition at 50 μg/ml) whereas seed extracts showed significant activity of 54–88% inhibition, respectively. In the seed extract of M. grandiflora, honokiol, magnolol and 4’-O-methylhonokiol strongly inhibited COX-2 (IC₅₀: 1.2–2.0 μg/ml), 3-O-methylmagnolol was moderately active while a new compound was inactive towards COX-2. The neolignans were not cytotoxic to macrophages (RAW 264.7) and kidney fibroblast (VERO) cells in vitro. Conclusions:  The results indicate that the reported ethnomedicinal use of the investigated Magnolia species is in agreement with anti-inflammatory activity of their respective compounds. Received 8 December 2007; accepted 16 January 2009     

Novel potential nonsedating H1 antagonists related to the gauche rotamer of PROS-NH-histamine

On the basis of the most stable stereorotameric (R) forms of ^πNH-histamine (2), the trans (1-TR) and gauche (1-GR) forms have both been reported to be involved in potentiation of H₁-receptors. Apart from the known classic models of H₁-antagonists that mostly belong to 1-TR, a new topographic receptor map for 1-GR has been postulated. Twenty-seven new compounds pertaining to novel nonclassic molecular models related to 1-GR have been postulated as potential nonsedating, less toxic H₁-antagonists. Representative members of the new agents were investigated for H₁-blocking activity by using isolated segments from guinea pig ileum. Many of the tested new compounds exhibited activities comparable to that of acrivastine as a reference nonsedating drug. The C log P values of the new agents were lower than that of acrivastine (4.34), which might indicate decreased tendency to cross the blood–brain barrier. The most pronounced activity was displayed by the 5-substituted aminomethylenepyrimidine-2,4,6-triones (21, 23) since they displayed nearly equal 50% inhibition concentrations (IC₅₀) (6.12 × 10⁻⁶ M) and lower C log P values.     

不同首剂量的牛肺表面活性剂对新生儿呼吸窘迫综合征的疗效

目的 通过分析肺表面活性物质（PS）的不同首剂量对新生儿呼吸窘迫综合征（NRDS）的临床疗效。方法 选取2015年4月—2018年3月在平顶山市第一人民医院收治确诊的NRDS 100例作为研究对象,采用随机数字表法分为70 mg/kg剂量组和100 mg/kg剂量组,每组各50例,分别给予注射用牛肺表面活性剂首剂量70、100 mg/kg出生体质量的治疗剂量。比较两组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率及治疗前后的氧分压（pO₂）、二氧化碳分压（pCO₂）、吸入氧浓度（FiO₂）、平均动脉压（MAP）。结果 治疗后,100 mg/kg组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率均低于70 mg/kg组,差异均有统计学意义（P<0.05）,但两组患儿住院时间相比没有显著差异。两组患儿经过治疗后pO₂、pCO₂、FiO₂、MAP均优于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）,其中100 mg/kg组患儿治疗后pCO₂、FiO₂、MAP明显优于70 mg/kg组,差异有统计学意义（P<0.05）,但治疗后两组pO₂差异无统计学意义。结论 注射用牛肺表面活性剂首剂量100 mg/kg出生体质量应用于新生儿呼吸窘迫综合症,能有效显著缩短患儿的氧疗时间及住院时间,降低住院肺炎发生率,具有较好的临床应用价值。     

Nickel and phosphorous sorption efficiencies, tissue accumulation kinetics and morphological effects on Eichhornia crassipes

The aim of the research was to assess the uptake efficiencies of Ni and P, their distribution in tissues along time and their toxic effects on the internal and external morphologies of Eichhornia crassipes. Aquaria with plants exposed to 1 mg Ni l⁻¹ or 5 mg P l⁻¹ and control were arranged in triplicate. Water and plants (aerial parts and roots) were sampled along 30 days. Ni uptake and tissue bioaccumulation kinetics was significantly faster than that of P. Mean root length, number of leaves, biomass and chlorophyll concentration were negatively affected by Ni, while these parameters were significantly increased by P in comparison with the control. Stele and metaxylem vessel cross-sectional areas (CSA) in the P treatment were significantly lower in comparison with that obtained in the Ni treatment and in control. Metaxylem vessels CSA in plants exposed to Ni were significantly higher while the number of vessels was significantly lower than those obtained in the control. Despite the toxic effects, E. crassipes efficiently accumulated Ni, probably due to the morphological plasticity of its root system.     

辣木叶和种子的提取及急性毒性评价

目的 测试辣木叶和种子的急性毒性以及安全剂量范围。方法 参照《中药药理研究方法学》设计实验,确定中药新药的最大耐受量和急性毒性。结果 小鼠对辣木叶超微粉和辣木叶醇提物的最大耐受量分别为0.4 g/20 g、0.8 g/20 g,辣木叶超微粉和辣木叶醇提物的成人日剂量分别在10 g/50 kg、20 g/50 kg以下为安全剂量。结论 辣木叶为较安全的药食两用植物,其药理作用值得进一步研究。     

Subcellular/tissue distribution and responses to oil exposure of the cytochrome P450-dependent monooxygenase system and glutathione S-transferase in freshwater prawns (Macrobrachium malcolmsonii, M. lamarrei lamarrei)

Subcellular fractions (mitochondrial, cytosolic and microsomal) prepared from the tissues (hepatopancreas, muscle and gill) of freshwater prawns Macrobrachium malcolmsonii and Macrobrachium lamarrei lamarrei were scrutinized to investigate the presence of mixed function oxygenase (MFO) and conjugating enzymes (glutathione-S-transferase, GST). Cytochrome P450 (CYP) and other components (cytochrome b₅; NADPH-cytochrome c (CYP) reductase and NADH-cytochrome c-reductase activities) of the MFO system were predominantly present in the hepatic microsomal fraction of M. malcolmsonii and M. lamarrei lamarrei. The results are in agreement with the notion that monooxygenase system is mainly membrane bound in the endoplasmic reticulum, and that the hepatopancreas is the major metabolic tissue for production of biotransformation enzymes in crustaceans. Further, the prawns were exposed to two sublethal (0.9 ppt (parts per thousand) and 2.3 ppt) concentrations of oil effluent. At the end of 30th day, hydrocarbons and detoxifying enzymes were analysed in the hepatopancreas. The accumulations of hydrocarbon in the tissues gradually increased when exposed to sublethal concentrations of oil effluent and were associated with significantly enhanced levels of cytochrome P450 (180.6±6.34 pmol mg⁻¹ protein (P<0.05 versus control, 136.5±7.1 pmol mg⁻¹ protein) for 2.3 ppt and 305.6±8.5 pmol mg⁻¹ protein (P<0.001 versus control, 132.3±6.8 pmol mg⁻¹ protein] for 0.9 ppt of oil exposed M. malcolmsonii; 150±6.5 pmol mg⁻¹ protein (P<0.01 versus control, 84.6±5.2 pmol mg⁻¹ protein) for 2.3 ppt and 175±5.5 pmol mg⁻¹ protein (P<0.01 versus control, 87.6±5.4 pmol mg⁻¹ protein) for 0.9 ppt of oil exposed M. lamarrei lamarrei), NADPH cytochrome c-reductase activity (14.7±0.6 nmol min⁻¹ mg⁻¹ protein (P<0.05 versus control, 6.8±0.55 nmol min⁻¹ mg⁻¹ protein) for 2.3 ppt and 12.1±0.45 nmol min⁻¹ mg⁻¹ protein (P<0.01 versus control, 6.9±0.42 nmol min⁻¹ mg⁻¹ protein) for 0.9 ppt of oil exposed M. malcolmsonii; 12.5±0.31 nmol min⁻¹ mg⁻¹ protein (P<0.001 versus control, 4.6±0.45 nmol min⁻¹ mg⁻¹ protein) for 2.3 ppt and 9.6±0.32 nmol min⁻¹ mg⁻¹ protein (P<0.01 versus control, 4.9±0.41 nmol min⁻¹ mg⁻¹ protein) for 0.9 ppt of oil exposed M. lamarrei lamarrei) and cytochrome b₅ (124.8±3.73 pmol mg⁻¹ protein (P<0.01 versus control, 76.8±4.2 pmol mg⁻¹ protein) for 2.3 ppt and 115.3±3.86 pmol mg⁻¹ protein (P<0.01 versus control, 76.4±4.25 pmol mg⁻¹ protein) for 0.9 ppt of oil exposed M. malcolmsonii and 110±3.11 pmol mg⁻¹ protein (P<0.01 versus control, 63.7±3.24 pmol mg⁻¹ protein) for 2.3 ppt and 95.3±2.63 pmol mg⁻¹ protein (P<0.01 versus control, 61.4±2.82 pmol mg⁻¹ protein) for 0.9 ppt of oil exposed M. lamarrei lamarrei). The enhanced levels of biotransformation enzymes in oil-exposed prawns demonstrate a well-established detoxifying mechanism in crustaceans, and the response offers the possibility of use as a biomarker for the early detection of oil pollution.Special Issue on Biomarkers of Marine Pollution and Bioremediation     

Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on temporal differentiation: evidence for the involvement of 5-HT2A but not 5-HT3 receptors in interval timing behaviour

Rationale Temporal differentiation refers to animals’ ability to regulate their behaviour during an ongoing interval. Striatal dopaminergic mechanisms are purported to be involved in temporal differentiation, and recent evidence also implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5-HT_2A receptors. There is evidence that 5-HT₃ receptors contribute to the regulation of dopamine release in the basal ganglia; however, it is not known whether 5-HT₃ receptor stimulation can influence temporal differentiation. Objective We examined the effects of a selective 5-HT₃ receptor agonist m-CPBG, a mixed 5-HT_2A/3 receptor agonist quipazine, and selective 5-HT₃ and 5-HT_2A receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal differentiation in a free-operant psychophysical procedure. Methods Twenty-four rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement (0.6 M, 50 μl) was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data [percent responding on B (%B) vs time from trial onset (t)], and quantitative indices of timing performance [T ₅₀ (value of t corresponding to %B=50), Weber fraction, and mean time of switching from A to B, S ₅₀] were derived. Results Quipazine (0.5, 1, and 2 mg kg⁻¹) altered timing performance, dose-dependently reducing T ₅₀ and S ₅₀; m-CPBG (2.5, 5, and 10 mg kg⁻¹) had no significant effect. The effect of quipazine was antagonized by ketanserin (2 mg kg⁻¹), but not by MDL-72222 (1 mg kg⁻¹). Conclusions The present results provide no evidence for the involvement of 5-HT₃ receptors in temporal differentiation and indicate that the effect of quipazine on performance was mediated by 5-HT_2A receptor stimulation. The results are consistent with previous evidence for the involvement of 5-HT_2A receptors in interval timing behaviour. Jonathan Francis Rickard (1977–2003), a gifted and dedicated PhD student, made a major contribution to this work.     

Antitubercular triterpenes and phytosterols from <Emphasis Type="Italic">Pandanus tectorius </Emphasis>Soland. var. <Emphasis Type="Italic">laevis</Emphasis>

Bioassay-guided chromatographic purification of the antitubercular chloroform extract of Pandanus tectorius Soland. var. laevis leaves afforded a new tirucallane-type triterpene, 24,24-dimethyl-5β-tirucall-9(11),25-dien-3-one (1), squalene and a mixture of the phytosterols stigmasterol and β-sitosterol. Microplate Alamar Blue Assay (MABA) showed that 1 inhibited the growth of Mycobacterium tuberculosis H₃₇Rv with a MIC of 64 μg/mL, while squalene and the sterol mixture have MICs of 100 and 128 μg/mL, respectively.