No abstract

No abstract

No abstract

1 cis-9,10-octadecenoamide (`oleamide') accumulates in CSF on sleep deprivation. It induces sleep in animals (the trans form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues. 2 Twenty mM cis-oleamide (but not trans) reversibly enhanced GABA A currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks. 3 cis-oleamide stereoselectively blocked veratridine-induced (but not K + -induced) depolarisation of mouse synaptoneurosomes (IC 50 , 13.9 mM). 4 The cis isomer stereoselectively blocked veratridine-induced (but not K + -induced) [ 3 H]-GABA release from mouse synaptosomes (IC 50 , 4.6 mM). 5 At 20 mM cis-oleamide, but not trans, produced a marked inhibition of Na + channel-dependent rises in intrasynaptosomal Ca 2+ . 6 The physiological signi®cance of these observations was examined by isolating Na + spikes in cultured pyramidal neurones. Sixty-four mM cis-oleamide did not signi®cantly alter the amplitude, rate of rise or duration of unitary action potentials (1 Hz). 7 cis-Oleamide stereoselectively suppressed sustained repetitive ®ring (SRF) in these cells with an EC 50 of 4.1 mM suggesting a frequency-or state-dependent block of voltage-gated Na + channels. 8 Oleamide is a stereoselective modulator of both postsynaptic GABA A receptors and presynaptic or somatic voltage-gated Na + channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics. 9 Oleamide may represent an endogenous modulator for drug receptors and an important regulator of arousal.

The biochemical mechanisms underlying the increased toxicity of several plant essential oils (thymol, eugenol, pulegone, terpineol, and citronellal) against fourth instar of Aedes aegypti L. when exposed simultaneously with piperonyl butoxide (PBO) were examined. Whole body biotransformational enzyme activities including cytochrome P450-mediated oxidation (ethoxyresorufin O-dethylase [EROD]), glutathione S-transferase (GST), and beta-esterase activity were measured in control, essential oil-exposed only (single chemical), and essential oil + PBO (10 mg/liter) exposed larvae. At high concentrations, thymol, eugenol, pulegone, and citronellal alone reduced EROD activity by 5-25% 16 h postexposure. Terpineol at 10 mg/liter increased EROD activity by 5 +/- 1.8% over controls. The essential oils alone reduced GST activity by 3-20% but PBO exposure alone did not significantly affect the activity of any of the measured enzymes. All essential oils in combination with PBO reduced EROD activity by 58-76% and reduced GST activity by 3-85% at 16 h postexposure. This study indicates a synergistic interaction between essential oils and PBO in inhibiting the cytochrome P450 and GST detoxification enzymes in Ae. aegypti.

Thymol readily penetrates the cuticle and interferes with flight muscle and central nervous function in the blowfly. The similarity of the action of thymol and GABA suggests that this terpenoid acts centrally in blowflies by mimicking or facilitating GABA action.

BackgroundThe present study was aimed to evaluate whether IgG, IgM and IgA antibodies levels detected against a novel Mycobacterium tuberculosis polyprotein 38 F-64 F (with 38 F being the abbreviation for 38kD-ESAT6-CFP10 and 64 F for Mtb8.4-MPT64-TB16.3-Mtb8) are suitable for diagnosing active tuberculosis, and for monitoring the efficacy of chemotherapy on TB patients.MethodsIn this study, a total of 371 active TB patients without treatment were selected and categorized into S+/C+ group (n = 143), S-/C+ group (n = 106) or S-/C- group (n = 122). A series of serum samples were collected from 82 active TB patients who had undergone anti-TB chemotherapy for 0–6 months at one month interval. Humoral responses (IgG, IgM and IgA) were determined for the novel Mycobacterium tuberculosis polyprotein using indirect ELISA methods in all of serum samples.ResultsFor S+/C+, S-/C+ and S-/C- active tuberculosis patients before anti-TB chemotherapy, the sensitivities of tests based on IgG were 65.7%, 46.2% and 52.5% respectively; the sensitivities based on IgM were 21.7%, 24.5% and 18.9%; and the sensitivities based on IgA were 25.2%, 17.9% and 23.8%. By combination of three isotypes, for all active tuberculosis patients, the test sensitivity increased to 70.4% with the specificity being 91.5%. After anti-TB chemotherapy, there were no significant differences between groups with different courses of anti-TB chemotherapy.ConclusionsThe novel Mycobacterium tuberculosis polyprotein 38 F-64 F represents potential antigen suitable for measuring IgG, IgM and IgA antibodies. However, the serodiagnostic test based on the 38 F-64 F polyprotein appears unsuitable for monitoring the efficacy of chemotherapy.

1. We examine the sensitivity of GABA(A) and glycine receptors (same ionotropic superfamily) to oleamide. We address subunit-dependence/modulatory mechanisms and analogies with depressant drugs. 2. Oleamide modulated human GABA(A) currents (alpha(1)beta(2)gamma(2L)) in oocytes (EC(50), 28.94+/-s.e.mean of 1.4 microM; Maximum 216%+/-35 of control, n=4). Modulation of human alpha1 glycine homo-oligomers (significant), was less marked, with a lower EC(50) (P<0.05) than GABA receptors (EC(50), 22.12+/-1.4 microM; Maximum 171%+/-30, n=11). 3. Only the hypnogenic cis geometric isomer enhanced glycine currents (without altering slope or maximal current, it reduced the glycine EC(50) from 322 to 239 microM: P<0.001). Modulation was not voltage-dependent or associated with a shift in E(r). 4. beta 1 containing GABA(A) receptors (insensitive to many depressant drugs) were positively modulated by oleamide. Oleamide efficacy was circa 2x greater at alpha(1)beta(1)gamma(2L) than alpha(1)beta(2)gamma(2L) (P=0.007). Splice variation in gamma subunits did not alter oleamide sensitivity. 5. cis-9,10-Octadecenoamide had no effect on the equilibrium binding of [(3)H]-muscimol or [(3)H]-EBOB to mouse brain membranes. It does not directly mimic GABA, or operate as a neurosteroid-, benzodiazepine- or barbiturate-like modulator of GABA(A)-receptors. 6. The transport of [(3)H]-GABA into mouse brain synaptoneurosomes was unaffected by high micromolar concentrations of cis-9,10-octadecenoamide. Oleamide does not enhance GABA-ergic currents or prolong IPSCs by inhibiting GABA transport. 7. Oleamide is a non-selective modulator of inhibitory ionotropic receptors. The sleep lipid exerts its effects indirectly, or at a novel recognition site on the GABA(A) complex.