IntroductionFever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.MethodsWe designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.ResultsWe recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).ConclusionsIn non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.Trial registrationClinicalTrials.gov: NCT00940654

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Microtoena patchoulii (Labiatae) is a perennial herb that grows in southern China. In the present study, the sedative activity of the essential oil of the leaves was evaluated using mice when the volatile oil was administered by inhalation. The inhalation of the oil by mice significantly reduced the spontaneous motor activity. Fractionation of the oil revealed that the main constituents in the oil were 1-octen-3-ol, terpinolene, patchouli alcohol, and methyl salicylate. Each 1-octen-3-ol, terpinolene, or patchouli alcohol significantly reduce the locomotor activity when it was administered singly. However, the essential oil fraction containing both patchouli alcohol and methyl salicylate did not exhibit any effects. It is suggested that methyl salicylate might negate the sedative effect of patchouli alcohol, and that the concentration ratios of the compounds in vapor would play important roles as sedatives. In order to clarify the mechanism of action, the effects of these compounds on caffeine-induced excitation and pentobarbital-induced elongation of sleeping time in mice were tested. Each 1-octen-3-ol or terpinolene reduced the locomotor activity excited by caffeine to those of normal levels. Elongation of sleeping time induced by pentobarbital was further elongated by the inhalation of terpinolene, but not by that of 1-octen-3-ol. It is indicated that terpinolene is a potent suppressor of the central nervous system.

Lantana camara Linn. (Verbenaceae) is used traditionally for its numerous medicinal properties such as antimalarial, antibacterial, anticancer and anti-inflammatory. In the present study, we investigated the chemical composition of essential oil from the leaves of L. camara (LCEO) occurring in the Republic of Benin (West Africa) in comparison with LCEOs from other regions; evaluated its sedative effects in mice via inhalation administration; and identified the compounds responsible for activity. LCEO was extracted by hydrodistillation and chemical analyses of the oil were performed by GC and GC/MS. The oil was dominated by monoterpene hydrocarbons (60.58%) and oxygenated monoterpenes (33.39%), among which sabinene (38.81%) and 1,8-cineole (28.90%) were the most abundant. LCEO administered via inhalation to mice significantly decreased locomotor activity in a dose-dependent manner, mainly at the doses of 0.0004 and 0.04 mg per 400 μL of triethyl citrate (TEC). The oil was fractionated to give two fractions, which were further investigated, and revealed that both sabinene and 1,8-cineole were the principal active compounds. The results of the present study indicated that via inhalation administration, LCEO and its main constituents could be considered as promising candidates for the management of dementia, insomnia, attention deficit hyperactivity disorder and other central nervous system-associated diseases.

Terpinolene is a cyclic monoterpene compound found in some Labiatae herbs. In our previous study, we evaluated the sedative effect of inhaled essential oils of Microtoena patchoulii leaves in mice and isolated terpinolene as an active ingredient. We investigated the structure-activity relationships of terpinolene to identify the structural part essential to its sedative effect. Comparison of terpinolene analog activities showed that a double bond in the side-chain or pi bonds in the six-membered ring play important roles in the sedative effect. In another experiment using olfactory impaired mice, we further revealed that inhaled terpinolene exerted the effect after nasal absorption into the body.

Novel triterpenoid saponins, ilexsaponins B1, B2 and B3, have been isolated from the roots of Ilex pubescens. Degradative and spectroscopic studies have established their structures as shown in formulae 5, 6, and 7. Ilexsaponin B3 was found to possess an activity against experimental hypercholesteremia in mice. Keywords Ilex pubescens; Aquifoliaceae; Mao-dong-qing, the dried roots of Ilex pubescens were first extracted with benzene, followed by MeOH. The MeOH extract was suspended in water, then extracted with benzene, EtOAc, 1-BuOH-H2O successively, and the antihypercholesteremic activity of each fraction was assayed. The BuOH-soluble fraction showed significant activity. From the EtOAc fraction, compounds 1 and 2 were isolated by reversed-phase and normal-phase column chromatography.5) Neither of them showed antihypercholesteremic activity. From the active BuOH-soluble fraction, in addition to compound 1, three new compounds, ilexsaponins B1 (5), B2 (6), and B3 (7), were isolated by chromatography on Diaion HP-20, followed by silica gel chromatography. By the carbon-13 nuclear magnetic

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High-quality perilla leaves are purple on upper and lower surfaces and have a good aroma. The Japanese Pharmacopoeia specifies the content of essential oils in perilla leaves but not that of anthocyanins. Several reports have described the chemical species of anthocyanins in red perilla, but a complete analysis of anthocyanins in perilla has not been reported. In this study, the anthocyanins in the leaves of cultivated and wild species of perilla and those in commercially available perilla herbs were studied. Red perilla and most P. citriodora strains accumulate cyanidin derivatives that differ in the acyl group on the glucose moiety at the 3-O- and 5-O-positions of the anthocyanins. Several strains of P. citriodora contain cyanidin derivatives that are different from those in red perilla and most P. citriodora species. Green perilla and wild species other than P. citriodora do not contain foliar anthocyanins. The anthocyanins in commercially available perilla herbs and natural dyes made from red perilla were in agreement with those in fresh red perilla leaves and most P. citriodora samples. The amounts and types of anthocyanins were not associated with place of cultivation, although some changes occurred due to degradation during storage. These results provide clues regarding the biosynthesis of anthocyanins in perilla and the evolution of red perilla. The characteristics and stability of anthocyanins are discussed.