Caralluma europaea (Guss.) N.E.Br.: Anti-Inflammatory, Antifungal, and Antibacterial Activities against Nosocomial Antibiotic-Resistant Microbes of Chemically Characterized Fractions.

Caralluma europaea (Guss.) N.E.Br.: (C. europaea) is a wild medicinal plant belonging to the family Apocynaceae. It is commonly used in traditional medicines for treating several diseases. The present work aims to evaluate the anti-inflammatory, antibacterial, and antifungal potentials of C. europaea fractions including hydro ethanol (ET CE), n-butanol (But CE), and polyphenol (Poly CE). The chemical composition of hydroethanol, n-butanol, and polyphenol-rich fractions from C. europaea were determined using GC-MS after silylation. The anti-inflammatory effect of hydroethanol, n-butanol, and polyphenol-rich fractions was studied by carrageenan-induced paw edema. Antibacterial and antifungal activities of hydroethanol, n-butanol, and polyphenol-rich fractions against Gram-positive bacteria, Gram-negative bacteria, and yeasts were assessed using the disc diffusion and micro-dilution assays. The findings of the chemical characterization affirmed the presence of interesting bioactive compounds in C. europaea fractions. The polyphenol-rich fraction was the best inhibitor of edema by75.68% after 6 h of treatment. The hydroethanol fraction was the most active against both bacteria and yeasts. This study contributes to society as it provides potential bioactive compounds in C. europaea extract, which may help in fighting nosocomial antibiotic-resistant microbes.

Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session.

OBJECTIVES: To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure. DESIGN: Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure. SETTINGS: Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper. PARTICIPANTS: 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls. OUTCOME MEASURES: 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels. RESULTS: MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls. CONCLUSIONS: MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.

Simultaneous multiagent hyperpolarized (13)C perfusion imaging.

PURPOSE: To demonstrate simultaneous hyperpolarization and imaging of three (13)C-labeled perfusion MRI contrast agents with dissimilar molecular structures ([(13)C]urea, [(13)C]hydroxymethyl cyclopropane, and [(13)C]t-butanol) and correspondingly variable chemical shifts and physiological characteristics, and to exploit their varying diffusibility for simultaneous measurement of vascular permeability and perfusion in initial preclinical studies. METHODS: Rapid and efficient dynamic multislice imaging was enabled by a novel pulse sequence incorporating balanced steady state free precession excitation and spectral-spatial readout by multiband frequency encoding, designed for the wide, regular spectral separation of these compounds. We exploited the varying bilayer permeability of these tracers to quantify vascular permeability and perfusion parameters simultaneously, using perfusion modeling methods that were investigated in simulations. "Tripolarized" perfusion MRI methods were applied to initial preclinical studies with differential conditions of vascular permeability, in normal mouse tissues and advanced transgenic mouse prostate tumors. RESULTS: Dynamic imaging revealed clear differences among the individual tracer distributions. Computed permeability maps demonstrated differential permeability of brain tissue among the tracers, and tumor perfusion and permeability were both elevated over values expected for normal tissues. CONCLUSION: Tripolarized perfusion MRI provides new molecular imaging measures for specifically monitoring permeability, perfusion, and transport simultaneously in vivo.

Effect of Bacopasides on acquisition and expression of morphine tolerance.

Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance.

Effects of laserneedle acupuncture on olfactory sensitivity of healthy human subjects: a placebo-controlled, double-blinded, randomized trial.

The aims of the present study were to investigate the influence of laserneedle acupuncture on olfactory sensitivity and to examine whether the attitude towards laserneedle acupuncture affects the outcome. Olfaction was tested repeatedly on two days using the olfactory detection threshold subtest of the Sniffin' Sticks test battery in sixty-four healthy subjects of which 32 showed a positive attitude towards the effects of laserneedle acupuncture and 32 were sceptic about its effects. Testing was accomplished three times on day one (T1 = 0 min, T2 = 35 min, T3 = 105 min) without laserneedle acupuncture and on day two (T1* = 0 min, T2* = 35 min, T3* = 105 min) when the subjects were randomized in a non-stimulation (placebo) and a stimulation (laserneedle acupuncture) group. Stimulation or non-stimulation was conducted in a double-blinded design. Following laserneedle acupuncture a significant decrease in olfactory detection thresholds was observed at both, T2* and T3*, whereas no significant changes were found in the baseline or placebo group. Effects of laserneedle acupuncture on the olfactory detection threshold did not differ between sceptic and non-sceptic subjects. In conclusion, laserneedle acupuncture is an effective method to improve olfactory sensitivity after one session of stimulation for at least one hour, independently of the attitude of subjects towards the stimulation method.

Olfactory detection thresholds and pleasantness of a food-related and a non-food odour in hunger and satiety.

The primary aim of this study was to investigate whether olfactory detection thresholds are dependent on different states of satiety. Using the threshold test of the Sniffin' Sticks test battery (single-staircase, three alternative forced choice procedure), sensitivity to a non-food odour (n-butanol) and a food-related odour (isoamyl acetate) was investigated. Twenty-four healthy, female subjects (mean age 24.2 years, SD 2.7 years) with normal olfactory function performed the tests when hungry and when satiated. Additionally, they rated their emotional condition, arousal, alertness as well as the intensity and pleasantness of both odorants. No significant change in the detection thresholds for the non-food odour n-butanol, but a significant change in detection threshold for the food-related odour isoamyl acetate was found. The detection threshold for isoamyl acetate was significantly lower in the state of satiety compared to the hungry condition. As expected, the perceived pleasantness of isoamyl acetate was significantly lower in satiety. In summary, the results indicate that in our experimental setting the actual state of satiety has effects on detection thresholds of a food-related odour, but not of a non-food odour. Interestingly, the higher sensitivity was found during the state of satiety challenging the current hypothesis that control of food intake is supported by a decrease in sensitivity to food odours. Instead our findings that satiety decreases the pleasantness of a food-related odour support the hypothesis that both odour threshold as well as pleasantness play an important role in the control of food intake.

Antiviral profile of Nyctanthes arbortristis L. against encephalitis causing viruses.

The ethanolic extracts, various fractions and two pure compounds isolated from the plant N. arbortris were tested against Encephalomyocarditis Virus (EMCV) and Semliki Forest Virus (SFV). Pronounced in vitro virus inhibitory activity was observed with the ethanolic and n-butanol fractions as well as with the pure compounds arbortristoside A and arbortristoside C. In addition, ethanolic extracts and n-butanol fraction protected EMCV infected mice to the extent of 40 and 60% respectively against SFV at a daily dose of 125 mg/kg body weight.

Allosteric modulation of a neuronal K+ channel by 1-alkanols is linked to a key residue in the activation gate.

The selective inhibition of neuronal Shaw2 K+ channels by 1-alkanols is conferred by the internal S4-S5 loop, a region that also contributes to the gating of voltage-gated K+ channels. Here, we applied alanine scanning mutagenesis to examine the contribution of the S5 and S6 segments to the allosteric modulation of Shaw2 K+ channels by 1-alkanols. The internal section of S6 is the main activation gate of K+ channels. While several mutations in S5 and S6 modulated the inhibition of the channels by 1-butanol and others had no effect, a single mutation at a key site in S6 (P410A) converted this inhibition into a dramatic dose-dependent potentiation (approximately 2-fold at 15 mM and approximately 6-fold at 50 mM). P410 is the second proline in the highly conserved PVP motif that may cause a significant alpha-helix kink. The P410A currents in the presence of 1-butanol also exhibited novel kinetics (faster activation and slow inactivation). Internal application of 15 mM 1-butanol to inside-out patches expressing P410A did not significantly affect the mean unitary currents (approximately 2 pA at 0 mV) or the mean open time (5-6 ms) but clearly increased the opening frequency and open probability (approximately 2- to 4-fold). All effects displayed a fast onset and were fully reversible upon washout. The results suggest that the allosteric modulation of the Shaw2 K+ channel by 1-alkanols depends on a critical link between the PVP motif and activation gating. This study establishes the Shaw2 K+ channel as a robust model to investigate the mechanisms of alcohol intoxication and general anesthesia.

[Comparative assessment of enteral and inhaled n-butanol in laboratory animals]. / Sravnitel'naia otsenka toksichnosti n-butanola pri énteral'nom i ingaliatsionnom postuplenii v organizm laboratornykh zhivotnykh.

Enteral and inhaled n-butanol given to albino rats was tested for toxicity in 2 series of subacute 30-day toxicological experiments. Enteral and inhalant administration caused membrano-, hepato-, adrenotoxic effects, and inhalant administration produced neurotoxic ones. The threshold dose was 0.2 mg/kg, the maximum ineffective one was 0.04 mg/kg. The threshold concentration was not established in the experiment. The less than 95% confidence limits of reference points (BMDL and BMCL), which cause a 10%-increase in the frequency of adverse reactions (blood catalase induction), were 0.052 mg/kg with enteral administration and 0.18 mg/m3 (0.076 mg/kg) on inhalation. The comparative toxicity coefficient (BMDLent/BMDLinh = 0.68) for n-butanol suggests that there is no difference in toxicity on different routes of administration.

Development of a continuous respiration olfactometer for odorant delivery synchronous with natural respiration during recordings of brain electrical activity.

The continuous respiration olfactometer (CRO) was designed as a respiration-synchronous method for delivering odorants during recordings of brain electrical activity, providing control and monitoring of the timing of the delivery as well as the quantities of odorant involved. The CRO incorporates a purpose-built electronic system designed with very specific temporal and quantitative characteristics, and is composed of four main parts: the respiratory monitoring apparatus, the odorant/air delivery system, the serial interface device and the respiratory monitoring software. Tests were undertaken to determine the performance of the system with reference to the accuracy and precision of timing and control of odorant delivery. Tests were also undertaken to determine the effects of variations in natural respiration between subjects on the capability of the respiratory monitoring system, using a group of 50 subjects, to test the success of a variable gain control to optimize the range of the digitized respiratory output. The delivery system was able to provide information concerning quantities of air or odorant delivered, and the stimulus timing information required for integration with neurophysiological recording techniques.

Acute upregulation of blood-brain barrier glucose transporter activity in seizures.

Brain extraction of (18)F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) was significantly higher in pentylene tetrazole (PTZ)-treated rats (32 +/- 4%) than controls (25 +/- 4%). The FDG permeability-surface area product (PS) was also significantly higher with PTZ treatment (0.36 +/- 0.05 ml. min(-1). g(-1)) than in controls (0.20 +/- 0.06 ml. min(-1). g(-1)). Cerebral blood flow rates were also elevated by 50% in seizures. The internal carotid artery perfusion technique indicated mean [(14)C]glucose clearance (and extraction) was increased with PTZ treatment, and seizures increased the PS by 37 +/- 16% (P < 0.05) in cortical regions. Because kinetic analyses suggested the glucose transporter half-saturation constant (K(m)) was unchanged by PTZ, we derived estimates of 1) treated and 2) control maximal transporter velocities (V(max)) and 3) a single K(m). In cortex, the glucose transporter V(max) was 42 +/- 11% higher (P < 0.05) in PTZ-treated animals (2.46 +/- 0.34 micromol. min(-1). g(-1)) than in control animals (1.74 +/- 0.26 micromol. min(-1). g(-1)), and the K(m) = 9.5 +/- 1.6 mM. Blood-brain barrier (BBB) V(max) was 31 +/- 10% greater (P < 0.05) in PTZ-treated (2.36 +/- 0. 30 micromol. min(-1). g(-1)) than control subcortex (1.80 +/- 0.25 micromol. min(-1). g(-1)). We conclude acute upregulation of BBB glucose transport occurs within 3 min of an initial seizure. Transporter V(max) and BBB glucose permeability increase by 30-40%.