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PubMed1993

Antimicrobial strategies in the prevention of dental caries.

Antimicrobial agents, applied either professionally or delivered from dentifrices or mouthwashes, could reduce caries by controlling plaque formation, suppressing cariogenic species, or by inhibiting bacterial metabolism. Chlorhexidine has proven anticaries activity; other agents might also prevent caries by means of their antiplaque properties. Sugar substitutes stabilize the microflora by reducing the number of acid challenges to plaque and stimulating saliva flow; some also have antimicrobial properties, especially against mutans streptococci. Vaccines have been prepared from purified antigens of mutans streptococci. These vaccines confer protection in non-human primates, but have yet to be tested in a human clinical trial.

Alkaloids↗
PubMed2006

Role of store-operated calcium channels and calcium sensitization in normoxic contraction of the ductus arteriosus.

BACKGROUND: At birth, the increase in oxygen causes contraction of the ductus arteriosus, thus diverting blood flow to the lungs. Although this contraction is modulated by substances such as endothelin and dilator prostaglandins, normoxic contraction is an intrinsic property of ductus smooth muscle. Normoxic inhibition of potassium channels causes membrane depolarization and calcium entry through L-type calcium channels. However, the studies reported here show that after inhibition of this pathway there is still substantial normoxic contraction, indicating the involvement of additional mechanisms. METHODS AND RESULTS: Using ductus ring experiments, calcium imaging, reverse-transcription polymerase chain reaction, Western blot, and cellular electrophysiology, we find that this depolarization-independent contraction is caused by release of calcium from the IP3-sensitive store in the sarcoplasmic reticulum, by subsequent calcium entry through store-operated channels, and by increased calcium sensitization of actin-myosin filaments, involving Rho-kinase. CONCLUSIONS: Much of the normoxic contraction of the ductus arteriosus at birth is related to calcium entry through store-operated channels, encoded by the transient receptor potential superfamily of genes, and to increased calcium sensitization. A clearer understanding of the mechanisms involved in normoxic contraction of the ductus will permit the development of better therapy to close the patent ductus arteriosus, which constitutes approximately 10% of all congenital heart disease and is especially common in premature infants.

Animals↗
PubMed1986

Pharmacological studies on the anti-inflammatory action of phenolic compounds.

The mechanism of the anti-inflammatory action of phenolic compounds was examined using neutrophil chemotaxis. Chemotactic activity of guinea pig peritoneal neutrophils to N-formylmethionyl-leucylphenylalanine (FMLP) was suppressed in a concentration-dependent manner. The order of drug potency in inhibiting the neutrophil chemotaxis was eugenol much greater than thymol greater than guaiacol much greater than phenol. The concentrations of phenolic compounds used in these experiments did not induce lactate dehydrogenase (LDH) release and did not affect neutrophil viability. There was a consistent positive relation between the ID50 of superoxide anion generation in neutrophils and the inhibitory dose for neutrophil chemotaxis by phenolic compounds. A free phenolic hydroxyl group is essential for scavenging oxygen free-radicals and is also essential for inhibiting leukocyte chemotaxis, as was demonstrated in these experiments. These findings suggest that inhibition of leukocyte chemotaxis may be involved in the anti-inflammatory action of phenolic compounds, and that one of the anti-inflammatory actions of phenolic compounds is the prevention of the production of oxygen free-radicals by leukocytes.

Animals↗
PubMed1977

A trial of Lotussin and linctus diphenhydramine in patients wth an irritant cough.

Lotussin and linctus diphenhydramine were compared for efficacy and patient preference in fifty patients suffering from post-infective cough. The trial was a single-blind randomized crossover one which was subjected to sequential analysis based on patient preferences. Under the conditions of the trial there appeared to be a significant difference in favour of Lotussin (p less than 0-01).

Ammonium Chloride↗
PubMed1978

Effect of Vaporub and petrolatum on frequency and amplitude of breathing in children with acute bronchitis.

Transthoracic impedance pneumographs from sixty children suffering from acute bronchitis were studied to investigate the effect of Vaporub on the amplitude and frequency of breathing. The experimental technique consisted of an observation period of 70 minutes after a 3-minute treatment with Vaporub or petrolatum as a control. Before the treatment, after an adaptation period of 20 minutes, the pneumogram was recorded for 10 minutes, after the treatment pneumograms were recorded for 70 minutes. The pneumograph data demonstrated an early increase in amplitude up to 33.0%, with subsequent return to slightly above control for the remaining test period. Such an increase was not observed in the Petrolatum-treated group. Breathing frequency demonstrated a progressive decrease to 19.4% of the pre-treatment value at the end of the test period, while the Petrolatum controls were between + 3.6 to - 4.2% difference. It is concluded that Vaporub treatment results in a change in breathing patterns. This, together with the clinical observation of the children suggests a condition of 'easier breathing'.

Acute Disease↗
PubMed1978

Effect of Vaporub and petrolatum on skin and rectal temperature in children with acute bronchitis.

Fifty-six children, suffering from acute bronchitis were studied. Skin temperature and rectal temperature were simultaneously recorded over a period of 90 minutes after 3-minute rub therapy on chest and back with either Vaporub or its base Petrolatum. A statistically significant increase in skin temperature as compared to the pre-treatment was observed; with Vaporub, however, the increase was 1.1 degrees C on average at the highest point of a large plateau reaching from 30 to 90 minutes after the treatment. Rubbing Petrolatum alone showed 0.2 degrees C on average on the top of the temperature plateau. Rectal temperature did not show significant changes with either therapy. On comparing temperature data of the same type in healthy children, the time course of the temperature elevation (which also was observed in healthy children after Vaporub treatment), was different from that of bronchitic children. In the bronchitic children the temperature rise was still 0.9 degrees C 60 minutes after treatment. In the healthy children after 60 minutes, the temperature elevation was only 0.4 degrees C above the pre-treatment value.

Acute Disease↗
PubMed1978

Effect of Vaporub on the restlessness of children with acute bronchitis.

In this study pneumographs of children with acute bronchitis treated with Vicks Vaporub or Petrolatum were used. Movement artifacts were used as a measure of the so-called "restlessness" of the children. The experimental schedule consisted of a 10-minute phase of recording before a 3-minute treatment with Vaporub or Petrolatum, followed by a 70-minute observation period, during which time pneumograms were also recorded. Thirty-four Vaporub-treated children showed an increase in periods without movement artifacts of up to 213.8%, the Petrolatum controls, twenty-six children, up to 62.4% as compared to the corresponding pre-treatment values. It is concluded that Vaporub is effective in decreasing restlessness in children suffering from acute bronchitis. This effect is quite marked and cannot be due solely to psychological effects of the rub therapy, or to effects of petrolatum without aromatics.

Acute Disease↗
PubMed2003

Monoterpene regulation of Ras and Ras-related protein expression.

Monoterpenes, derived primarily from plants, are products of the isoprenoid biosynthetic pathway and function as chemical messengers with diverse functions. The biochemical bases for these activities are largely undefined. The Ras small GTPase superfamily of proteins consists of isoprenylated proteins that play key roles in signal transduction pathways known to regulate diverse cellular functions. In these studies, we have examined the effects of the monoterpenes on expression of Ras and Ras-related proteins, in the absence and presence of mevalonate depletion. Although prior studies have suggested that monoterpenes inhibit isoprenyl transferases, our studies clearly show that select monoterpenes inhibit up-regulation of Ras and the Ras-related proteins. A structure-activity relationship model for these effects was defined. The ability of monoterpenes to regulate the expression of the Ras-related proteins was found to be independent of effects on cell proliferation or total cellular protein synthesis/degradation. This regulatory function of monoterpenes suggests a role for these plant-derived compounds in altering signal transduction elements.

Cell Division↗
PubMed1999

Sex steroids and odorants modulate gonadotropin-releasing hormone secretion in primary cultures of human olfactory cells.

Olfactory neurons and GnRH neurons share a common origin during development. In the nasal epithelia, GnRH neurons persist throughout fetal life and adulthood. The fate and function of these neurons in vivo have remained unknown. In a previous in vitro study, we isolated, cloned, and propagated primary long term cell cultures from the olfactory neuroepithelium of 8- to 12-week-old human fetuses. These cells expressed both neural proteins as well as olfactory genes and were responsive to odorant stimuli. We now report that these human olfactory cells also express the GnRH gene and protein. Combined HPLC and RIA studies have indicated that these cells release authentic GnRH in spent media. The release of GnRH was time dependent and was positively affected by sex steroids and odorants. Immunohistochemical data demonstrated the presence of sex steroid receptors in these cells. The presence of the alpha- and beta-subtypes of the estrogen receptor was also demonstrated by RT-PCR and Western blot analysis. When the cells were stimulated with increasing concentrations of 17beta-estradiol in the presence of a fixed concentration of progesterone (10(-7) mol/L), the combination of the two steroids induced a 3- to 4-fold increase in GnRH secretion. This stimulatory effect was completely blunted by tamoxifen. Neither 17beta-estradiol nor progesterone was effective when tested separately. Treatment with increasing concentrations of the odorant, l-carvone, induced a time- and dose-dependent dramatic increase in GnRH protein release (1000-fold increase) and gene expression. Repeated application of the stimulus resulted in a progressive lower responsiveness of the cells. To our knowledge, this is the first time that primary cell cultures from human fetal olfactory neuroepithelium have been shown to express and release GnRH. Our results also demonstrate that these cultures, which are sensitive to sex steroids and odorants, can be useful models in the study of the complex array of regulatory factors that finely tune GnRH secretion in humans.

Acyclic Monoterpenes↗
PubMed2001

A near-infrared method for the assay of cineole in eucalyptus oil as an alternative to the official BP method.

Thirty different eucalyptus oil samples were scanned on the FOSS NIRSystems 6500 Rapid Content Sampler using a reflectance vessel as sample presentation method. The cineole content of each sample was determined by the BP method and these reference data were used to construct two calibration equations for cineole content in the oils using Vision software. The mean accuracy for the NIR method differed by 1.01% or less, and the mean bias by +/-0.33% or less, compared with the BP method. Calculation of the 95% confidence intervals for the slope and intercept of plots of NIR predicted values against BP method reference values showed that there was no evidence of fixed or relative systematic errors. Tests for short-term and intermediate repeatability were conducted. The standard deviation was 0.83% w/w or less and the coefficient of variation was 1.11% or less. The confidence intervals for both short-term and intermediate repeatability overlapped with that for the BP method, suggesting that there was no evidence for a difference in values obtained by the BP and NIR methods. The range of cineole contents used in the calibrations was extended by incorporating five samples of eucalyptus oil spiked with cineole, and five samples of two essential oils known to have a lower cineole content than eucalyptus oil, to give a range of 52.5 to 99.0% w/w. The mean accuracy decreased to an error of 1.26% or less and the bias to +/-0.50% or less. Again, confidence intervals suggested there was no evidence for fixed or systematic errors in the NIR calibrations. We propose that NIR spectroscopy could be used as an alternative method for the determination of cineole content in eucalyptus oils.

Cyclohexanols↗
PubMed2001

1,8-cineole protects against liver failure in an in-vivo murine model of endotoxemic shock.

The effects of 1,8-cineole on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg(-1), i.p.) and LPS (5 microg kg(-1), i.p.) greatly elevated serum concentrations of tumour necrosis factor-alpha (TNF-alpha), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg(-1), p.o.) and dexamethasone (1 mg kg(-1), s.c.), 60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-alpha and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPS-induced liver injury through the inhibition of TNF-alpha production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies.

Animals↗
PubMed1995

Percutaneous penetration of fluorescein isothiocyanate-dextrans and the mechanism for enhancement effect of enhancers on the intercellular penetration.

To identify the mechanism involved in the enhancement effect of enhancers on the intercellular penetration of large polar molecules, the skin penetration of fluorescein isothiocyanate (FITC)-dextrans (average molecular weight; 4400, 9400, and 69000 Da) and the lipid removal from the intercellular spaces by enhancers were studied using hairless rat skin. Pretreatment of hairless rat skin with enhancers such as n-octanol (20%), laurocapram (2%), isopropylmyristate (IPM, 20%), oleic acid (5%) and cineol (2%), which are water-immiscible, significantly enhanced the flux of FITC-dextrans, while pretreatment with water-miscible enhancers, i.e. dimethyl sulfoxide (DMSO, 5%) and N-methyl-2-pyrrolidone (NMP) did not increase the flux compared with the control. The penetration of FITC-dextrans was approximately size dependent. n-Octanol, laurocapram, IPM and oleic acid dramatically removed ceramides which are the intercellular lipids, whereas NMP and DMSO partly extracted the sphingolipids. A linear relationship was observed between the flux and removal of ceramides (p < 0.01), indicating that the removal of intercellular lipids would cause dramatic dilations between adherent cornified cells and enhance the penetration through the intercellular pathways. When the penetration of FITC-dextrans through Wistar rat skin was compared with that via hairless rat skin, the steady state flux of FITC-dextrans through Wistar rat skin pretreated with water-immiscible enhancers was 1.2- to 4.9-fold higher, suggesting that the penetration of large polar molecules through follicles may play at least some role in the percutaneous absorption.

Animals↗
PubMed2006

Biotransformation of (-)-menthone by human liver microsomes.

The aim of the current study was to investigate the metabolism of (-)-menthone by liver microsomes of humans. (-)-Menthone (1) was metabolized to (+)-neomenthol (2) (3-reduction) and 7-hydroxymenthone (3) by human liver microsomes. The metabolites formed were analyzed on GC and GC-MS. Kinetic analysis showed that K(m) and V(max) values for the metabolized (-)-menthone to respective (+)-neomenthol and 7-hydroxymenthone by liver microsomes of human sample HG70 were 0.37 mM and 4.91 nmol/min/mg protein and 0.07 mM and 0.71 nmol/min/mg protein.

Biotransformation↗