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Women and tobacco.

Smoking prevalence is lower among women than men in most countries, yet there are about 200 million women in the world who smoke, and in addition, there are millions more who chew tobacco. Approximately 22% of women in developed countries and 9% of women in developing countries smoke, but because most women live in developing countries, there are numerically more women smokers in developing countries. Unless effective, comprehensive and sustained initiatives are implemented to reduce smoking uptake among young women and increase cessation rates among women, the prevalence of female smoking in developed and developing countries is likely to rise to 20% by 2025. This would mean that by 2025 there could be 532 million women smokers. Even if prevalence levels do not rise, the number of women who smoke will increase because the population of women in the world is predicted to rise from the current 3.1 billion to 4.2 billion by 2025. Thus, while the epidemic of tobacco use among men is in slow decline, the epidemic among women will not reach its peak until well into the 21st century. This will have enormous consequences not only for women's health and economic wellbeing but also for that of their families. The health effects of smoking for women are more serious than for men. In addition to the general health problems common to both genders, women face additional hazards in pregnancy, female-specific cancers such as cancer of the cervix, and exposure to passive smoking. In Asia, although there are currently lower levels of tobacco use among women, smoking among girls is already on the rise in some areas. The spending power of girls and women is increasing so that cigarettes are becoming more affordable. The social and cultural constraints that previously prevented many women from smoking are weakening; and women-specific health education and quitting programmes are rare. Furthermore, evidence suggests that women find it harder to quit smoking. The tobacco companies are targeting women by marketing light, mild, and menthol cigarettes, and introducing advertising directed at women. The greatest challenge and opportunity in primary preventive health in Asia and in other developing areas is to avert the predicted rise in smoking among women.

Advertising↗

Stimulatory actions of thymol, a natural product, on Ca(2+)-activated K(+) current in pituitary GH(3) cells.

Drugs that influence the opening of potassium (K(+)) channels and as a consequence cause hyperpolarization of cell membrane possess clinical potential. The large conductance Ca(2+)-activated K(+) (BK) channel is highly selective for K(+). Activation of this channel is Ca(2+)- and voltage-dependent. We have investigated the effects of thymol, a natural product, on ion currents in pituitary GH(3) cells. The patch-clamp technique was used to investigate the effect of thymol (100 microM) in these cells. Thymol reversibly stimulated the Ca(2+)-activated K(+) current with an EC (50) value of 75 microM. In a cell-attached configuration, application of thymol to the bath increased the activity of BK channels. BAPTA (1 mM) attenuated thymol-stimulated channel activity. In an experiment using the inside-out configuration, thymol exposed to the intracellular face of excised patches did not modify the single-channel conductance of these channels whereas it enhanced the channel activity. Neither menthol (100 microM) nor zingerone (100 microM) had an effect on BK-channel activity while AAPH (100 microM) suppressed it significantly. The stimulatory actions of thymol on Ca(2+)-activated K(+) currents may be associated with the underlying cellular mechanisms through which it affects neuronal or neuroendocrine functions.

Animals↗

The influence of verbal labeling on the perception of odors: evidence for olfactory illusions?

Using the definition that an illusion is observed when a stimulus is invariant but context alters its perception, we examined whether verbal context could produce olfactory illusions. To test this effect, we chose five odors with minimally fixed sources and that could be interpreted with various hedonic connotations. The odors were violet leaf, patchouli, pine oil, menthol, and a 1:1 mixture of isovaleric and butyric acids. Subjects individually sniffed each odor at two different sessions separated by one week. At each session an odor was given a different verbal label (either positive or negative) and subjects rated the odors on several hedonic scales and provided perceptual and interpretative responses to them. Results showed that the perception of an odor could be significantly influenced by the label provided for it. We propose that the cases where verbal labels inverted odor perception are the first empirical demonstrations of olfactory illusions.

Adult↗

Photochemical gating of heterologous ion channels: remote control over genetically designated populations of neurons.

Heterologous proteins capable of transducing physical or chemical stimuli into electrical signals can be used to control the function of excitable cells in intact tissues or organisms. Restricted genetically to circumscribed populations of cellular targets, these selectively addressable sources of depolarizing current can supply distributed inputs to neural circuits, stimulate secretion, or regulate force and motility. In an initial demonstration of this principle, we have used elements of a G protein coupled signaling system, the phototransduction cascade of the fruit fly, to sensitize generalist vertebrate neurons to light [Zemelman, B. V., Lee, G. A., Ng, M. & Miesenböck, G. (2002) Neuron 33, 15-22]. We now describe the use of ectopically expressed ligand-gated ion channels as transducers of optical or pharmacological stimuli. When either the capsaicin receptor, TRPV1, the menthol receptor, TRPM8, or the ionotropic purinergic receptor P2X(2) was introduced into hippocampal neurons, the cells responded to pulsed applications of agonist with characteristic sequences of depolarization, spiking, and repolarization. Responses required cognate matches between receptor and agonist, peaked at firing frequencies of approximately 40 Hz, initiated and terminated rapidly, and did not attenuate. Precise dose-response relationships allowed current amplitudes and firing frequencies to be tuned by varying the concentration of ligand. Agonist could be administered either pharmacologically or, in the cases of TRPV1 and P2X(2), optically, through photorelease of the active compounds from the respective "caged" precursors, 4,5-dimethoxy-2-nitrobenzyl-capsaicin and P(3)-[1-(4,5-dimethoxy-2-nitrophenyl)ethyl]-ATP.

Animals↗

2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3.

The transient receptor potential (TRP) superfamily contains a large number of proteins encoding cation permeable channels that are further divided into TRPC (canonical), TRPM (melastatin), and TRPV (vanilloid) subfamilies. Among the six TRPV members, TRPV1, TRPV2, TRPV3, and TRPV4 form heat-activated cation channels, which serve diverse functions ranging from nociception to osmolality regulation. Although chemical activators for TRPV1 and TRPV4 are well documented, those for TRPV2 and TRPV3 are lacking. Here we show that in the absence of other stimuli, 2-aminoethoxydiphenyl borate (2APB) activates TRPV1, TRPV2, and TRPV3, but not TRPV4, TRPV5, and TRPV6 expressed in HEK293 cells. In contrast, 2APB inhibits the activity of TRPC6 and TRPM8 evoked by 1-oleolyl-2-acetyl-sn-glycerol and menthol, respectively. In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes. In dorsal root ganglia neurons, supra-additive stimulations were evoked by 2APB and capsaicin or 2APB and acid. Our data suggest the existence of a common activation mechanism for TRPV1, TRPV2, and TRPV3 that may serve as a therapeutic target for pain management and treatment for diseases caused by hypersensitivity and temperature misregulation.

Animals↗

Functional expression of thermo-transient receptor potential channels in dental primary afferent neurons: implication for tooth pain.

Temperature signaling can be initiated by members of transient receptor potential family (thermo-TRP) channels. Hot and cold substances applied to teeth usually elicit pain sensation. This study investigated the expression of thermo-TRP channels in dental primary afferent neurons of the rat identified by retrograde labeling with a fluorescent dye in maxillary molars. Single cell reverse transcription-PCR and immunohistochemistry revealed expression of TRPV1, TRPM8, and TRPA1 in subsets of such neurons. Capsaicin (a TRPV1 agonist), menthol (a TRPM8 agonist), and icilin (a TRPM8 and TRPA1 agonist) increased intracellular calcium and evoked cationic currents in subsets of neurons, as did the appropriate temperature changes (>43 degrees , <25 degrees , and <17 degrees C, respectively). Some neurons expressed more than one TRP channel and responded to two or three corresponding stimuli (ligands or thermal stimuli). Immunohistochemistry and single cell reverse transcription-PCR following whole cell recordings provided direct evidence for the association between the responsiveness to thermo-TRP ligands and expression of thermo-TRP channels. The results suggest that activation of thermo-TRP channels expressed by dental afferent neurons contributes to tooth pain evoked by temperature stimuli. Accordingly, blockade of thermo-TRP channels will provide a novel therapeutic intervention for the treatment of tooth pain.

Animals↗

Bisandrographolide from Andrographis paniculata activates TRPV4 channels.

Many transient receptor potential (TRP) channels are activated or blocked by various compounds found in plants; two prominent examples include the activation of TRPV1 channels by capsaicin and the activation of TRPM8 channels by menthol. We sought to identify additional plant compounds that are active on other types of TRP channels. We screened a library of extracts from 50 Chinese herbal plants using a calcium-imaging assay to find compounds active on TRPV3 and TRPV4 channels. An extract from the plant Andrographis paniculata potently activated TRPV4 channels. The extract was fractionated further, and the active compound was identified as bisandrographolide A (BAA). We used purified compound to characterize the activity of BAA on certain TRPV channel subtypes. Although BAA activated TRPV4 channels with an EC(50) of 790-950 nm, it did not activate or block activation of TRPV1, TRPV2, or TRPV3 channels. BAA activated a large TRPV4-like current in immortalized mouse keratinocytes (308 cells) that have been shown to express TRPV4 protein endogenously. This compound also activated TRPV4 currents in cell-free outside-out patches from HEK293T cells overexpressing TRPV4 cDNA, suggesting that BAA can activate the channel in a membrane-delimited manner. Another related compound, andrographolide, found in abundance in the plant Andrographis was unable to activate or block activation of TRPV4 channels. These experiments show that BAA activates TRPV4 channels, and we discuss the possibility that activation of TRPV4 by BAA could play a role in some of the effects of Andrographis extract described in traditional medicine.

Andrographis↗

Atopic dermatitis. Clinical spectrum and approach to treatment.

The fact that atopic dermatitis is such a common medical problem underlies the need for better understanding of the basic disease processes and the development of new therapeutic approaches. Infection is now recognized as an important exacerbating factor, and the role of inflammatory and immunologic mediators is receiving scrutiny. The development of potent topical corticosteroids has provided a new component in the therapeutic armamentarium that previously included only cool soaks, menthol or phenol, tars, antihistamines, and combinations of these. Appropriate and aggressive therapy given early seems to offer the patient the best chance for recovery. Patient education is important in minimizing recurrent flares of disease.

Administration, Topical↗

Suitability of the odor stick identification test for the Japanese in patients suffering from olfactory disturbance.

We studied the suitability of the Odor Stick Identification Test for the Japanese (OSIT-J) in patients suffering from olfactory disturbance. In 120 patients with olfactory disturbance (age range 12-85 years) there were statistically significant correlations between the odor identification rate on the OSIT-J, the results of the Japanese standardized olfactory test (T&T olfactometry) and subjective symptom scores. In every patient treated for olfactory disturbance, the OSIT-J reflected the grade of recovery from the olfactory disturbance as determined by means of T&T olfactometry. The odor identification rate on the OSIT-J also correlated significantly with the results of the i.v. Alinamin test. Regarding the rate of correct recognition of odors on the OSIT-J, menthol and curry odors were recognized with a high rate and orange and wood odors with a low rate. Although the OSIT-J includes 13 kinds of odorants, the number of odorants used can be reduced to a minimum of 5 as the results obtained with this reduced form of the OSIT-J also correlated with the results of T&T olfactometry and the subjective symptom scores as well as with the results obtained with the 13-odorant OSIT-J. We conclude that the OSIT-J is suitable not only as a screening test for olfactory disturbance but also for practical use in clinical otorhinolaryngology.

Adolescent↗

Why do women stop smoking during pregnancy? Cigarettes taste and smell bad.

There are high rates of cigarette smoking resumption among women who have quit smoking while pregnant, and the reasons for this are poorly understood. Our purpose in this study was to obtain an in-depth description of the context surrounding smoking behaviors during pregnancy and the first 3 months after women give birth in order to gain insight into the reasons women resume smoking. We used a longitudinal qualitative descriptive approach with in-depth interviews conducted early in pregnancy, at 36 weeks of pregnancy, and 3 months postpartum. Our purposive sample consisted of 15 pregnant women who had stopped smoking without assistance by their first prenatal visit. All women smoked mentholated cigarettes prior to pregnancy and 40% were primiparas. A thematic content analysis of 43 interviews revealed that the majority of women experienced an aversion to the taste or smell of tobacco smoke while pregnant and attributed these sensation changes to being pregnant. The taste and smell of tobacco smoke returned to prepregnancy states postpartum, and by 3 months postpartum 73% of the women had resumed smoking. This physiologic change can be conceptualized as a pregnancy-specific motivation for smoking cessation that can inform our efforts toward relapse prevention.

Adult↗

Pain relief using cutaneous modalities, positioning, and movement.

Positioning, movement, and certain cutaneous modalities may be easily used by all caregivers, including the family, to bring comfort and pain relief to terminally ill patients with pain. For such patients, these techniques are most appropriately used in addition to pharmacologic control of pain. Patients themselves may use some of the cutaneous modalities with minimal assistance from others, thereby promoting a sense of independence. Other techniques may be performed by family and friends, providing them with the assurance that they are assisting a loved one. The techniques presented here can be readily used in the home or hospital setting and are relatively low risk, simple, and inexpensive. This paper presents specific guidelines for patients and caregivers in relation to the use of superficial massage, superficial heat and cold, menthol application to skin, transcutaneous electrical nerve stimulation (TENS), positioning, and movement. Because of their simplicity and ease of use, these techniques tend to be overlooked. However, taking the time to introduce these techniques to patients and families often results in a significant contribution to the comfort of the dying patient.

Cryotherapy↗

Relationship of serum thiocyanate concentrations to smoking characteristics.

Thiocyanate (SCN) concentrations were determined in serum samples from 130 young healthy persons (60 smokers) and related to their smoking and physiologic characteristics. Serum thiocyanate correlated strongly and approximately equally with the number of cigarettes/d X kg of ideal body weight (IBW) (r = 0.748), total nicotine intake in mg/d X kg IBW (r = 0.735), and total tar intake in mg/d X kg IBW (r = 0.731). Multiple linear regression analysis that included these factors as well as sex, marijuana use, menthol, and degree of inhalation only increased the multiple r to 0.803. A more sensitive statistical method (NYBAID) was also used to determine the most significant influences of these variables on serum SCN. The association with depth of inhalation (i.e., smoking versus nonsmoking) was dominant among the relationships considered. The highest SCN levels were exhibited in heavy nicotine users (8.58 +/- 3.00 mg/l), while average users had slightly lower concentrations (6.49 +/- 2.37 mg/l) (p less than 0.03). In nontobacco smokers, those who smoked marijuana several times weekly had higher SCN levels (4.66 +/- 2.16 mg/l) than noncannabis users (2.38 +/- 1.38 mg/l) (p less than 0.03). These studies confirm the utility of serum SCN as an index of smoking rate and demonstrate the role of secondary variables in accounting for the chemical in serum.

Adult↗

Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells.

Rapamycin (rapa)-induced heterodimerization of the FRB domain of the mammalian target of rapa and FKBP12 was used to translocate a phosphoinositide 5-phosphatase (5-ptase) enzyme to the plasma membrane (PM) to evoke rapid changes in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) levels. Rapa-induced PM recruitment of a truncated type IV 5-ptase containing only the 5-ptase domain fused to FKBP12 rapidly decreased PM PtdIns(4,5)P(2) as monitored by the PLCdelta1PH-GFP fusion construct. This decrease was paralleled by rapid termination of the ATP-induced Ca(2+) signal and the prompt inactivation of menthol-activated transient receptor potential melastatin 8 (TRPM8) channels. Depletion of PM PtdIns(4,5)P(2) was associated with a complete blockade of transferrin uptake and inhibition of epidermal growth factor internalization. None of these changes were observed upon rapa-induced translocation of an mRFP-FKBP12 fusion protein that was used as a control. These data demonstrate that rapid inducible depletion of PM PtdIns(4,5)P(2) is a powerful tool to study the multiple regulatory roles of this phospholipid and to study differential sensitivities of various processes to PtdIns(4,5)P(2) depletion.

Adenosine Triphosphate↗

Bromodeoxyuridine-labeled oligonucleotides as tools for oligonucleotide uptake studies.

The mechanisms by which various oligonucleotides (ODNs) and their analogs enter cells are not fully understood. A common technique used in studies on cellular uptake of ODNs is their conjugation with fluorochromes. However, fluorescently labeled ODNs may vary from the parent compounds in charge and hydrophilicity, and they may interact differently with some components of cellular membranes. In this report, we present an alternative method based on the immunofluorescent detection of ODNs with incorporated 5-bromo-2'-deoxyuridine (BrdUrd). Localization of BrdUrd-modified ODNs has been achieved using FITC-labeled anti-BrdUrd antibodies. This technique allowed determination of the differences in cellular uptake of phosphodiester (PO) and phosphorothioate (PS) ODNs and their derivatives conjugated with cholesterol and menthol. The immunocytochemical method also has shown that the cellular uptake of some ODNs may be influenced by specific sequences that are responsible for the formation of higher-order structures.

Animals↗

Plant monoterpenes do not raise plasma high-density-lipoprotein concentrations in humans.

BACKGROUND: Low plasma concentrations of HDLs are associated with an increased risk of coronary artery disease. Two uncontrolled studies suggested that plant monoterpenes may have substantial HDL-cholesterol-elevating activity in humans. Each study used a proprietary mixture of 6 monoterpenes in olive oil. OBJECTIVE: The present study was undertaken to test more rigorously the hypothesis that monoterpenes raise HDL concentrations in men with hypoalphalipoproteinemia. DESIGN: A double-blind, placebo-controlled crossover design was used. Twenty-four men aged 58-68 y (x: 62.3 y) with plasma HDL cholesterol <1.1 mmol/L, plasma triacylglycerols <3.5 mmol/L, and plasma total cholesterol <5.5 mmol/L at recruitment were randomly assigned to 6 capsules daily of a proprietary mixture of 6 monoterpenes in olive oil or 6 capsules daily of olive oil alone for 24 wk, followed by a washout period of 8 wk, and then the alternative capsules for 24 wk. RESULTS: Five men dropped out. In the others, compliance was excellent as judged by capsule counts and urinary menthol glucuronide concentrations. No significant effects were observed on plasma HDL-cholesterol or apolipoprotein A-I concentrations, nor on plasma triacylglycerol, LDL-cholesterol, or apolipoprotein B concentrations. CONCLUSIONS: Plant monoterpenes have no HDL-elevating activity of potential value for coronary artery disease prevention.

Aged↗

Inhibition of azoxymethane-induced neoplasia of the large bowel by 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol).

The inhibitory capacities of four terpenes on azoxymethane (AOM)-induced neoplasia of the large bowel and duodenum was studied in male F344 rats. A complete course of AOM administrations was given and 3 days later the rats were fed a semipurified diet containing 5 mg/g of the test compounds, i.e. 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol), beta-citronellol, (+/-)-linalool and (1R,2S,5R)-(-)-menthol or a corresponding control diet. The experiment was terminated 22 weeks after the last dose of AOM. Under these conditions, nerolidol showed an inhibitory effect on carcinogenesis of the large bowel. The number of rats bearing large bowel neoplasms (adenomas) was reduced from 82% in the controls to 33% in rats fed nerolidol and the number of tumors/rat from 1.5 in the controls to 0.7 in the nerolidol group. A reduction in adenocarcinomas of the duodenum was found but the data are not statistically significant. The effects of nerolidol are of interest in terms of the identification of a new inhibitor of carcinogenesis of the large bowel. The chemical structure of nerolidol suggests the possibility that the compound might have an impact on protein prenylation or some other aspect of the mevalonate pathway, but this remains to be established.

Animals↗

Central processing of odor concentration is a temporal phenomenon as revealed by chemosensory event-related potentials (CSERP).

Chemosensory event-related potentials (CSERP) can be used to examine central nervous odor processing. An important question for understanding odor perception is how different concentrations are processed. In the present study two odors were chosen which activate either the olfactory (linalool) or the trigeminal (menthol) system. Both odors were presented to 11 subjects in four different concentrations. Four subjects had to attend actively to the odors while the others perceived the odors under passive attention. The results showed that increased concentrations of the olfactory stimulus resulted in shorter latencies of the N1 component but did not affect the amplitudes of the CSERP. However, the amplitudes of the stimulus dependent, exogenous components (N1, P2) increased with higher concentrations of the trigeminal stimulus. The amplitude of the late positive complex, which reflects endogenous processes, was usually larger when the odorous stimuli had to be attended to actively. It is concluded that olfactory intensity coding results in a qualitatively different but not in a stronger neuronal response of the human brain.

Adult↗

Olfactory discrimination ability of human subjects for ten pairs of enantiomers.

We tested the ability of human subjects to distinguish between enantiomers, i.e. odorants which are identical except for chirality. In a forced-choice triangular test procedure 20 subjects were repeatedly presented with 10 enantiomeric odor pairs and asked to identify the bottle containing the odd stimulus. We found (i) that as a group, the subjects were only able to significantly discriminate the optical isomers of alpha-pinene, carvone and limonene, whereas they failed to distinguish between the (+)- and (-)-forms of menthol, fenchone, rose oxide, camphor, alpha-terpineol, beta-citronellol and 2-butanol; (ii) marked individual differences in discrimination performance, ranging from subjects who were able to significantly discriminate between 6 of the 10 odor pairs to subjects who failed to do so with 9 of the 10 tasks; (iii) that with none of the 10 odor pairs were the antipodes reported to differ significantly in subjective intensity when presented at equal concentrations; and (iv) that error rates were quite stable and did not differ significantly between sessions, and thus, we observed a lack of learning or training effects. Additional tests of the degree of trigeminality and threshold measurements of the optical isomers of alpha-pinene, carvone and limonene suggest that the discriminability of these three enantiomeric odor pairs is indeed due to differences in odor quality. These findings support the assumption that enantioselective molecular odor receptors may only exist for some but not all volatile enantiomers and thus that chiral recognition of odorants may not be a general phenomenon but is restricted to some substances.

Adult↗