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The mode of action of essential oils from two buchu species (Agathosma betulina and A. crenulata, Rutaceae) from the Cape region of South Africa has been studied on smooth muscle in-vitro using guinea-pig ileum. At high concentration, the oils had an initial spasmogenic activity followed by spasmolysis. The spasmolytic action was post-synaptic, not atropine-like and did not involve adrenoceptor or guanylyl cyclase activation. In the presence of the phosphodiesterase inhibitor rolipram, the spasmolytic action of A. betulina was significantly increased whilst that due to A. crenulata was also increased but not to a significant level. These results suggested a mode of action for the oils involving cyclic adenosine monophosphate. In addition, A. betulina appeared to block calcium channels but this was not seen with A. crenulata, possibly because the initial spasmogenic activity complicated the study of its spasmolytic action. Neither essential oil (10 microL, undiluted) demonstrated antimicrobial action against Enterococcus hirae and Pseudomonas aeruginosa but very low activity was observed against Escherichia coli, Saccharomyces cerevisiae and Staphylococcus aureus, suggesting little potential for these oils as antimicrobial agents/preservatives.
Salvia lavandulaefolia Vahl. (Spanish sage) essential oil and individual monoterpenoid constituents have been shown to inhibit the enzyme acetylcholinesterase in-vitro and in-vivo. This activity is relevant to the treatment of Alzheimer's disease, since anticholinesterase drugs are currently the only drugs available to treat Alzheimer's disease. Other activities relevant to Alzheimer's disease include antioxidant, anti-inflammatory and estrogenic effects. Results of in-vitro tests for these activities are reported here for S. lavandulaefolia extracts, the essential oil and its major constituents. Antioxidant activity (inhibition of bovine brain liposome peroxidation) was found in the EtOH extract of the dried herb (5 mg mL(-1)) and the monoterpenoids (0.1 M) alpha- and beta-pinene and 1,8-cineole. Thujone and geraniol had lower antioxidant effects, while camphor had no antioxidant effects. Possible anti-inflammatory activity (eicosanoid inhibition in rat leucocytes) was found in the EtOH extract (50 microg mL(-1)) and was shown by the monoterpenoids alpha-pinene and geraniol (0.2 mM), but not 1,8-cineole, thujone or camphor. Possible estrogenic activity (via induction of beta-galactosidase activity in yeast cells) was found in the essential oil (0.01 mg mL(-1)) and the monoterpenoid geraniol (0.1-2 mM). 1,8-Cineole, alpha- and beta-pinene and thujone did not exhibit estrogenic activity in this analysis. These results demonstrate that S. lavandulaefolia, its essential oil and some chemical constituents have properties relevant to the treatment of Alzheimer's disease and provide further data supporting the value of carrying out clinical studies in patients with Alzheimer's disease using this plant species.
Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems.
OBJECTIVES: This study compared the prevalence of cigarette smoking and alcohol use among lesbians and bisexual women with that among heterosexual women. METHODS: Logistic regression models were created with data from an extensive member health survey at a large health maintenance organization. Sexual orientation was the primary predictor, and alcohol consumption and cigarette smoking were outcomes. RESULTS: Lesbians and bisexual women younger than 50 years were more likely than heterosexual women to smoke cigarettes and drink heavily. Lesbians and bisexual women aged 20 to 34 reported higher weekly alcohol consumption and less abstinence compared with heterosexual women and older lesbians and bisexual women. CONCLUSIONS: Lesbians and bisexual women aged 20 to 34 years are at risk for alcohol use and cigarette smoking.
We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.
Seven mutations in the amelogenin gene are associated with X-linked amelogenesis imperfecta. These mutations can produce reductions in the amount of enamel and the degree of mineralization. Two families have been identified from western North Carolina exhibiting features of amelogenesis imperfecta, characterized by brown enamel in affected males and interposed vertical bands of normal appearing and brown enamel in presumably heterozygous females. Mutational analysis reveals a C-A mutation in exon 6 at codon 41 of the X-chromosomal amelogenin gene, resulting in a pro-thr change in all individuals having the amelogenesis imperfecta phenotype. This mutation was previously reported in a family with X-linked hypomaturation amelogenesis imperfecta. There is no known relationship between any of the three families but the presence of similar phenotypes and common mutations suggests they may be distantly related. For individuals from all three families, the haplotype for six highly polymorphic loci flanking the amelogenin gene was determined. A common haplotype was demonstrated among two of the three families, suggesting that the mutation may have been inherited from a common ancestor. The finding that the third family had a distinct haplotype may indicate that the C-A mutation at codon 41 represents a mutational hotspot that occurs with greater frequency than other known amelogenin gene mutations. The phenotype resulting from this mutation was highly consistent in affected male members of the same family and between families.
STUDY OBJECTIVE: To determine the outcome of hysteroscopic endometrial resection for dysfunctional uterine bleeding according to women's age. DESIGN: Long-term follow-up by telephone interview (Canadian Task Force classification II-2). SETTING: University-affiliated medical center. Patients. One hundred sixty-nine women with abnormal uterine bleeding unresponsive to conservative medical management. INTERVENTION: Hysteroscopic endometrial resection. MEASUREMENTS AND MAIN RESULTS: Questionnaires were completed for 162 (95.9%) patients with mean +/- SD follow-up of 32 +/- 17 months. The frequency of postoperative complications was not related to age. After ablation, the rate of amenorrhea was significantly higher in 31 women age 50 years or older than in younger women (p <0.001), and also in 72 women age 45 to 49 than in 59 age 44 or less (p <0.05). Complete relief of dysmenorrhea was achieved significantly more often in women age 45 to 49 (p <0.005) and 50 or older (p <0.05) than in those age 44 or younger. Dissatisfaction with the outcome of endometrial resection was uncommon, but most frequent among women age 44 or younger (p <0.10). There was no difference in the proportion of women requiring second ablation or hysterectomy in any age group. CONCLUSION: Significantly higher rates of amenorrhea and complete relief of dysmenorrhea after endometrial resection are achieved in older than in younger women.
Twenty-four women meeting Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for premenstrual dysphoric disorder (PDD) were randomly assigned to a massage therapy or a relaxation therapy group. The massage group showed decreases in anxiety, depressed mood and pain immediately after the first and last massage sessions. The longer term (5 week) effects of massage therapy included a reduction in pain and water retention and overall menstrual distress. However, no long-term changes were observed in the massaged group's activity level or mood. Future studies might examine the effects of a longer massage therapy program on these symptoms. Overall, the findings from this study suggest that massage therapy may be an effective adjunct therapy for treating severe premenstrual symptoms.
Demographic, psychosocial and medical risk factors for postpartum depression (PPD) were studied prospectively in a community cohort of 288 Israeli women. An Edinburgh Postnatal Depression Scale score of > or = 10 at 6 weeks postpartum was the criterion for PPD. Psychosocial risk factors were found to be the most potent. Lack of social support, marital disharmony, depressive symptoms during pregnancy, history of emotional problems and prolonged infant health problems were most predictive of PPD. The major role of psychosocial factors in PPD was similar to that found in other countries. The results were somewhat different for new Russian immigrants. These findings indicate that early identification of women at risk for PPD is feasible, and that consideration should be taken of subgroups that may be at heightened risk, or for whom risk factors play different roles.
This study examined the central effects of rat prepro-TRH 178-199, a peptide with corticotropin release inhibiting activity at the pituitary, on the Porsolt forced swim test (FST) of depressive behavior in rats. Subacute intracerebroventricular administration of prepro-TRH 178-199 dose-responsively reduced floating and increased active behaviors in the FST. Chronic administration of 6 microg/kg prepro-TRH 178-199 decreased floating more than subacute treatment, but there were no significant differences between chronic and subacute treatment effects on active behavior. Biological activity of this peptide resides in the C-terminal fragment as prepro-TRH 178-199 and prepro-TRH 191-199 were equally potent in the FST. These data suggest that endogenous prepro-TRH 178-199 with its antidepressant-like activity might contribute to the etiology or manifestation of depressive behavior.
Lavender (Lavandula angustifolia, P. Miller) is used in aromatherapy as a holistic relaxant and is said to have carminative, antiflatulence and anticolic properties. Its sedative nature, on inhalation, has been shown both in animals and man. Lavender has a spasmolytic activity on guineapig ileum and rat uterus in vitro and it also decreases the tone in the skeletal muscle preparation of the phrenic nerve-diaphragm of rats. As the mechanism of action has not been studied previously, the spasmolytic activity was studied in vitro using a guinea-pig ileum smooth muscle preparation. The mechanism of action was postsynaptic and not atropine-like. The spasmolytic effect of lavender oil was most likely to be mediated through cAMP, and not through cGMP. The mode of action of linalool, one of lavender's major components, reflected that of the whole oil. The mode of action of lavender oil resembled that of geranium and peppermint oils.
BACKGROUND: Attempts at smoking cessation have been correlated with severe withdrawal symptoms, including intense cigarette cravings, anxiety, and depressed mood. Massage therapy has been shown to reduce anxiety and stress hormones and improve mood. METHOD: Twenty adult smokers (M age = 32.6) were randomly assigned to a self-massage treatment or a control group. The treatment group was taught to conduct a hand or ear self-massage during three cravings a day for 1 month. RESULTS: Self-reports revealed lower anxiety scores, improved mood, and fewer withdrawal symptoms. In addition, the self-massage group smoked fewer cigarettes per day by the last week of the study. CONCLUSIONS: The present findings suggest that self-massage may be an effective adjunct treatment for adults attempting smoking cessation to alleviate smoking-related anxiety, reduce cravings and withdrawal symptoms, improve mood, and reduce the number of cigarettes smoked.
Consistent with its putative anxiogenic actions, administration of the benzodiazepine receptor partial inverse agonist FG 7142 has been shown to potentiate defensive-like cardiovascular reactivity to an acoustic stimulus in the rat, an effect that appears to be mediated by the basal forebrain cholinergic system. The present studies tested the hypothesis that the basal forebrain cholinergic projections to the medial prefrontal cortex, an area that has been implicated in both anxiety and autonomic control, may be a relevant pathway underlying this response potentiation. Infusions of the muscarinic receptor agonist carbachol into the medial prefrontal cortex, but not into the lateral prefrontal cortex or the basolateral amygdala, mimicked the effects of systemically administered FG 7142 on the cardioacceleratory response. Infusions of the muscarinic antagonist atropine blocked this effect, as well as the response-potentiating actions of FG 7142. The effects of FG 7142 were also blocked by lesions of the cholinergic inputs to the medial prefrontal cortex produced by local infusions of the immunotoxin 192 immunoglobulin G-saporin into this area. These findings indicate that cholinergic activation of the medial prefrontal cortex is sufficient to enhance the cardioacceleratory defensive response, and that cholinergic inputs to the medial prefrontal cortex are necessary for the response-potentiating effects of FG 7142. These results are consistent with a recent neurobiological model of anxiety and autonomic control that attributes the enhanced processing of anxiety-related stimuli and contexts to increases in activity in cortical cholinergic inputs.
Although the psychosocial concomitants of early-stage breast cancer have been well-documented, the relationship between cancer recurrence and quality of life remains less clear. We conducted a prospective, longitudinal study in order to clarify the relationship between recurrent cancer and quality of life, and to determine predictors of quality of life following recurrence. Sixty-nine women with recurrent breast cancer completed questionnaires assessing multiple components of quality of life at three time points: prior to recurrence, immediately after the diagnosis of recurrence, and at follow-up 6 months later. Perceptions of overall quality of life, general health status, emotional, social, and physical functioning were poorer immediately following the diagnosis of recurrence than they had been prior to recurrence. These women also evidenced significant improvement in several domains of quality of life between initial recurrence and follow-up; nonetheless, most areas of quality of life were impaired compared to pre-recurrence. Self-reported physical symptoms were a strong predictor of post-recurrence ratings of overall quality of life. These data suggest that the recurrence of breast cancer is associated with significant changes in quality of life. Quality of life did not progressively deteriorate, however, attesting to the resilience of women coping with this major stressor. These data shed light on issues of potential importance to patients managing this serious illness and may have implications for health-care professionals working with this population.
This study examined behaviors of intrusive/depressed versus withdrawn/depressed mothers and their one-year-old infants during a structured teaching interaction. Group comparisons revealed that intrusive/depressed mothers showed more positive responses, more demonstrating toys, and more physical guidance, and their infants demonstrated less toy manipulation. Withdrawn/depressed mothers maintained infant play more frequently and showed more restricted affect, and their infants demonstrated less affective behavior, both positive and negative. These findings suggested that exposure to depressed mothers' nonoptimal interaction styles represents different types of risk to infants' cognitive and affective development.
PURPOSE: Radical cystectomy for bladder cancer is associated with many changes in bodily function with sexual and urinary dysfunction most prevalent. However, little research has been done on how efforts to improve erectile function relate to quality of life. Also, the psychological benefits associated with continent urinary diversion have not been fully explored. We compared long-term quality of life outcomes among 3 urinary diversion groups, and between patients who had and had not received an inflatable penile prosthesis. MATERIALS AND METHODS: The 224 participating patients completed 4 self-reporting questionnaires, including the profile of mood states, and adapted versions of the sexual history form, body image dissatisfaction scale and quality of life questionnaire. We compared self-reports of emotional distress, global quality of life, sexuality, body image dissatisfaction, urinary diversion problems, and problems with social, physical and functional activities in patients with advanced bladder cancer who underwent urinary diversion, including an ileal conduit in 25, cutaneous Kock pouch in 93 and urethral Kock pouch in 103. Patients who had or had not received an inflatable penile prosthesis after cystectomy were also compared in regard to quality of life variables. RESULTS: Regardless of type of urinary diversion the majority of patients reported good overall quality of life, little emotional distress and few problems with social, physical or functional activities. Problems with urinary diversion and sexual functioning were identified as most common. After controlling for age analysis of variance showed no significant differences among urinary diversion subgroups in any quality of life area. However, t tests controlling for age indicated that penile prosthesis placement was significantly associated with better sexual function and satisfaction. CONCLUSIONS: Quality of life appears good in these long-term survivors of advanced bladder cancer. The type of urinary diversion does not appear to be associated with differential quality of life. Findings suggest that physicians may wish to discuss urinary diversion problems and sexual dysfunction as long-term correlates of radical cystectomy for bladder cancer. Furthermore, they may also wish to discuss the option of erectile aids in men with erectile dysfunction after cystectomy.
Twenty-six pregnant women were assigned to a massage therapy or a relaxation therapy group for 5 weeks. The therapies consisted of 20-min sessions twice a week. Both groups reported feeling less anxious after the first session and less leg pain after the first and last session. Only the massage therapy group, however, reported reduced anxiety, improved mood, better sleep and less back pain by the last day of the study. In addition, urinary stress hormone levels (norepinephrine) decreased for the massage therapy group and the women had fewer complications during labor and their infants had fewer postnatal complications (e.g., less prematurity).