Managing patients with vulvovaginal candidiasis

Epidemiologic studies have demonstrated a continuing increase in the prevalence of vulvovaginal candidiasis. Although in the past most of these infections were caused by Candida albicans, an increasing percentage are caused by non-albicans Candida species that are less sensitive to the most frequently used antifungal agents. An accurate diagnosis of these infections and the subsequent choice of the most appropriate therapy can only be made after a thorough evaluation of the patient. Successful treatment of vulvovaginal candidiasis is dependent on compliance with therapy; thus, the treatment regimen chosen should fit the patient's daily lifestyle. Newer single-dose regimens offer the option of completing therapy with a single treatment for most patients with uncomplicated vaginal candidiasis. Use of topical agents avoids the potential systemic adverse effects and drug interactions that have been noted with oral antifungals. Patient education and support can also enhance satisfaction with the treatment plan and promote compliance.     

Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

Nicotine-stimulated release of [3H]norepinephrine from fetal rat locus coeruleus cells in culture

Acute nicotine administration stimulated [3H]norepinephrine ([3H]NE) release from cultured fetal locus coeruleus (LC) cells. The effect was concentration dependent, with an EC50 of 0.9 microM, and was abolished by removal of calcium from, or addition of tetrodotoxin (500 nM) to, the assay buffer. Other nicotinic receptor agonists stimulated [3H]NE release, with the rank order of potency being (+)-epibatidine > (-)-nicotine > 1,1-dimethyl-4-phenylpiperazinium (DMPP). Whereas (-)-nicotine and (+/-)-epibatidine exhibited equal maximal responses, DMPP was a partial agonist and (-)-cytisine had no agonist activity. Nicotine-stimulated release of [3H]NE was blocked by nicotinic receptor antagonists, with an order of potency of mecamylamine > lobeline > cytisine > methyllycaconitine > dihydro-beta-erythroidine. The pharmacological profile of this nicotinic receptor is largely consistent with that described previously for an alpha4beta2 subunit combination, although discrepancies in the efficacies of agonists were observed. No additivity in NMDA- and nicotine-stimulated [3H]NE release was observed, suggesting a common signal transduction mechanism. However, the pharmacological characteristics of MK-801 blockade of nicotine-induced responses were not consistent with those of an NMDA receptor. We therefore conclude that nicotine directly releases [3H]NE from LC cells and does not act indirectly via activation of glutamate release.     

Honey revisited: a reappraisal of honey in pre-industrial diets

In pre-industrial times, honey was the main source of concentrated sweetness in the diets of many peoples. There are no precise figures for per capita consumption during most periods in history because honey was part of either a hunter-gatherer or subsistence economy. Until now, historians and food writers have proposed that it was a scarce commodity available only to a wealthy few. We do know, however, that in a cash economy honey was sold in large units (gallons and even barrels) and it was present in such abundance that mead, made from honey, was a common alcoholic drink. A reappraisal of the evidence from the Stone Age, Antiquity, the Middle Ages and early Modern times suggests that ordinary people ate much larger quantities of honey than has previously been acknowledged. Intakes at various times during history may well have rivalled our current consumption of refined sugar. There are implications therefore for the role of sugar in modern diets. Refined sugar may not have displaced more nutrient-rich items from our present-day diets but only the nutritionally comparable food, honey.     

Dental plaque flora of the dog with reference to fastidious and anaerobic bacteria associated with bites

Animal bite wounds are amongst the most common types of traumatic injuries in humans. The organisms isolated from these wounds generally reflect the oral flora of the biting animal, and may be fastidious in nature and difficult to identify. This study was undertaken to determine the prevalence of Eikenella corrodens, Actinobacillus actinomycetemcomitans, Porphyromonas and Prevotella spp. in supragingival dental plaque collected from the right maxillary canine and carnassial teeth and the right mandibular canine tooth of dogs. In part one of the study, 30 dogs were used. E. corrodens was found in 62% of these dogs and 44% of individual plaque samples. A. actinomycetemcomitans was not detected in any of the dogs sampled. In part two, 34 dogs were used to determine the prevalence of the black pigmented anaerobic bacilli (Porphyromonas and Prevotella spp.). Porphyromonas gingivalis was present in 68% of these dogs and 47% of individual plaque samples. Prevotella intermedia was present in 44% of the dogs and 23% of individual plaque samples. The recently described Porphyromonas canoris, Porphyromonas salivosa, Porphyromonas cangingivalis, Porphyromonas cansulci, Porphyromonas crevioricanis and Prevotella denticola species were isolated from only 9%, 6%, 3%, 3%, 3% and 3% of dogs respectively. Porphyromonas gingivicanis was not isolated from any of the animals sampled. In conclusion, black-pigmented anaerobic bacilli were isolated from 91% of the animals sampled and therefore constitute a significant risk with respect to bite wound infections. It is also suggested that the prevalence of E. corrodens in wound infections has been underestimated in previous reports because of use of inappropriate techniques for detecting this organism.     

Misinterpretation of body sensations in panic disorder

Cognitive accounts of panic predict that panic disorder patients will be particularly prone to misinterpret autonomic sensations. Several studies have produced results consistent with this prediction, but each is open to alternative interpretation. To clarify matters, 2 studies administered the Body Sensations Interpretation Questionnaire (BSIQ) to panic patients and controls. Panic patients were more likely to interpret ambiguous autonomic sensations as signs of immediately impending physical or mental disaster and were more likely than other anxiety disorder patients and nonpatients to believe these interpretations. In a 3rd study, a brief version of the BSIQ was shown to have satisfactory test-retest reliability, to change with treatment, and to discriminate treatments that varied in their effects on panic.