Sulfamate Esters Guide C(3)-Selective Xanthylation of Alkanes.

Owing to the pervasiveness of hydroxyl groups in natural isolates, alcohol derivatives are alluring directing groups. Herein, an alcohol-derived sulfamate ester guides the light-initiated xanthylation of primary, secondary, or tertiary centers. This process enables formal directed deuteration, azidation, thiolation, and vinylation reactions.

"They never tell you about the consequences": young people's awareness of sexually transmitted infections.

Young people are at risk from sexually transmitted infections (STIs)--the incidence of chlamydia in the UK is highest among young women aged 16-19. Despite this, young people lack knowledge about STIs and are more aware of the risks of unwanted pregnancy than their risk of acquiring an STI. This study used qualitative and quantitative methods to examine what teenagers know about STIs, their prevention, symptoms, treatment and services. Only one-third of respondents recognized chlamydia as an STI. The little knowledge of STIs that was revealed was superficial. Few were aware that special services existed for STIs. Condoms were seen as contraception, not as a method of preventing infection transmission. High teenage pregnancy rates have received much publicity but less attention has been paid to rising STI incidence. Programmes aimed at decreasing pregnancy rates through adoption of effective hormonal contraception not only fail to address STIs but may be detrimental to prevention efforts.

Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds.

Using the patch clamp technique we investigated the effects of the centrally acting muscle relaxant chlorzoxazone and three structurally related compounds, 1-ethyl-2-benzimidazolinone (1-EBIO), zoxazolamine, and 1,3-dihydro-1-[2-hydroxy-5-(triflu oromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS 1619) on recombinant rat brain SK2 channels (rSK2 channels) expressed in HEK293 mammalian cells. SK channels are small conductance K(+) channels normally activated by a rise in intracellular Ca(2+) concentration; they modulate the electrical excitability in neurons and neuroendocrine cells. When applied externally, chlorzoxazone, 1-EBIO, and zoxazolamine activated rSK2 channel currents in cells dialyzed with a nominally Ca(2+)-free intracellular solution. The activation was reversible, reproducible, and depended on the chemical structure and concentration. The order of potency was 1-EBIO > chlorzoxazone > zoxazolamine. Activation of rSK2 channels by chlorzoxazone, 1-EBIO, and zoxazolamine declined at higher drug concentrations. Zoxazolamine, when applied in combination with chlorzoxazone or 1-EBIO, partially inhibited the rSK2 channel current responses, suggesting a partial-agonist mode of action. 1-EBIO failed to activate rSK2 channel currents when applied to excised inside-out membrane patches exposed to a Ca(2+)-free intracellular solution. In contrast, 1-EBIO activated rSK2 currents in a concentration-dependent manner when coapplied to the patches with a solution containing 20 nM free Ca(2+). NS 1619 did not activate rSK2 channel currents; it inhibited rSK2 channel currents activated by the other three test compounds or by high intracellular Ca(2+). We conclude that chlorzoxazone and its derivatives act through a common mechanism to modulate rSK2 channels, and SK channel modulation in the brain may partly underlie the clinical effects of chlorzoxazone.

Repeat use of emergency contraception: How frequent is it?

OBJECTIVE: To measure the level of repeat use of emergency contraception (EC) in family planning clinics (FPCs) in North and East Devon. DESIGN: An audit of repeat use of EC was carried out in seven FPCs, in parallel with a client survey. All women seeking EC in the study period were included (n = 572). RESULTS: Nearly 70% of women had 'ever' used EC prior to the study visit; over half had previously used EC in the year of the study; a quarter had previously used EC three or more times in the same period. Teenagers were more likely to have previously used EC in the study year, but half of all repeat users were aged 20 and older. Asked why EC was needed today, most women reported current use of regular contraception, but almost a quarter had had unprotected sex, and half reported a condom mishap. CONCLUSIONS: These results show frequent repeat use of EC and do not support recent research based on general practice records, which suggests that repeat use is rare. If EC users use multiple sources of EC, or prefer alternative sources, repeat use of EC will be underestimated if calculated using general practitioner (GP) records alone.

Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.

SK channels are small conductance, Ca(2+)-activated K(+) channels that underlie neuronal slow afterhyperpolarization and mediate spike frequency adaptation. Using the patch clamp technique, we tested the effects of eight clinically relevant psychoactive compounds structurally related to the tricyclic antidepressants, on SK2 subtype channels cloned from rat brain and functionally expressed in the human embryonic kidney cell line, HEK293. Amitriptyline, carbamazepine, chlorpromazine, cyproheptadine, imipramine, tacrine and trifluperazine blocked SK2 channel currents with micromolar affinity. The block was reversible and concentration-dependent. The potency differed according to chemical structure. In contrast, the cognitive enhancer linopirdine was ineffective at blocking these channels. Our results point to a distinct pharmacological profile for SK channels.

Patch-clamp analysis of anesthetic interactions with recombinant SK2 subtype neuronal calcium-activated potassium channels.

UNLABELLED: Small conductance calcium-activated potassium channels (SK) mediate spike frequency adaptation and underlie the slow afterhyperpolarization in central neurons. We tested the actions of several anesthetics on the SK2 subtype of recombinant SK channels, cloned from rat brain and functionally expressed in a mammalian cell line. Butanol, ethanol, ketamine, lidocaine, and methohexital blocked recombinant SK2 channel currents, measured in the whole-cell patch clamp recording mode. The block was reversible, dose-dependent, and of variable efficacy. The inhaled anesthetics chloroform, desflurane, enflurane, halothane, isoflurane, and sevoflurane produced little or no block when applied at 1 minimum alveolar anesthetic concentration; varying degrees of modulation were observed at very large concentrations (10 minimum alveolar concentration). The extent of block by inhaled anesthetics did not appear to depend on concentration or membrane voltage. IMPLICATIONS: We describe differential effects of anesthetics on cloned small conductance calcium-activated potassium channels from brain that may play a role in generating the effects or side effects of anesthetics.

General practitioners' attitudes to sexual activity in under-sixteens.

In the UK, under-sixteen-year-olds with some exceptions can be provided with contraceptive care even if unwilling to inform their parents. Nonetheless, many teenagers express doubts about confidentiality in these circumstances, as well as fear of being judged. The attitudes of general practitioners in North and East Devon towards the Gillick ruling regarding the treatment of under sixteens for sexual health matters were assessed. They were asked to indicate their level of agreement or disagreement with a series of statements. 235 (73%) responded, and only 15 (6.5%) rejected the notion that the same duty of confidentiality applies to under-sixteens as to older patients. 76% did, however, prefer parents to know they had been consulted about contraception. Only 7 GPs believed that provision of contraception encourages under-age sex. Despite GPs' general acknowledgment of the importance of confidentiality in relation to sexual activity, teenagers may well be discouraged from seeking advice if they expect strong pressure to tell their parents.

Epidemiological issues in alcohol-related violence.

Epidemiological research on alcohol and violence exhibits a number of methodological limitations. This is the case whether it is event based (i.e., based on samples of victims and/or perpetrators of violence) or based on samples of the general population. The chapter identifies some of the limitations that confront researchers, policymakers, and other end-users of the research. The methodological issues are illustrated by exploring one type of violent event-rape-and one general population study-Kai Pernanen's research on alcohol-related violence in a Canadian community. It is argued the epidemiological research would benefit from further qualitative research on the natural history of violent events.