N4hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat hepatic microsomes. Drug Metab

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The Supercooling of a Nematic Liquid Crystal

We investigate the supercooling of a nematic liquid crystal using fluctuating non-linear hydrodynamic equations. The Martin-Siggia-Rose formalism is used to calculate renormalized transport coefficients to one-loop order. Similar theories for isotropic liquids have shown substantial increases of the viscosities as the liquid is supercooled or compressed due to feedback from the density fluctuations which are freezing. We find similar results here for the longitudinal and various shear viscosities of the nematic. However, the two viscosities associated with the nematic director motion do not grow in any dramatic way; i.e.\ there is no apparent freezing of the director modes within this hydrodynamic formalism. Instead a glassy state of the nematic may arise from a ``random anisotropy" coupling of the director to the frozen density.Comment: Late

Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings

Social status strategy in early adolescent girls: Testosterone and value-based decision making

There has been strong interest, spanning several disciplines, in understanding adolescence as a developmental period of increased risk-taking behavior. Our goals focus on one line of investigation within this larger developmental risk framework. Specifically, we examined levels of pubertal hormones in girls in relation to their willingness to take greater financial risks to gain social status. To this end, we tested the hypothesis that higher levels of testosterone during the ages of pubertal maturation are associated with a greater willingness to sacrifice money for social admiration. Sixty-three girls ages 10-14 (Mage=12.74) participated in laboratory measures and completed at-home saliva sample collection. The Pubertal Development Scale (PDS) and basal hormone levels (testosterone, estradiol, DHEA) measured pubertal maturation. We made use of a developmentally appropriate version of an Auction Task in which adolescents could take financial risks in order to gain socially motivated outcomes (social status). PDS and testosterone were each associated with overall levels of financial risk taking over the course of the Auction Task. In hierarchical models, PDS and testosterone were predictors of the slope of overbidding over the course of the task. Results provide evidence for the role of testosterone and pubertal maturation in girls' motivations to engage in costly decision making in order to gain social status. Findings contribute to our understanding of the developmental underpinnings of some interesting aspects of adolescent risk behavior

Anticonvulsant Hypersensitivity Syndrome In Vitro Assessment of Risk

Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity ( % dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anticonvulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62 % of reactions involved more than two organs. Cells from patients ' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy

Pediatric therapeutics and medicine administration in resource-poor settings: A review of barriers and an agenda for interdisciplinary approaches to improving outcomes

The lack of affordable, available pediatric drug formulations presents serious global health challenges. This article argues that successful pharmacotherapy for children demands an interdisciplinary approach. There is a need to develop new medicines to address acute and chronic illnesses of children, but also to produce formulations of essential medicines to optimize stability, bioavailability, palatability, cost, accurate dosing and adherence. This, in turn, requires an understanding of the social ecologies in which treatment occurs. Understanding health worker, caregiver and patient practices, limitations, and expectations with regard to medicines is crucial to guiding effective drug development and administration. Using literature on pediatric tuberculosis as a reference, this review highlights sociocultural, pharmacological, and structural barriers that impede the delivery of medicines to children. It serves as a basis for the development of an intensive survey of patient, caregiver, and health care worker understandings of, and preferences for, pediatric formulations in three East African countries.Pediatric drug formulations Pharmaceutical practice Social use of medicines Child health Tuberculosis Review

Maximum number of pills parents/caregivers or healthcare workers think children should take at one time or per day.

*<p>If leading choice represented less than 50% of interviewees, second most popular response was included.</p

Acute illness medicine administration practices of parents/caregivers.

*<p>The location of the tap (village or household) was not specified.</p>**<p>Depth of the well was not indicated so this may represent a spring source, or deep or shallow well.</p