University of California, San Francisco

About: University of California, San Francisco is a education organization based out in San Francisco, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 83381 authors who have published 186236 publications receiving 12068420 citations. The organization is also known as: UCSF & UC San Francisco.

Molecular Biology of Steroid Hormone Synthesis

Abstract: Introduction STEROID hormones are familiar clinically and physiologically as regulators of physiological processes. Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal tubules to retain sodium; glucocorticoids, which are named for their carbohydratemobilizing properties but have many other effects as well; estrogens, which induce female secondary sexual characteristics; progestins, which are essential for reproduction; and androgens, which induce male secondary sexual characteristics. These classes of steroid hormones are structurally similar and arise from a common series of pathways. They are distinguished by their actions on one or more specific steroid hormone receptors. The hormone/receptor complexes function as tissue-specific transcriptional regulators of distinct domains of genes and, consequently, exert their broad array of physiological effects. (For reviews, see Refs. 1 and 2.) The pathways by which the...

A new taxonomy for describing and defining adherence to medications

Abstract: Interest in patient adherence has increased in recent years, with a growing literature that shows the pervasiveness of poor adherence to appropriately prescribed medications. However, four decades of adherence research has not resulted in uniformity in the terminology used to describe deviations from prescribed therapies. The aim of this review was to propose a new taxonomy, in which adherence to medications is conceptualized, based on behavioural and pharmacological science, and which will support quantifiable parameters. A systematic literature review was performed using MEDLINE, EMBASE, CINAHL, the Cochrane Library and PsycINFO from database inception to 1 April 2009. The objective was to identify the different conceptual approaches to adherence research. Definitions were analyzed according to time and methodological perspectives. A taxonomic approach was subsequently derived, evaluated and discussed with international experts. More than 10 different terms describing medication-taking behaviour were identified through the literature review, often with differing meanings. The conceptual foundation for a new, transparent taxonomy relies on three elements, which make a clear distinction between processes that describe actions through established routines (‘Adherence to medications’, ‘Management of adherence’) and the discipline that studies those processes (‘Adherence-related sciences’). ‘Adherence to medications’ is the process by which patients take their medication as prescribed, further divided into three quantifiable phases: ‘Initiation’, ‘Implementation’ and ‘Discontinuation’. In response to the proliferation of ambiguous or unquantifiable terms in the literature on medication adherence, this research has resulted in a new conceptual foundation for a transparent taxonomy. The terms and definitions are focused on promoting consistency and quantification in terminology and methods to aid in the conduct, analysis and interpretation of scientific studies of medication adherence.

SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation

Abstract: Sirtuins are NAD(+)-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2 (refs 1, 2). Mice lacking both Sirt3 alleles appear phenotypically normal under basal conditions, but show marked hyperacetylation of several mitochondrial proteins. Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues. During fasting, livers from mice lacking SIRT3 had higher levels of fatty-acid oxidation intermediate products and triglycerides, associated with decreased levels of fatty-acid oxidation, compared to livers from wild-type mice. Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3. LCAD is deacetylated in wild-type mice under fasted conditions and by SIRT3 in vitro and in vivo; and hyperacetylation of LCAD reduces its enzymatic activity. Mice lacking SIRT3 exhibit hallmarks of fatty-acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold exposure. These findings identify acetylation as a novel regulatory mechanism for mitochondrial fatty-acid oxidation and demonstrate that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting.

Predicting skin permeability.

Abstract: Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physicochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an “aqueous-polar (pore) pathway” across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to >750, and log Koct ranging from −3 to + 6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values. Overall, then, we present a facile interpretation of a considerable body of skin permeability measurements that (a) very adequately describes the dependence of Kp upon permeant size and lipophilicity, (b) generates parameters of considerable physicochemical and mechanistic relevance, and (c) implies that the SC lipids alone can fully characterize the barrier properties of mammalian skin.

Validation of a Caregiver Strain Index.

Abstract: This paper outlines the development of a Caregiver Strain Index (CSI) with a sample of spouses, family, friends, and neighbors, aged 22 to 83, who provided varying degrees of care to recently hospitalized hip surgery and heart patients aged 65 and over. Internal consistency (Cronbach's alpha) for the 13-item CSI on 81 cases was .86. Evidence of construct validity was obtained in three areas: ex-patient characteristics; subjective perceptions of the care-taking relationship by caregivers; and emotional health of caregivers. These results indicate that the CSI is a brief, easily administered instrument which identified strain within our sample of informal care providers. Further development of the CSI is being undertaken for predicting specific caregiver populations at risk. This simple index might be usefully included in any interview or assessment package that examines intergenerational relations involving dependency and care.