Transdermal delivery of dideoxynucleoside-type anti-HIV drugs. 2. The effect of vehicle and enhancer on skin permeation.

The effects of vehicles and enhancers on the skin permeation of the dideoxynucleoside-type anti-HIV drugs Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT) were studied using hairless rat skin at 37 degrees C. After each drug was saturated in various volume fractions of ethanol (EtOH)/water or EtOH/tricaprylin (TCP) cosolvent system for 48 h at 37 degrees C, an in vitro skin permeation study was conducted using Valia-Chien permeation cells for 30 h. The skin permeation rates of DDC, DDI, and AZT from both EtOH/water and EtOH/TCP cosolvent systems increased as the volume fraction of ethanol was increased, reached maximum values at 50-60% (v/v) of ethanol, and then decreased with further increase of ethanol volume fraction.

Comparative in vitro spermicidal activity of chelating agents and synergistic effect with nonoxynol-9 on human sperm functionality.

Nonoxynol-9 (N-9), a nonionic surfactant, exerts both spermicidal and anti-viral activities and is the most widely used spermicide. Although N-9 has been regarded as an efficient spermicidal agent for barrier contraception, it has been reported to cause vaginal irritation and allergic vaginitis, and its spermicidal action in the vaginal mucus may be limited. To address these problems, the spermicidal activity of several chelating agents against human semen and their synergistic effect on the spermicidal activity of N-9 were evaluated using computer-assisted semen analysis and a cervical mucus penetration test.

Randomized, Double-Blind, Placebo-Controlled Study of Clonidine in Restless Legs Syndrome.

Ten patients with idiopathic restless leg syndrome (RLS) were asked to rate their symptoms at baseline during 2 weeks of placebo and 2 weeks of clonidine treatment by using a four-point scale. On two consecutive nights of each treatment period, polysomnography (PSG) and actigraphic studies were performed. Patients subjectively reported improvement in leg sensations (p = 0.

Quantitative autoradiographic analysis of D1 and D2 dopamine receptors in rat brain in early and late pregnancy.

This study examined the levels of D1 and D2 dopamine receptors in the rat brain during pregnancy, a physiologically unique and important naturally occurring state. We are particularly interested in changes in the dopamine receptor complement of the brain during pregnancy because these receptors might support some components of the immediate postpartum onset of normal maternal behavior. Quantitative in vitro receptor autoradiography was applied particularly focusing on brain areas that control maternal behavior.

A rapid and simple method for the analysis of 1-hydroxypyrene glucuronide: a potential biomarker for polycyclic aromatic hydrocarbon exposure.

The present study describes a simple method of analyzing metabolites of pyrene in urine. This method is capable of detecting the glucuronic acid and sulfate conjugates of pyrene as well as free 1-hydroxypyrene in a single analysis. In comparison to other analytical methods for detecting pyrene metabolites, this new method does not require an overnight enzymatic hydrolysis step and is much more rapid method of analysis.

Effects of H+ liberated from hydrolytic cleavage of polyester microcapsules on their permeability and degradability.

Microcapsules prepared from blends of poly(d,l-lactide-coglycolide) with a lactide:glycolide ratio of 75:25 (PLGA75:25) and poly-(d,l-lactide) (PLA5000) or poly(d,l-lactic acid-co-glycolic acid) (PLGA5000) were dispersed in phosphate-buffered saline, and their hydrolytic rates were investigated. Using the Henderson-Hasselbalch equation and an L-lactic acid experiment, the concentration of hydrogen ions released into the bulk medium was calculated from the change in buffer pH. The rate of H+ formation was found to be dependent upon the polymer composition of the microcapsules.

Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion.

Commercial grade curcumin (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemethoxycurcumin) is widely used as a yellow coloring agent and spice in foods. In the present study topical application of commercial grade curcumin, pure curcumin or demethoxycurcumin had an equally potent inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in ornithine decarboxylase activity and TPA-induced tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Bisdemethoxycurcumin and tetrahydrocurcumin were less active.

Effects of children with Down syndrome on parents' activities.

Effects of children with Down syndrome on parents' daily activities were investigated. Data on the allocation of time to daily activities were obtained from time diaries provided by two samples of parents with at least one child under age 17. Parents in one sample had a child with Down syndrome and parents in the other sample did not.

Form and magnitude of beta-sympathetic and parasympathetic influences on pulse transit time.

In this study, we examined autonomic influences on pulse transit time measured from the R-wave of the electrocardiogram (R-PTT). Six subjects received three doses each of isoproterenol and atropine. Isoproterenol produced a significant linear decrease in R-PTT, a significant linear increase in heart rate (HR), and a significant linear decrease in diastolic blood pressure (DBP).

Effect of dietary acid or aluminum on growth and growth-related hormones in young chickens.

The effect of two concentrations of dietary acid (sulfuric acid) or aluminum (aluminum sulfate) on growth and growth-related hormones was examined in a heavy (broiler) strain of chicken between 4 and 18 days old. Growth (body weight, average daily gain, and tibial length) in chicks receiving either dietary acid or aluminum-containing diets were compared to chicks fed a control diet and to chicks fed diets containing sodium sulfate. Despite the reduced growth in acid-fed chicks, there were no changes in the plasma concentrations of growth hormone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding proteins (IGF-BP).

Dynamics of active lamellae in cultured epithelial cells: effects of expression of exogenous N-ras oncogene.

We examined the functional consequences of cellular transformation of rat IAR-2 epithelial cells, by a mutant N-ras oncogene, on the dynamics of active lamellae, structures that play an important role in cell motility, adhesion, and surface-receptor capping. Lamellar activity was assessed by measuring the rate of outer-edge pseudopodial activity and by analyzing the motility of Con A-coated beads placed on lamellar surfaces with optical tweezers. Although transformation dramatically affected the shape and size of active cellular lamellae, there was little detectable effect on either pseudopodial activity or bead movement.

Measuring grade-school children's ability to represent the Euclidean horizontal coordinate.

Seventy-five grade-school children were administered three tasks that measured their ability to represent the Euclidean horizontal coordinate: a traditional water-level test (WLT) that used a square-shaped vessel, a WLT that used a spherical vessel, and a task that used a crossbar apparatus. The latter two tasks differed from the traditional task in terms of the degree to which the apparatus presented a frame of reference that conflicted with environmental Euclidean coordinates. Performance was analyzed according to Piaget and Inhelder's (1956) stage-scoring system; that is, the testing procedures (a) allowed children to inspect the apparatus when it was rotated to discrete orientations; (b) corrected initial errors; and (c) included 0 degrees, 30 degrees, 60 degrees, and 90 degrees trials.

Electronic performance monitoring and social context: impact on productivity and stress.

In a laboratory study, the presence of individual- or work-group-level electronic performance monitoring (EPM) was manipulated as participants worked on a data-entry task alone, as a member of a noninteracting aggregate, or as a member of a cohesive group. The pattern of results suggested the operation of a social facilitation effect, as highly skilled monitored participants keyed more entries than highly skilled nonmonitored participants. The opposite pattern was detected among low-skilled participants.

Analysis of sequence-specific binding activity of cis-elements in human thymidine kinase gene promoter during G1/S phase transition.

Expression of thymidine kinase (TK) gene in normal human diploid, cells is both cell cycle and age dependent and appears to be transcriptionally regulated. Several studies have indicated that the G1/S control sequence may reside within the region of about 130 bp upstream of the transcription initiation site. We have previously shown that a trans-acting factor, CBP/tk (CCAAT binding protein for TK gene), binds to either one of the two inverted CCAAT boxes in a cell cycle- and age-dependent manner (Pang and Chen, 1993, J.

Self-complexity, self-evaluation, and depression: an examination of form and content within the self-schema.

Six studies examined the relationship between self-complexity and variables related to self-evaluation. Self-complexity was found to comprise two components: positive self-complexity and negative self-complexity. Positive self-complexity was sensitive to methodological factors, namely, variations in stimulus materials used for self-ratings.

Construction of a trans-dominant inhibitor for members of the TGA family of transcription factors conserved in higher plants.

Activating sequence factor 1 (ASF-1) is a conserved DNA-binding activity that interacts with sequence elements containing TGACG motifs, some of which have been demonstrated to respond to exogenous application of auxin and salicylic acid. Genes encoding transcription factors with similar DNA-binding specificity to ASF-1 have been cloned from diverse plant species and these factors all contain a distinct basic-leucine-zipper (bZIP) motif. Members of this family of DNA-binding proteins, designated as TGA factors, have been shown to interact with similar DNA sequences and at least seven distinct TGA genes are present in the Arabidopsis genome.

The thermodynamics of DNA structures that contain lesions or guanine tetrads.

It is becoming increasingly apparent that energetic as well as structural information is required to develop a complete appreciation of the critical interrelationships between structure, energetics, and biological function. Motivated by this recognition, we have reviewed in this article the current state of the thermodynamic databases associated with lesion-containing DNA duplexes and DNA quadruplexes, while highlighting important considerations concerning the methods used to obtain the requisite data.

Thermodynamics of an intramolecular DNA triple helix: a calorimetric and spectroscopic study of the pH and salt dependence of thermally induced structural transitions.

We have characterized thermodynamically the melting transitions of a DNA 31-mer oligonucleotide (5'-GAAGAGGTTTTTCCTCTTCTTTTTCTTCTCC-3') which is designed to fold into an intramolecular triple helix. The first 19 residues fold back on themselves to form an antiparallel Watson-Crick hairpin duplex with a T5 loop. The 3'-terminal seven residues, which are connected to the Watson-Crick hairpin duplex by a second T5 loop, form Hoogsteen interactions in the major groove of the Watson-Crick hairpin.

Rapid activation of the heat shock transcription factor, HSF1, by hypo-osmotic stress in mammalian cells.

Osmoregulation is important to living organisms for survival in responding to environmental changes of water and ionic strength. We demonstrated here for the first time that exposure of HeLa cells to a hypotonic medium (30% growth medium and 70% water) prominently induced the binding activity of the heat shock transcription factor (HSF). Pretreatment of cells with cycloheximide did not inhibit the induction of HSF-binding activity, indicating that the mechanisms of induction are independent of new protein synthesis.

Development of a K(+)-channel probe and its use for identification of an intracellular plant membrane K+ channel.

Polyclonal antibodies were generated against a 9-amino acid, synthetic peptide corresponding to the selectivity filter in the pore region of K(+)-channel proteins. The sequence of amino acids in the ion-conducting pore region of K+ channels is the only highly conserved region of members of this protein family. The objectives of the present work were (i) to determine whether the anti-channel pore peptide antibody was immunoreactive with known K(+)-channel proteins and (ii) to demonstrate the usefulness of the antibody by employing it to identify a newly discovered K(+)-channel protein.

B-DNA twisting correlates with base-pair morphology.

The observed sequence dependence of the mean twist angles in 38 B-DNA crystal structures can be understood in terms of simple geometrical features of the constituent base-pairs. Structures with low twist appear to unwind in response to severe steric clashes of large exocyclic groups (such as NH2-NH2) in the major and minor grooves, while those with high twist are subjected to lesser contacts (H-O and H-H). We offer a simple clash function that depends on base-pair morphology (i.

Resistance of personal risk perceptions to debiasing interventions.

The tendency to believe that one's own risk is less than that of others may reduce interest in health-protective behaviors. This article describes 4 attempts to reduce such optimistic biases. In Study 1, New Jersey residents (N = 222) were provided with lists of risk factors for several health problems.

Apomorphine for motor fluctuations and freezing in Parkinson's disease.

Objective: To review the pharmacokinetics and use of apomorphine in patients with Parkinson's disease; to report a case of beneficial outcome with apomorphine in a patient with Parkinson's disease with severe levodopa "on-off" fluctuations and freezing; and to outline the types of patients or situations where apomorphine may be useful.

Data Sources: Case reports, review articles, and relevant clinical studies identified by a MEDLINE search of the English-language literature published between 1975 and October 1994.

Study Selection: Because all but 2 reports were of open-label design with small sample sizes, all studies identified were evaluated.

Blood-brain barrier breakdown and edema formation following frontal cortical contusion: does hormonal status play a role?

The present experiment was designed to evaluate and correlate the time course of blood-brain barrier (BBB) integrity and cerebral edema in adult male rats given medial frontal cortex contusions. The effect of sex hormones on BBB integrity in the same injury model was also examined, because previous work has shown that progesterone can reduce cerebral edema (Roof et al., 1993).

Biodegradable microcapsules prepared by a w/o/w technique: effects of shear force to make a primary w/o emulsion on their morphology and protein release.

A water-in-oil-in-water (w/o/w) technique, sometimes known as in-water drying method, was used to prepare microcapsules consisting of polylactic acid and poly(lactide-co-glycolide). The influence of shear force to produce an initial water-in-oil (w/o) emulsion on the characteristics of microcapsules and protein release was investigated. Bovine serum albumin (BSA) was used as the model protein drug for encapsulation.