Early sexual debut and risky sex in young adults: the role of low self-control.

BACKGROUND: The purpose of this study was to examine the role of low self-control as a mediator or moderator between early age at sexual debut and risky sexual behavior in young adulthood. METHODS: Data on 5734 male and female Add Health participants were used. Self-control (waves 1 & 3), age at sexual debut (wave 3) and risky sexual behavior (wave 4) were used in a structural equation modeling framework to assess the relationships of interest. RESULTS: Approximately 17% of respondents were < 15 years at first sexual intercourse. Among females only, both early age at first intercourse (Parent-report: z = 5.08, p < .001; Self-report: z = 2.05, p < .05) and low self-control at wave 3 (Parent-report: z = 2.30, p < .05; Self-report: z = 2.31, p < .05) mediated the relationship between low self-control at wave 1 and risky sexual behaviors in young adulthood. Similarly in the male-only model, both early age at first intercourse (Parent-report: z = 2.92, p < .01; Self-report: z = 3.04, p < .01) and low self-control at wave 3 (Parent-report: z = 1.99, p < .05; Self-report: z = 3.15, p < .01) mediated the relationship between low self-control and risky sexual behaviors in young adulthood. There was evidence of moderation in the male-only model (- 0.26, p < .01), such that lower impulsivity strengthened the relationship between early sex and risky sex. CONCLUSIONS: This study confirms the role of executive functions in sexual behaviors and suggests that interventions aimed at improving self-control may be beneficial in reducing risky sexual behavior.

Percutaneous absorption of steroids: determination of in vitro permeability and tissue reservoir characteristics in human skin layers.

The skin localization of steroids following topical application is largely unknown. We determined the distribution of five steroids in human skin using excised epidermal, dermal, and full-thickness membranes in vitro. There was no significant difference in steroid maximum flux through epidermal and full-thickness membranes, other than significantly lower fluxes for the most polar steroid, aldosterone. Hydrocortisone had the highest dermal diffusivity and dermal penetration, and the accumulation of hydrocortisone and corticosterone was higher than that of the other steroids. Slower penetration and higher accumulation in the viable epidermis of progesterone in full-thickness skin were consistent with dermal penetration limitation effects associated with high lipophilicity.

The effect of region of application on absorption of ethanol and hexanol through canine skin.

The effect of region of application on the percutaneous penetration of solutes with differing lipophilicity was investigated in canine skin. Skin from the thorax, neck, back, groin, and axilla regions was harvested from Greyhound dogs and placed in Franz-type diffusion cells. Radiolabelled (14C) ethanol (Log P 0.19) or hexanol (Log P 1.94) was applied to each skin section for a total of 5h. The permeability coefficient (kP, cm h(-1)) and residue of alcohol remaining in the skin were significantly (P=0.001) higher for hexanol compared to ethanol. In contrast, ethanol had a far greater maximum flux (Jmax, mol (cm2)(-1) h(-1)) than hexanol (P=0.001). A comparison of regional differences shows the kP and Jmax for ethanol in the groin was significantly lower (P=0.035) than the back. The kP and Jmax for hexanol were significantly higher (P=0.001) in the axilla than the other four skin sites. An understanding of factors influencing percutaneous drug movement is important when formulating topical preparations for the dog.

Effect of solute lipophilicity on penetration through canine skin.

OBJECTIVE: To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin. DESIGN: Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radiolabelled (14C) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19-3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (kP, cm/h), maximum flux (Jmax, mol/cm2/h) and residue remaining within the skin were determined. RESULTS: The kP increased with increasing lipophilicity (6.2 x 10(-4) +/- 1.6 x 10(-4) cm/h for ethanol to 1.8 x 10(-2) +/- 3.6 x 10(-3) cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. CONCLUSION: Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin.

Veterinary drug delivery: potential for skin penetration enhancement.

A range of topical products are used in veterinary medicine. The efficacy of many of these products has been enhanced by the addition of penetration enhancers. Evolution has led to not only a highly specialized skin in animals and humans, but also one whose anatomical structure and skin permeability differ between the various species. The skin provides an excellent barrier against the ingress of environmental contaminants, toxins, and microorganisms while performing a homeostatic role to permit terrestrial life. Over the past few years, major advances have been made in the field of transdermal drug delivery. An increasing number of drugs are being added to the list of therapeutic agents that can be delivered via the skin to the systemic circulation where clinically effective concentrations are reached. The therapeutic benefits of topically applied veterinary products is achieved in spite of the inherent protective functions of the stratum corneum (SC), one of which is to exclude foreign substances from entering the body. Much of the recent success in this field is attributable to the rapidly expanding knowledge of the SC barrier structure and function. The bilayer domains of the intercellular lipid matrices within the SC form an excellent penetration barrier, which must be breached if poorly penetrating drugs are to be administered at an appropriate rate. One generalized approach to overcoming the barrier properties of the skin for drugs and biomolecules is the incorporation of suitable vehicles or other chemical compounds into a transdermal delivery system. Indeed, the incorporation of such compounds has become more prevalent and is a growing trend in transdermal drug delivery. Substances that help promote drug diffusion through the SC and epidermis are referred to as penetration enhancers, accelerants, adjuvants, or sorption promoters. It is interesting to note that many pour-on and spot-on formulations used in veterinary medicine contain inert ingredients (e.g., alcohols, amides, ethers, glycols, and hydrocarbon oils) that will act as penetration enhancers. These substances have the potential to reduce the capacity for drug binding and interact with some components of the skin, thereby improving drug transport. However, their inclusion in veterinary products with a high-absorbed dose may result in adverse dermatological reactions (e.g., toxicological irritations) and concerns about tissue residues. These are important considerations when formulating a veterinary transdermal product when such compounds are added, either intentionally or otherwise, for their penetration enhancement ability.

Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH.

Besides its well known endocrinological effects, thyrotropin-releasing hormone (TRH) has potential clinical value in the treatment of neurotrauma and various neurologic and psychiatric disorders. The aim of this study was to assess if transdermal delivery of TRH and its analogue, M-TRH, in the presence of enhancers, is an effective means for administration of the peptides. Using the in vitro diffusion cell method, the effect of ethanol and a terpene on the transdermal penetration of the peptides across full-thickness rat skin were studied. Steady-state permeability values for TRH and M-TRH were 8.7 +/- 2.2 and 6.7 +/- 1.4 microg/cm(2) h, respectively. The addition of 3 % terpene in combination with 47 % ethanol increased the penetration of TRH and M-TRH to 16.2 +/- 1.7 and 14.6 +/- 2.1 microg/cm(2) h, respectively. Rats were studied in vivo for release of thyroid-stimulating hormone (TSH) as a biologic effect after transdermally delivered peptide. Topical application of TRH and M-TRH induced an increase in TSH serum concentration from 0.32 +/- 0.09 ng/ml to 32.6 +/- 5.0 and 22.9 +/- 7.6 ng/ml, respectively, after 30 min. The addition of terpene and ethanol in combination with TRH or M-TRH, increased the TSH release to 43.0 +/- 3.8 and 48.4 +/- 4.0 ng/ml, respectively. It is concluded that, in the rat, peptides can be absorbed through the skin with retained biologic activity, and in amounts sufficient to elicit a physiological response.

In vitro percutaneous penetration of topically applied capsaicin in relation to in vivo sensation responses.

Capsaicin, the primary pungent element in several spices, elicits a variety of physiological effects which are due to neurogenic responses. The aim of the study was to explore the in vivo sensation responses of capsaicin and to compare the results with the in vitro percutaneous absorption of the substance. The overall objectives were to determining an in vitro-in vivo correlation for capsaicin. Capsaicin was applied in a chamber on the volar forearm of twelve volunteers and in a flow-through diffusion chamber on excised human epidermal membranes. Topical administration of capsaicin produced a complex cutaneous sensation that changed in intensity and quality as a function of time and was characterized by sting, prick, burn and pain. Percutaneous steady-state penetrations of capsaicin with a receptor fluid consisting either of 4% bovine serum albumin in phosphate buffered saline or 50% ethanol in water were 28.2+/-2.7 and 29.6+/-2.9 microg/cm(2) per h, respectively. The corresponding cumulative penetrated amounts of capsaicin after 30 min were 14. 7+/-1.7 and 19.2+/-2.1 microg/cm(2), respectively. The present investigation indicates that there is a good correlation between in vivo physiological responses and in vitro percutaneous penetration of topically applied capsaicin.

Effect of penetration enhancers on the permeation of the thyrotropin releasing hormone analogue pGlu-3-methyl-His-Pro amide through human epidermis.

The effect of the enhancers, cineole and ethanol, on the transdermal penetration of the tripeptide, pGlu-3-methyl-His2-Pro amide (M-TRH), across human epidermal membrane was studied by flow-through diffusion chambers. The aim of the study was to assess whether the biologically active analogue M-TRH displays similar transdermal penetration properties as those demonstrated earlier for the parental peptide, thyrotropin-releasing hormone (TRH) (Magnusson et al., 1997a Int. J. Pharm. 157, 113-121). Steady-state fluxes with a donor solution of phosphate-buffered saline (PBS) were 0.34 +/- 0.01 microgram/cm2h for M-TRH and 0.27 +/- 0.01 microgram/cm2h for TRH. Measured over 30 h the total amount penetrated was 8.6 +/- 1.0 and 7.8 +/- 1.7 micrograms/cm2, respectively. In the presence of 50% ethanol, the flux of the peptides increased approximately 3-fold. A donor solution of 3% cineole, in combination with 47% ethanol, increased the penetration of M-TRH to 1.60 +/- 0.02 micrograms/cm2h, compared to 0.92 +/- 0.03 microgram/cm2h for TRH, as reported previously. The corresponding total amount penetrated over 30 h was 41.5 +/- 4.9 and 24.9 +/- 1.7 micrograms/cm2, respectively. Our data suggests that enhancers added together with the penetrant can theoretically induce changes in the permeability of the stratum corneum sufficient to promote the transdermal absorption of therapeutically relevant amounts of these peptides. This demonstrates the possibility to deliver classes of compounds that have been viewed as not suitable for transdermal administration.

Terpene-enhanced transdermal permeation of water and ethanol in human epidermis.

The study was performed to investigate the effect of penetration enhancers on the stratum corneum barrier. Epidermal membranes were prepared from freeze-stored (-70 degrees C) Caucasian breast skin and mounted in a flow-through diffusion cell. The validity of the freeze storage procedure was verified by measurement of [3H]-water penetration. The effect of the cyclic terpene, carveol, on the transdermal penetration of water and ethanol was studied in vitro. Control ethanol and water penetration measured with a donor solution of 50% ethanol/PBS (w/w) was 1.9+/-0.2 and 3.6+/-0.5 x 10(-3) cm/h. The addition of 3% carveol to the donor solution increased the permeation of ethanol and water after 4 h to 8.3+/-1.1 and 12.5+/-1.9 x 10(-3) cm/h, respectively. In a separate experiment, terpinen-4-ol and alpha-terpineol were also tested, in addition to carveol, for effect on tritium flux. No significant difference in maximum tritium flux was obtained between the three terpenes studied. The maximum increase in permeability coefficients of carveol, terpinen-4-ol and alpha-terpineol was 10.6, 8.7 and 10.9, respectively.

Effects of topical application of capsaicin to human skin: a comparison of effects evaluated by visual assessment, sensation registration, skin blood flow and cutaneous impedance measurements.

A new non-invasive device, which enables local measurements of electrical impedance, has been used to evaluate the degree of irritation in human skin. The results have been compared with visual scoring, sensations and laser Doppler flowmetry. Capsaicin (50 microliters 1% solution) and control solutions (50 microliters 50% ethanol) were applied in a chamber for 30 min on the volar forearm of 7 volunteers. Values were recorded before application and during the total test period of 4.5 h. Sensations like sting/prick, burn and pain were produced by this treatment, and the flare response was observed. Using the non-invasive laser Doppler flow technique to measure blood flow in human skin, we have shown that topical application of capsaicin abolishes the vasodilator response to local heat provocation (40 degrees C). There was close agreement among values obtained using visual assessments, sensations and laser Doppler flowmetry. Results obtained using electrical impedance measurements were not consistent with the other three methods.