Biomedical subjects

R Harland

Publications and source records attributed to R Harland.

At least 19 recordsLinked to original sources

PubMed2001

Effects of immunization against GnRH, melengestrol acetate, and a trenbolene acetate/estradiol implant on growth and carcass characteristics of beef heifers.

A 2 x 3 factorial experiment was conducted to determine the effects of an implant (trenbolene acetate/estradiol or no implant) and method of estrus suppression (immunization against GnRH, melengestrol acetate, or no suppression) on growth performance and carcass characteristics of heifers fed for slaughter. At the start of a 21-d feed adaption phase, crossbred beef heifers (n = 144, 390+/-2.8 kg) were given their first dose of an anti-GnRH vaccine or started on melengestrol acetate (MGA). Thereafter, heifers were fed a high-concentrate diet (78% barley grain) for 84 d (Days 0 to 83), received implants on Day 0, a second vaccination on Day 21, and were slaughtered on Days 84 or 85. Implanting increased average daily gain (1.72 vs 1.50 kg/d, P < 0.01), feed efficiency (6.02 vs 6.75 kg dry matter intake/kg gain, P < 0.01), preslaughter weight (532 vs 513 kg, P < 0.01), carcass weight (301 vs 289 kg, P < 0.01), and ribeye area (88.6 vs 85.9 cm2, P < 0.05), but had no affect (P > 0.05) on dry matter intake, grade fat thickness, marbling score, or lean yield. Compared to heifers fed MGA, those immunized against GnRH had a greater ribeye area (90.0 vs 84.6 cm2) and lean yield (63 vs 61%), and had thinner grade fat (7.5 vs 8.6 mm; P < 0.05 for each). Furthermore, immunized heifers had lower (P < 0.001) plasma progesterone concentrations than control heifers on Days 42, 63 and 83. Heifers fed MGA had less estrus mounting activity (P < 0.05) and lower plasma progesterone concentrations (P < 0.001) than the remaining heifers. Method of estrus suppression did not affect (P > 0.05) preslaughter weight, average daily gain, dry matter intake, feed efficiency, carcass weight, or marbling score. In conclusion, implanting significantly increased growth performance and preslaughter and carcass weights. Compared to heifers fed MGA, immunization against GnRH significantly increased ribeye area and lean yield, and reduced grade fat thickness

Adipose Tissue↗

PubMed2000

An early requirement for FGF signalling in the acquisition of neural cell fate in the chick embryo.

BACKGROUND: In Xenopus embryos, fibroblast growth factors (FGFs) and secreted inhibitors of bone morphogenetic protein (BMP)-mediated signalling have been implicated in neural induction. The precise roles, if any, that these factors play in neural induction in amniotes remains to be established. RESULTS: To monitor the initial steps of neural induction in the chick embryo, we developed an in vitro assay of neural differentiation in epiblast cells. Using this assay, we found evidence that neural cell fate is specified in utero, before the generation of the primitive streak or Hensen's node. Early epiblast cells expressed both Bmp4 and Bmp7, but the expression of both genes was downregulated as cells acquired neural fate. During prestreak and gastrula stages, exposure of epiblast cells to BMP4 activity in vitro was sufficient to block the acquisition of neural fate and to promote the generation of epidermal cells. Fgf3 was also found to be expressed in the early epiblast, and ongoing FGF signalling in epiblast cells was required for acquisition of neural fate and for the suppression of Bmp4 and Bmp7 expression. CONCLUSIONS: The onset of neural differentiation in the chick embryo occurs in utero, before the generation of Hensen's node. Fgf3, Bmp4 and Bmp7 are each expressed in prospective neural cells, and FGF signalling appears to be required for the repression of Bmp expression and for the acquisition of neural fate. Subsequent exposure of epiblast cells to BMPs, however, can prevent the generation of neural tissue and induce cells of epidermal character.

Animals↗

PubMed2000

Neural induction.

Development of neural fates from ectoderm is accompanied by the blockage of BMP signals at both protein and mRNA levels. Recent work has employed zebrafish, chick and mouse in addition to amphibians as models. Genetics has supplemented experimental embryology in enriching the understanding of the mechanism of neural induction and in posing new questions.

Animals↗

PubMed2000

The effects of active immunization against gnRH on testicular development, feedlot performance, and carcass characteristics of beef bulls.

The objective was to determine the effects of a recombinant fusion protein anti-GnRH vaccine on testicular development, feedlot performance, and carcass quality of beef bulls. Crossbred beef bulls (n = 58, average weight 306 kg, 9 mo of age), were randomly allocated to two groups and received either an anti-GnRH vaccine (GnRH) or placebo (Control) by intramuscular injection on d 0, 56, and 112. There were group effects (P < 0.01; as a percentage of Control) on testicular weight (53%), daily sperm production (40%), and epididymal sperm reserves (16%). There were group x time interactions (P < 0.0001) for scrotal circumference and serum testosterone concentrations; at slaughter, bulls in the GnRH group had a smaller (P < 0.05) scrotal circumference (28.3 vs 33.9 cm) and lower (P < 0.05) serum testosterone concentrations (2.2 vs 8.6 ng/mL) than those in the Control group. Average daily gain, feed intake, and feed efficiency were not different between treatments during the backgrounding phase (d 0 to 84). During the finishing phase (d 98 to 182), ADG was greater (P < 0.05) for bulls in the Control group (1.69 vs 1.42 kg/d), as was carcass weight (6.9%; P < 0.01). However, GnRH bulls had numerically better feed efficiency (6.12 vs 7.08 kg DMI/kg gain; P < 0.23) and shear force values for ribeye that were 16% lower (P < 0.14) than Control bulls, warranting further investigation. Vaccinating bulls against GnRH suppressed testicular function, with growth and carcass characteristics similar to that expected with steers.

Animal Husbandry↗

PubMed1999

Ectopic noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear.

Bone morphogenetic protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is expressed in each presumptive sensory organ, as well as in the mesenchymal cells surrounding the region of the otocyst that is destined to form the semicircular canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the semicircular canals. To address the role of this gene in inner ear development, we blocked BMP4 function(s) by delivering one of its antagonists, Noggin, to the developing inner ear in ovo. Exogenous Noggin was delivered to the developing otocyst by using a replication-competent avian retrovirus encoding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin protein. Noggin treatment resulted in a variety of phenotypes involving both sensory and nonsensory components of the inner ear. Among the nonsensory structures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proliferation of the primordial canal outpouch, as well as the continual outgrowth of the canal after its formation. In addition, Noggin affected the structural patterning of the cristae, possibly via a decrease of Msx1 and p75NGFR expression. These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development.

Animals↗

PubMed1998

Do certain countries produce only positive results? A systematic review of controlled trials.

OBJECTIVE: To determine whether clinical trials originating in certain countries always have positive results. DATA SOURCES: Abstracts of trials from Medline (January 1966-June 1995). STUDY SELECTION: Two separate studies were conducted. The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo, no treatment, or a nonacupuncture intervention. In the second study, randomized or controlled trials of interventions other than acupuncture that were published in China, Japan, Russia/USSR, or Taiwan were compared to those published in England. DATA EXTRACTION: Blinded reviewers determined inclusion and outcome and separately classified each trial by country of origin. DATA SYNTHESIS: In the study of acupuncture trials, 252 of 1085 abstracts met the inclusion criteria. Research conducted in certain countries was uniformly favorable to acupuncture; all trials originating in China, Japan, Hong Kong, and Taiwan were positive, as were 10 out of 11 of those published in Russia/USSR. In studies that examined interventions other than acupuncture, 405 of 1100 abstracts met the inclusion criteria. Of trials published in England, 75% gave the test treatment as superior to control. The results for China, Japan, Russia/USSR, and Taiwan were 99%, 89%, 97%, and 95%, respectively. No trial published in China or Russia/USSR found a test treatment to be ineffective. CONCLUSIONS: Some countries publish unusually high proportions of positive results. Publication bias is a possible explanation. Researchers undertaking systematic reviews should consider carefully how to manage data from these countries.

Humans↗

PubMed1998

Seizure sensitivity and GABAergic modulation of ethanol sensitivity in selectively bred FAST and SLOW mouse lines.

FAST and SLOW selected mouse lines were bred for differences in locomotor response to low-dose ethanol. FAST mice exhibit an extreme stimulant response and SLOW mice exhibit locomotor depression at the same ethanol dose. We tested the hypothesis that gamma-aminobutyric acid (GABA) systems modulate ethanol's stimulant effects by examining convulsant responses to GABAA receptor ligands, and by assessing the effects of GABAA and GABAB ligands on locomotor activity in the presence and absence of EtOH. FAST mice were more sensitive to the convulsant effects of GABAA drugs, and to one of two non-GABAergic drugs also tested. FAST and SLOW mice differed in locomotor responses to two benzodiazepines, but not to other GABAA receptor ligands. Ethanol's stimulant effects were not selectively altered by bicuculline or picrotoxin. The selected lines differed in sensitivity to the locomotor depressant effects of the GABAB agonist, baclofen. Ethanol-stimulated activity of FAST mice was inhibited by baclofen, and this effect was reversed by administration of the GABAB antagonist, CGP-35348. These GABAB receptor mediated effects were replicated in DBA/2J inbred mice that exhibit extreme sensitivity to ethanol's stimulant effects. In summary, we found moderate to strong evidence that some sites on the GABAA receptor complex were altered as a consequence of selection of FAST and SLOW mice, but found little support for GABAA mediation of EtOH-stimulated activity. In contrast, we found moderate evidence for differential alteration of GABAB receptor function; however, GABAB receptor involvement in ethanol-stimulated activity was strongly supported by results in the selected lines and an inbred strain.

Animals↗

PubMed1997

Maternal immunization of pregnant cattle with recombinant VP8* protein of bovine rotavirus elicits neutralizing antibodies to multiple serotypes. Colostral neutralizing antibody by rotavirus VP8*.

Neonatal calf diarrhoea caused by bovine rotavirus is one of the most common diseases in cattle. VP8 portion of the rotavirus VP4 protein is known to contain neutralizing epitopes and hemagglutination activity. We expressed the VP8* portion of bovine rotavirus strain C486 (G6P1 serotype) in E. coli, and examined potential of the recombinant VP8* protein for induction of neutralizing antibody responses in host animals. One hundred twenty pregnant beef cows were selected and immunized eight weeks prior to parturition with the recombinant VP8* protein. Colostral and milk samples were collected 12 hours and 10 days post-calving, respectively, and the virus neutralizing titers elicited by the recombinant subunit antigen were determined by plaque reduction assay. Colostral antibody titres of the vaccinated group were significantly higher than those of the unvaccinated control group, and these titers were equivalent to the titers elicited by a commercial vaccine. While titers of the control group rapidly decreased to 220 after 10 days of calving, neutralizing titers in the milk of the vaccinees remained 510. Rabbit and bovine antibodies induced by the recombinant VP8* protein were also able to neutralize bovine rotavirus P5 serotype (B641) at significant level and P11 serotype (B223) moderately. Our results suggest that the E. coli-produced recombinant VP8* protein can be an useful subunit vaccine candidate to prevent rotavirus infection in new-born calves.

Animals↗

PubMed1997

Formation and function of Spemann's organizer.

The organizer is formed in an equatorial sector of the blastula stage amphibian embryo by cells that have responded to two maternal agents: a general mesoendoderm inducer (involving the TFG-beta signaling pathway) and a dorsal modifier (probably involving the Wnt signaling pathway). The meso-endoderm inducer is secreted by most vegetal cells, those containing maternal materials that had been localized in the vegetal hemisphere of the oocyte during oogenesis. As a consequence of the inducer's distribution and action, the competence domains of prospective ectoderm, mesoderm, and endoderm are established in an animal-to-vegetal order in the blastula. The dorsal modifier signal is secreted by a sector of cells of the animal and vegetal hemispheres on one side of the blastula. These cells contain maternal materials transported there in the first cell cycle from the vegetal pole of the egg along microtubules aligned by cortical rotation. The Nieuwkoop center is the region of blastula cells secreting both maternal signals, and hence specifying the organizer in an equatorial sector. Final steps of organizer formation at the late blastula or early gastrula stage may involve locally secreted zygotic signals as well. At the gastrula stage, the organizer secretes a variety of zygotic proteins that act as antagonists to various members of the BMP and Wnt families of ligands, which are secreted by cells of the competence domains surrounding the organizer. BMPs and Wnts favor ventral development, and cells near the organizer are protected from these agents by the organizer's inducers. The nearby cells are derepressed in their inherent capacity for dorsal development, which is apparent in the neural induction of the ectoderm, dorsalization of the mesoderm, and anteriorization of the endoderm. The organizer also engages in extensive specialized morphogenesis, which brings it within range of responsive cell groups. It also self-differentiates to a variety of axial tissues of the body.

Amphibians↗

PubMed1996

Silastic cuffed catheters for hemodialysis vascular access: thrombolytic and mechanical correction of malfunction.

Silastic cuffed catheters are assuming a greater role in providing long-term vascular access for hemodialysis patients. However, catheter thrombosis, fibrin sheath formation, and catheter malposition are recurrent problems that reduce extracorporeal flow rates and shorten catheter life. We reviewed 163 consecutive episodes of catheter malfunction that occurred in 121 catheters in 88 patients over a 3.5-year period. Intraluminal instillation of urokinase was successful in reestablishing an extracorporeal flow rate of > or = 300 mL/min in 74% of episodes. The 42 remaining episodes (26%) were radiologically evaluated. Two catheters required replacement for catheter kinking or insufficient catheter length. Two additional catheters were malpositioned; both were successfully repositioned with percutaneous techniques. A fibrin sheath was detected encasing the catheter in 38 instances. The fibrin sheath was successfully stripped from the distal portion of the catheter in 36 of the 38 instances. Using endoluminal thrombolytic therapy and percutaneous mechanical techniques, we have extended the mean survival for catheters intended for permanent vascular access to 12.7 months and have allowed 95% of the catheters inserted for temporary use to reach their use goal. Tunnel tract infection and catheter-mediated bacteremia were the primary reasons for catheter removal.

Catheterization, Central Venous↗

PubMed1996

Effect of recombinant bovine interleukin-1 beta in normal calves and in calves infected with bovine herpesvirus type 1.

Bovine herpesvirus-1 (BHV-1) is an important pathogen of respiratory infections in cattle. Its continuing importance lies in its ability to predispose infected hosts to bacterial infections. In this present study, we determined whether the immunoregulatory effects induced by interleukin-1 (IL-1) could stimulate appropriate host defense mechanisms to influence the course of BHV-1 infection in cattle. We first evaluated the effect of different doses (10-1000 ng/kg) of IL-1 in normal cattle. A single administration of IL-1 was able to induce a dose-dependent increase in polymorphonuclear (PMN) cells as well as monocytes in peripheral blood. The number of CD3+ lymphocytes and gamma/delta T cells in peripheral circulation decreased transiently in a dose-dependent manner. In the disease model, the effect of IL-1 administration (300 ng/kg) 24 h before, at the time of, and 24 h after the BHV-1 challenge was assessed. As a single therapeutic modality, IL-1 did not significantly reduce the establishment or progression of BHV-1-induced disease. Nevertheless, our results demonstrated that the significant modulation of diverse immune parameters did not exacerbate disease. Thus, the use of IL-1 as an adjunct therapy or as a vaccine adjuvant in cattle can be safely considered in situations where BHV-1 infection is likely to occur.

Adjuvants, Immunologic↗

PubMed1996

Immunogenicity of bovine herpesvirus 1 glycoprotein D in mice: effect of antigen form on the induction of cellular and humoral immune responses.

For the development of veterinary subunit vaccines, modifications to the antigen may be needed to make the production of these vaccines cost effective. To investigate the effect of antigen modifications on immune response, we used glycoprotein D, one of the major glycoproteins of bovine herpesvirus-1 (BHV-1), as a model antigen. We developed a mouse model to assess the immune response elicited by immunization with either a recombinant truncated (tgD) or the authentic full-length (gD) form of BHV-1 gD in VSA3, a novel water-in-oil adjuvant. Both forms of BHV-1 gD antigen induced good levels of cell-mediated immunity, as evaluated by antigen-specific proliferative response and cytokine (IFN-gamma and IL-4) production. Following primary immunization, the humoral immune response induced by gD was superior to that elicited by vaccination with tgD. However, after a secondary immunization, a strong and similar antibody response to BHV-1 gD was induced by both forms of the antigen. The difference in immunogenicity between gD and tgD after primary immunization was not due to the loss of immunogenic epitopes in the truncated antigen or the ability to associate with the adjuvant VSA3. Our results indicate that both gD and tgD are capable of efficiently inducing a cell-mediated immune response, and although recombinant tgD is less efficient in inducing a primary humoral immune response when compared to the full-length gD, tgD effectively primed for a secondary antibody response.

Animals↗

PubMed1995

Effect of recombinant bovine interleukin-1 beta on viral/bacterial pneumonia in cattle.

Bovine herpesvirus-1 (BHV-1) is an important pathogen of respiratory infections in cattle. Its continuing importance lies in its ability to predispose infected hosts to bacterial infections (e.g., Pasteurella haemolytica). In this study we determined whether the immunoregulatory effects induced by recombinant bovine interleukin-1 (rbIL-1) could stimulate appropriate host defense mechanisms to influence the course of BHV-1 and P. haemolytica infection in cattle. We first evaluated the effect of multiple doses (5 doses of 300 ng/kg) of rbIL-1 in normal cattle. An increase in polymorphonuclear (PMN) cells, as well as monocytes, in peripheral blood was observed during the course of IL-1 administration. In addition, the phagocytic activity of monocytes was increased. Although the phagocytic and oxidative burst activities in PMN decreased during the course of rbIL-1 treatment, no changes were observed in the bactericidal capacity of these cells. Lymphocyte numbers in peripheral blood remained unchanged; however, the functional activity of these cells, as measured by IFN-gamma production upon in vitro stimulation, was decreased. In the bovine respiratory disease model, multiple administration of IL-1 did not influence significantly the progression of BHV-1/P. haemolytica infection in cattle. Thus, our results demonstrated that IL-1, although not therapeutically effective, could be administered safely as an adjuvant, even during the course of BHV-1/P. haemolytica infection.

Animals↗

PubMed1995

Immunological response to recombinant VP8* subunit protein of bovine roravirus in pregnant cattle.

Bovine rotavirus VP8*, N-terminal trypsin cleavage product of VP4, was produced in Escherichia coli. To examine if this antigen could induce neutralizing antibody responses, different species of animals were immunized with the recombinant VP8* protein. The VP8* antigen was found to stimulate a neutralizing immune response in rabbits. When VP8*-immunized mice were exposed to bovine rotavirus strain C486, significantly higher antibody responses were observed than if they were only exposed to C486. To stimulate a current vaccination protocol in the field with livestock, mice were exposed to live C486 virus first and then to VP8*. These mice had the elevated immune responses indicating that VP8* could boost immunity in primed mice. The immune response to VP8* was also tested in pregnant cows. The efficacy of VP8* in stimulating milk antibody was compared with a commercial inactivated vaccine. Differences in colostral antibody titres between VP8*-vaccinated and unvaccinated cows were statistically significant (P < 0.05) and equivalent to the commercial vaccine (P = 0.0569). The milk antibody titres on day 10 were comparable between VP8*- and commercial vaccine-vaccinated animals and were significantly higher (P < 0.05) than in unvaccinated controls. Furthermore, rabbit and bovine antibodies induced by VP8* were able to neutralize different P types of bovine rotaviruses to varying degrees, suggesting that serotype-specific and cross-reactive epitope(s) are present on the VP8* protein of rotavirus. Taken together, E. coli-expressed VP8* may be useful as a subunit vaccine candidate for bovine rotavirus.

Animals↗

PubMed1994

Ventral expression of GATA-1 and GATA-2 in the Xenopus embryo defines induction of hematopoietic mesoderm.

The early embryonic events involved in the commitment of mesoderm to form blood have not been studied in detail for lack of molecular markers. We have studied the expression of the hematopoietic transcription factors GATA-1 and GATA-2 during Xenopus embryogenesis. During development GATA-1 expression is localized to the ventral region of the embryo and precedes the expression of embryonic globins. GATA-2 is highly expressed in the ventral region of the embryo by the end of gastrulation and later is expressed in the blood island region and the central nervous system. Lithium-induced dorsalization of embryos abrogates GATA-2 expression, and uv-induced ventralization of embryos leads to a radially symmetrical expression of GATA-2. Therefore, GATA-2 expression reflects the ventral character of the embryo. The expression of the GATA-binding proteins and globin in ventral marginal zone explants demonstrates that hematopoiesis is programmed as early as the blastula stage. GATA-1 and GATA-2 are also expressed in cultured animal cap explants, suggesting that these cells have hematopoietic potential. The developmental expression of GATA-1 and GATA-2 is consistent with their role in hematopoiesis in higher organisms and defines the ventral regions of the early embryo that give rise to hematopoietic progenitors. Our studies indicate that these genes will be useful in defining the inductive events that lead to the formation of hematopoietic mesoderm.

Animals↗

PubMed1994

A subunit gIV vaccine, produced by transfected mammalian cells in culture, induces mucosal immunity against bovine herpesvirus-1 in cattle.

A truncated version of bovine herpesvirus-1 (BHV-1) glycoprotein IV (tgIV) was produced in a novel, non-destructive expression system based upon regulation of gene expression by the bovine heat-shock protein 70A (hsp70) gene promoter in Madin Darby bovine kidney (MDBK) cells. In this system, up to 20 micrograms ml-1 of secreted tgIV, which is equivalent to the yield from 4 x 10(6) cells, was produced daily over a period of up to 18 days. Different doses of tgIV were injected intramuscularly into seronegative calves. Virus-neutralizing antibodies were induced by all doses of tgIV, both in the serum and in the nasal superficial mucosa. However, the low dose (2.3 micrograms) induced significantly (p < 0.05) lower antibody titres than the medium (7 micrograms) and high (21 micrograms) doses. The medium and high doses of tgIV conferred protection from BHV-1 infection, as demonstrated by a significant (p < 0.05) reduction in clinical signs of respiratory disease and virus shedding in the nasal secretions postchallenge. However, the 2.3 micrograms group, although partially protected, was not significantly (p > 0.05) different from the placebo group. This study demonstrated the potential of an intramuscularly administered tgIV subunit vaccine to induce mucosal immunity to BHV-1 using an economic protein production system and an acceptable vaccine formulation. In addition, a strong correlation was observed between neutralizing antibodies in the serum and nasal superficial mucosa, virus shedding and clinical disease. Thus, serum neutralizing antibody levels in tgIV-immunized animals may be a good prognosticator of protection from BHV-1 infection and disease.

Animals↗

PubMed1993

Protection of cattle from BHV-1 infection by immunization with recombinant glycoprotein gIV.

High levels of recombinant bovine herpesvirus-1 (BHV-1) glycoprotein IV were produced in baculovirus, adenovirus, vaccinia virus and Escherichia coli expression systems. The different recombinant forms as well as authentic gIV were injected intramuscularly into seronegative calves. With the exception of E. coli-produced gIV, all forms of gIV induced high levels of neutralizing antibodies both in the serum and in the nasal superficial mucosa. Animals immunized with gIV produced in insect or mammalian cells were completely protected from infection with BHV-1, as demonstrated by the absence of temperature responses, clinical signs or detectable virus in the nasal secretions after challenge exposure. The E. coli-derived gIV induced partial protection from clinical disease, even though it was not glycosylated and did not induce appreciable levels of neutralizing antibodies. This study demonstrated that all forms of glycosylated gIV, whether authentic or recombinant, confer protection from BHV-1 infection and thus may be useful as an effective subunit vaccine.

Animals↗

PubMed1993

Phonophoresis of methyl nicotinate: a preliminary study to elucidate the mechanism of action.

The skin penetration enhancement effect of ultrasound (phonophoresis) on methyl nicotinate was investigated in 10 healthy volunteers in a double-blind, placebo-controlled, crossover clinical trial. Each treatment consisted of the application of ultrasound massage (3.0 MHz, 1.0 W/cm2 continuous output) or placebo massage (0 MHz) for 5 min to the forearms of the volunteers, followed by a standardized application of methyl nicotinate at intervals of 15 sec, 1 min, and 2 min post-massage. Percutaneous absorption of methyl nicotinate was monitored using laser Doppler velocimetry. Ultrasound treatment applied prior to methyl nicotinate led to enhanced percutaneous absorption of the drug, for example, ultrasound treatment data versus control data at 2 min showed significant increases (P < 0.05; analysis of variance) in the peak blood flow (125.8 +/- 12.0 vs 75.3 +/- 10.4% flux) and in the area under the curve for blood flow (2630.3 +/- 387.5 vs 1567.6 +/- 183.5% flux.min). The results of this study suggest that ultrasound affects the skin structure to provide skin penetration enhancement. This finding is consistent with the proposed hypothesis that phonophoresis acts by disordering the structured lipids in the stratum corneum.

Double-Blind Method↗