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Topical Administration (topical + administration)

Distribution by Scientific Domains

Medical Sciences	96%

Distribution within Medical Sciences

Dermatology	33%
General & Introductory Veterinary Medicine	7%

Selected Abstracts

Gastrin-Releasing Peptide, a Bombesin-like Neuropeptide, Promotes Cutaneous Wound Healing

DERMATOLOGIC SURGERY, Issue 4 2002
Yuji Yamaguchi MD
Background. Little is known about the effects of neuropeptides on wound healing. Objective. To investigate the effect of gastrin-releasing peptide (GRP), one of the bombesin-like neuropeptides, on wound healing. Methods. The effects of GRP on cultured keratinocyte proliferation and migration were measured by BrdU uptake and in vitro scratch assay, respectively. Various concentrations of GRP ointments (0, 10,9, 10,8, 10,7, 10,6 M) were topically applied to 1.0 mm wounds on porcine flanks. Results. GRP stimulated keratinocyte growth and locomotion in a dose-dependent manner. Topical administration of GRP accelerated macroscopic epidermal regeneration in a dose-dependent manner, as measured by planimetry. Histologic studies also showed that GRP promoted reepithelialization, including epidermal thickness as well as superficial skin coverage. conclusion. Topical use of GRP may clinically accelerate wound healing of burns, injuries, chronic ulcers, and skin graft donor sites through the enhancement of keratinocyte growth and spreading. [source]

Topical administration of simvastatin recovers alveolar bone loss in rats

JOURNAL OF PERIODONTAL RESEARCH, Issue 3 2008
H. Seto
Background and Objective:, Simvastatin, a cholesterol-lowering drug, has been reported to show anabolic effects on bone metabolism. We examined the effects of simvastatin in vitro using cultured rat calvaria cells and in vivo using periodontitis-induced rats. Material and Methods:, Alkaline phosphatase activity and bone nodule formation were measured in cultured rat calvaria cells. Nylon ligature was placed around the maxillary molars of Fischer male rats for 20 d to induce alveolar bone resorption. After ligature removal, simvastatin was topically injected into the buccal gingivae for 70 d and then microcomputed tomography and histological examinations were performed. Results:, Simvastatin maintained high alkaline phosphatase activity and increased bone nodule formation in rat calvaria cells in a dose-dependent manner, showing that simvastatin increased and maintained a high level of osteoblastic function. Microcomputed tomography images revealed that treatment with simvastatin recovered the ligature-induced alveolar bone resorption, showing a 46% reversal of bone height. Histological examination clarified that low-mineralized alveolar bone was formed in simvastatin-treated rats. Conclusion:, These findings demonstrate that simvastatin has the potential to stimulate osteoblastic function and that topical administration of simvastatin may be effective for the recovery of alveolar bone loss in rats. [source]

In vitro and in vivo antifungal activity of cetrimide (cetyltrimethyl ammonium bromide) against fungal keratitis caused by Fusarium solani

MYCOSES, Issue 1 2007
Yehia A.-G.
Summary Mycotic keratitis is a devastating eye infection acquired after eye injury. Cetrimide at 15 and 20 mg ml,1 produced no surviving Fusarium solani growth with minimal inhibitory concentration value of 0.10 mg ml,1. Topical administration of three drops (0.3 ml) of cetrimide aqueous solution of 10 mg ml,1 at pH 6.4 three times daily succeeded to cure human severe resistant F. solani keratitis in a time course of <3 weeks, and with complete healing after 6 weeks. Cetrimide-treated rabbit corneas section appeared with normal compact epithelium and endothelium with no vacuolation in Descemet's endothelial complex: an indication that cetrimide has no significant toxic effects. So, cetrimide at 10 mg ml,1 may be effective and safe topical therapy in patients with mycotic keratitis, especially F. solani ulcers. Currently, there is no antimycotic drug with a good corneal penetration, which is safe and has a fungicidal activity. [source]

Halofuginone inhibition of COL1A2 promoter activity via a c-Jun,dependent mechanism

ARTHRITIS & RHEUMATISM, Issue 10 2002
Tracy L. McGaha
Objective The naturally occurring compound halofuginone has been shown to antagonize collagen synthesis by fibroblasts both in vitro and in vivo. We previously demonstrated that this inhibitory property was related to the ability of halofuginone to disrupt transforming growth factor , signal transduction. The present study further analyzed the ability of halofuginone to affect transcription factors that can regulate type I collagen gene expression by examining its effect on c-Jun, the negative regulator of collagen gene transcription. Methods The phosphorylation state of c-Jun in the presence of halofuginone was examined via direct Western blotting, and the transcriptional activity of the activator protein 1 (AP-1) binding element via electrophoretic mobility shift assay and luciferase reporter assay. We determined whether the effect of halofuginone on collagen synthesis was dependent on the presence of c-Jun by ectopic expression of a wild-type or dominant-negative c-Jun construct in the presence of halofuginone and assaying ,2(I) collagen promoter strength via luciferase reporter assay. The effect of halofuginone on ,2(I) collagen message levels in fibroblasts when wild-type or dominant-negative c-Jun was overexpressed was determined. We also determined whether halofuginone had an effect on the phosphorylation state of c-Jun in the skin of TSK/+ mice via immunohistochemistry. Results Treatment of fibroblasts with 10,8M halofuginone enhanced basal and mitogen-mediated phosphorylation of c-Jun in culture. This elevated phosphorylation of c-Jun correlated with enhanced DNA binding and transcriptional activation of an AP-1 complex consisting of c-Jun and Fos but lacking the c-Jun antagonist JunB. Overexpression of c-Jun enhanced in a dose-dependent manner the ability of halofuginone to inhibit the activity of a luciferase reporter construct under control of the ,3200-bp to +54-bp COL1A2 promoter, whereas the expression of a dominant-negative c-Jun construct abolished this effect. Northern blotting showed that overexpression of c-Jun enhanced the ability of halofuginone to reduce collagen ,2(I) messenger RNA levels in fibroblasts, whereas expression of the dominant-negative c-Jun abolished this effect. Topical administration of a halofuginone-containing cream for 20 days to TSK mice, which spontaneously develop dermal fibrosis, greatly increased the phosphorylated form of c-Jun in the skin; this was followed by a decrease in skin thickness and type I collagen messenger RNA expression. Conclusion Our findings illustrate the powerful down-regulatory property of c-Jun toward type I collagen and establish that halofuginone exerts its effect on collagen synthesis in a c-Jun,dependent manner. [source]

5-Aminolevulinic Acid Photodynamic Therapy: Where We Have Been and Where We Are Going

DERMATOLOGIC SURGERY, Issue 8 2004
Michael H. Gold MD
Background. Photodynamic therapy, utilizing the topical administration of 20% 5-aminolevulinic acid, has generated a great deal of interest in the dermatology community over the past several years. Objective. The purpose of this article is to review the history of photodynamic therapy in dermatology and to review recent new advances with this technology that will increase its appeal to all dermatologists. Methods. A literature review and results of new clinical trials with regards to photorejuvenation and acne vulgaris treatments with 5-aminolevulinic acid photodynamic therapy are presented. Results. Short-contact, full-face 5-aminolevulinic acid photodynamic therapy treatments with a variety of lasers and light sources have shown to be successful in treating all facets of photorejuvenation and the associated actinic keratoses as well as disorders of sebaceous glands, including acne vulgaris. The treatments are relatively pain-free, efficacious, and safe. They are also making already available laser/light source therapies work better for acne vulgaris and photorejuvenation. Conclusions. The use of 5-aminolevulinic acid photodynamic therapy with short-contact, full-face broad-application therapy is now able to bridge the world of medical and cosmetic dermatologic surgery. This therapy is available for all dermatologists to utilize in the care of their patients. [source]

Polyamines and hair: a couple in search of perfection

EXPERIMENTAL DERMATOLOGY, Issue 9 2010
Yuval Ramot
Please cite this paper as: Polyamines and hair: a couple in search of perfection. Experimental Dermatology 2010; 19: 784,790. Abstract:, Polyamines (spermidine, putrescine and spermine) are multifunctional cationic amines that are indispensable for cellular proliferation; of key significance in the growth of rapidly regenerating tissues and tumors. Given that the hair follicle (HF) is one of the most highly proliferative organs in mammalian biology, it is not surprising that polyamines are crucial to HF growth. Indeed, growing (anagen) HFs show the highest activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, while inhibition of ODC, using eflornithine, results in a decreased rate of excessive facial hair growth in vivo and inhibits human scalp hair growth in organ culture. In sheep, manipulation of dietary intake of polyamines also results in altered wool growth. Polyamine-containing nutraceuticals have therefore been proposed as promoters of human hair growth. Recent progress in polyamine research, coupled with renewed interest in the role of polyamines in skin biology, encourages one to revisit their potential roles in HF biology and highlights the need for a systematic evaluation of their mechanisms of action and clinical applications in the treatment of hair disorders. The present viewpoint essay outlines the key frontiers in polyamine-related hair research and defines the major open questions. Moreover, it argues that a renaissance in polyamine research in hair biology, well beyond the inhibition of ODC activity in hirsutism therapy, is important for the development of novel therapeutic strategies for the manipulation of human hair growth. Such targets could include the manipulation of polyamine biosynthesis and the topical administration of selected polyamines, such as spermidine. [source]

Pimecrolimus , an anti-inflammatory drug targeting the skin

EXPERIMENTAL DERMATOLOGY, Issue 12 2004
M. Grassberger
Abstract:, Pimecrolimus is the most recent member of calcineurin inhibitors available for the therapy for inflammatory skin diseases. It targets T-cells and mast cells and inhibits the production and release of cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus and much less than corticosteroids. It, thus, has a lower potential for transcutaneous resorption after topical administration, resulting in a lower risk of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal models of skin inflammation, including a model reflecting neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than tacrolimus. Pimecrolimus does not affect sensitization in a murine model of allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to tacrolimus. In conclusion, the results of preclinical studies show that pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory skin diseases. [source]

Effect of the lactic acid bacterium Streptococcus thermophilus on stratum corneum ceramide levels and signs and symptoms of atopic dermatitis patients

EXPERIMENTAL DERMATOLOGY, Issue 5 2003
Luisa Di Marzio
Abstract:, A reduced amount of total ceramides could be responsible for functional abnormalities of the skin of atopic dermatitis (AD) patients. The ability of an experimental cream containing sonicated Streptococcus thermophilus to increase skin ceramide levels in healthy subjects has been previously reported. The aim of the present work was to investigate the effects of the topical administration of a S. thermophilus -containing cream on ceramide levels of stratum corneum from AD patients. A 2-week application of the cream, containing a sonicated preparation of the lactic acid bacterium S. thermophilus, in the forearm skin of 11 patients led to a significant and relevant increase of skin ceramide amounts, which could have resulted from the sphingomyelin hydrolysis through the bacterial sphingomyelinase. Moreover, in all patients the topical application of our experimental cream also resulted in the improvement of the signs and symptoms characteristic of AD skin (i.e. erythema, scaling, pruritus). [source]

Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia,reperfusion injury in rats

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 7 2010
Yi Wang
Abstract The development of non-invasive ocular drug delivery systems is of practical importance in the treatment of retinal disease. In this study, we evaluated the efficacy of transactivator of transcription protein transduction domain (TAT-PTD, TAT49,57) as a vehicle to deliver acidic FGF (aFGF) to retina in rats. TAT-conjugated aFGF-His (TAT-aFGF-His) exhibited efficient penetration into the retina following topical administration to the ocular surface. Immunochemical staining with anti-His revealed that TAT-aFGF-His proteins were readily found in the retina (mainly in the ganglion cell layer) at 30 min. and remained detectable for at least 8 hrs after administration. In contrast, His+ proteins were undetectable in the retina after topical administration of aFGF-His, indicating that aFGF-His cannot penetrate the ocular barrier. Furthermore, TAT-aFGF-His, but not aFGF-His, mediated significant protection against retinal ischemia,reperfusion (IR) injury. After IR injury, retina from TAT-aFGF-His-treated rats showed better-maintained inner retinal layer structure, reduced apoptosis of retinal ganglion cells and improved retinal function compared to those treated with aFGF-His or PBS. These results indicate that conjugation of TAT to aFGF-His can markedly improve the ability of aFGF-His to penetrate the ocular barrier without impairing its biological function. Thus, TAT49,57 provides a potential vehicle for efficient drug delivery in the treatment of retinal disease. [source]

Effect of ketoprofen in topical formulation on vascular endothelial growth factor expression and tumor growth in nude mice with osteosarcoma

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2004
Kenshi Sakayama
Abstract OST cells, a low metastatic cell line established from human osteosarcoma, were inoculated under the periosteum of the ossa cranii of nude mice. Four weeks later, tumors were percutaneously treated for an additional 4 weeks with a patch containing either placebo or ketoprofen (KP). In the placebo group, OST cells formed osteoid and invaded the cranial bone. Tumor mass weighed 3.54 g. Approximately 85% of cells within the tumor expressed proliferating cell nuclear antigen (PCNA), indicating that they were proliferating with a high mitotic activity. Many feeder vessels were located within the tumor. The majority of tumor cells expressed intensely vascular endothelial growth factor (VEGF). In the KP group, invasion of OST cells into the cranial bone was suppressed and the tumor mass was 47% of that of the placebo group. Approximately 65% of cells within the tumor were PCNA-negative, indicating that their growth was arrested. There were considerably fewer feeder vessels within the tumor in the KP group than in the placebo group. Only a small number of cells expressed VEGF. Based on these findings, we concluded that topical administration of KP to nude mice with osteosarcoma inhibited VEGF expression, reduced the development of feeder vessels for supply of nutrients and oxygen, and suppressed tumor growth. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]

Topical administration of simvastatin recovers alveolar bone loss in rats

Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts

JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2002
Noriko Maizumi
The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) was studied. Pel cells were exposed for 48 h to erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form colonies. The cytocidal effect of the macrolides was measured as a decrease in colony-forming efficiency and was found to increase with the concentration. To obtain a quantitative measure of the cytocidal effect, the LD50, i.e. the concentration that decreases colony-forming efficiency 50% relative to control cells, was extrapolated from the concentration-response curves. The rank of the macrolides according to their cytocidal effect (LD50) was RKM > RXM > CAM > AZM > JM > MDM , EM. RKM, RXM, CAM, AZM, and JM were at least 1.7,12.2 times more cytocidal than MDM or EM. When extrapolated from the concentration-response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC90 concentrations for periodontopathic bacteria was estimated to be: ,,53.8% for RKM, , 92.7% for RXM, , 94.6% for CAM, , 97.1% for AZM, and , 86.2% for EM. The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which exhibited strong, moderate, and weak cytocidal activity. The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at ,3 ,M, CAM at ,10 ,M, and AZM or EM at ,3 ,M. The MIC90 against periodontopathic bacteria is ,4.8 ,M for RXM, 5.3 ,M for CAM, 2.7 ,M for AZM, and 21.8 ,M for EM. These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament. It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions. [source]

Phycocyanin liposomes for topical anti-inflammatory activity: in-vitro in-vivo studies

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2009
Maria Manconia
Abstract Objectives The aim of this work was to investigate the anti-inflammatory activity of C-phycocyanin (C-PC) on skin inflammation after topical administration and the influence of liposomal delivery on its pharmacokinetic properties. Methods Liposomes of different size and structure were prepared with different techniques using soy phosphatidylcholine and cholesterol. Vesicular dispersions were characterised by transmission electron microscopy, optical and fluorescence microscopy for vesicle formation and morphology, dynamic laser light scattering for size distribution, and Zetasizer for zeta-potential. C-PC skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either free or liposomal drug dispersed in a Carbopol gel. Key findings The protein was mainly localised in the stratum corneum, while no permeation of C-PC through the whole skin thickness was detected. Two percent C-PC-encapsulating liposomes showed the best drug accumulation in the stratum corneum and the whole skin, higher than that of the corresponding free 2% C-PC gel. Moreover, skin deposition of liposomal C-PC was dose dependent since skin accumulation values increased as the C-PC concentration in liposomes increased. The topical anti-inflammatory activity of samples was evaluated in vivo as inhibition of croton oil-induced or arachidonic acid-induced ear oedema in rats. Conclusions The results showed that C-PC can be successfully used as an anti-inflammatory drug and that liposomal encapsulation is effective in improving its anti-inflammatory activity. [source]

Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studies

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2007
Vanna Sanna
Solid lipid nanoparticles (SLN) designed for topical administration of econazole nitrate (ECN), were prepared by o/w high-shear homogenization method using different ratios of lipid and drug (5:1 and 10:1). SLN were characterized in terms of particle size, morphology, encapsulation efficiency and crystalline structure. After incorporation of SLN into hydrogels, rheological measurements were performed, and ex-vivo drug permeation tests were carried out using porcine stratum corneum (SC). In-vivo study of percutaneous absorption of ECN as a function of application time and composition of gels was carried out by tape-stripping technique. Penetration tests of the drug from a conventional gel were performed as comparison. High-shear homogenization method resulted in a good technique for preparation of ECN-loaded SLN. Particles had a mean diameter of about 150 nm and a regular shape and smooth surface. The encapsulation efficiency values were about 100%. Ex-vivo tests showed that SLN were able to control the drug release through the SC; the release rate depended upon the lipid content on the nanoparticles. In-vivo studies demonstrated that SLN promoted a rapid penetration of ECN through the SC after 1 h and improved the diffusion of the drug in the deeper skin layers after 3 h of application compared with the reference gel. [source]

Sustained ocular delivery of tilisolol to rabbits after topical administration or intravitreal injection of lipophilic prodrug incorporated in liposomes

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2001
Shigeru Kawakami
To improve the retention time of tilisolol in the precorneal area or vitreous body, we prepared liposomes incorporating the O -palmitoyl prodrug of tilisolol. O -Palmitoyl tilisolol was completely incorporated in the liposomes. After topical administration of O -palmitoyl tilisolol liposomes to the rabbit eye, O -palmitoyl tilisolol rapidly disappeared from the tear fluid. The inclusion of 2% carmellose sodium slightly prolonged the retention of O -palmitoyl tilisolol in the tear fluid. After intravitreal injection of O -palmitoyl tilisolol liposomes, there was a relatively prolonged retention of O -palmitoyl tilisolol in the vitreous body. At 24 and 48 h after intravitreal injection of O -palmitoyl tilisolol liposomes, the tilisolol concentration in the vitreous body was significantly higher compared with the concentration after intravitreal injection of tilisolol liposomes. [source]

Skin benefits from continuous topical administration of a zinc oxide/petrolatum formulation by a novel disposable diaper

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2001
S Baldwin
Abstract Background Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have advanced in our development of a novel diaper that delivers dermatological formulations to help protect the skin from over-hydration and irritation. Objective To determine the clinical benefits of a novel disposable diaper designed to deliver a zinc oxide and petrolatum-based formulation continuously to the skin during use. Methods All studies were independent, blinded, randomized clinical trials. Study A was conducted to confirm transfer of the zinc oxide/petrolatum (ZnO/Pet) formulation from the diaper to the child's skin during use. Children wore a single diaper for 3 h or multiple diapers for 24 h. After the use period, stratum corneum samples were taken from each child and analysed for ZnO/Pet. Study B evaluated the prevention of skin irritation and barrier damage from a standard skin irritant (SLS) in an adult arm model. Study C evaluated skin erythema and diaper rash in 268 infants over a 4-week usage period. One half of the infants used the ZnO/Pet diaper, while the other half used a control diaper that was identical except for the absence of the ZnO/Pet formulation. Results The ointment formulation and ZnO transferred effectively from the diaper to the child's skin during product use. Transfer of ZnO increased from 4.2 µg/cm2 at 3 h to > 8 µg/cm2 at 24 h. Exposure to the formulations directly on adult skin prior to an irritant challenge was associated with up to a 3.5 reduction in skin barrier damage and skin erythema. Greatest reductions were seen for the ZnO containing formulations. Wearing of the formulation treated diaper was also associated with a significant reduction in skin erythema and diaper rash compared to the control product. Conclusions The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper. [source]

Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 7 2008
Kirill I. Shingel
Abstract The paper describes preparation and biological characterization of the solid hybrid biomaterial that was designed for cell-targeted lipid delivery in healing tissues. The material referred to as ,solid emulsion gel' combines a protein-stabilized lipid emulsion and a hydrogel structure in a single compartment. The potential of the omega-3 (n-3)-fatty acids rich solid emulsion gel for tissue repair applications was investigated at the macro-, micro-, molecular and gene expression levels, using human fibroblasts and endothelial cells and a porcine model of full-thickness wounds. Being non-cytotoxic in vitro and in vivo, the biomaterial was found to affect cell metabolism, modulate expression of certain genes, stimulate early angiogenesis and promote wound repair in vivo. The neovascular response in vivo was correlated with upregulated expression of the genes involved in lipid transport (e.g. adipophilin), anti-apoptosis (e.g. heat shock proteins, haem oxygenase 1) and angiogenesis (vascular endothelial growth factor, placental growth factor). Collectively, the results of this study provide first evidence that the angiogenic response provided by solid emulsion gel-mediated delivery of n-3 fatty acids is an alternative to the topical administration of exogenous growth factors or gene therapy, and can be advantageously used for the stimulation of tissue repair in complex wounds. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Licking induced changes to the pattern of moxidectin milk elimination after topical treatment in dairy cows

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
F. IMPERIALE
Pour-on administration of the macrocyclic lactones anti-parasitic compounds in beef and dairy cattle is now worldwide accepted. However, the information available on their milk excretion pattern, after topical administration is rather limited. Additionally, the cattle licking behaviour has been proven to affect the kinetics of these anti-parasitic compounds. The purpose of this study was to investigate the influence of the natural licking behaviour on the plasma and milk disposition of moxidectin (MXD), topically administered (500 ,g/kg) in lactating dairy cows. Ten lactating Holstein dairy cows (705 kg body weight) were allocated into two experimental groups (n = 5). The licking was prevented during 5 days postadministration in animals in group I, and the remaining cows (group II) were allowed to lick freely. MXD concentrations profiles were measured in plasma and milk over 15 days posttreatment. The licking restriction period caused marked changes in MXD disposition kinetics both in plasma and milk. Both plasma and milk MXD concentrations (partial AUC 0,5 days) were significantly lower (P < 0.05) in licking-restricted cows. After the 5-day of restriction period, the animals were allowed to lick freely, which permitted the oral ingestion of MXD, situation clearly reflected both in plasma profile and milk excretion pattern. Despite the enhanced MXD milk concentrations measured in free-licking cows, drug concentrations did not reach the maximum MXD residues limit. [source]

Therapeutic doses of glucocorticoids: implications for oral medicine

ORAL DISEASES, Issue 5 2006
SK Baid
Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic,pituitary,adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use. [source]

Neural control of eustachian tube function,,

THE LARYNGOSCOPE, Issue 6 2009
Murat Songu MD
Abstract Objectives/Hypothesis: It has been hypothesized that middle ear pressure can be controlled by the Eustachian tube through a neuronal reflex arc in animal models. We aimed to define the role of the neuronal control mechanisms in regulating middle ear pressure in humans. Study Design: Prospective study. Methods: The study population consisted of 95 ears of 95 volunteers. The mechanoreceptors on the tympanic membrane and the baroreceptors in the middle ear, which are assumed to form the afferent plexus of the neuronal reflex arc, were blocked by topical administration of lidocaine hydrochloride, in various patient groups. The Eustachian tube functions forming the efferent plexus of the neuronal reflex arc were evaluated by manometric tests both before and after blocking the possible afferent plexus in each study group. Results: The baroreceptors established in the tympanic plexus might possibly have an effective role in this mechanism where the mechanoreceptors on the tympanic membrane seem to have a minor effect. Conclusions: Neuronal control mechanism could play an important role in regulating Eustachian tube function in humans. Laryngoscope, 2009 [source]

Efficacy against Fasciola hepatica and the pharmacokinetics of triclabendazole administered by oral and topical routes

AUSTRALIAN VETERINARY JOURNAL, Issue 5 2009
PJ Martin
Objective To determine the efficacy of triclabendazole (TCBZ) against 28-day-old, early immature liver fluke in cattle and its pharmacokinetics following administration by the oral or topical (pour-on) route. Procedures Cattle (n = 18) were infected with 500 TCBZ-susceptible liver fluke metacercariae and randomly allocated to three groups. At 28 days after infection, the groups were: (1) untreated controls; (2) treated with oral TCBZ at 12 mg/kg in combination with oxfendazole and selenium (TOS); (3) treated with pour-on TCBZ at 30 mg/kg in combination with abamectin (TA). Blood samples were taken immediately prior to treatment and serially after treatment to assess the plasma profile of TCBZ metabolites. Ten weeks after treatment all animals were slaughtered and total liver fluke counts, fluke egg counts and liver pathology were assessed. Results Both the TOS and TA treatments resulted in significant reductions of 28-day-old liver fluke, as assessed by fluke counts and fluke egg counts at slaughter, and the reductions following TOS treatment were significantly greater than those following TA treatment. The blood profile of TCBZ metabolites in TOS-treated animals showed a significantly greater area under the plasma concentration time curve and a higher maximum observed concentration than those treated with TA. There was significantly less liver pathology in TOS-treated animals than in the TA-treated animals. Conclusion TCBZ administered orally at 12 mg/kg resulted in greater efficacy against 28-day-old, early immature liver fluke than was achieved by topical administration at 30 mg/kg. Plasma metabolites of TCBZ were higher and liver pathology was less in TOS-treated animals than in TA-treated animals. [source]

Cilomilast, tacrolimus and rapamycin modulate dendritic cell function in the elicitation phase of allergic contact dermatitis

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005
W. Bäumer
Summary Background, Cilomilast and tacrolimus as well as rapamycin are potential drugs for the treatment of allergic skin diseases like atopic dermatitis and allergic contact dermatitis. Objectives, To compare the in vitro and in vivo immunomodulatory effects of the phosphodiesterase 4 inhibitor cilomilast with those of tacrolimus and rapamycin. Methods, The in vitro action of cilomilast, tacrolimus and rapamycin were tested in a mixed leucocyte reaction (MLR). In vivo, the inhibitory action of the immunomodulatory drugs was compared in the toluene-2,4-diisocyanate (TDI)-induced allergic inflammatory response with particular focus on dendritic cell (DC) function. Results, Cilomilast, tacrolimus and rapamycin were all able to inhibit DC-mediated T-cell activation in a MLR. But it was demonstrated for cilomilast that the target cells are T cells rather than DC. In vivo, a combination of systemic and topical administration of each of these three substances significantly inhibited swelling in the murine ear 16 h after TDI challenge. There was also a reduction in the weight of the draining auricular lymph node, in lymphocyte cell count, and in the number of emigrated DC. The density of Langerhans cells in the epidermis was correspondingly higher in mice treated with cilomilast, tacrolimus and rapamycin than in those treated with vehicle. All three substances were found to inhibit DC migration ex vivo in a skin DC migration assay performed on ear tissue after TDI challenge. Conclusions, DC migration into the draining lymph node also takes place in the elicitation phase of allergic contact dermatitis and this migration can be influenced by tacrolimus and rapamycin, and, to a lesser extent, by cilomilast. [source]

In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008
J J McDougall
Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor-mediated responses was also tested. Experimental approach: Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees. Key results: In normal animals, JWH015 and JWH133 caused a concentration-dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid-1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow. Conclusion and implications: In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated. British Journal of Pharmacology (2008) 153, 358,366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007 [source]

Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits

ACTA OPHTHALMOLOGICA, Issue 3 2010
Thorsteinn Loftsson
Abstract. Purpose:, This study aimed to develop low-viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits. Methods:, Aqueous eyedrops with hydroxypropyl-,-cyclodextrin containing 0.01,2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments ± standard error of the mean) are expressed as the change from baseline (24.7 ± 3.3 mmHg). Results:, Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf-life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 ± 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 ± 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10,22 hours after administration and duration of up to 32 hours. Conclusions:, Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low-viscosity aqueous eyedrop formulations. [source]

Characterization of efflux proteins in human corneal epithelial cells

ACTA OPHTHALMOLOGICA, Issue 2007
KS VELLONEN
Purpose: Corneal epithelium is the main barrier for absorption of drugs into intraocular tissues after topical administration and part of this barrier may be formed by efflux proteins which translocate molecules from the cell interior to the extracellular space. The aim of this study was to characterize the gene expression and the activity of the efflux transporters in the cell culture model of immortalized human corneal epithelial cells (HCE cells), in primary cell line (HCEpiC), and in the human corneal epithelium. Methods: The mRNA levels of MDR1, MRP1-MRP6, and BCRP were determined by the quantitative RT-PCR. Immunohistochemistry was used to study protein expression and localization of efflux transporters. Functionality of these proteins was assessed with calcein-AM efflux assay and by measuring the efflux of CDCF. Furthermore, bidirectional permeability of rhodamine 123 (Rh123) was studied. Results: The mRNA of MRP1 and MRP5 were detected in the human cornea and in both cell lines. These efflux proteins were found in the cell membranes of the human corneal epithelium. At mRNA level some efflux proteins were over-expressed in the HCE and the primary cell lines. Increased calcein retention and decreased CDCF efflux in the presence of inhibitors suggested efflux protein activity in both primary and HCE cells. Likewise, directionality in Rh123 permeability was diminished in the presence of verapamil in HCE model. Conclusions: Functionality of the efflux proteins was demonstrated in the human corneal epithelial cells. MRP1 and MRP5 proteins may have important protecting role in corneal surface by transporting molecules out from the epithelial cells. It seems that the efflux activity in the HCE model differs from that of the corneal epithelium in vivo [source]

Imiquimod in the treatment of eyelid basal cell carcinoma

ACTA OPHTHALMOLOGICA, Issue 5 2007
Jari Leppälä
ABSTRACT. Purpose:, To assess the efficacy and safety of topical imiquimod 5% cream in the treatment of eyelid basal cell carcinoma. Methods:, Four patients with eyelid basal cell carcinoma were treated with imiquimod once daily, 5 days per week, for 6 weeks. Tissue biopsy was taken and clinical examination with slit-lamp microscopy was performed at the beginning of the study and after a follow-up of 12 weeks. Photographic follow-up was performed from the baseline visit to 6, 12 and 26 weeks. Results:, In the 12-week follow-up after imiquimod treatment, histopathological tissue sample analysis showed no signs of basal cell carcinoma in any of the patients. Conclusions:, The results indicate that 5% imiquimod cream with topical administration may represent a new therapy option for eyelid basal cell carcinoma. [source]