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At least 73 records · Page 4Linked to original sources

PubMed1997

Transdermal testosterone administration in hypogonadal men: comparison of pharmacokinetics at different sites of application and at the first and fifth days of application.

In this study of 13 hypogonadal men (25-69 years of age), three open-label, randomized treatments were administered to determine the pharmacokinetics of serum testosterone after application of an investigational testosterone transdermal system to the upper buttocks, upper arm, and back. Testosterone in vivo input kinetics profiles were estimated by DeMonS, a recently developed numerical deconvolution method for estimating drug absorption at different time intervals and/or drug disposition model parameters, and compared on the first and fifth days of system application. Area under the concentration-time curve from 0 to 27 hours (AUC0-27) values for testosterone after one-day applications to the upper buttocks, upper arm, and back were 9,560 ng.hr/dL, 8,651 ng.hr/dL, and 8,988 ng.hr/dL, respectively. Maximum observed concentration (Cmax) values were 482 ng/dL, 462 ng/dL, and 499 ng/dL, respectively. Serum testosterone concentrations were equivalent to each other, and Cmax values fell within the normal range. No drug accumulation was seen with repeated dosing over 5 days.

Administration, Cutaneous↗

PubMed1976

[Reflexphotometric determinations of vasoconstriction after topical application of steroids. V. Vasoconstriction phaenomenon and tachyphylaxis after repeated steroid application (author's transl)].

On the basis of reflexphotometrical vasoconstriction tests it is demonstrated, that the intensity of vasoreactions caused by a first topical application of steroids, diminishes rapidly after repeated applications, until there is no response of vessels to a new application. This phaenomenon is know as tachyphylaxis and has been found in all tested glucocorticoids.

Administration, Topical↗

PubMed1985

Thrombus formation by the application of thrombin to the outer surface of mouse mesenteric vein: comparison with the application of ADP.

Mesenteries of mice under anesthesia were stretched over an inverted microscope. A micropipette filled with solution containing various concentrations of ADP or thrombin was brought into contact with the outside of a mesenteric vein by micromanipulation, and then poured over the outer surface of the vein. Morphological characteristics of the thrombi and the time needed for thrombus formation were examined. Application of either thrombin or ADP to the adventitia of mesenteric veins caused thrombus formation. Although thrombi by application of ADP seemed to be anchored by direct adhesion of platelets to the exposed subendothelium, thrombi by application of thrombin seemed to be anchored by deposited fibrin.

Adenosine Diphosphate↗

PubMed2006

The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: design, application, treatment planning, and dosimetric results.

PURPOSE: To present a combined intracavitary and interstitial dedicated applicator and magnetic resonance imaging (MRI) treatment planning for cervical cancer brachytherapy. METHODS AND MATERIALS: A modified ring applicator allows interstitial needles to be implanted in parallel to the intrauterine tandem. MRI treatment planning based on a standard loading pattern with stepwise dwell weight adaptation and needle loading is performed to achieve optimal dose coverage and sparing of organs at risk. Dose constraints are applied for dose-volume histogram parameters. RESULTS: The use of additional interstitial needles provides prescription dose up to 15 mm lateral to point A. Twenty-two patients with high-risk clinical target volumes of mean 44 cm3 were treated with a mean prescribed total dose of 85 Gy (biologically equivalent to 2 Gy fractionation, alpha/beta = 10 Gy) and 93% coverage (V100). The dose to organs at risk was within standard limits for intracavitary brachytherapy alone. CONCLUSIONS: A combined interstitial-intracavitary applicator results in reproducible implants for cervical cancer brachytherapy. MRI-based treatment planning based on a target concept, dose-volume constraints, and limitations for the relative dwell weight allows for an increase in target coverage, treated volume, and total dose without increasing the dose to critical structures.

Brachytherapy↗

PubMed2006

Mechanistic applicability domains for nonanimal-based prediction of toxicological end points: general principles and application to reactive toxicity.

In light of new legislation (e.g., the REACH program in the European Union), several initiatives have recently emerged to increase acceptance of (quantitative) structure-activity relationships [(Q)SARs] to reduce reliance on animal (in vivo) testing. Among the principles for assessing the validity of (Q)SARs is the need for a defined domain of applicability, i.e., identification of the range of compounds for which the (Q)SAR can confidently be applied for purposes of toxicity prediction. Here, we attempt to develop a "natural" classification into applicability domains based on considering how a compound and the target organism between them "decide" on the nature and extent of the toxic effect. With particular emphasis on reactive toxicity, we present rules, based on organic reaction mechanistic principles, for classifying reactive toxicants into their appropriate mechanistic applicability domains.

Animal Testing Alternatives↗

PubMed1997

In vivo and in vitro diclofenac sodium evaluation after rectal application of soft gelatine capsules enabling application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) for controlled release.

PURPOSE: Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release from these systems after rectal application. METHODS: In vitro drug release was determined in a self-constructed dissolution apparatus to simulate rectal application. For in vivo bioavailability studies rabbits were used as animal models. In vitro release and in vivo bioavailability of the capsules was compared to Voltaren suppositories. RESULTS: The release profiles of the in vitro experiments show zero-order kinetics. The in vivo bioavailability studies show bioequivalence in terms of AUC for both formulations (capsules and Voltaren suppositories). The mean residence time (parameter of sustained release) of the capsules is three time longer in comparison to Voltaren suppositories. CONCLUSIONS: Rectal administration of capsules provides an appropriate route for controlled release via AIT-SSLC which could be clearly verified in rabbits.

Administration, Rectal↗

PubMed1986

The modelling of biological systems in three dimensions using the time domain finite-difference method: II. The application and experimental evaluation of the method in hyperthermia applicator design.

The three-dimensional time domain finite-difference (TDFD) method was used to design a 433 MHz circular waveguide applicator for electromagnetic hyperthermia. This applicator has a water-filled lens at one end, providing surface cooling as well as some shaping of the emergent electromagnetic field. An experimental system for scanning the EM field in three dimensions is described. The experimental data were compared with those calculated from the TDFD program and good agreement was found. A realistic three-dimensional model based on an ultrasound scan of a surface tumour was built. Both the EM field and the specific absorption rate (SAR) within the model when irradiated by the applicator were calculated.

Humans↗

PubMed2003

Biological monitoring for selected herbicide biomarkers in the urine of exposed custom applicators: application of mixed-effect models.

Metabolites and/or parent compounds of the herbicides atrazine, alachlor, metolachlor, cyanazine and the 2-ethylhexyl ester of 2,4-dichlorophenoxyacetic acid (2,4-D) were measured in the urine of 15 custom applicators who each provided from five to seven 24 h urine samples during a 6 week period (n = 87). Each applicator provided a pre-season urine sample and a reference population (n = 46) provided first-morning urine samples. Urinary biomarkers were measured by either immunoassay or gas chromatography. During the spraying season, the geometric mean amount of alachlor mercapturate equivalents (eq.), atrazine eq., 2,4-D and metolachlor mercapturate eq. excreted in 24 h was 17, 19, 110 and 22 nmol, respectively. Mixed-effect models were used to determine predictors of the amount of atrazine eq. and 2,4-D excreted in 24 h. The specific days of herbicide spraying associated with increased biomarker excretion varied for the two analytes, and included one or more days prior to urine collection. This confirms the importance of collecting covariate information on day(s) most relevant to the biomarker of interest. The within-worker variance component, expressed as a geometric standard deviation ((W)GSD range: 2.5-2.9), was substantially larger than the between-worker component ((B)GSD range: 1.3-1.5) for the modeled biomarkers. Alachlor mercapturate eq. and metolachlor mercapturate eq. were detected in more than half of the applicator pre-season urine samples. All biomarkers were detected infrequently in the reference population. Evaluation of non-spray exposure determinants was limited by inclusion of prior day spraying, adjustment for time and the small sample size.

Agriculture↗

PubMed1990

A study of systemic and topical effects of topical steroid application through the comparison of two application schedules.

We compared two application schedules of a topical steroid, BV (Betamethasone valerate). The schedules were once daily and twice a week on juvenile Wistar rats treated for four weeks. Steroid actions were assessed topically (skin thickness and epidermal Langerhans cell density) and systemically (body weight and internal organ wet weights). The results revealed some rather severe systemic effects caused by frequent steroid application. And we also found a uniquely weak BV effect with Langerhans cells compared to obvious systemic effects on rats. We came to the conclusion that frequent steroid application to the young should be avoided.

Administration, Topical↗

PubMed1979

Local anesthetics: importance of mode of application, concentration and adrenaline for the appearance of nerve lesions. An experimental study of axonal degeneration and barrier damage after intrafascicular injection or topical application of bupivacaine (Marcain).

Local anesthetics are designed for application in or close to nerve tissue. In spite of their wide clinical use, surprisingly few investigations deal with the neural toxicity of modern local anesthetics. In this experimental study, the effects were investigated of intrafascicular or topical application of the long-acting local anesthetic bupivacaine on the rabbit sciatic nerve. Axonal degeneration was histologically evaluated and a fluorescence-microscopic technique used to detect lesions in the blood-nerve barrier. Topical application of bupivacaine in clinically recommended concentrations around the nerve caused no detectable nerve injury, while intrafascicular injections caused considerable axonal degeneration and damaged the blood nerve barrier. Axonal degeneration was the same after injection of physiologic saline solution and bupivacaine 0.5%, but it increased with increasing bupivacaine concentration and especially with the addition of adrenaline. On the other hand, the acute effects of intrafascicular injection, as visualized in the barrier experiments, changed little with the addition of adrenaline, indicating that it is the injection trauma itself which is deleterious. It is concluded that intraneural injections should be avoided and that plain bupivacaine solutions should be routinely used.

Administration, Topical↗

PubMedDate not supplied

Endoscopic ultrasound instrumentation, applications in humans, and potential veterinary applications.

Endoluminal scanning under endoscopic guidance, or endoscopic ultrasonography (EUS), has become the most significant advance for imaging the gastrointestinal (GI) tract wall and contiguous organs in the past 20 years. It was originally designed to overcome the limitations in humans to imaging the abdominal organs transabdominally, such as large penetration depths and GI air. This imaging modality provides detailed images of pathological processes both within and outside of the GI wall since a high-frequency transducer can be brought into close proximity with the target regions. It has found most success in humans for the staging of lung, gastric, and esophageal cancer, the detection of both lymphatic and hepatic metastases, and diagnosis of pancreatitis and pancreatic cancer, as well as achieving an important role in interventional and therapeutic procedures. The EUS examination can be performed to examine both the thorax and abdomen in animals when both conventional transthoracic or transabdominal ultrasound are inadequate due to intervening air, bone, large penetration depths, or obesity. The echoendoscope is similar to a conventional endoscope but has an ultrasound transducer at its tip. Both radial and linear multifrequency scanners are available. Linear scanners allow fine-needle aspiration (FNA) of the bowel wall or extraluminal structures. Transducer coupling is either by direct mucosal contact or by inflation of a water-filled balloon surrounding the transducer. Current thoracic applications for EUS in veterinary medicine include examination of the mediastinum, bronchial lymph nodes, esophagus, and pulmonary lesions as well as FNA of pulmonary masses. Abdominal applications include examination of both pancreatic limbs and the liver, including portosystemic shunts, detection of lymphadenomegaly, and examination of the gastric wall, duodenum, and jejunum. Other potential applications in dogs and cats include tumor staging and intrapelvic ultrasound.

Animals↗

PubMed2002

Studies on dental erosion: An in vivo-in vitro model of endogenous dental erosion--its application to testing protection by fluoride gel application.

BACKGROUND: The objective in this study was to develop an in vivo-in vitro model of endogenous erosion, with a view to exploring the potential for some degree of its control by the use of topical fluoride gel application to teeth. METHODS: Six volunteers each wore a small clasp retained palatal acrylic appliance to which six sterilized enamel tiles were bonded. Three tiles on each appliance were coated extra-orally with either 1.23 per cent acidulated phosphate fluoride (APF) or 2.2 per cent sodium fluoride (NaF) neutral gel for four minutes prior to multiple periods of exposure to the simulated gastric acid, cumulating in 16, 36, 80 and 150 minutes of exposure. Impressions of the enamel tiles prior to and following acid exposure permitted dies to be prepared. These were sectioned through the exposed areas and examined under a stereomicroscope to assess maximum depths of erosion. RESULTS: The depth of erosive demineralization of enamel was found to be greatly reduced with increased frequency of APF gel application. The reduction in enamel loss was less following topical application of NaF gel. CONCLUSIONS: It was concluded that fluoride gels significantly reduced enamel erosion using this in vivo-in vitro model and therefore, if prescribed appropriately, should help reduce tooth tissue loss from endogenous erosion.

Acidulated Phosphate Fluoride↗

PubMed1995

Skin atrophy induced by initial continuous topical application of clobetasol followed by intermittent application.

BACKGROUND: The most frequent side effect of a long-term topical corticosteroid therapy is skin atrophy. To avoid or to reduce atrophy often an initial continuous application is followed by an intermittent maintenance therapy. OBJECTIVE: In this study we measured the skin thickness before and after the two-phase application schedule with the superpotent topical steroid clobetasol propionate (CP). For 16 days CP samples were applied twice daily on the test areas of 12 volunteers (phase 1). Then CP was applied to the same skin areas in accordance with the following timing: every 5th day, every 7th day, every 10th day, every 14th day (phase 2). Phase 2 lasted for 45 days. During the entire period of the study the skin thickness was measured regularly by the skin compression and thickness method as described previously. RESULTS: It could be seen that in phase 1 the skin became about 15% thinner. In phase 2 the steroid-induced skin thinning was approximately the same when CP was applied every 5th or 7th day. The skin thickness reached a more or less normal level when CP was applied every 10th day. After the 14th day a completely normal level was found. By measuring the skin thickness every day it was further shown that the skin thinning process lasted for 3 days when CP was applied once only. CONCLUSION: These results demonstrate that skin thinning must be expected by an intermittent maintenance therapy applied at relatively short intervals. The longer the intervals, the weaker the skin thinning. Moreover, these investigations showed that the skin thinning effect after a single CP application persists for nearly 3 days.

Administration, Topical↗

PubMed1990

Determination of the interval during which one application of compound 48/80 to the rat conjunctiva influences the response to a second application.

We studied the effect of one application of compound 48/80 to the conjunctiva of the rat on the response to a subsequent challenge. Rats treated once showed conjunctival edema and marked degranulation of conjunctival mast cells. A second exposure to compound 48/80, applied after an interval of 24 h, produced slight clinical effects but had marked effects on conjunctival mast cells. Approximately 90% of the mast cells could no longer be observed by light microscopy. As the interval between initial challenge and rechallenge was increased, the clinical response returned, mast cells were again observable in normal numbers, and the extent of degranulation returned to approximately 50%. After an interval of 7 days, rats responded clinically as they had to the first application of compound 48/80. Although the number of mast cells in the conjunctiva was normal and extensive degranulation occurred, exocytosis was not observed. Thus some effects of the first application of compound 48/80 persisted for at least 1 week. Whether the effects observed depend upon the continued presence of compound 48/80 in the mast cell or granule membrane remains to be determined.

Analysis of Variance↗

PubMed1989

[Application of local drug delivery system to periodontal therapy. 5. Clinical and microbiological effects of TC film application in furcation involvements].

Two molars having furcation grade II involvements were selected from each of six patients with periodontal diseases. One molar received a local application of tetracycline immobilized cross-liked collagen film four times at one-week intervals (TC film-treated group) and the other received no treatment (non-treated group). The clinical and microbiological effects were, as follows, 1. Throughout the experimental period, no significant differences in pocket depth, attachment level, bleeding on pocket probing, periotron unit, gingival index and plaque index were noted between the TC film-treated group and the non-treated group. 2. One week after TC-film application, the treated group showed significant decreases in the density of microorganisms and the proportion of spirochetes compared with the non-treated group. The results revealed the insufficient effectiveness of the local application of TC film by itself for the treatment of teeth having furcation grade II involvements.

Collagen↗

PubMed1999

[The indications for and results of HDR afterloading therapy in diseases of the skin and mucosa with standardized surface applicators (the Leipzig applicator)].

BACKGROUND: In our department we have developed a standardized applicator for HDR brachytherapy of surface lesions, the so called Leipzig-applicator. We have used this method since September 1987, initially with a Decatron remote afterloading machine, but more recently from November 1990 with a microSelectron-HDR. We report about our experience of 10 years. PATIENTS AND METHOD: Since 1987 we treated 520 patients in 3,026 fractions with this method. In most of the cases we irradiated tumors of the skin of the face, but we also treated tumors of the mouth, of the tongue, of the perianal region and the external genitalia. The histological types were in most of the cases squamous cell carcinomas and basal cell carcinomas, but we also treated tumors like Kaposi-sarcomas, melanomas and skin manifestations of lymphomas and solid organ tumors. We also irradiated benign lesions like keloids after excision. We use single doses between 5 and 10 Gy once to twice a week. The isodose distribution was depending of the tissue infiltration of the tumor. The total dose was 30 to 40 Gy. RESULTS: In 91% of the cases we obtained a complete remission of the tumor, in 6% a partial remission. Recurrences appeared in 8% of the patients. In most cases the reason of the recurrence was a lower brachytherapy dose because of a prior radiotherapy. We didn't observe any severe late radiation reaction. CONCLUSION: We consider that our series of patients treated with HDR brachytherapy and a range of standardized applicators demonstrates that this is a successful method of treating surface lesions.

Adult↗

PubMed2002

The Vivostat application system: a comparison with conventional fibrin sealant application systems.

The method of applying fibrin sealants may affect their physical properties and surgical performance. In this study, the characteristics of a novel fibrin-sealant application system (Vivostat were compared with conventional fibrin sealant spray systems. Delivery rates of Vivostat were highly reproducible in both high and low delivery modes (coefficient of variation [CV] < 1.0%) Airflow rates of Vivostat were 578 ml/min (6.6% (6.5% were lower and less variable than conventional systems, which ranged from 5000 to 10000 ml/min depending on the pressure. Spray forces of Vivostat were consequently lower than other systems and the deposited fibrin films formed were of more consistent thickness. Unlike other systems, blockages with Vivostat were rare on intermittent use. The Vivostat system offers the surgeon a controlled, precise and efficient means of fibrin sealant application with potential performance advantages over conventional spray application systems.

Biomedical Technology↗

PubMed2004

[Vitamin D3 for external application--history of development and clinical application].

The study of vitamin D(3) topical applications has begun at Osaka University after Morimoto S. reported a patient with senile osteoporosis whose psoriasis was cured after treatment with 1-alpha-hydroxyvitamin D(3) [1 alpha (OH) D(3)]. Another study of the first use of vitamin D(3) for psoriasis was reported in the same year in both Europe and the United States independently. Calcipotriol ointment came first onto the market for the treatment of psoriasis in Denmark in 1990. In Japan, where tacalcitol ointment was first approved in 1993, six kinds of topical vitamin D(3) applications are now available. Now new applications of vitamin D(3) are anticipated to replace therapeutic drugs currently in use for psoriasis and other skin diseases.

Administration, Topical↗