volumes about 2–3 times larger than those for uniform patches (Figure 7a). This difference is found along both chromatic (Figure 7b) and luminance (Figure 7c) dimensions, though the ratios are higher for chromatic projections. A similar increase in chromatic thresholds was reported by Hansen et al. (2008) for natural textures, and for synthetic textures with color distri- butions similar to natural textures. Montag and Berns (2000) also reported similar effects in luminance thresholds. A possible explanation of these results could lie in the proposition by Webster and Mollon (1997) that polychromatic natural stimuli entail not only adaptation to the mean luminance of the scene but also a contrast adaptation to the color distribution within the scene. They reasoned that although light adaptation could adjust for changes in mean color, it cannot compensate for changes in the statistics of the color distributions. They further proposed that con- trast-adaptation mechanisms might operate by whit- ening the stimulus color distribution based on changes in postreceptoral channel tunings, with new tunings emerging due to inhibition between channels which produce the most correlated responses (Atick, Li, & Redlich, 1993; Barlow & F¨oldi´ak, 1989; Webster & Mollon, 1997). Considering that in the current study the observer could view the entire scene (the interior of the testing booth), one cannot ignore contrast adapta- tion regardless of whether the tested stimuli were uniform or textured. Even so, it is likely that the amount of possible contrast adaptation in case of uniform stimuli was lower than that for the simulated skinpatches (since there is no contrast within a uniform foveal stimulus). Thus, the observers were compara- tively less adapted, and hence less capable of constancy or discounting the illuminant in the uniform color condition, which in turn would predict better discrim- ination performance or lower thresholds compared to skin stimuli.
Testosterone replacement has undergone somewhat of a revolution in the past decade with the introduction of topical administration techniques, including patches and gels, as well as an increasing interest in the treatment of older men with low testosterone levels for what is now termed andropause. Increasingly, testosterone replacement therapy is being individually tailored. Side effects to skinpatches have been reported with irritant contact dermatitis being the most common. However, ulceration has previously not been reported. Herein, we present a case that highlights testosterone transdermal therapies, their potential side effects and management strategies, and broadens our knowledge as we approach an era where these types of treatments are likely to be more common. KEYWORDS: testosterone, androgen, cutaneous administration, ulcer, dermatitis, hypogonadism, urology
good candidates for a more detailed analysis. Pharmacological analysis consisted in (i) dose–light response curves to determine the sensitivity of the tissue, (ii) use of antagonists (Table2) to signal the presence of a specific receptor in the tissue investigated, and (iii) use of second messenger analogues and enzyme activators and inhibitors (Table2) to determine the intrinsic control of the photophores in E. spinax. When inhibitors or antagonists were used, the ventral skinpatches were first immersed for 20min [except for the janus kinase 2 (JAK2) inhibitor, which necessitated a longer pre-treatment (Sandberg et al., 2005)] in a saline containing the inhibitor (or antagonist) at the desired final concentration and then received an injection of saline containing both the inhibitor (or antagonist) at the desired final concentration and the drug at a concentration that allows the final concentration to be the best working dilution. Due to large individual variability in the amplitude of light responses in E. spinax, dose–light response curves were given in relative units, and effect of antagonists, inhibitors and activators in percentage of control, i.e. the luminescence induced by the tested drug injected alone. All the experiments were conducted at room temperature (18°C).
test was performed by lightly pressing a thumb on the patch for 5 sec and then quickly removing it. By varying the pressure, time of contact, and considering the difficulty of pulling the thumb from the adhesive, it was possible to guess how easily, quickly, and strongly the adhesive formed a bond with the skin. The test was performed blindly on different patches to determine the proper formulation for further studies. The adhesive properties of the patches were expressed by the following value range: good adhesion, poor adhesion, and no adhesion. 11
In the ﬁ lm formation, the plasticiser maintains elasticity and prevents cracking of the ﬁ lm. Plasticisers can also maintain the stability of active substances 25,26,79 and increase the permeation of drugs. Polyethylene glycol (PEG) and propylene glycol (PG) are reported to have a role in increasing the permeation of antifungal drugs. Apart from being a plasticiser, PG also has a role as a solubiliser, which is also useful in carrying drugs through the skin. 41,98 PG has a signi ﬁ cant effect on the viscosity of the ﬁ lm-forming solution, so the concentration needs to be considered (see Table 3). 68,99 The use of PG in a mixture with water and ethanol does not have a good effect as a mixed solvent in preventing the crystallisation of testosterone. 68 The effective PG concentration for increasing drug permeation is below 5 %. 34,100
Gill et al (2007) have been studied on coating of Microneedle. A novel micron-scale dip-coating process and a GRAS coating formulation were designed to reliably produce uniform coatings on both individual and arrays of microneedles. This process was used to coat compounds including calcein, vitamin B, bovine serum albumin and plasmid DNA. Modified vaccinia virus and microparticles of 1 to 20 μm diameter were also coated. In conclusion, this study presents a simple, versatile, and controllable method to coat microneedles with proteins, DNA, viruses and microparticles for rapid delivery into the skin. 17 Recently Lee et al (2008) has studied on dissolving microneedles for transdermal drug delivery. This study presents a design that encapsulates molecules within microneedles that dissolve within the skin for bolus or sustained delivery and leave behind no biohazardous sharp medical waste. 18
Vitiligo is an autoimmune and autoinflammatory condition which is caused due to our own immune system attacking itself and it causes white colored patches (the loss of skin color in blotches). This is the kind of disease which is observed in 1% of the total population. The extent and rate of color loss from vitiligo is unpredictable and have sharp margins. The hair from the skin also becomes white. The inside of the mouth and nose may also be involved. It occurs in people with all skin types and color but mostly occurs in people with dark skin where all the areas of their body are dark and effected areas are white in color. This condition even causes much psychological stress to the effected people from relatives and society. The risk of autoimmune and auto inflammatory diseases is assumed to depend upon interactions between environmental factors and specific variants of specific genes. This may result in many other diseases to attack these individuals. It is very easy to diagnose this disease as it can be directly done by the physical examination. Descriptions of a disease believed to be vitiligo date back to a passage in the medical text Ebers Papyrus circa 1500 BCE in ancient Egypt. Mentions of whitening of the skin were also present circa 1400 BCE in sacred Indian texts such as Atharvaveda as well as Shinto prayers in East Asia circa 1200 BCE. The Hebrew word "Tzaraath" from the Old Testament book of Leviticus dating to 1280 BCE (or 1312 BCE]) described a group of skin diseases associated with white spots, and a subsequent translation to Greek led to continuing conflation of these with vitiligo with Hansen's disease and spiritual uncleanliness.
Ex-vivo Release of GA: The prepared F4 transdermal patch of GA was evaluated for ex-vivo release pattern. The mechanism of permeation enhancement of menthol could involve its distribution preferentially into the intercellular spaces of stratum corneum and the possible reversible disruption of the intercellular lipid domain 21 . Bioenhancer, piperine increase the bioavailability of the drug by a biphasic mechanism involving partial extraction of stratum corneum (SC) lipid and interaction with SC keratin 22 . Ex- vivo study using fresh abdominal skin of goat as permeability membrane confirms the release of GA in the patch as controlled delivery over 10 h as 91.58%.
To participate in the study, subjects had to be healthy males or healthy non-pregnant, non-lactating females over the age of 18 years with a Fitzpatrick skin type of I to IV and no upper age limit. Facial measurement of melanin was used to help determine Fitzpatrick skin type. Subjects all had at least mildly severe fine wrinkling and mottled hyperpigmentation. The subjects could not be using photosensitizing medications, anticoagulation or cortisone therapies, or facial photoaging or hyperpigmentation treatments. They had to be free of skin diseases, any known metabolic disorders such as diabetes, and any known malignancies. They could not have recent or current histories of chemotherapy, inflammation within the treatment area, or allergies to gluten or known hyper- sensitivity to any component(s) or excipient(s) of the study products. All participants had to agree to use a sunscreen with SPF $15 and avoid prolonged exposure to ultraviolet (UV) light during the study. Potential risks associated with this study included redness, burning, dryness, stinging, and irritated and peeling skin. Because TAZ can harm a fetus if administered during pregnancy, pregnant and nursing women were precluded from participating in the study. Adverse reac- tions were mild and the study did not record any instances of medication discontinuation or study withdrawals.
In order to determine the relationship between physiographical factors and regeneration changes in forests, and to improve and model natural regenera- tion status, Gorazbon district in Kheyrod Forest was selected for the study. All available regeneration patches in the area were selected. To achieve spatial structure and quantify metrics related to regeneration patches, the analysis of landscape metrics was used. The results show that 692 regeneration patches were identified at the level of different directions. LAND Metric show the most regeneration percent is related to the western (9%), southern (8.66%), flat areas (8.33%), northern (5.68%) and eastern (4.73%), respectively. In total, the patch coverage level percentage was calculated in the landscape (8 . 31%). The results related to patch shape metric show that most shapes of patches follow polygon structures and do not have fixed shapes. Results related to the average area of the patch metric show that the average level of patches is be- tween 4 and 5 R. The maximum and minimum distance between patches was observed in the survey between 39 and 520 m respectively. According to the results of the distance average between patch metric, the distribution of patches is random in the southern and western directions, flat areas and pile, but it is uniform in northern directions. It should be noted that the distribu- tion and structure of patches in the northern directions has a better distribu- tion and homogeneity than the other directions. Its canals are used as a natu- ral regeneration model to follow the natural phenomena in forest sustainable management.
Psoriasis is a very long lasting disease affecting millions of people worldwide. In the patients affected by psoriasis, the skin cells multiply faster than normal and raised and red plaques appeared over the skin. Psoriasis also has association with psoriatic arthritis, increased risk of depression, diabetes and cardiovascular disease. It is an autoimmune disease and complete cure cannot be achieved when all the current treatment options can relieve the symptoms only for a short time. After a very long searching of more sustainably effective drugs for psoriasis, the FDA recently approved the new drug ixekizumab. Ixekizumab is a humanized IgG4 variant IL- 17A neutralizing monoclonal antibody. It has high affinity for human IL- 17A and effectively inhibits the binding of IL- 17A to IL- 17A receptor. As the pathogenesis of autoimmune psoriasis is contributed by IL- 17A producing pathogenic T-cells, ixekizumab can completely or almost completely clear the disease in moderate to severe psoriasis. The major drawback is that ixekizumab is an immunosuppressive agent causing increased risk of infection. Ixekizumab brings the hope to psoriatic patients but further immense research needs to be performed in the treatment of psoriasis.
In the greenhouse experiment, two levels of PSF heterogeneity (spatially homogeneous PSF and spatially heterogeneous PSF) were created using soil conditioned by A. odoratum and C. jacea from the same field block (Figure 1). In the heterogeneous soil treatments, each pot was equally divided into four patches using a metal grid and each patch was alternately filled with 1.4 kg soil conditioned by monocultures of A. odoratum or C. jacea. In the homogeneous soil treatments, each pot was filled with 5.6 kg of a 1:1 (w:w) homog- enized mixture of soil conditioned by monocultures of A. odoratum and C. jacea (Figure 1). In this way, there were pots that differed in spatial variation in plant–soil feedbacks, while the abiotic and biotic soil conditions in the homogeneous and heterogeneous soils were kept constant. We allocated pots filled with soils originated from the same field block in the same block in the greenhouse experiment so that there were five blocks. Pots of different treatments were randomized within each block. Holes were made in the bottom of each pot to allow vertical movement of water. To prevent soil from passing through holes, a piece of filter paper (15 cm in diameter) was placed at the bottom of each pot before filling the pot with soil. Each pot was placed on a tray to prevent possible contamination through leachate. The metal grid was removed after each pot was filled so that plants could grow freely across different patches. We randomly selected three field blocks and collected subsamples from the soil of each plot in those blocks for soil chemical analysis. We measured soil organic matter content, nutrient content (NH 4 , NO 3 and PO 4 ), water content and pH (Supporting Information Table S1). The amount of NH 4 , NO 3 and PO 4 (mg/kg dry soil) was determined by adding 30.0 ml of 0.01 mol/L CaCl 2 solution to soil samples (3.0 g), shak- ing mechanically for at least 2 hr at room temperature (20°C), filter- ing the solution and analysing the nutrients in the soil extracts in a flow analyser (SKALAR SAN plus system). Soil pH- H 2 O was deter- mined by adding 25.0 ml demi- water to soil samples (volume 5.0 ml), shaking for 5 min and measuring 2 hr later. Soil organic matter was determined by measuring the difference between weights of the oven- dried (105°C) soil samples (5.0–10.0 g) before and after being heated in a furnace at 550°C. The weight of each sample was deter- mined after cooling it down in the air to handwarm temperature and further cooling it for at least 45 min in a desiccator. Soil moisture content was determined by measuring the difference between the weights of each soil samples before and after oven- drying (105°C).
Geometry of the proposed antenna is shown in Fig. 1. The antenna is constructed on an FR-4 substrate with a dielectric constant of 4.4, loss tangent of 0.02 and thickness 1.6 mm. The gap coupled 2 × 1 array consist of four rectangular patches, where the two patches in the lower layer are driven elements and the two patches in the upper layer acts as parasitic elements with same dimensions printed on the top side of the substrate, A tapered arrow headed dumbbell shaped slot is etched in the ground plane on the other side. The microstrip line and the patches are etched on the top side of the substrate. Figs. 1(a) and 1(b) show the top and bottom view of the proposed design. The simulation and optimization were carried out using CST Microwave Studio. This array conﬁguration shows dual-band operation at 2.45 GHz WLAN band and 3.5 GHz WiMAX band for optimized dimensions. The optimised design parameters of the antenna are as follows (unit: mm), S L = 100, S W = 100, P W = 33.5, P L = 27.6,
This research project allowed both short-term and long-term visual monitoring of the performance of the test patches containing the fiber additive. Polypropylene fiber reinforcement has been used in other applications, but not in a concrete patch on an interstate highway. The addition of the polypropylene fibers initially (short-term) may prevent or retard shrinkage cracking. Patched cement concrete roadways on many projects are overlaid with a Superpave bituminous overlay for ride quality shortly after the patches are placed and cured. However, on this project, the road surface of the entire project was diamond ground to achieve ride quality, thus allowing the concrete fibers in the patch to remain exposed. Over the long term, the fibers may prevent cracking due to loading and/or freeze-thaw. The 2-inch length polypropylene fibers (see photographs 3 and 4 on page 2) were dispersed throughout the Class AA Concrete (3,750 psi, 28 day compressive strength) at a rate of 5 lbs/ C.Y. as recommended by the manufacturer. The polypropylene fibers were introduced at the central mix plant as the concrete was discharged from the mixing bowl into two transit mixer trucks, owned by New Enterprise Stone and Lime, just prior to being delivered to the I-99 project for placement (see photographs 5 and 6 on page 5).
The in-vitro permeation of drug from the formulated patches were carried out in Franz diffusion cell through rat skin membrane using 15 ml phosphate buffer (pH 7.4) as diffusion media for a period of 24 hours. In case of batch TD-1, TD-2 and TD-3, where ethyl cellulose (hydrophobic polymer) concentration is in gradual increasing order, showed a controlled release of the loaded drug over an extended period of 24 hours. It was also observed that the patches prepared with higher concentration of hydrophilic polymer just like in formulations TD-4, TD-5, TD-6, where concentration of PVP is in gradual increasing order, the drug release was very quick and the patches releases more than 98% of the loaded drug far before 24 hours. In this case the drug release was not in a controlled manner. A burst release was also observed for the patch formulations where concentration of hydrophilic polymer is in gradual increasing and hydrophobic polymer is in decreasing order (formulation - TD-4, TD-5, and TD-6). These patches exhibited the highest and fastest releasing pattern within 16‐18 hours with no control on releasing of drug. This may be due to rapid dissolution of the surface and the rapid leaching of hydrophilic fraction of the film former which results in the formation of pores and thus leads to the decreasing of mean diffusional path length of the drug molecules to