The views expressed are those of the authors and not necessarily

The views expressed are those of the authors and not necessarily those of FORCE, the NHS, the National Institute for Health Research, or the Department of Health. “
“Worldwide, gastric cancer is the fourth most common cancer and the second most common cause of cancer deaths [1]. China has a high incidence PD0332991 price of gastric carcinoma. The incidence of gastric cancer

has been increasing in China. In 2008, Chinese cases of gastric cancer accounted for more than 42% of the worldwide incidence [2]. According to the Chinese National Office for Cancer Prevention and Control (Beijing, China), gastric cancer incidence is still the most common cause of cancer death in China, and gastric cancer mortality accounted for nearly one fourth of all cancer deaths [3]. Complete surgical eradication of a gastric tumor represents the best chance for long-term survival. Nevertheless, nearly half of patients will develop recurrence or metastasis in a short period after radical surgery. In the United States, adjuvant chemoradiotherapy is the standard treatment for resectable gastric cancer. In much of Europe, neoadjuvant chemotherapy has become the

preferred treatment strategy. However, the standard of care in Asia is still adjuvant chemotherapy. Many randomized trials have compared adjuvant systemic chemotherapy to surgery alone, with variable results. Some meta-analyses have shown that adjuvant chemotherapy OSI-744 molecular weight has a significant survival benefit [4]. To date, outcomes of adjuvant treatment in gastric cancer remain disappointing. For locally advanced gastric cancer (AGC), the 5-year survival rate reported mafosfamide in the Japanese literature is approximately 50% [5] and is only 8% to 20% in the United States [6]. With the development of new chemotherapy agents, gastric cancer survival has improved. However, the question of which regimen is most effective for gastric cancer

remains unresolved. This study was a single-center prospective phase II trial. In this study, we evaluated the efficacy and safety of docetaxel plus cisplatin and 5-fluorouracil (5-FU) (DCF) regimen as adjuvant chemotherapy for gastric cancer. Eligibility criteria for this study included the following: age of 18 years or older, histologically confirmed gastric or gastroesophageal junction adenocarcinoma, complete resection of the tumor, enrollment between 3 and 6 weeks after radical resection, American Joint Committee on Cancer (AJCC) (version 7.0) stage of IB to IIIC, no prior treatment for gastric cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate hepatic, renal, and hematologic function [as indicated by serum bilirubin ≤ 1.5 × upper limit of normal (ULN), serum aspartate aminotransferase ≤ 2.5 × ULN, alkaline phosphatase ≤ 2.5 × ULN, creatinine ≤ 1.5 × ULN, hemoglobin ≥ 80 g/l, platelets ≥ 75×109 per liter, and absolute neutrophil count ≥ 1.5×109 per liter]. Patients were ineligible if distant metastases or severe/uncontrolled medical comorbidities were present.

The UNGA also requested that FAO develop “Guidelines for the mana

The UNGA also requested that FAO develop “Guidelines for the management of deep-seas fisheries on the high seas.” These Guidelines, adopted in August 2008, call for rigorous management of deep-sea fisheries throughout all stages of their development, and for keeping catch rates low until knowledge, management capacity and measures for monitoring, control and surveillance increase [143]. A review

of progress in implementing the UNGA resolution in late 2009 revealed that, while a number of RFMOs had adopted measures such as closed areas to reduce the impact of fishing on deep-sea habitats, few RFMOs had taken steps to ensure the sustainability of deep-sea fisheries [144]. As a result, the UNGA

adopted a new resolution with clear language calling for States and RFMOs not to authorize deep-sea fisheries unless an impact assessment had been performed and selleck chemicals llc measures adopted to prevent significant impacts on deep-sea ecosystems. It then explicitly called for States and RFMOs, where scientific information is uncertain, unreliable or inadequate, to “adopt precautionary management measures to ensure that fishing effort, capacity and catch levels did not exceed levels consistent with the sustainability of the fish stocks and non-target species.” [UNGA resolution 64/72, paragraph 119(d) (emphasis added) [142]. Improved adherence to the 2006 and 2009 UNGA resolutions and FAO Guidelines could help towards achieving sustainability of deep-sea

fisheries. Phospholipase D1 check details However, until states fully implement their obligations, including through better flag state and RFMO performance, and better data, the preconditions for sustainability for deep-sea fisheries on the high seas will not be met. And as unlikely as that is in deep-sea portions of countries’ EEZs, it is even less likely on the high seas under current conditions. A UNGA review of progress by States and RFMOs in implementing the 2006 and 2009 resolutions in late 2011 provides an opportunity for all States to insist that deep-sea fisheries on the high seas be managed on a sustainable basis, or not allowed to proceed. After briefly reviewing key aspects of the biology of deep-sea fishes, the authors of this paper conclude that sustainable exploitation is feasible for very few of them under prevailing economic conditions and governance arrangements. The authors do note that catches of a handful of species can be or can give the appearance of being sustained, primarily ones that (a) can occur shallower than 200 m, (b) have relatively high population resilience and (c) are fished with low-tech, non-trawl methods. The surplus production of deep-sea fishes is generally low, but their biomass can be attractively high.

Preferred prey items for flounder and eelpout were gammarideans a

Preferred prey items for flounder and eelpout were gammarideans and bivalves Macoma balthica, while priapulids Halicryptus spinulosus and soft-shell clams Mya arenaria were eaten only by flounder. Flounder had the most diverse diet composition (a total of eight prey items), while eelpout and cod preyed upon six and four prey items respectively.

Half of the prey items were eaten by all three species, while two items (H. spinulosus and M. arenaria) selleck products were exclusively fed on by flounder. Different weights were assigned to every fish species separately according to the occurrence and importance of prey items ( Table 3). According to the coefficient of variation of mean absolute deviation (Table 4) the most accurate model was obtained for blue mussel M. edulis (16%). Models of S. entomon, Gammaridea, H.

spinulosus and M. arenaria were also relatively accurate (< 50%). The model of M. balthica was less accurate (61%), and the accuracy was the lowest for both polychaete models (> 70%). The mean decrease accuracy (%IncMSE) was calculated for each predictor in order to evaluate its importance to the response variable (Table 5). The most important predictor was near-bottom oxygen concentration especially for deep-living species like M. balthica, S. entomon and H. spinulosus (28.7, 12.1 and 24.6 %IncMSE respectively). BMS 354825 Orbital velocity, salinity and sediments were also important: the biomasses of amphipods M. edulis were mostly dependent on sediments (9.3 and 34.8 %IncMSE respectively), while salinity had a major influence on both polychaete worms and M. balthica, and orbital velocity on H. spinulosus 5-Fluoracil molecular weight and S. entomon (12.7 and 18.9 respectively). Near-bottom current velocity was less important, while the halocline and thermocline were only of minor importance or of no importance at all in some cases. The map of seabed quality for the feeding of cod, flounder and eelpout is presented in Figure 3. The highest quality feeding grounds for all three fish species is the stony bottom in the coastal area situated in the northernmost part of LEZ. Other high quality

areas are located in the offshore zone: one in an offshore bank with heterogeneous sediments at 50 m depth (western part of LEZ), another in the soft bottom at 40–50 m depths (central part of LEZ). The accuracy assessment indicates that the most accurate areas of the approach are at 10–40 m depths. The low accuracy areas were justified by only 18% of total samples and were set in very shallow areas (down to 3 m depth) and for the deepest areas. Accuracy was moderate for offshore areas in the central part of LEZ and for the coastal area. More than half the samples were taken in the coastal area, but because of the rapid changes in some environmental parameters (especially salinity and near-bottom orbital velocity) the quartiles of these predictors were only moderately justified in terms of accuracy.

To date, freezing extender containing 23% (v/v) egg yolk, 8% (w/v

To date, freezing extender containing 23% (v/v) egg yolk, 8% (w/v) lactose monohydrate has been most commonly used extender used to cryopreserve rat sperm [34]. All of these previous studies cooled straws containing rat sperm by holding 2 cm above the liquid nitrogen level (at −150 to −170 °C) for 10–15 min before plunging into LN2 [34], [56], [57] and [58]. However, they did not report exact cooling rates. To date there has been only one fundamental cryobiologic study investigating optimal cooling rate for rat sperm. Hagiwara et al. [19]

evaluated the biophysics (membrane permeability) Crizotinib price of rat sperm to better understand the cooling rate response that contributes to cryopreservation Ion Channel Ligand Library chemical structure success. A differential scanning calorimeter studies predicted and experimentally tested optimal cooling rates that ranged from 53 to 70 °C /min for rat sperm. Maximum motility was obtained with cooling rates between 50 and 80 °C/min. This is one of the first studies which aimed at determining optimal cooling rate using a Linkam Cryostage. Optimal cooling rate varies from species to species. It has been shown for mouse sperm that cryo-survival

is depended significantly on the cooling rate, and less strongly associated with the warming rates as long as rapid warming (∼1000 °C/min) is used. In this study we also used the rapid warming (∼1000 °C/min). Cooling rate significantly affected post-thaw motility of SD sperm in TL-HEPES, m-KRB and TES-R extenders and motility of F344 sperm in TL-HEPES, SM, TES-R and TES-S extenders. In these extenders, post-thaw motility decreased

significantly in 10 °C/min cooling rate compared to 100 °C/min cooling rate. The highest motility was obtained Interleukin-3 receptor when rat sperm was cooled between 40 and 100 °C/min. This is consistent with the previous report from Hagiwara et al. [19] in that maximum motility was obtained with cooling rates between 50 and 80 °C/min. In this study we did not investigate cooling rate higher than 100 °C/min because of the limitation of Linkam cooling stage. Most commonly used cooling machines in laboratories cannot reach controlled cooling rate of 100 °C/min and above. It is accepted that constant cooling of rat sperm cannot be achieved in LN2 which cools sperm between 100 and 130 °C/min. Stacy et al. [47] has elegantly demonstrated low reproducibility of freezing protocols due mainly to variation in cooling rate in LN2 vapor. For mouse sperm, cooling rate of 114 °C/min resulted in higher motility than cooling rate of 39 °C/min but, cooling rate of 192 °C/min led to the lowest motility [47]. Similarly, Koshimoto and Mazur [27] showed that cooling rate between 27 and 130 °C/min resulted in more motile sperm compared to the lower or higher rates. In this study, freezing and thawing of rat sperm resulted in decrease in motility, plasma membrane integrity, acrosome integrity and MMP.

001, paired

Student’s t test) ( Figure 1B) On incubation

001, paired

Student’s t test) ( Figure 1B). On incubation of dihydrorhodamine-1,2,3-loaded monocytes with CRLP (7.5–30 μg cholesterol/ml) there was a rapid increase in ROS formation in comparison to that observed in control cells; after 1 h exposure to CRLP at a dose of 7.5 μg cholesterol/ml there was a 7.5 fold increase selleckchem which was maintained for at least 24 h and was not dose dependent (Figure 2). PDTC, a well-characterised antioxidant with reported ability to inhibit NF-κB activity, reduced both basal and CRLP-induced ROS production (Figure 3A). In contrast, inhibitors of NADPH oxidase (apocynin; PAO; DPI Figure 3C–E) or xanthine oxidase (allopurinol; Figure 3F) had no significant effect on ROS production in CRLP-treated cells. Similarly, neither the MEK inhibitor U0126 (Figure 3B) nor its inactive analogue U0124 (data not shown), affected ROS generation in the presence of CRLP. Freshly isolated human monocytes were incubated with or without CRLP for 6 or 24 h and the secretion of MCP-1 and IL-8 into the medium was measured (n = 5). In the absence of CRLP, the cells secreted high quantities of MCP-1 (CCL2) (5.01 ± 1.58 ng/ml) and IL-8 (CXCL8) (1.54 ± 0.24 ng/ml) after 24 h. Secretion of MCP-1 was decreased by CRLP treatment and this effect was significant after 24 h (6 h, 2.78 ± 0.84 ng/ml; 24 h, 0.65 ± 0.01 ng/ml (P < 0.05)) ( Figure 4A), whilst IL-8 secretion

into the medium was increased ALK inhibitor review Resveratrol at 6 h (3.34 ± 0.30 ng/ml, P < 0.001) and returned to control levels by 24 h (2.77 ± 0.11 ng/ml) ( Figure 4B). Constitutive secretion of both MCP-1 and IL-8 was significantly reduced by treatment with U0126. Production of MCP-1 and IL-8 was also inhibited by PDTC, whereas the NADPH oxidase inhibitor, apocynin, had no effect (Figure 4A, B). Incubation with CRLP did not influence the reduced MCP-1 secretion observed following

treatment with U0126 or PDTC (Figure 4A) but restored IL-8 secretion to constitutive levels in the presence of either inhibitor (Figure 4B.). We hypothesised that the CRLP-driven reduction in MCP-1 secretion may result in increased monocyte chemotaxis due to the resulting increased MCP-1 concentration gradient in the monocyte microenvironment. This was investigated in vitro by testing the migration of cells towards MCP-1 using Transwell chambers ( Figure 5). After pre-exposure to control preparations for 24 h, the number of monocytes migrating to the lower chamber of the Transwells was not significantly different in the presence or absence of MCP-1 in the lower chamber ( Figure 5). Pre-treatment with CRLP, however, caused a significantly higher percentage of monocytes to migrate towards recombinant MCP-1. Addition of recombinant MCP-1 to CRLP-treated monocytes before commencement of the migration assay abolished this effect ( Figure 5). Recent studies have suggested that the interaction of CMR with monocytes may play a part in their atherogenic effects [22], [24] and [27].

Additionally, this ratio at periosteal cortical surfaces correlat

Additionally, this ratio at periosteal cortical surfaces correlated with maximum energy to failure (inversely). Structural properties TriSmi and Tb.Th correlated only with maximum force to failure. In contrast, μFE analysis did not show any effect of treatment on stiffness,

potentially due to the fact that the alteration of collagen cross-links was combined with preservation of the mineralization parameters as described by qBEI analysis. To determine the anatomical locations of compromised mechanical performance bone, nanoindentation tests (corrected for amount of mineral present based on qBEI analysis) were performed. The results indicated that the mechanical performance differences between control and β-APN treated animals are limited to areas of lower Pirfenidone mw Selleckchem Inhibitor Library mineralization, a logical outcome given the fact that the β-APN effect on bone was necessarily restricted to bone that was formed during the period of treatment. It is also in the same anatomical areas that the spectroscopically determined collagen cross-link ratio (Pyd/divalent) was altered. The fact that there were no differences in these bone areas between the animals either in mineral content or in maturity/crystallinity suggests that the observed differences in mechanical properties were due to alterations of collagen. In

this context it may be worth remarking that small local confined changes in mechanical properties of a composite material are not likely to affect the overall modulus of the bone material, which is always an average (though not necessarily an arithmetic average) of the local properties. However, it may have a profound effect on its strength, because strength depends essentially on the strength

of the weakest link in the chain. This seems to fit well also to the observation in the present study that the overall modulus of whole bone is essentially not affected, while the strength is reduced. It should be kept in mind when considering the results of the present study that not all of the expected changes in collagen due to β-APN administration were monitored. For example, we did not Niclosamide analyze for pyrroles (important trivalent cross-links), as no microspectroscopic parameters have been developed to date describing them, thus the anatomical spatial distribution could not be established. In summary, the results of the present study show the good correspondence between biochemically and spectroscopically determined pyd/divalent collagen cross-link ratio. They suggest that normalization for tissue age is critical as it excludes interference in the results from specimen age induced variability. They also indicate that collagen cross-link alterations, even when limited to certain anatomical areas (as in the case of the present study where they were confined to bone forming areas only), coupled with structural properties alterations are capable of affecting the mechanical performance of the whole bone.

, 2010 and Marin et al , 2011) The mechanism by which the antiox

, 2010 and Marin et al., 2011). The mechanism by which the antioxidant astaxanthin improves phagocytic capacity of neutrophils remains to be elucidated in future studies. Although it is well known that phagocytosis in neutrophil cells is a process which involves intracellular calcium mobilization, in the present study we did not observe any changes in intracellular calcium concentration among all groups. By means of Maillard reaction, MGO is able to cross-link with cellular proteins on targeted amino acids (arginine,

lysine), leading to the formation of advanced glycation end-products (AGEs), and thus contributing to aging and complications in chronic GSK-3 cancer diseases (Fleming et al., 2011 and Thornalley, 2005). Similarly to our results, some authors showed which MGO inactivate the enzyme glutathione reductase (Paget et al., 1998, Park et al., 2003 and Wu and Juurlink, LY2835219 solubility dmso 2002). Glutathione reductase recycles GSSG using NADPH

as a cofactor, reestablishing the intracellular content of reduced glutathione (GSH) (Juurlink, 1999 and Wu and Juurlink, 2002). Other studies have shown that MGO reduced GSH content making cells more sensitive to oxidative stress (Kikuchi et al., 1999, Meister, 1988 and Shinpo et al., 2000). The inactivation of MGO is a process catalyzed by the glyoxalase system that uses glutathione (GSH) as a cofactor. MGO inactivated bovine glutathione peroxidase in a time and dose-dependent manner, forming a connection with glutathione to sites of arginine 184 and 185 (Park et al., 2003). High concentration of MGO in plasma and aorta are associated with increased levels of superoxide, significantly reduced levels of GSH, decreased activity of glutathione peroxidase

and glutathione reductase in SHR MRIP rats with high blood pressure (Wang et al., 2005). Contrasting with these studies, we did not observe any change in the content of GSH, GSSG and in the rate GSH/GSSG (Table 2). Studies by Chang and colleagues (Chang et al., 2005) demonstrated that MGO caused mitochondrial oxidative stress by increasing the mitochondrial production of superoxide, nitric oxide and peroxynitrite. MGO can inhibit complex III and thereby disrupt the electron transport chain, leading to leakage of electrons to form superoxide anion (Wang et al., 2009). The direct effect of MGO on mitochondria was investigated by Desai and colleagues (Desai and Wu, 2007) using MitoSOX, a mitochondrial specific probe used to detect mitochondrial superoxide production. Incubation of vessel smooth muscle cells with MGO 30 μmol/L significantly induced mitochondrial superoxide production as compared with the group of untreated cells.

A small linear association was suggested The slope of the regres

A small linear association was suggested. The slope of the regression line was significantly greater than zero, suggesting that as microglial cell body number increased, DG volume increased (slope = 0.000019 mm3; 95% C.L. 0.00000564–0.00003169 mm3; t28 = 6.12; p < 0.01; Y = 0.22 mm3 + (0.00019 mm3 × X); adj r2 = 0.20). Previous research suggested

that via diverse mechanisms Pb exposure promotes neuroimmune disruption, and perhaps chronic microglial activation and microglial proliferation (Kraft and Harry, 2011). Neuroimmune system changes following early chronic exposure to Pb and blood levels between 2 μg/dL and 20 μg/dL have rarely been examined. Hippocampus/DG regions have been implicated

in animal models (Azzaoui selleck inhibitor et al., Selleckchem PD0325901 2009, Kasten-Jolly et al., 2012 and Leasure et al., 2008) and clinical studies of asymptomatic Pb exposed children (Canfield et al., 2003, Chiodo et al., 2004 and Lanphear et al., 2005). Thus, we compared neuroinflammatory markers in anterior (without hippocampus) and posterior (with hippocampus) brain sections; and we compared the volume and number of neuroimmune cells in the DG. We predicted dose-dependent changes in gene expression of neuroinflammatory biomarkers consistent with heightened microglial activation, and increased microglial mean cell body volume and number. Understanding whether dose–response relationships exist between Pb and outcome variables can be critical for

understanding the nature of possible mechanisms of action, and also for comparison in subsequent studies that aim to replicate and refine the current findings. We also measured DG volume to examine evidence of neurodegeneration. The range of blood Pb levels achieved in the 30 ppm exposure groups (study 1 = 2.86–6.78 μg/dL; study 2 = 2.48–4.65 μg/dL) replicated the blood Pb levels of approximately 65% of low-income children tested in our child Pb exposure studies (unpublished data). Significant differences between exposure groups on outcome variables were found, but were not suggestive of heightened microglial activation. Increased neuroinflammatory response in Pb exposed animals was discounted by the absence of group effects for five of six neuroinflammatory markers examined, science including TNF-α, IFN-γ, IL10, iNOS and HO-1. Only IL6 differed in Pb exposed animals, and a dose-dependent reduction was observed. Astrocytes absorb free-floating brain Pb; within astrocytes 78 kDa glucose-regulated protein (GRP78) sequesters Pb, a process which inactivates this chaperone protein (Lindahl et al., 1999) and results in decreased release of IL6 (White et al., 2007). IL6 serves neuroprotective and neuroadaptive functions (Gruol et al., 2011 and Inomata et al., 2003) thus reduced IL6 may suggest one source of increased neurotoxic vulnerability in Pb exposed animals.

We thank Ron Dotsch for making his code available and Steven McNa

We thank Ron Dotsch for making his code available and Steven McNair for help with participant recruitment. This research was supported by Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/J018929/1 to P.G.S., G.A.R., and N.v.R. and by a BBSRC DTP (WestBio) scholarship to K.J. “
“Tuberomamillary nucleus (TMN) neurons expressing the histidine decarboxylase (hdc) gene are the sole neuronal source of histamine [ 13, 14 and 15]. The hdc gene shows haploinsufficiency: a 2-fold

decrease in hdc mRNA levels halves the brain learn more content of histamine in mice [ 16 and 17], and in humans, having only one functional hdc allele produces a type of Tourette syndrome [ 16]. Thus, modest changes in hdc transcript levels in TMN neurons can change the amount of histamine released and influence behavior. Changes in hdc mRNA levels also seem to occur in the normal daily cycle. hdc mRNA levels in human hypothalamus are 1.6-fold higher for daytime deaths [ 18], and HDC enzyme activity and histamine levels in rat brain vary with selleck compound time of day [ 19, 20 and 21]. In agreement with these data, immunocytochemical staining for HDC protein in

mouse TMN neurons was stronger at zeitgeber time (ZT)18 (night, mid-lights off, the period when the animals are more active) than at ZT6 (day, mid-lights on) (3.5 ± 0.19 versus 1 ± 0.09 arbitrary units [AUs]; unpaired two-tailed t test, p < 0.001) ( Figures 1A and 1B). In control mice there was also a 1.5-fold variation in hdc transcript levels over 24 hr (unpaired two-tailed, t test, p < 0.05):

hdc mRNA was highest at the start of the night (ZT12), declined during the night, and increased during the day ( Figure 1C). By contrast, transcripts encoding the enzyme that inactivates histamine, histamine N-methyltransferase (HNMT), did not show daily variation in the TMN area ( Figure 1C). This daily variation in HDC expression Phloretin could indicate a clock-like mechanism in histaminergic neurons. Indeed, histaminergic neurons express the core clock protein BMAL1 ( Figure 1D). (BMAL1 antisera specificity was confirmed by the absence of staining in suprachiasmatic nucleus [SCN] sections from BMAL1 global knockout brains [ Figure S1A available online].) We crossed HDC-Cre mice [ 22] with animals containing a floxed Bmal1 gene [ 23] ( Figure S1B). The resulting HDC-ΔBmal1 mice were similar to littermate controls in weight (control weight, 26.6 ± 0.6 g, n = 5; HDC-ΔBmal1 weight, 27 ± 0.7 g, n = 5; unpaired two-tailed t test, p = 0.34) and seemed healthy. All the HDC-positive cells lost BMAL1 ( Figure 1D). In our characterization of the HDC-Cre mice, we found that transient developmental expression of the hdc gene produced recombination in several additional places, in particular the dorsal lateral geniculate (DLG) thalamic nucleus, the ventral medial (VM) hypothalamic nucleus, and Purkinje neurons [ 22].

As shown in Fig 4A–C, complete removal of the epidermis leaving

As shown in Fig. 4A–C, complete removal of the epidermis leaving just the underlying dermal tissue reduced the ER from 8 kΩ to less than 1.0 kΩ. The TEWL in the same skin samples increased from about 5 g/m2/h to 61 g/m2/h. Both of these changes were highly significant (p < 0.0001) for n = 20 unpaired samples. Similarly, the Tritiated Water Flux (TWF) was

much higher in the same heat-separated membranes (p < 0.001) with the skin permeability coefficient (Kp) rising from about 2 to 15 × 10−3 cm/h for n = 10. Essentially, these skin samples with “damaged” membranes had very little barrier to prevent water movement through the skin. This investigation has examined the potential of using the skin integrity find more methods used in OECD guidelines for in vitro dermal absorption studies together with the tape stripping approach used to assess disposition of chemicals and drugs in the stratum corneum, in order to develop a new model for assessing skin penetration in situations where the skin barrier is abnormally permeable. We recognise that the use of ER measurements with tape stripped skin may be highly impractical Selleckchem Talazoparib when assessing the penetration of compounds through a compromised skin barrier in vivo. The ER method involves hydration of the anatomical face of the skin therefore, its applicability to disease situations involving changes in hydration of the stratum corneum may be limited.

However, in this investigation, we have identified that tape stripping and use of ER, in particular, is a rapid, robust and practical in vitro approach that may be useful to study the absorption of chemicals and drugs through skin that has impaired barrier properties. Furthermore, being an in vitro model it avoids the ethical issues associated with creating surface damage to the organ in a living animal. Our objective was to determine which is the most practical and robust in vitro method of barrier impairment

using a step-wise approach of sequential Adenosine triphosphate tape stripping of dermatomed pig skin. Based on our own laboratory’s equipment, which has been described in more detail in our previously published work in this journal, we have shown that of the three measures of skin integrity, only ER was robust enough to discriminate between the barrier property changes effected by sequential tape stripping ( Davies et al., 2004). It is also a very rapid assessment and not prone to the effects of humidity stabilisation, air flow, temperature fluctuation and time-consuming instrument calibration. The measurement of water flux through the skin (TEWL or TWF) requires a long period of stabilisation, due to the equilibration of water in the spacial compartments of the skin layers and microenvironment immediately above the tissue (in the case of TEWL) taking time to reach stable readings between strips. These measures of water movement proved to be unsuitable as a rapid test for skin damage.