The Hairless Rat: A Relevant Animal Model to Predict In Vivo Percutaneous Absorption in Humans?

Percutaneous absorption of 4 radiolabeled molecules was compared in the hairless rat (back) and in different anatomic sites in human (arm, abdomen, postauricular, forehead). The conditions under which these 4 compounds were administered (area treated, dose, vehicle, contact time, etc.) were similar in both species. The results showed that, in humans and rats, there exists the same rank order in total absorption: benzoic acid sodium salt < caffeine < benzoic acid < acetylsalicylic acid. In both species there was a factor of 3 between the most and the least absorbed molecule. Although skin permeability varied significantly with the physicochemical nature of the compound administered, it also depended on the anatomic site involved. Independent of the molecule studied, the rank order of permeability of the sites tested in humans appeared as follows: arm ≤ abdomen < postwar < forehead. There was a factor of 3 between the most and the least permeable sites. For each molecule and each anatomic site, the ratios of total percutaneous absorption human/hairless rat (back) were determined. For a given anatomic site and whatever the molecule tested, these ratios were constant. It thus appears that when conditions are carefully controlled, it may be possible, by measurements on animals, to predict the absorption of a compound in humans. Further experimentation with chemicals of varied physicochemical properties will be required for validation of the model

Applied Barcoding: The Practicalities of DNA Testing for Herbals

open access articleDNA barcoding is a widely accepted technique for the identification of plant materials, and its application to the authentication of commercial medicinal plants has attracted significant attention. The incorporation ofDNA-based technologies into the quality testing protocols of international pharmacopoeias represents a step-change in status, requiring the establishment of standardized, reliable and reproducible methods. The process by which this can be achieved for any herbal medicine is described, using Hypericum perforatum L. (St John’sWort) and potential adulterant Hypericum species as a case study. A range of practical issues are considered including quality control of DNA sequences from public repositories and the construction of individual curated databases, choice of DNA barcode region(s) and the identification of informative polymorphic nucleotide sequences. A decision tree informs the structure of the manuscript and provides a template to guide the development of future DNA barcode tests for herbals

Reproductive health services for refugees by refugees in Guinea I: family planning.

BACKGROUND: Comprehensive studies of family planning (FP) in refugee camps are relatively uncommon. This paper examines gender and age differences in family planning knowledge, attitudes, and practices among Sierra Leonean and Liberian refugees living in Guinea. METHODS: In 1999, a cross-sectional survey was conducted of 889 reproductive-age men and women refugees from 48 camps served by the refugee-organised Reproductive Health Group (RHG). Sampling was multi-stage with data collected for socio-demographics, family planning, sexual health, and antenatal care. Statistics were calculated for selected indicators. RESULTS: Women knew more about FP, although men's education reduced this difference. RHG facilitators were the primary source of reproductive health information for all respondents. However, more men then women obtained information from non-health sources, such as friends and media. Approval of FP was high, significantly higher in women than in men (90% vs. 70%). However, more than 40% reported not having discussed FP with their partner. Perceived service quality was an important determinant in choosing where to get contraceptives. Contraceptive use in the camps served by RHG was much higher than typical for either refugees' country of origin or the host country (17% vs. 3.9 and 4.1% respectively), but the risk of unwanted pregnancy remained considerable (69%). CONCLUSION: This refugee self-help model appeared largely effective and could be considered for reproductive health needs in similar settings. Having any formal education appeared a major determinant of FP knowledge for men, while this was less noticeable for women. Thus, FP communication strategies for refugees should consider gender-specific messages and channels

Conformational modulation of sequence recognition in synthetic macromolecules

The different triplet sequences in high molecular weight aromatic copolyimides comprising pyromellitimide units ("I") flanked by either ether-ketone ("K") or ether-sulfone residues ("S") show different binding strengths for pyrene-based tweezer-molecules. Such molecules bind primarily to the diimide unit through complementary π-π-stacking and hydrogen bonding. However, as shown by the magnitudes of 1H NMR complexation shifts and tweezer-polymer binding constants, the triplet "SIS" binds tweezer-molecules more strongly than "KIS" which in turn bind such molecules more strongly than "KIK". Computational models for tweezer-polymer binding, together with single-crystal X-ray analyses of tweezer-complexes with macrocyclic ether-imides, reveal that the variations in binding strength between the different triplet sequences arise from the different conformational preferences of aromatic rings at diarylketone and diarylsulfone linkages. These preferences determine whether or not chain-folding and secondary π−π-stacking occurs between the arms of the tweezermolecule and the 4,4'-biphenylene units which flank the central diimide residue

Orthoptic Services in the UK and Ireland During the COVID-19 Pandemic.

AimCOVID-19 has widely impacted hospital services. The purpose of this study was to determine the impact of COVID-19 on Orthoptists and their clinical practice in the UK, Ireland, and Channel Islands.MethodsWe conducted a prospective survey-based cross-sectional study using an online survey aiming for coverage of orthoptic departments across the UK, Ireland, and Channel Islands. We circulated the online survey through the British and Irish Orthoptic Society that reaches over 95% of UK and Irish orthoptic services, and through social media and orthoptic research networks.ResultsThe survey response rate was 79%. The survey was completed by orthoptic departments, on average 10 days post lockdown. Many orthoptic services were cancelled/paused with remaining services largely reserved for emergency cases and urgent care. A substantial rise in tele-consultations was reported by 94%, which largely consisted of telephone and video calls and which was regarded generally as working well. Barriers to tele-consultations were mainly IT related but with concerns also raised regarding ethical and confidentiality issues. Shortage of personal protective equipment (PPE) was reported by one third of departments along with issues relating to conflicting information about the use of PPE.ConclusionsWe have reported information on the changing face of orthoptic clinical practice during the COVID-19 pandemic. The survey has highlighted emerging tele-consultation practice and the importance of centralised profession-specific guidelines

Ex-vivo perfusion bioassay : an excellent technique to measure the bioactivity of inhalable insulin coated microcrystals

Purpose: To measure the bioactivity of inhalable insulin coated microcrystals using a perfusion bioassay that measures its vasodilatory effect on smooth muscle arterial tissue. Methods: The bioactivity of an insulin protein coated microcrystal (PCMC), a potential candidate for pulmonary drug delivery and commercial insulin was determined on a Danish Myo Tech P110 pressure myograph system. 12 week old Mesenteric resistance arteries from Male Wistar rats were isolated and immersed in a physiological salt solution (PSS) and attached to 2 opposing hollow glass micro-cannula (outer diameter 80 microns). The PSS was gradually warmed to 37°C (at a pressure less than 5mm Hg) for 1hr. Subsequently the pressure was increased up to 40mm Hg over a period 15 minutes and equilibrated for a further 15 minutes after gassing with 95%O2 / 5%CO2 to achieve a pH of 7.4 at 37°C. After normalisation by two washes of 123mM KCl and exposure to 1-10mM noradrenaline the arteries were exposed intraluminally to each insulin preparation by gradual infusion directly into the lumen via a fetal microcannulae inserted to the tip of the glass mounting cannula, at a constant pressure. Results: The preliminary results (full cummulative response curve yet to be determined) demonstrate insulin mediated relaxation to noradrenaline preconstriction. The level of constriction drops from 100% to 42% as the concentration of insulin increases from -11 to -9 Log M for the PCMC compared with a drop from 100 % to 65% for the commercial insulin preparation. However the more potent vasodilatory effect found for the insulin PCMC is more likely to be a result of variance introduced in each dilution step than a real increase in potency. Conclusion: The perfusion bioassay technique provides an excellent method of measuring insulin bioactivity and indicates the insulin loaded on the microcrystal support is fully active

A nexus perspective on competing land demands: Wider lessons from a UK policy case study

As nations develop policies for low-carbon transitions, conflicts with existing policies and planning tools are leading to competing demands for land and other resources. This raises fundamental questions over how multiple demands can best be managed. Taking the UK as an empirical example, this paper critiques current policies and practices to explore the interdependencies at the water-energy-food nexus. It considers how current land uses and related policies affect the UK’s resilience to climate change, setting out an agenda for research and practice relevant to stakeholders in land-use management, policy and modelling. Despite recent progress in recognising such nexus challenges, most UK land-related policies and associated science continue to be compartmentalised by both scale and sector and seldom acknowledge nexus interconnections. On a temporal level, the absence of an over-arching strategy leaves inter-generational trade-offs poorly considered. Given the system lock-in and the lengthy policy-making process, it is essential to develop alternative ways of providing dynamic, flexible, practical and scientifically robust decision support for policy-makers. A range of ecosystem services need to be valued and integrated into a resilient land-use strategy, including the introduction of non-monetary, physical-unit constraints on the use of particular services

Low cost, SPF aluminum cryogenic tank structure for ALS

Past production work has shown that cryogenic tank structure for the Shuttle Booster Rockets and the Titan system have very high life cycle costs for the fuel tank structure. The tanks are machined stiffener-skin combination that are subsequently formed into the required contour after machining. The material scrap rate for these configurations are usually high, and the loss of a tank panel due to forming or heat treatment problems is very costly. The idea of reducing the amount of scrap material and scrapped structural members has prompted the introduction of built-up structure for cryogenic tanks to be explored on the ALS program. A build-up structure approach that has shown improvements in life cycle cost over the conventional built-up approach is the use of superplastically formed (SPF) stiffened panels (reducing the overall part count and weight for the tank) resistance spot welded (RSW) to outer tank skin material. The stiffeners provide for general stability of the tank, while the skin material provides hoop direction continuity for the loads

How knowledge of the gastrointestinal absorption of elements could be used to predict transfer to milk

The quality and quantity of data used to derive transfer parameter values for milk are variable and there are many data gaps for elements/radionuclides which may need to be considered for risk assessment of the agricultural foodchain. There has been a recent focus on critically evaluating current methods to fill data gaps and on identifying extrapolation methods to derive suitable values for the elements, and particularly radioisotopes, with no or sparse data. The relationship between fractional absorption of elements in the ruminant gastrointestinal tract and transfer to milk has been explored to determine whether knowledge of the former can be used to predict the latter. A relationship has been derived between fractional absorption of elements and two empirical ratios commonly used to quantify transfer to milk; transfer coefficients (element concentration in milk divided by element daily intake) and concentrations ratios (concentration in milk divided by concentration in feed). We propose that fractional absorption may be used to predict the order of magnitude of the transfer to milk of elements/radionuclides for which no relevant data have yet been identified or collated