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Introduction: Zambia is experiencing a critical shortage of radiologists responsible for interpreting X-ray images. Nine radiologists serve the entire population of over 18 million people. Consequently, referring physicians can receive reports late and often receive X-ray images without radiological reports attached, which may lead to delayed diagnoses and treatment of critically injured patients. This challenge could be alleviated if radiographers could assist with interpreting X-ray images. This study was undertaken to subject a cohort of Zambian radiographers to a training intervention, however, the COVID-19 pandemic necessitated using a novel approach to the intervention by delivering the training mainly through social media but also through face-to-face lectures., Methods: A cohort of 27 radiographers employed at eight public hospitals in the Copperbelt Province of Zambia undertook a training intervention using face-to-face training and image discussions on the social media WhatsApp® platform. The participants underwent a pre-and post-test in which they were asked to interpret 20 adult trauma CXR images. For the training intervention, the radiographers attended a face-to-face image interpretation lecture, after which they received training images with a radiologist report weekly for eight weeks via the WhatsApp® platform. Participants were encouraged to discuss and pose questions via the platform., Results: The cohort of radiographers (n = 27) showed an improvement in their interpretation skills for trauma CXR images. The interpretation median scores ranged from approximately 82% to 93% in the pre-test and 85% to 97% in the post-test. The Wilcoxon signed-rank tests revealed significant differences in the interpretation ability skills for 12 of the 20 CXR images after the 8-week training, demonstrating the successful implementation of the program. When comparing three categories of radiographers' years of experience (1-5; >5-10; and >10 years), the Kruskal Wallis test could not identify significant differences in the CXR image interpretation skills among the different categories of experience (P = 0.1616). When comparing the interpretation skills of radiographers working at the three different hospital levels (Level 3 with a full-time radiologist and more than ten radiographers; Level 1 and 2 without a full-time radiologist; Level 2 with six to ten radiographers; and Level 1 with five or less radiographers), the Kruskal Wallis test revealed that the level of the hospital where the radiographers were employed significantly influenced their skills to interpret the CXR images (P = 0.0323)., Conclusion: This type of novel training intervention is urgently required in the Copperbelt Province of Zambia. The results show that the training process was implemented successfully to improve radiographers' image interpretation skills of adult trauma CXR images., Implications for Practice: Promoting radiographers' involvement in image interpretation will likely improve imaging services in Zambia, considering the critical shortage of radiologists., (Copyright © 2024. Published by Elsevier Inc.)

Halogenated platinum salts are known respiratory sensitizers in the workplace, and occupational exposure to platinum via the respiratory system and skin has been reported. The aim of this study was to compare the permeability and skin retention of potassium hexachloroplatinate to previously published data of potassium tetrachloroplatinate. Experiments were performed using female Caucasian skin and Franz diffusion cells with the application of 0.3 mg Pt/mL in the donor solution for 24-h. After 8-h of exposure, 1.87 ng/cm 2 of Pt was detected in the receptor solution with exposure to potassium hexachloroplatinate, whereas 0.47 ng/cm 2 was detected with exposure to potassium tetrachloroplatinate. After 24-h of exposure the Pt retention in the skin was 1861.60 ng/cm 2 and 1486.32 ng/cm 2 with exposure to potassium hexa- and tetrachloroplatinate respectively. The faster rate of Pt permeation from exposure to potassium hexachloroplatinate was confirmed by the flux and permeability coefficient values. The results indicate a higher permeability and skin retention of Pt when exposed to potassium hexachloroplatinate, confirming a higher risk associated with occupational exposure to this platinum compound relative to potassium tetrachloroplatinate., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof A Franken reports financial support was provided by Johnson Matthey. Prof A Franken reports financial support was provided by The International Platinum Group Metals Association. Barbara Sylvia Bosch reports financial support was provided by International PGM Association (IPA). Johnson Matthey (UK) provided the analysis of the samples., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16-18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis, development of organ failure and high short-term mortality. Whether the outcome in patients admitted to the intensive care unit (ICU) with ACLF differs from other ICU populations is unknown. We compared the clinical course and host response in ICU patients with or without ACLF, matched for baseline severity of illness scores and characteristics., Methods: From the large prospective EPaNIC randomized control trial database (n = 4,640), 133 patients were identified with cirrhosis of whom 71 fulfilled the Chronic Liver Failure Consortium criteria for ACLF. These patients were matched for type and severity of illness and demographics to 71 septic and 71 medical ICU patients from the same database without chronic liver disease. Clinical, biochemical and outcome parameters were compared in this cohort study of 213 patients. In a subset of 100 patients, day 1 serum cytokines were quantified., Results: The outcome of ACLF, when compared to septic or medical ICU patients, matched for baseline parameters of illness severity, was similar regarding length of ICU stay, development of new infections, organ failure and septic shock. ICU, hospital and 90-day mortality were similar between the groups. C-reactive protein and platelet levels were lower in patients with ACLF throughout the first week. Cytokines, including IL-10, IL-1β, IL-6, and IL-8, were similarly elevated in ACLF and septic ICU patients on day 1. However, TNF-α levels were higher in patients with ACLF., Conclusion: Patients with ACLF admitted to the ICU showed comparable clinical and ICU outcomes as ICU patients without chronic liver disease, but with similar baseline severity of illness characteristics. This suggests that ICU admission criteria should not be different in ACLF populations., Lay Summary: Liver function may abruptly deteriorate in patients with chronic liver disease with cirrhosis, often resulting in these patients being admitted to an intensive care unit (ICU) with organ failure. Previous studies have indicated that this sudden deterioration, called acute-on-chronic liver failure is associated with very high mortality rates, which often resulted in deferred ICU care because of a perception of futility. Our study now shows that the ICU course and outcome are not different when patients with acute-on-chronic liver failure are compared to other ICU patients matched for severity of illness. This demonstrates that patients with acute-on-chronic liver failure deserve the same ICU care given to other ICU populations., (Copyright © 2018. Published by Elsevier B.V.)

Background: Cervical myelopathy is a complex pathology and dynamic compression of the tethered cervical cord, which may be responsible for clinical symptoms., Methods: Patients with cervical canal stenosis who had magnetic resonance imaging in flexion and extension positions were retrospectively reviewed. All cases were evaluated in Nurick grade. The cervical parameters-cervical cord (CC) angle, cervical lordosis, and spine/cord (S/C) angle ratio-were measured on the magnetic resonance imaging. Mean values of these parameters were compared between nonmyelopathic (Nurick grade 0) and myelopathic groups (Nurick grades 1-5). A multinomial ordinal logistic regression was used to predict outcome for Nurick grade using the CC angle, the cervical lordosis angle, and the S/C angle ratio as independent variables., Results: A total of 65 patients (35 men) with the mean age of 58.6 ± 11.4 years were analyzed. A comparison of means between Nurick grade 0 against each of myelopathic grades 1-5 revealed significant differences only for the S/C angle ratio. A cumulative comparison between nonmyelopathic and myelopathic grades for the S/C angle ratio showed significant difference of 0.29 (1.16 ± 0.5 vs. 1.45 ± 0.6, respectively; P < 0.05). Cumulative comparison for the CC angle difference in flexion and extension lordosis did not show substantial differences. The S/C angle ratio was the only significant parameter in the prediction of the Nurick grade with an odds ratio of 2.63 (95% confidence interval 2.11-2.79)., Conclusions: A positive correlation between Nurick grade and cervical spine and cord angle mismatch was found., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: A dynamic compression injury of the cervical spinal cord (SC) is widely accepted in the pathophysiology of cervical myelopathy. Flexion/extension magnetic resonance imaging (MRI) provides information on the dynamic cervical injury. We sought to compare morphometric parameters on neutral and flexion/extension MRI in cervical spondylotic myelopathy., Methods: Patients with cervical canal stenosis who had MRI in neutral, flexion, and extension positions were reviewed retrospectively. A morphometric comparison of following parameters at compression level was performed: SC area, cerebrospinal fluid (CSF) area, and CSF reserve ratio (CSF/CSF plus SC). Patients were classified according to the presence of high signal (HS) in SC, and predictors of HS were calculated by the use of logistic regression analysis., Results: In total, 55 patients, 26 men, with mean age of 57 ± 13 were analyzed. Significant difference was found in mean CSF reserve ratio between flexion and extension (0.47 ± 0.18 vs. 0.40 ± 0.21, P < 0.05). SC area was significantly smaller in flexion (58.8 ± 13.3 mm 2 ) than in both neutral (66.9 ± 22.3 mm 2 ) and extension (68.3 ± 19.1 mm 2 ). HS was found in 22 cases, and predictors of HS were smaller SC area on extension (odds ratio 1.46; 95% confidence interval 1.07-1.84) and smaller CSF plus SC area on flexion (OR 1.32; 95% confidence interval 1.06-1.45). Cut-off values on the receiver operating characteristic curve were 55 mm 2 for SC and 99 mm 2 for CSF plus SC area., Conclusions: Application of dynamic MRI in cervical stenosis reveals significant differences of both SC and CSF reserve ratio in flexion/extension and neutral positions. Patients with smaller SC area in extension and smaller CSF plus SC area in flexion have greater risk of HS on MRI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient survival was 92%. One patient died at 9 months due to aspergillosis, another at 12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early acute rejection (AR) developed in two (15%); late AR in three (23%); all were reversible. No chronic rejection (CR) occurred. No malignancies developed and estimated glomerular filtration rate remained stable post-Tx. At last follow-up (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11 survivors were total parenteral nutrition free with a Karnofsky score >90% in 8 recipients (follow-up >1 years). A high frequency of circulating CD4 + CD45RA - Foxp3 hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx, KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a low-inflammatory/pro-regulatory environment activates Tregs at levels similar to tolerant-KTx, without causing sensitization. LIP limits rejection under reduced IS and thereby prolongs long-term survival to an extent not previously attained after ITx., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F >> control > EPO >> Pheroid. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum-epidermis and the epidermis-dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Artemisone is a 10-amino-artemisinin derivative that is markedly superior in vitro and in vivo to current artemisinins against malaria and also possesses antitumor activity. In seeking to capitalise on the last property, we have examined the encapsulation of artemisone in nano-vesicular niosomes and solid lipid nanoparticles, and have evaluated efficacies of the free and encapsulated artemisone against human melanoma A-375 cells and effects on human keratinocytes (HaCaT). Artemisone is successfully encapsulated into the nano-vesicles with encapsulation efficiencies of 67±6% and 79±5%, and with average particle sizes being 211±10nm and 295±18nm respectively. The formulations displayed highly selective cytotoxicity towards the melanoma cells with negligible toxicity towards the normal skin cells. The artemisone-loaded nano-vesicles almost completely inhibited the melanoma cells compared to the free drug. The results overall suggest a potentially more useful therapeutic strategy that needs to be evaluated for the treatment of melanoma and other cancers., From the Clinical Editor: Apart from being an effective anti-malarial drug, a surprising action of artemisone also has antitumor activity. Nonetheless, its low water solubility and bioavailability has limited its clinical use. In this article, the authors enacapsulated artemisone in nano- vesicles and solid lipid nano-particles (SLNs). In-vitro studies confirmed the selective cytotoxicity towards melanoma cells. Further in-vivo and pre-clinical studies are awaited., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The majority of the South African workforce are Africans, therefore potential racial differences should be considered in risk and exposure assessments in the workplace. Literature suggests African skin to be a superior barrier against permeation and irritants. Previous in vitro studies on metals only included skin from Caucasian donors, whereas this study compared the permeation of platinum through African and Caucasian skin. A donor solution of 0.3 mg/ml of potassium tetrachloroplatinate (K₂PtCl₄) dissolved in synthetic sweat was applied to the vertical Franz diffusion cells with full thickness abdominal skin. Skin from three female African and three female Caucasian donors were included (n=21). The receptor solution was removed at various intervals during the 24 h experiment, and analysed with high resolution inductively coupled plasma-mass spectrometry (ICP-MS). Skin was digested and analysed by inductively coupled plasma-optical emission spectrometry (ICP-OES). Significantly higher permeation of platinum through intact African skin (p=0.044), as well as a significantly higher mass of platinum retention in African skin in comparison with Caucasian skin (p=0.002) occurred. Significant inter-donor variation was found in both racial groups (p<0.02). Results indicate that African workers have increased risk of dermal permeation and therefore possible sensitisation caused by dermal exposure to platinum salts. These results are contradictory to limited literature suggesting a superior barrier in African skin and further investigation is necessary to explain the higher permeation through African skin., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background & Aims: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis., Methods: Forty-four patients with NASH/ASH cirrhosis (decompensated n=29, compensated n=15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duodenal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and supernatant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immunohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and permeability studies., Results: Increased plasma LPS, LBP levels and higher numbers of duodenal CD33(+)/CD14(+)/Trem-1(+) macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS(+) and CD68(+), but not with CD11c(+) cells. Electron microscopy demonstrated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal permeability were detected in decompensated cirrhosis., Conclusions: Our study shows the presence of activated CD14(+)Trem-1(+)iNOS(+) intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, suggesting that these cells may produce factors capable of enhancing permeability to bacterial products., (Copyright © 2013. Published by Elsevier B.V.)

In the present study, the influence of calcium ion deposition on the apatite-inducing ability of porous titanium (Ti) was investigated in a modified simulated body fluid (m-SBF). Calcium hydroxide (Ca(OH)(2)) solutions with five degrees of saturation were used to hydrothermally deposit Ca ions on porous Ti with a porosity of 80%. Apatite-inducing ability of the Ca-ion-deposited porous Ti was evaluated by soaking them in m-SBF for up to 14 days. Scanning electron microscopy (SEM) and X-ray diffractometry (XRD) confirmed that a thin layer of calcium titanate (CaTiO(3))/calcium oxide (CaO) mixture with a nanostructured porous network was produced on porous Ti substrates after hydrothermal treatment at 200 degrees C for 8 h. X-ray photoelectron spectroscopy results demonstrated that the content of the Ca ions deposited on Ti and the thickness of the CaTiO(3)/CaO layer increased with increasing saturation degree of the Ca(OH)(2) solution. The thickest (over 10 nm) CaTiO(3)/CaO layer with the highest Ca content was achieved on the Ti treated in an oversaturated Ca(OH)(2) solution (0.2 M). SEM, XRD, transmission electron microscopy and Fourier transformed infrared spectroscopy analysis indicated that the porous Ti samples deposited with the highest content of Ca ions exhibited the best apatite-inducing ability, producing a dense and complete carbonated apatite coating after a 14 day soaking in m-SBF. The present study illustrated the validity of using Ca ion deposition as a pre-treatment to endow desirable apatite-inducing ability of porous Ti for bone tissue engineering applications.

A sensitive and accurate gas chromatographic-mass spectrometric (GC-MS) method has been developed for the quantitative determination of salicylic acid (SA) and hydroquinone (HQ) from human skin samples and cosmetic emulsions. Deuterium labeled SA-d(6) and HQ-d(6) were used as internal standards (IS). The samples were extracted with methanol, dried under nitrogen and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA)+1% trimethylchlorosilane (TMCS). Quantification was performed in SIM mode with a limit of quantification (LOQ) of 50 ng ml(-1) for SA and 10 ng ml(-1) for HQ. The inter-day variation (R.S.D.) was less than 5% and the accuracy was better than 13.3% for both compounds. The recoveries from the different matrices ranged between 93.1 and 103.3% for SA, and 97.3 and 100.8% for HQ.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required., (Copyright 2005 Wiley-Liss, Inc. and the American Pharmacists Association.)

Cowdria ruminantium is a rickettsial parasite which causes heartwater, a economically important disease of domestic and wild ruminants in tropical and subtropical Africa and parts of the Caribbean. Because existing diagnostic methods are unreliable, we investigated the small-subunit ribosomal RNA (srRNA) gene from heartwater-infected material to characterise the organisms present and to develop specific oligonucleotide probes for polymerase chain reaction (PCR) based diagnosis. DNA was obtained from ticks and ruminants from heartwater-free and heartwater-endemic areas from Cowdria in tissue culture. PCR was carried out using primers designed to amplify only rickettsial srRNA genes, the target region being the highly variable V1 loop. Amplicons were cloned and sequenced; 51% were C. ruminantium sequences corresponding to four genotypes, two of which were identical to previously reported C. ruminantium sequences while the other two were new. The four different Cowdria genotypes can be correlated with different phenotypes. Tissue-culture samples yielded only Cowdria genotype sequences, but an extraordinary heterogeneity of 16S sequences was obtained from field samples. In addition to Cowdria genotypes we found sequences from previously unknown Ehrlichia spp., sequences showing homology to other Rickettsiales and a variety of Pseudomonadaceae. One Ehrlichia sequence was phylogenetically closely related to Ehrlichia platys (Group II Ehrlichia) and one to Ehrlichia canis (Group III Ehrlichia). This latter sequence was from an isolate (Germishuys) made from a naturally infected sheep which, from brain smear examination and pathology, appeared to be suffering from heartwater; nevertheless no Cowdria genotype sequences were found in this isolate. In addition no Cowdria sequences were obtained from uninfected ticks. Complete 16S rRNA gene sequences were determined for two C. ruminantium genotypes and for two previously uncharacterised heartwater-associated Ehrlichia spp. Sequenced difference within the V1 loop were sufficient for the derivation of four Cowdria genotype-specific oligonucleotide probes. Four further probes were designed; one for the detection of any Cowdria genotype, one for the detection of any Group II Ehrlichia sp., one for any Group III Ehrlichia sp. and one for all Pseudomonadaceae. All the probes were specific except that for the Cowdria (Ball 3) genotype. The high prevalence (96%) in field samples of pseudomonad-like 16S sequences was the result of environmental contamination. The probes were used to screen DNA from goats in an area free of both Amblyomma ticks and clinical heartwater. A substantial proportion (42%) gave positive reactions for the apparently apathogenic Cowdria (Omatjenne), indicating that this genotype is relatively common.

The extent of uptake of gamma interferon (gamma-IFN) in various strata of hairless mouse, human and hamster skin upon application of a liposomal formulation and an aqueous solution were determined by in vitro diffusion cell experiments. For each of the animal species studied, 70-80% of the liposomally entrapped IFN was deposited onto or penetrated into the skin as determined 24 h after in vitro application. However, a significant fraction of this total amount (approximately 0.25-0.30) is either adsorbed to or associated with the stratum corneum. The drug content found in the deeper skin strata, where the receptor sites reside, suggests that drug deposition is strongly influenced by the skin species tested. The percent of applied drug found in this strata 24 h after application followed the order: hamster (6.1) much greater than human (0.9) greater than hairless mouse (0.3), although the amounts of drug in the total skin of each species tested were approximately the same. This indicates that the deposition of drug into the living epidermis and/or dermis cannot be predicted by determination of the amount of drug in the total skin. The amounts in the deeper skin strata were also in the order of increasing number of follicles/hair in the skin species, suggesting that the transfollicular route is an important pathway for liposomal topical therapeutics.

Vervet monkeys (Cercopithecus aethiops pygerethrus) were fed cholesterol-free, semipurified diets containing 40% sucrose, 25% casein, 15% cellulose and 14% peanut oil (PNO), randomized peanut oil (RPNO) or corn oil (CO). After 4 months, serum cholesterol and triglyceride levels, serum lecithin-cholesterol acyl transferase (LCAT) activity and plasma lipoprotein lipase (LPL) activity were similar in all groups. Livers of monkeys fed CO converted 156% more acetate and 24% more mevalonate to cholesterol than those of monkeys fed RPNO. Cholesterogenesis in RPNO-fed monkeys was enhanced compared to PNO (68% from acetate; 62% from mevalonate). Incidence of atherosclerosis was 33% in monkeys fed RPNO, 80% in those fed CO and 90% in those fed PNO. Extent of sudanophilia was lowest in aortas of monkeys fed RPNO. Incidence of arteriosclerosis was 40% in monkeys fed CO, 56% in those fed RPNO and 70% in those fed PNO. Extent of aortic surface showing arteriosclerosis was highest in monkeys fed RPNO.

Vervet monkeys ( Ceropithecus aethiops pygerethrus ) were placed on semipurified diets containing 14% fat of which 3.2 or 6.0% was present as trans-unsaturated fatty acid (t-FA). Two groups were fed the high and low levels of t-FA for a year and two others were fed t-FA for 6 months and then returned to the control diet for 6 months more. One other group was fed the control diet for a year. The control diet contained 14% fat which was a mixture of 72% olive oil and 28% corn oil. There were no significant differences in weight gain. Monkeys fed 6% t-FA or control diets for one year had lowest liver weights. Serum cholesterol and triglycerides in monkeys fed 3.2% t-FA for one year were 134 and 55 mg/dl, respectively; in monkeys returned to control diet after 6 months on 6% t-FA the values were 146 and 50 g/dl. Serum and triglyceride levels for the other 3 groups were 166 +/- 2 and 70 +/- 2 mg/dl. Liver cholesterol levels ranged from 4.0 mg/g (3.2% t-FA) to 4.7 mg/g (control) and 4.8 mg/g (6% t-FA). Lecithin:cholesterol acyltransferase (LCAT) activity was 59.0 microM/h for controls and ranged from 52.4 microM/h (3.2% t-FA) to 73.4 microM/h (6% t-FA). Cholesterol synthesis by liver slices was not affected by diet when the substrate was acetate. When mevalonate was used, the monkeys fed either level of t-FA for 12 months exhibited greatly reduced (about 80%) cholesterogenesis. The levels of t-FA in serum and liver reflected the amount in the diet. After being returned to control diet levels of t-FA in serum and liver of monkeys (fed 3.2% t-FA) fell by 97 and 94%, respectively, and those in serum and liver of monkeys fed 6% t-FA fell by 65 and 91%. There were no significant differences in aortic atherosclerosis or arteriosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)