Occupational Exposure to Solar Radiation and the Eye: A Call to Implement Health Surveillance of Outdoor Workers.

Globally, hundreds of millions of outdoor workers are exposed to solar radiation (SR) for the majority of their working life. Such occupational exposure is known to induce various adverse health effects to the eyes, mainly related to its ultraviolet (UV) component. The present work is a call-to-action aimed at raising the awareness on the need of health surveillance for the prevention of the chronic ocular diseases in outdoor workers. Photo-chemical chronic damage can induce pterygium at the outer layer of the eye and cataract in the lens. Considering carcinogenic effects, rare squamous-cells tumors of the cornea and/or of the conjunctiva and the ocular melanomas are associated with UV radiation exposure. Solar UV-related eye diseases should be considered as "occupational diseases" when there is sufficient exposure in workers, but they are often not recognized, and/or frequently not reported to the national compensation authorities. Therefore, to prevent the burden of these work-related eye pathologies, an adequate risk assessment with identification of appropriate preventive measures, and a provision of periodic health surveillance to the exposed workers, in particular considering those at higher risk of exposure or with individual susceptibility, should be urgently implemented.

Profiled polyethylene terephthalate filaments that incorporate collagen and calcium phosphate enhance ligamentisation and bone formation.

Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.

A magneto-microfluidic platform for fluorescence immunosensing using quantum dot nanoparticles.

This study reports the online fluorescent detection of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) biomarker proteins in microfluidic channels using functional nanoparticles. Functional magnetic nanoparticles labeled with two antibodies were predeposited on separated microfluidic channels. Antigens were passed through each microfluidic channel to react with the respective antibodies. Two types of fluorescent nanoparticles labeled with antibodies were then used to detect and confirm antigens in the immunocomplex. Results indicate that online fluorescent detection of proteins can provide advantages for real-time monitoring and diagnostic applications. The running time was less than 20 min for each trial. The detection limits of CEA and AFP were found to be 0.6 and 0.2 pg ml-1. These detection limits are lower than those of ELISA. The linear ranges of CEA and AFP detection were from 1.8 pg ml-1 to 1.8 ng ml-1 and from 0.68 pg ml-1 to 0.68 ng ml-1 for two deposition zones in a magnetic sandwich immunoassay. The linear ranges of this method are wider than those of ELISA and those of most other methods. The measurements of CEA and AFP in serum samples from this method differed from ELISA results by 11% and 9.4%, respectively. The detection limit of online detection has achieved the same range as those of previous offline detection. This method has a good potential for automation and multichannel analysis to increase the throughput with some modifications in the future. The proposed method can provide simple, fast, and sensitive online detection for biomarkers.

Demographic and mortality analysis of hospitalized children at a referral hospital in Addis Ababa, Ethiopia.

BACKGROUND: Global childhood mortality rates remain high. Millennium Development Goal 4 focused efforts on reducing rates by two-thirds between 1990 and 2015. In Ethiopia, child mortality rates dropped 71 % from 1990 to 2015, however it is estimated that 184,000 Ethiopian children die each year. There is limited information about pediatric hospital admissions in Ethiopia. Our aims were to examine the temporal relationship of mortality to admission, describe the demographics, and identify cause mortality of children admitted to the Zewditu Memorial Hospital (ZMH). METHODS: A four-year retrospective review of pediatric admissions was conducted at the pediatric emergency room and pediatric hospital ward at ZMH in Addis Ababa, Ethiopia. Admission entries from 2011-2014 of children age 29 days-14 years were reviewed. Age, gender, admission date, disease classification, discharge status and date were obtained. Patient gender was compared using Chi-square analysis. A descriptive analysis was used for age and cause mortality. RESULTS: A total of 6866 patient entries were reviewed. The proportion of admissions younger than age 5 was 0.747 (95 % CI 0.736-0.757). Overall mortality was 0.042 (95 % CI, 0.037-0.047). The proportion of recorded deaths occurring within 2 days of admission was 0.437 (95 % CI 0.380-0.494). The proportion of male admissions was significantly higher than female admissions in all age groups (male 0.575, p < 0.0001, 95 % CI 0.562-0.586). The main causes of mortality were pneumonia (0.253, 95 % CI, 0.203-0.303), severe acute malnutrition (0.222, 95 % CI 0.174-0.27), HIV/AIDS-related complications (0.056, 95 % CI 0.029-0.083), spina bifida (0.049, 95 % CI 0.024-0.074), and hydrocephalus (0.045, 95 % CI 0.021-0.069). CONCLUSIONS: Our study revealed a lower mortality rate than previously reported in Ethiopia. Despite this, 44 % of pediatric hospital mortality occurred early during hospitalization, higher than reported at other Ethiopian hospitals. This adds further evidence that systematic efforts should be dedicated to improve pediatric emergency care. Admissions included 58 % male patients, similar to other reports in Ethiopia implying that this may be a nation-wide phenomenon. The observed disparity may be due to societal factors regarding care-seeking behaviors or male predilection for respiratory illness warranting further investigation. Cause mortality patterns were similar to reports in analogous settings.

Effect of Ultraviolet Exposure on Impact Resistance of Ophthalmic Lenses.

PURPOSE: To investigate the effect of ultraviolet radiation (UVR) on the impact resistance of organic ophthalmic lens materials. METHODS: Plano power CR39, Phoenix, Trilogy, and polycarbonate lenses with various scratch-resistant (SR) and/or antireflection (AR) coatings were obtained in batches of 40 units. All lenses had a nominal thickness of 2 mm. Half of each batch was conditioned following the European Standard EN 168 protocol for the test of resistance to UVR (exposed group). The remaining lenses comprised an unexposed group for that combination of lens substrate and coating treatment. Each group was subjected to ballistic impact with 6-mm steel balls following the ZEST protocol to determine its mean breakage velocity. The difference in mean breakage velocity between exposed and unexposed groups of each combination of lens substrate and coating was assessed for statistical significance. RESULTS: Exposed uncoated CR39 showed a reduction in fracture velocity of 10.3 m/s whereas CR39 with ultra hard coat had a reduction of 3.5 m/s and CR39 with AR and SR coating had a reduction of 4.1 m/s. Scratch-resistant coated Phoenix had a reduction of 4.8 m/s whereas AR-coated Phoenix had a reduction of 3.7 m/s. The corresponding reductions for Trilogy were 3.9 and 17.8 m/s. All differences were significant at the p level of less than 0.05. Although we were unable to break unexposed SR-coated polycarbonate lenses with our test apparatus, exposed SR-coated polycarbonate had a mean breakage velocity of 142 m/s. CONCLUSIONS: Our data suggest that extended UVR exposure causes a significant reduction in the impact resistance of the ophthalmic lens substrates commonly used for occupational eye protectors. Protective lenses that have been exposed to high levels of UVR for extended periods should be replaced regularly to maintain optimal impact protection, even if they do not show visible damage owing to wear and tear.

Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive. OBJECTIVES: To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. METHODS: Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines. RESULTS: Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1ß and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples. CONCLUSIONS: Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1ß and TNF-α, thereby ameliorating psoriatic plaques.

Preclinical assessment of the absorption, distribution, metabolism and excretion of GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide), an orally bioavailable systemic Hedgehog signalling pathway inhibitor.

GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide) is a potent, selective Hedgehog (Hh) signalling pathway inhibitor being developed for the treatment of various cancers. The in vivo clearance of GDC-0449 was estimated to be 23.0, 4.65, 0.338, and 19.3 ml min(-1) kg(-1) in mouse, rat, dog and monkeys, respectively. The volume of distribution ranged from 0.490 in rats to 1.68 l kg(-1) in mice. Oral bioavailability ranged from 13% in monkeys to 53% in dogs. Predicted human clearance using allometry was 0.096-0.649 ml min(-1) kg(-1) and the predicted volume of distribution was 0.766 l kg(-1). Protein binding was extensive with an unbound fraction less than or equal to 6%, and the blood-to-plasma partition ratio ranged from 0.6 to 0.8 in all species tested. GDC-0449 was metabolically stable in mouse, rat, dog and human hepatocytes and had a more rapid turnover in monkey hepatocytes. Proposed metabolites from exploratory metabolite identification in vitro (rat, dog and human liver microsomes) and in vivo (dog and rat urine) include three primary oxidative metabolites (M1-M3) and three sequential glucuronides (M4-M6). Oxidative metabolites identified in microsomes M1 and M3 were formed primarily by P4503A4/5 (M1) and P4502C9 (M3). GDC-0449 was not a potent inhibitor of P4501A2, P4502B6, P4502D6, and P4503A4/5 with IC50 estimates greater than 20 microM. K(i)'s estimated for P4502C8, P4502C9 and P4502C19 and were 6.0, 5.4 and 24 microM, respectively. An evaluation with Simcyp suggests that GDC-0449 has a low potential of inhibiting P4502C8 and P4502C9. Furthermore, GDC-0449 (15 microM) was not a potent P-glycoprotein/ABCB1 inhibitor in MDR1-MDCK cells. Overall, GDC-0449 has an attractive preclinical profile and is currently in Phase II clinical trials.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of occupational exposure to solar ultraviolet radiation and of the effect of occupational exposure to solar ultraviolet radiation on cataract.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. Here, we present the protocol for two systematic reviews of parameters for estimating the number of disability-adjusted life years of cataracts from occupational exposure to solar ultraviolet radiation, to inform the development of the WHO/ILO joint methodology. OBJECTIVES: We aim to systematically review studies on occupational exposure to solar ultraviolet radiation (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to solar ultraviolet radiation on the development of cataract (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework and conducting both systematic reviews in tandem and in a harmonized way. DATA SOURCES: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and Web of Sciences. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA: We will include working-age (≥15 years) workers in WHO and/or ILO Member States, but exclude children (<15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative studies on the prevalence of relevant levels of occupational exposure to solar ultraviolet radiation and of the total working time spent outdoors from 1960 to 2018, stratified by sex, age, country and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of any occupational exposure to solar ultraviolet radiation (i.e. ≥30 Jm-2/day of occupational solar UV exposure at the surface of the eye) on the prevalence or incidence of cataract, compared with the theoretical minimum risk exposure level (i.e. <30 Jm-2/day of occupational solar UV exposure at the surface of the eye). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration: CRD42018098897.

When is protection from impact needed for the face as well as the eyes in occupational environments?

BACKGROUND: The most commonly identified reason for requiring or using occupational eye and face protection is for protection against flying objects. Standards vary on what risk may require protection of the eyes alone and what requires protection for the whole face. Information on the minimum energy transfer for face damage to occur is not well-established. METHODS: The heads of pigs were used as the common model for human skin. A 6 mm steel ball projected at velocities between 45 and 135 m/s was directed at the face area. Examples of impacts were filmed with a high-speed camera and the resulting damage was rated visually on a scale from 1 (no visible damage) to 5 (penetrated the skin and embedded in the flesh). RESULTS: The results for the cheek area indicate that 85 m/s is the velocity above which damage is more likely to occur unless the skin near the lip is included. For damage to the lip area to be avoided, the velocity needs to be 60 m/s or less. CONCLUSION: The present data support a maximum impact velocity of 85 m/s, provided the thinner and more vulnerable skin of the lids and orbital adnexa is protected. If the coverage area does not extend to the orbital adnexa, then the absolute upper limit for the velocity is 60 m/s. At this stage, eye-only protection, as represented by the lowest level of impact test in the standards in the form of a drop ball test, is not in question.

Effect of multiple antireflection coatings on impact resistance of Hoya Phoenix spectacle lenses.

PURPOSE: To investigate how the impact resistance of Hoya Phoenix spectacle lenses is affected by centre thickness and the application of a multilayer antireflection (MAR) coating. METHODS: Four groups of plano lenses were tested: dress thickness with scratch resistant (SR) coating on both surfaces, dress thickness with SR and MAR, industrial thickness with SR and industrial thickness with SR and MAR. Lenses were edged to a clear circular aperture of 50 mm with a 0.5 mm hidden bevel and mounted in a specially-designed lens support. A pneumatic gun was used to propel a 6.35 mm steel ball at the centre of each lens. Impact speed was varied using the ZEST protocol to determine the threshold breakage speed. RESULTS: The threshold breakage speeds of the dress and industrial thickness SR lenses were 55.1 and 63.2 m/s, respectively and the corresponding threshold breakage speeds for SR-MAR lenses were 50.1 and 54.7 m/s. All comparisons were statistically significant using Student's t-test with a rejection level of p < 0.005. Unlike polycarbonate lenses, dress thickness Phoenix lenses do not display 'oilcanning' deformation on high energy impact and therefore are less likely to be dislodged from their mountings. CONCLUSIONS: We found that the mean impact resistance of the Phoenix lenses was greater than the level required of eye protector lenses by the standards AS/NZS 1337:1992, ANSI Z87.1-2003 and CSA Z94.3-02. Similar to CR39 and polycarbonate, the application of MAR to Phoenix lenses reduces their impact resistance, however, they provide an acceptable level of impact protection in industrial settings, where there is little danger of exposure to pointed or sharp-edged high-speed missiles.

Clonal isolation of populations of gamma-glutamyl transpeptidase-positive and -negative cells from rat liver epithelial cells chemically transformed in vitro.

In a population of cultured rat liver epithelial cells transformed by 11 brief treatments with N-methyl-N'-nitro-N-nitrosoguanidine, 9% of the cells stained intensely for gamma-glutamyl transpeptidase (GGT). We have isolated from this phenotypically heterogeneous tumorigenic cell population 11 GGT-positive and 7 GGT-negative clonal subpopulations (from single cells) and have analyzed the ploidy and selected biochemical, histochemical, and growth properties of the cells in these clonal sublines. As compared to the GGT-negative strains and normal diploid rat liver epithelial cells, cells of the GGT-positive strains are larger in size, have greater DNA content, proliferate more slowly in culture, and have higher specific activities of NADH diaphorase, glucose-6-phosphate dehydrogenase, pyruvate kinase, and lactate dehydrogenase. The GGT-positive strains also show greater alteration and heterogeneity than do the GGT-negative strains in their ability to store glycogen and in their expression of lactate dehydrogenase isozymes. The results indicate that enzymatic changes commonly observed in "altered" hepatocytes in rat livers exposed to chemical carcinogens in vivo can also be produced in vitro in cultured hepatic epithelial cells by treatment with carcinogens. Moreover, treatment of a cell line with a chemical carcinogen generates a population of cells vastly heterogeneous in both their phenotypes and genotypes. Isolation of clonal subpopulations from the resulting cell line allows critical examination of the linkage and mechanistic relationship between tumorigenicity and many paratumorigenic phenotypes.

Carcinogenicity of 1,3-butadiene in C57BL/6 x C3H F1 mice at low exposure concentrations.

The carcinogenicity of inhaled 1,3-butadiene was evaluated in C57BL/6 x C3H F1 mice exposed to concentrations of this gas ranging from 6.25 to 625 ppm. Butadiene is a high production volume chemical, used mainly in the manufacture of synthetic rubber. In these 2-yr inhalation studies, a potent multisite carcinogenic response was observed, including neoplasms of the lung at concentrations as low as 6.25 ppm. Early occurrence and extensive development of lethal lymphocytic lymphomas in mice exposed to 625 ppm of butadiene reduced the number of animals at risk for the expression of later developing neoplasms at other sites; at lower exposure concentrations, dose responses were demonstrated for hemangiosarcomas of the heart and neoplasms of the lung, forestomach, Harderian gland, preputial gland, liver, mammary gland, and ovary. So far, no long-term studies on butadiene have been conducted at exposure concentrations that have not shown a carcinogenic response. In separate experiments with reduced exposure durations, butadiene induced neoplastic responses at multiple organ sites even after only 13 wk of exposure. Because of the correspondence between these animal data and recent epidemiology findings, there is a worldwide public health need to reevaluate current workplace exposure standards for 1,3-butadiene.

Isoprene, an endogenous hydrocarbon and industrial chemical, induces multiple organ neoplasia in rodents after 26 weeks of inhalation exposure.

Isoprene, the 2-methyl analogue of 1,3-butadiene, is a high production chemical used largely in the manufacture of synthetic rubber and is the major endogenous hydrocarbon exhaled in human breath. Thirteen-week inhalation toxicology studies of isoprene were conducted in male and female F344 rats and B6C3F1 mice at exposure concentrations of 0, 70, 220, 700, 2200, and 7000 ppm (6 h/day; 5 days/week). In addition, 26-week inhalation studies at the same exposure levels, followed by a 26-week recovery period, were conducted in male rats and mice. The 13-week exposures produced no discernible exposure-related toxic effects in rats. Interstitial cell hyperplasia of the testis was observed in all male rats in the 7000 ppm group after 26 weeks of exposure; following the 26-week recovery period the only effect in rats was a marginal increase in benign testicular interstitial cell tumors. In mice, isoprene induced toxic and carcinogenic effects at multiple organ sites. Following the 26-week exposure and 26-week recovery periods, incidences of neoplastic lesions in the liver, lung, forestomach, and harderian gland were significantly increased. Neoplastic effects were observed at 700 ppm and higher exposures. Non-neoplastic lesions in mice exposed to isoprene included spinal cord degeneration, testicular atrophy, degeneration of the olfactory epithelium, and epithelial hyperplasia of the forestomach. A partial hindlimb paralysis and a nonresponsive macrocytic anemia were also seen in mice. Most of the toxic and carcinogenic effects caused by isoprene, as well as the species' difference in response, had been observed after inhalation exposures to 1,3-butadiene.

Peripheral nociceptive effects of alpha 2-adrenergic receptor agonists in the rat.

We have previously shown that norepinephrine can produce hyperalgesia via an alpha 2-adrenergic receptor mechanism. The alpha 2-adrenergic receptor agonist clonidine has, however, also been shown to produce peripheral analgesia. In view of the multiple alpha 2-subtypes currently known (i.e. alpha 2A, alpha 2B and alpha 2C), we evaluate the alpha 2-receptor subtypes mediating norepinephrine-induced peripheral hyperalgesia and clonidine analgesia. Norepinephrine and the alpha 2-adrenergic agonists clonidine and UK 14,304 (1-1000 ng), when co-injected with the calcium ionophore A23187 (1000 ng) produced dose-dependent hyperalgesia in the Randall-Selitto paw withdrawal test. Norepinephrine (100 ng) hyperalgesia was dose-dependently antagonized by alpha 2-adrenergic receptor antagonists. From the estimated ID50, the rank order of potency was: SK&F 104856 (alpha 2B) approximately imiloxan (alpha 2B) > rauwolscine (alpha 2C) >> BRL 44408 (alpha 2A). Norepinephrine hyperalgesia was not significantly affected by pertussis-toxin treatment. Prostaglandin E2 (100 ng) hyperalgesia was inhibited dose-dependently, by clonidine and UK 14,304. Rauwolscine was more potent in reversing the inhibitory effect of clonidine on prostaglandin E2 than imiloxan while BRL 44408 was ineffective. The inhibitory effect of clonidine on prostaglandin E2 hyperalgesia was reversed by pertussis toxin. These data suggest that alpha 2B-subtype receptors mediate (norepinephrine hyperalgesia while the antinociceptive effect of alpha 2-agonist is mediated by the alpha 2C-subtype receptor. Differential coupling of these receptor subtypes to second messenger systems and location on different cell types in the rat paw may explain, at least in part, their differential responses to alpha 2-agonist stimulation, leading to hyperalgesia and analgesia.

Is there more than one prostaglandin E receptor subtype mediating hyperalgesia in the rat hindpaw?

Five synthetic prostaglandin E analogs (11-deoxyPGE1, 17-phenyl-ol-trinor prostaglandin E2, enisoprost, MB28767 and misoprostol) have been evaluated for their ability to produce mechanical hyperalgesia in rats. The Randall-Selitto paw withdrawal model of mechanical hyperalgesia was used. Following intradermal injections (2.5 microliters) into the dorsal surface of the hindpaw, each prostaglandin E analog produced a dose-dependent (1-1000 ng) decrease in nociceptive threshold (i.e. hyperalgesia). Hyperalgesia produced by 17-phenyl-ol-trinor prostaglandin E2 and MB28767, was inhibited by the prostaglandin E1 antagonist SC19220 (7.5 ng), while the hyperalgesia produced by 11-deoxyprostaglandin E1, enisoprost and misoprostol was not inhibited by this antagonist. Hyperalgesia produced by all five analogs was significantly attenuated or completely blocked by inhibiting stimulatory guanine nucleotide-binding regulatory protein with guanosine 5'-O-(2-thiodiphosphate), adenylyl cyclase with 2'5'-dideoxyadenosine and protein kinase A with WIPTIDE. These results suggest the presence of more than one prostaglandin E-receptor subtype, which mediate hyperalgesia, predominantly via the cAMP second messenger system, in the hindpaw of the rat.

Action spectrum and recovery for in vitro UV-induced cataract using whole lenses.

PURPOSE: To establish the in vitro action spectrum for acute UV cataractogenesis using whole cultured lenses. The recovery pattern of the induced cataract was also investigated. METHODS: Aseptically dissected porcine lenses were cultured in glass chambers. At 1 week, lenses were exposed to a predetermined UV energy (J/cm(2)) at specific wavebands ranging from 270 to 370 nm at 5- and 10-nm intervals. The UV energy was generated by a PRA integrated arc lamp system using a water-cooled 1000 W, high-pressure xenon lamp. The lamp output was limited using a deionized water filter, a monochromator, and secondary optics. An electronic shutter was used to control the exposure time. The median effective dose, ED(50) (i.e., UV energy threshold) for each waveband was statistically determined using probit analysis. Irradiated spots (3.06 mm(2)) on the lenses were monitored every 6 to 12 hours up to 48 hours postirradiation for any UV-induced opacity with a dissecting microscope and photomicrography. The ED(50)s were plotted against wavelengths to obtain the action spectrum. RESULTS: The threshold values for 270, 300, and 365 nm were 0.057, 0.069, and 137.19 J/cm(2), respectively. Permanent UV-induced cataract was obtained at twice the threshold values for UVB and UVA. CONCLUSIONS: An action spectrum for in vitro UV-induced cataract using whole cultured lens is established. These data are comparable to published in vitro (with isolated lens epithelial cells) and in vivo action spectra. The recovery pattern appears to be similar to the in vivo situation.

Inhalation toxicology and carcinogenicity of 1,3-butadiene in B6C3F1 mice following 65 weeks of exposure.

1,3-Butadiene, a large-production volume chemical used mainly in the manufacture of synthetic rubber, was found to induce multiple-organ carcinogenicity in male and female B6C3F1 mice at exposure concentrations (625 and 1250 ppm) equivalent to and below the OSHA standard of 1000 ppm. Since this study was terminated after 60 weeks of exposure because of reduced survival due to fatal tumors, and because dose-response relationships for 1,3-butadiene-induced neoplastic and nonneoplastic lesions were not clearly established, a second long-term inhalation study of 1,3-butadiene in B6C3F1 mice was conducted at lower exposure concentrations, ranging from 6.25 to 625 ppm. Both the histopathological findings from animals dying through week 65 and the results of evaluations of animals exposed for 40 and 65 weeks are presented in this report. Exposure to 1,3-butadiene caused a regenerative anemia at concentrations of 62.5 ppm and higher. Testicular atrophy was induced at 625 ppm, and ovarian atrophy was observed at 20 ppm and higher. During the first 50 weeks of the study, lymphocytic lymphoma was the major cause of death of mice exposed to 625 ppm 1,3-butadiene. Neoplasms of the heart, forestomach, lung, Harderian gland, mammary gland, ovary, and liver were frequently observed in 1,3-butadiene-exposed mice that died between week 40 and week 65 of the study. Studies in which exposure to 1,3-butadiene was stopped after limited periods were also included to assess the relationship between exposure levels and duration of exposures on the outcome of 1,3-butadiene-induced carcinogenicity. In these studies, lymphocytic lymphomas were induced in male mice exposed to 625 ppm 1,3-butadiene for only 13 weeks. The incidence of lymphocytic lymphoma in male mice exposed to 625 ppm 1,3-butadiene for 26 weeks was two times that in mice exposed to 625 ppm for 13 weeks. However, when the exposure concentration was reduced by half to 312 ppm and the exposure duration extended to 52 weeks, the incidence of lymphocytic lymphoma was reduced by 90%. Thus, the multiple of the exposure concentration times the exposure duration did not predict the incidence of lymphocytic lymphoma in mice. The early mortalities resulting from lymphocytic lymphomas in male mice exposed to 625 ppm 1,3-butadiene limited the expression of tumors at other sites. A clearer dose-response for 1,3-butadiene-induced neoplasia should be apparent from experiments in mice exposed to lower concentrations of this chemical for 2 years.

Inhalation toxicology of isoprene in F344 rats and B6C3F1 mice following two-week exposures.

Isoprene (2-methyl-1,3-butadiene) was selected for toxicologic evaluations because of its structural similarity to 1,3-butadiene, a potent rodent carcinogen. Two-week inhalation toxicology studies of isoprene were conducted in F344 rats and B6C3F1 mice at exposure concentrations of 0, 438, 875, 1750, 3500, or 7000 ppm. For rats, there were no chemically related changes in survival, body weight gain, clinical signs, hematologic or clinical chemistry parameters, or gross or microscopic lesions. Exposure of mice to isoprene did not produce mortalities and only caused a decrease in body weight gain for male mice in the 7000 ppm exposure group; however, hematologic changes and microscopic lesions including testicular atrophy, olfactory epithelial degeneration, and forestomach epithelial hyperplasia were observed in isoprene-exposed mice. Similar toxicologic effects have been previously observed in B6C3F1 mice exposed to 1,3-butadiene. A species difference in susceptibility between rats and mice exposed to isoprene was evident in these short-term exposure studies.

Microstructural characterization of plasma-sprayed hydroxyapatite-10 wt% ZrO2 composite coating on titanium.

Previous research showed that the concept of adding ZrO2 as second phase to hydroxyapatite (HA) significantly increased the bonding strength of plasma-sprayed composite material. The present work aimed to investigate the microstructural characteristics of plasma-sprayed hydroxyapatite-10 wt% ZrO2 composite coating on titanium using X-ray diffractometry (XRD) and transmission electron microscopy (TEM). In TEM, phases such as HA, amorphous calcium phosphate, alpha-TCP, ZrO2 and minor transformed CaZrO3 are identified. The cubic phase of ZrO2 in HA-10 wt% ZrO2 powders before coating maintains during plasma spraying, and zirconia particle apparently bonds well to the calcium phosphate matrix with local crystallographic relationship. The transformed CaZrO3 does not exist as interface interphase between calcium phosphate matrix and zirconia particle. Instead, reaction of calcium phosphate and zirconia occurs rapidly to transform ZrO2 into CaZrO3. The toughening mechanism of the material studied and its biological implication of the system are discussed.