Activated STING in a vascular and pulmonary syndrome.

BACKGROUND: The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS: We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-ß, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS: We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors. CONCLUSIONS: STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.).

Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study.

OBJECTIVES: Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. METHODS: ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% ß-tricalcium phosphate (ß-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. RESULTS: Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. CONCLUSION: The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of ß-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices.Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266-274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2.

A comparison of uric acid levels in Black African vs Caucasian women from South Africa: the POWIRS study.

OBJECTIVES: Elevated levels of uric acid are often associated with cardiometabolic risk factors. The aim of this study was to determine whether uric acid levels differ between African and Caucasian women and whether uric acid is associated with cardiometabolic risk factors within the two ethnic groups. METHODS: Women from African (N=102) and Caucasian (N=115) descent were recruited and their uric acid levels measured. Anthropometric measurements included height (stature), weight, and waist circumference. Correlations between uric acid and cardiometabolic variables within each ethnic group were also determined. RESULTS: African women had significantly lower levels of uric acid (P<.01) and significantly higher levels of blood pressure (P=.05) compared to the Caucasian women. There was a significant increase in blood pressure from the lower to higher uric acid tertiles in the African women. Uric acid strongly correlated with waist circumference in both ethnic groups. CONCLUSIONS: Despite their higher blood pressure, the African women had lower uric acid levels, yet they showed a significant increase in blood pressure from a low uric acid tertile to high uric acid tertile, which was not noticeable in the Caucasian women. A possible explanation is a lower waist circumference in African women compared to Caucasian women.

An audit of study casts used to monitor tooth wear in general practice.

OBJECTIVE: To assess the outcome of compliance of advice sent to patients and dentists about monitoring tooth wear in general practice. METHOD: Postal questionnaires were sent to 70 patients and their dentists requesting information on the outcome of letters of advice sent to general dental practitioners regarding monitoring tooth wear with study casts. They also requested information about the reasons for the patients' referral, the outcome of treatment and whether study models had been taken. RESULTS: Replies were received from 60 dentists (87%) and 53 patients (75%). Of these, 16 patients and 16 dentists had moved from their recorded address. Study casts were reported as having been taken by 23 dentists (38%) and reported by 18 patients (34%). The most common reason for referral was advice about monitoring the wear and the appearance of their teeth. CONCLUSIONS: The compliance of the patients and dentists in monitoring tooth wear by using study casts in general practice was not successful. It raises issues regarding the value of consultant advice letters to this common clinical problem.

[Management of vaginal infection following failure of a probabilistic treatment: is the vaginal swab really useful?]. / Prise en charge des infections vaginales après échec d'un traitement probabiliste : le prélèvement vaginal est-il réellement utile ?

OBJECTIVE: The aim of this observational national multi-centre study was to describe medical care of vaginal infections resisting a primary probabilistic treatment. PATIENTS AND METHODS: Two hundred and seventy female patients were included during a 9-month period (from 2013, March 20th to 2013, December 7th) by 155 gynaecologists located throughout France. RESULTS: All patients were presenting a vulvo-vaginitis episode which started about three weeks ago and which was characterized by leucorrhea (93 % cases), itching (88 % cases) and/or vulvar and/or vaginal irritation (88 % cases). In most cases, this episode was previously treated by a short course of an azole antifungal medication. This treatment was initiated by the patient herself without any doctor's prescription in six out of 10 cases and had no influence on the evolution of the original clinical symptoms. Second line treatments included azole antifungal medications (56 % cases), local fixed combinations (antifungal agent and bactericidal antibiotic) (29 %), metronidazole (9 %), oral antibiotics (7.4 %). At the end of the treatment, 85 % patients recovered from vaginitis symptoms. The recovery rate was 82.6 % for patients who got a bacteriological examination and 87.6 % for patients who were treated without any bacteriological examination. The difference is not statistically significant. DISCUSSION AND CONCLUSION: These results seem to show that a probabilistic medical care is as effective as (but probably more economical than) a therapeutic strategy guided by the results of further examinations in case of failure of a primary treatment. This conclusion should be confirmed by a medico-economic comparison after randomization.

Refined solution structure and backbone dynamics of HIV-1 Nef.

The tendency of HIV-1 Nef to form aggregates in solution, particularly at pH values below 8, together with its large fraction of highly mobile residues seriously complicated determination of its three-dimensional structure, both for heteronuclear solution NMR (Grzesiek et al., 1996a, Nat Struct Biol 3:340-345) and for X-ray crystallography (Lee et al., 1996, Cell 85:931-942). Methods used to determine the Nef structure by NMR at pH 8 and 0.6 mM concentration are presented, together with a detailed description of Nef's secondary and tertiary structure. The described techniques have general applicability for the NMR structure determination of proteins that are aggregating and/or have limited stability at low pH values. Extensive chemical shift assignments are reported for backbone and side chain 1H, 13C, and 15N resonances of the HIV-1 Nef deletion mutants NEF delta 2-39, NEF delta 2-39, delta 159-173, and of NEF delta 2-39, delta 159-173 in complex with the SH3 domain of the Hck tyrosine protein kinase. Besides a type II polyproline helix, Nef's structure consists of three alpha-helices, a 3(10) helix, and a five-stranded anti-parallel beta-sheet. The analysis of 15N relaxation parameters of the backbone amide sites reveals that all the secondary structure elements are non-mobile on the picosecond to nanosecond and on the millisecond time scale. A large number of slowly exchanging amide protons provides evidence for the stability of the Nef core even on the time scale of hours. Significant internal motions on the ps to ns time scale are detected for residues 60 to 71 and for residues 149 to 180, which form solvent-exposed loops. The residues of the HIV-1 protease cleavage site (W57/L58) do not exhibit large amplitude motions on the sub-nanosecond time scale, and their side chains insert themselves into a hydrophobic crevice formed between the C-terminus of helix 1 and the N-terminus of helix 2. A refined structure has been determined based on additional constraints for side-chain and backbone dihedral angles derived from a large number of three-bond J-coupling and ROE data.

Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and beta-sheet topology with the A chain of ricin, a type-II RIP.

MAP30 is a 30 kDa single-stranded, type-I ribosome inactivating protein (RIP) possessing anti-tumor and anti-HIV activities. It binds both ribosomal RNA and the HIV-1 long-terminal repeat DNA. To understand the structural basis for MAP30 activities, we undertook the study of MAP30 by solution NMR spectroscopy. We report nearly complete 1H, 13C, and 15N chemical shift assignments of its 263 amino acids. Based upon an analysis of secondary 13C chemical shifts, 3J(HNHA) coupling constants, hydrogen exchange data, and nuclear Overhauser effect patterns, we find that the secondary structure and beta-sheet topology of MAP30 are very similar to those of the ricin A chain, a subunit of the well-known type-II RIP, even though two proteins display distinct activities. We therefore suggest that MAP30 and ricin A chain share a similar three-dimensional fold, and that the reported functional differences between two proteins arise primarily from differences in local three-dimensional structure and other structural properties such as surface electrostatic potentials.

Selenoamino acids in tissues of rats administered inorganic selenium.

There are conflicting reports in the literature concerning the synthesis of selenoamino acids from inorganic selenium in animals, and this work was undertaken to further investigate this. Pronase digests of acetone powders of liver and kidney tissue from rats administered 75SeO3= were subjected to fractionation by cation exchange chromatography using current methods for separating the various amino acids. Very little, if any, selenocystine was found in the digests. However, good evidence was obtained for the occurrence of 2,7-diamino-4-thia-5-selenaoctanedioic acid. It is suggested that the selenocysteine portion of this compound was formed by the reduction of the selenite to selenide with its subsequent incorporation into the amino acid by the action of serine hydrolase (E C 4.2.1.22). No selenomethionine was found under the conditions of this study.

Occupational risk factors for ill health in Gulf veterans of the United Kingdom.

OBJECTIVES: To study the association between occupational factors specific to the Armed Forces (rank, functional roles, Service, regular or reservist status and deployment factors) and symptomatic health problems in Gulf veterans, after sociodemographic and lifestyle factors have been accounted for. DESIGN: A postal cross sectional survey of randomly selected UK Gulf veterans was conducted six to seven years after the Gulf conflict. Physical ill health was measured using the Fatigue Questionnaire and a measure of the Centers for Disease Control and Prevention (CDC) multi-symptom syndrome. Psychological ill health was measured using the General Health Questionnaire and a post-traumatic stress measure. SETTING: Population of servicemen who were serving in the UK Armed Forces during the Gulf conflict between 1 September 1990 and 30 June 1991. PARTICIPANTS: 3297 Gulf veterans. MAIN RESULTS: In multivariate logistic regression, there was an inverse relation between higher rank and psychological and physical ill health (test of trend: General Health Questionnaire, p=0.004; post-traumatic stress, p=0.002; fatigue, p=0.015; CDC case, p=0.002). Having left the Armed Forces was associated with a two to three times increase in reporting ill health. Of the deployment factors, there was a weak association between being deployed as an individual reinforcement in a combat role and post-traumatic stress but there was no association between receiving pre-deployment training or post-deployment leave and ill health. Marital status and smoking were associated with psychological and physical ill health. CONCLUSIONS: Rank was the main occupational factor associated with both psychological and physical ill health in Gulf veterans. This may parallel the associations between socioeconomic status and morbidity in civilian populations. Ill health seems to be greater in those who return to civilian life. Sociodemographic factors also seem to be important in ill health in Gulf veterans.

Chronic fatigue syndrome. A practical guide to assessment and management.

Chronic fatigue and chronic fatigue syndrome (CFS) have become increasingly recognized as a common clinical problem, yet one that physicians often find difficult to manage. In this review we suggest a practical, pragmatic, evidence-based approach to the assessment and initial management of the patient whose presentation suggests this diagnosis. The basic principles are simple and for each aspect of management we point out both potential pitfalls and strategies to overcome them. The first, and most important task is to develop mutual trust and collaboration. The second is to complete an adequate assessment, the aim of which is either to make a diagnosis of CFS or to identify an alternative cause for the patient's symptoms. The history is most important and should include a detailed account of the symptoms, the associated disability, the choice of coping strategies, and importantly, the patient's own understanding of his/her illness. The assessment of possible comorbid psychiatric disorders such as depression or anxiety is mandatory. When the physician is satisfied that no alternative physical or psychiatric disorder can be found to explain symptoms, we suggest that a firm and positive diagnosis of CFS be made. The treatment of CFS requires that the patient is given a positive explanation of the cause of his symptoms, emphasizing the distinction among factors that may have predisposed them to develop the illness (lifestyle, work stress, personality), triggered the illness (viral infection, life events) and perpetuated the illness (cerebral dysfunction, sleep disorder, depression, inconsistent activity, and misunderstanding of the illness and fear of making it worse). Interventions are then aimed to overcoming these illness-perpetuating factors. The role of antidepressants remains uncertain but may be tried on a pragmatic basis. Other medications should be avoided. The only treatment strategies of proven efficacy are cognitive behavioral ones. The most important starting point is to promote a consistent pattern of activity, rest, and sleep, followed by a gradual return to normal activity; ongoing review of any 'catastrophic' misinterpretation of symptoms and the problem solving of current life difficulties. We regard chronic fatigue syndrome as important not only because it represents potentially treatable disability and suffering but also because it provides an example for the positive management of medically unexplained illness in general.

Selenium intake and urinary excretion in persons living near a high selenium area.

Selenium intake by adults consuming self-selected levels of four different diets averaged 209 micrograms. per day and correlated well with caloric and protein intake. Urinary selenium concentration averaged 0.108 microgram. per milliliter, and 24-hour excretion for the various diets averaged 58.0% to 88.6% of the intake. The data suggest that the RDA upper limit of 200 micrograms. of selenium per day and the suggested maximum urine selenium concentration may be too restrictive. The data further indicate that even though there are differences in the absorption of selenium from different sources, the average is about 70% for foods purchased in the Northern Great Plains area.

Human ocular melanocytes and retinal pigment epithelial cells differ in their melanogenic properties in vivo and in vitro.

PURPOSE: The vertebrate eye contains both melanocytes and retinal pigment epithelial (RPE) cells. Little is known of the pigmentary behaviour of these embryologically dissimilar cells. The aim of this study was to examine aspects of the pigmentary properties of both cell types in vitro and ex vivo to learn more of the function of these cells. METHODS: Sections of normal adult human eye were stained for tyrosinase related protein 1(TRP1), and cultures of RPE cells and choroidal melanocytes were examined immunocytochemically for TRP1 and 2 and enzymatically for tyrosinase activity (by assaying dopa oxidase activity). RESULTS: Over half of the choroidal melanocytes expressed TRP1 ex vivo; in contrast, a very small percentage of RPE cells were TRP1 positive. In vitro, passage 1 to 3 ocular melanocytes expressed TRP1 and TRP2 and had tyrosinase activity, which was influenced by the choice of substrate on which the cells were grown. Tyrosinase activity was highest when cells were grown on fibronectin and plastic, intermediate on laminin and lowest on vitreous extracellular matrix (ECM) containing pigment to which they attached and spread out poorly. In contrast, passage 3 RPE cells (which were unpigmented) showed little evidence of tyrosinase activity in short-term culture, irrespective of the substrate on which they were grown, and failed to express TRP1 and TRP2. When cells were grown on plastic for greater than 3 weeks in culture, a very low percentage of cells (< 0.1%) became TRP1 positive and this percentage was increased threefold if cells were cultured on laminin in the presence of bFGF. A few cells were also seen to contain pigment but cultures failed to show any tyrosinase activity. In contrast, RPE cells (but not melanocytes) showed a marked ability to take up pigment granules in vitro. CONCLUSIONS: The data suggest that normal human ocular melanocytes retain the capacity to produce pigment throughout adult life, and this can be demonstrated both ex vivo and in vitro. In contrast, we were unable to confirm that the majority of RPE cells play any significant role in active pigment production in the adult.

Influence of pigment content, intracellular calcium and cyclic AMP on the ability of human retinal pigment epithelial cells to contract collagen gels.

PURPOSE: The aim of the study was to determine to what extent collagen gel contraction could be reduced by calcium and calmodulin antagonists and agents that elevate cyclic AMP in order to develop a pharmacological approach to prevent/arrest RPE contraction of epiretinal membranes in proliferative vitreoretinopathy. We also explored a possible role of pigment in collagen gel contraction. METHOD: We measured RPE mediated contraction of 3D collagen gels in the presence and absence of the calcium and calmodulin antagonists TMB8, Verapamil and Tamoxifen and the cAMP elevating agents IBMX and Forskolin. The effect of pigment on collagen gel contraction was assessed by comparing gel contraction mediated by RPE cells re-pigmented with melanin with that mediated by unpigmented RPE. The effect of IBMX on RPE proliferation was assessed using a BrdU ELISA and the effects of IBMX on RPE cytoskeleton and cell shape were assessed using Actin and Cytokeratin immunocytochemistry. RESULTS: We report that both cAMP elevating agents and calcium and calmodulin antagonists reduce RPE mediated collagen gel contraction. Cyclic AMP elevation was more effective than a reduction in calcium in reducing contraction. There were no significant advantages in combining both approaches. The presence of melanin had no effect on gel contraction. Calcium antagonists and particularly agents which elevate cAMP caused RPE cells in collagen gels to extend fewer and shorter processes. cAMP elevation in particular caused RPE cells to become more rounded and develop arborized cell processes. Immunostaining for actin and cytokeratin revealed changes in cytoskeletal organisation in response to IBMX in that cells contained less actin than untreated cells and concentrated cytokeratins more centrally. CONCLUSION: We have identified two possible pharmacological approaches which may provide a new direction for preventing or slowing down the development of PVR.

Involvement of calcium in retinal pigment epithelial cell proliferation and pigmentation.

PURPOSE: The aim of this study is to explore the role of intracellular calcium in the mechanism of co-regulation of retinal pigment epithelial cells (RPE) by vitreous fluid and platelet mitogens, in order to evaluate the use of calcium modulating drugs in preventing RPE cell proliferation and contraction of fibrocellular membranes. METHODS: Monolayers of human RPE cells were loaded with Fura-2-AM and examined in a fluorimeter for changes in intracellular free calcium in response to platelet mitogens (PDGFAB or TGFbeta1) and vitreous fluid (containing vitreous substrate proteins), both alone or in combination. The effect of the calcium antagonists TMB8 and verapamil and the calmodulin antagonists J8 and tamoxifen were then examined on RPE cell proliferation and pigmentation, both in the presence and absence of vitreous substrate and platelet mitogens. RESULTS: We report that co-exposure of RPE cells to platelet mitogens and vitreous fluid produces an increase in intracellular free calcium of greater duration than that with either PDG-FAB, TGFbeta1 or vitreous fluid alone. Calcium and calmodulin antagonists significantly reduce RPE cell proliferation in both the presence and absence of vitreous substrate and platelet mitogens. Calcium antagonists also stimulate the accumulation of autofluorescent granules within RPE cells. CONCLUSIONS: Calcium signalling plays a role in the co-regulation of RPE cells by vitreous substrate and platelet mitogens. Drugs that lower intracellular calcium or inhibit calmodulin may offer an additional approach to preventing the hyperproliferation of RPE cells in PVR.

The effect of subclinical selenium toxicosis on pregnant beef cattle.

A field investigation conducted by the South Dakota Animal Disease Research and Diagnostic Laboratory suggested that subclinical selenium toxicosis in pregnant cows may have contributed to an outbreak of aborted/stillborn calves in a high-selenium region of South Dakota. This study was undertaken to evaluate the relationship between abortion and subclinical selenium toxicosis in the dam and to assess the effects of subclinical selenium toxicosis on the bovine immune system. Fifteen pregnant cows were fed diets containing 0.25 (control), 6.0, and 12.0 ppm selenium beginning at 80-110 days gestation. Although selenium toxicosis has been reported to cause abortion, this study failed to reproduce abortions. A single cow in the 12-ppm selenium treatment group gave birth to a weak calf, which subsequently died. This calf had myocardial lesions consistent with those described for selenium toxicosis and had hepatic selenium levels of 9.68 ppm (wet weight). Elevated dietary selenium resulted in the depression of several leukocyte function parameters in pregnant cows. A statistically significant depression in forced antibody response was identified in both selenium-supplemented groups. A significantly diminished mitogenic response to concanavalin A and pokeweed mitogen was also observed in the 12-ppm selenium group. Although a similar pattern of depression was also observed with phytohemagglutinin, differences were not significant. These findings indicate that even in the absence of clinical alkali disease, elevated selenium levels may adversely affect both pregnancy outcome and the bovine immune system.

Improving emergency obstetric care at a district hospital, Makeni, Sierra Leone. The Freetown/Makeni PMM Team.

PRELIMINARY STUDIES: A facility review and focus group discussions revealed poor capacity to manage obstetric complications. INTERVENTIONS: In response, a physician with obstetric skills was posted, and a second physician was trained. Courses in life-saving obstetric skills were held for nurses and midwives. An unused operating theater was made functional with simple modifications. A generator and blood bank were installed. Drugs and supplies were made available through a revolving fund. Subsequently, community interventions focused on improving utilization. RESULTS: The number of women seeking treatment for major obstetric complications at the district hospital increased from 31 in 1990 to 98 in 1995, while the case fatality rate (CFR) among these women dropped from 32% to 5%. Cesarean sections increased from two in 1990 to 38 in 1995. In 1995, 444 abortion-related procedures were performed--almost all of them for unwanted pregnancy--compared with only 22 in 1990. COSTS: The cost of material improvements and training was approximately US$39,000, of which 46% was from project funds, 41% from non-governmental organizations and 13% from government. CONCLUSIONS: Women with obstetric complications will seek hospital care if services are available. Government hospital services can be improved by building on existing resources. Obstetric CFR can be dramatically reduced. The need for safe abortion services, which are currently illegal in Sierra Leone, is demonstrated.

Toxic effects of selenium on growing swine fed corn-soybean meal diets.

A total of 96 crossbred pigs received various levels of sodium selenite to determine the effect of dietary selenium (Se) on growing swine fed corn-soybean meal diets. Levels of supplemental Se were 0, 4, 8, 12, 16 and 20 micrograms/g. There were linear decreases (P less than .01) in both gain and feed intake with increasing levels of dietary Se. Feed/gain increased numerically as dietary Se increased. Hair Se increased quadratically (P less than .01) and blood Se increased linearly (P less than .01) with increasing level of dietary Se. Cell volume and hemoglobin were not affected by dietary treatment. Increasing dietary Se significantly increased glutathione peroxidase (GSH-Px), glutamic-oxalacetic transaminase (GOT). and glutamic-pyruvic transaminase (GPT). External signs of selenosis were noted in some pigs fed 12 or 20 micrograms/g of Se. The toxic level of Se in a corn-soybean meal diet for crossbred pigs appears to be between 4 and 8 micrograms/g. Of variables studied, growth rate was the most sensitive indicator of chronic selenosis in swine.

Effects of seleniferous grains and inorganic selenium on tissue and blood composition and growth performance of rats and swine.

Two experiments were conducted to determine the effect of varying dietary selenium (Se) levels and Se source on growing swine. In Exp. 1, seleniferous wheat and oats were used to formulate diets containing .47, 2.58, 5.60 or 8.40 micrograms/g organic Se. Dietary Se level had no effect on pig performance during the 6-wk experiment as measured by daily gain, daily feed intake or feed/gain. Blood composition and enzyme activity were not affected by dietary treatment. Selenium concentrations of blood, hair, liver, kidney, heart, spleen and diaphragm muscle were increased linearly (P less than .01) as dietary Se increased. In addition, liver weight as a percentage of body weight was increased linearly (P less than .01) as dietary Se level increased. No signs of chronic Se poisoning were observed. Dietary treatments in Exp. 2 were similar to Exp. 1 with the exception that sodium selenite was utilized as the Se source and the diets were fed for 17 wk. Inorganic Se levels of .54, 2.63, 5.69 or 8.33 micrograms/g had no effect on pig performance as measured by daily gain, daily feed intake or feed/gain. Selenium concentrations of blood, hair, liver, kidney, spleen and diaphragm muscle were significantly increased as dietary Se level increased. Liver weight as a percentage of body weight was increased at the two highest dietary Se levels. Blood glutathione peroxidase activity was significantly increased by dietary treatment, while other blood variables were not affected. No signs of chronic Se poisoning were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Porcine focal symmetrical poliomyelomalacia: experimental reproduction with oral doses of encapsulated sodium selenite.

Sodium selenite (encapsulated as doses of 1.4 mg, 2.6 mg and 4.2 mg per kilogram of body weight) was given orally on a daily basis to male weaner pigs, and features of these animals were compared to a control group. Porcine focal symmetrical poliomyelomalacia was produced in all experimental groups between 3 and 20 days after initiation of the treatment. Analysis of blood and several tissues revealed an elevated selenium content for all pigs. Histological lesions in the brain and the cervical lumbar/sacral spinal cord enlargements included endothelial proliferation, neuronal degeneration, microcavitation and glial cell reaction.

Porcine focal symmetrical poliomyelomalacia: test for an interaction between dietary selenium and niacin.

Experiments were conducted to test the hypothesis that dietary supplementation with nicotinamide would retard or eliminate the signs of selenium induced porcine focal symmetrical poliomyelomalacia (PFSP). Mixed-sex feeder pigs, approximately five weeks old, were divided into four groups and daily received, by oral capsule, the following treatments: no supplementation (control); 2.86 mg sodium selenite per kg body wt (selenium only); 44 mg nicotinamide per kg body wt (niacin only); or both the niacin and selenium (niacin + selenium). Over the ten day treatment body weights and behavior scores were recorded, as well as collection of fluid (blood, serum, urine) samples. Upon death, tissue samples (kidney, liver, brain, spinal cord and muscle) were obtained. All of these samples were analyzed for total selenium and bioactive niacin compounds. After gross pathological analysis, 11 samples from specific brain and spinal cord regions were taken for fixation and processing for histological analysis by light microscopy. The selenium only group showed behavior signs related to PFSP after two days of treatment with the average time of death at 6.5 days. Tissue levels of selenium were elevated and histological analyses established the expected lesions of PFSP. No disorders were noted in the control and niacin only groups. The niacin + selenium groups had slightly retarded changes in behavior scores (first differences from controls on day 4) but their mean day of death (7.5 days of treatment) did not differ from that of the selenium only groups. Histological analyses of these tissues revealed similar lesions to the selenium only group, but they may have been of lesser magnitude. The data were consistent with, but only partially supportive of, the above hypothesis.