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In the summer of 1967, a relatively complete skeleton of a juvenile was excavated from the Ishkeenickh River Cave Site (now the Ksi Hlginx River) in British Columbia, Canada, dating from approximately 2000 years ago. This individual, likely aged between 10 and 12 years at time of death, displays osteological features consistent with a chronic arthropathy. The most striking pathological changes are on the spine, with bony ankylosis present on several of the cervical and thoracic vertebrae. Lesions can also be observed on the ribs, the ilia, the femora, and a tibia. The arthritic conditions of juvenile-onset ankylosing spondylitis, juvenile psoriatic arthritis, and juvenile-onset adult-type rheumatoid arthritis, along with Klippel-Feil syndrome, are possible aetiologies discussed as part of a differential diagnosis. The presence of post-mortem damage as well as missing bones makes an absolute diagnosis of a disease impossible, however the lesions present on this skeleton seem to be most consistent with juvenile-onset ankylosing spondylitis. The majority of published research on these diseases appears in clinical contexts, therefore this case study represents a unique opportunity to observe the bony changes that occur with juvenile idiopathic arthritis in the context of palaeopathology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Naphthenic acids (NAs) are naturally occurring saturated linear and cyclic carboxylic acids found in petroleum, including the bitumen contained in the Athabasca Oil Sands deposit in Alberta, Canada. The processing of these oil sands leads to elevated concentrations of NAs, as well as increased salinity from produced waters as a result of ions leaching from the ores, the process aids, and the water associated with the deeper aquifers. These changes can result in waters that challenge reclamation of impacted waters associated with oil sands development. Laboratory tests examined the effects of salinity on NA toxicity using local young-of-the-year yellow perch exposed to a commercially available mixture of NAs (CNA) and an NA mixture that was extracted from oil sands process-affected water (ENA), with and without the addition of sodium sulfate (Na(2)SO(4)). Gill and liver histopathological changes were evaluated in the surviving fish after 3 weeks of exposure. At 6.8 mg/L ENA and 3.6 mg/L CNA, 100% mortality was observed, both with and without the addition of salt. Exposure of yellow perch to 25% of the NA required to give an LC100 (0.9 mg/L CNA; 1. 7 mg/L ENA) resulted in high levels of gill proliferative (epithelial, mucous, and chloride cell) changes, a response that was increased with the addition of 1g/L salt (Na2SO4) for the ENA. The significance of these changes was a reduced gill surface area, which likely caused a reduction in both the transport of NAs within the fish and the exchange of vital respiratory gases. While the gills were affected, no liver alterations were identified following NA or NA+salt exposures. Differences in the chemical composition of the NAs tested may explain the differences in the lethality and histopathology of yellow perch.

The extraction of bitumen from the Athabasca oil sands (Alberta, Canada) produces significant volumes of process-affected water containing elevated levels of naphthenic acids (NAs), ions, and polycyclic aromatic hydrocarbons (PAHs). The sublethal response of aquatic organisms exposed to oil sands constituents in experimental aquatic environments that represent possible reclamation options has been studied. In this study, the effects of process-affected waters on gill and liver tissues in yellow perch (Perca flavescens) and caged goldfish (Carassius auratus) held in several reclamation ponds at Syncrude's Mildred Lake site have been assessed. Following a 3-week exposure, significant gill (epithelial cell necrosis, mucous cell proliferation) and liver (hepatocellular degeneration, inflammatory cell infiltration) histopathological changes were noted in fish held in waters containing high levels of oil sands process-affected water. In addition, measurements of gill dimensions (gill morphometrical indices) proved sensitive and provided evidence of a physiological disturbance (gas exchange) with exposure to oil sands materials. Due to the complexity of oil sands process-affected water, the cause of the alterations could not be attributed to specific oil sands constituents. However, the histopathological parameters were strong indicators of exposure to oil sands process-affected water and morphometrical data were sensitive indicators of pathological response, which can be used to identify the interactive effects of ionic content, NAs, and PAHs in future laboratory studies.

The main factors affecting the evolution of drug resistance in malaria according to theoretical models are reviewed here. The overwhelming influence on the emergence and rate of spread of drug resistance is the proportion of infected hosts that are treated with drugs. A second important effect is drug efficacy in killing parasites. Factors such as average transmission rate, recombination, the biological cost of resistance, and the mode of gene action also influence the rate of spread but have relatively minor impacts. A simple population dynamics model that captures the epidemiological effects of drug treatment and resistance, as opposed to a population genetics model that does not, is presented in order to illustrate the main conclusions.

The Japanese medaka (Oryzias latipes) early-life stage assay was used to investigate the effects of a number of commercially available dimethylated polycyclic aromatic hydrocarbons (PAHs) (3,6-dimethylphenanthrene, 7,12-dimethylbenz[a]anthracene, and 4,6-dimethyldibenzothiophene) and their unsubstituted congeners, dimethylated and unsubstituted tertiary mixtures, and a complex environmental mixture (with elevated C2-substituted dibenzothiophene) on embryo larval development. Unsubstituted PAHs showed trends of increased blue sac disease (BSD) relative to dimethylated PAHs, although the severity of BSD induction varied. Results demonstrated that the dibenzothiophene congeners were the strongest inducers of BSD of the commercial PAHs tested. These compounds reduced the hatching success of embryonic medaka, an effect that was enhanced in the mixture. The base neutral extract significantly increased the frequency and severity of BSD abnormalities, while significantly reducing larval hatch length. Based on these results, a sublethal maximum allowable toxicant concentration (MATC) of 13.91 microg PAHs/L was calculated.

Adult yellow perch were stocked into experimental ponds designed to test the biological effects of aquatic reclamation alternatives currently being pursued by the oil sands mining industry. Water-quality characteristics of oil sands-influenced water in the experimental ponds included increased salinity and elevated trace organics associated with raw oil sands (bitumen). After 3 and 10 months of exposure to affected waters, perch gross pathologies including severe fin erosion and virally induced tumors were observed in exposed individuals. Gill histopathology revealed large aneurysms accompanied by a proliferation of chloride and epithelial cells in the interlamellar spaces. Gill pathologies were not paralleled by a decrease in plasma sodium, calcium, or chloride. The frequencies of gross pathologies and gill changes were correlated to the concentrations of the oil sands-related compounds. As inorganic and organic compounds associated with oil sands activities are highly intercorrelated, and the observed lesions and changes are not diagnostic of particular toxicants, it was not possible to isolate the causative chemical factor(s) responsible. The incidence of observed lesions and gill pathologies could not be conclusively linked to increased mortality rates observed in the exposed populations. Evidence of recovery in the pathologies was observed between 3 and 10 months of exposure, coincident with a stabilization in population numbers., (Copyright 2000 Academic Press.)

The fatty acid composition of plasma phospholipids differs between infants fed formula and infants fed human milk, but the extent to which this is accompanied by differences in tissue phospholipid fatty acids is unclear. This paper describes analysis of plasma, liver and brain fatty acids from piglets fed one of seven formulas, varying in saturated, monounsaturated, (n-6) and (n-3) fatty acids or sow milk from birth for 18 d. Bile fatty acids were analyzed because they are secreted from liver and may be an important source of fatty acids for intestinal lipoprotein synthesis. The results were used to determine the relation between diet-related differences in plasma phospholipid fatty acids and those in brain, liver and bile. Where significant associations were found, prediction limits were constructed to assess the usefulness of analysis of plasma phospholipid fatty acids to predict diet-induced changes in tissue fatty acids. The proportions (g/100 g fatty acids) of 16:0, 18:0, 18:1, 18:2(n-6) and 20:4(n-6) in plasma phospholipids were significantly associated with the proportions of the same fatty acids in liver and bile, but not brain. The results show a reasonably precise, predictable association between plasma and liver, and plasma and bile fatty acids. Brain 20:4(n-6) and 22:6(n-3), in contrast, were not reliably associated with plasma phospholipid 20:4(n-6) and 22:6(n-3) for piglets fed milk or formula providing about 1.5% energy as 18:3(n-3).

Background/aims: The hypothesis that chronic alcohol ingestion potentiates iron-associated liver injury was investigated in the 'carbonyl iron-overload rat model'., Methods: Newborn male and female Wistar-Furth rats (seven per group) were used to investigate iron-alcohol interaction over a 26-week period. Groups 1 and 2 were iron loaded from birth, while the others received normal diet. At 10 weeks all rats commenced Lieber-DeCarli liquid diet; additional treatments were: group 1 6 g carbonyl iron/1000 ml diet plus alcohol; group 2 carbonyl iron in the liquid diet; group 3 alcohol in the liquid diet; group 4, the controls, received liquid diet only., Results: This study confirmed our previous observation that iron-loading from birth resulted in grade III-IV siderosis, in both male and female rats, and caused fibrosis associated with periportal macrophages. Alcohol-feeding, in addition to iron-feeding for 26 weeks significantly lowered the hepatic iron concentration in both male and female rats compared to those fed iron only (p < 0.05). Alcohol feeding did increase hepatic fibrosis in the iron-loaded animals. However, serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups (p < 0.05)., Conclusions: Thus, contrary to expectation, chronic alcohol feeding failed to potentiate hepatic fibrosis in iron-overloaded rats, although there was rather more hepatocyte necrosis, and the serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups.

Docosahexaenoic acid and arachidonic acid are deposited in large amounts in the developing central nervous system, and concentrations are particularly high in synaptic plasma membrane and retina ethanolamine phospholipids. Arachidonic acid and docosahexaenoic acid are present in human milk. The precursors linoleic [18:2(n-6)] and alpha-linolenic [18:3(n-3)] acid, but not arachidonic acid or docosahexaenoic acid, are present in formulas. Desaturation and elongation of 18:2(n-6) and 18:3(n-3) to arachidonic acid and docosahexaenoic acid, respectively, depend on the dietary content and ratio of 18:2(n-6) and 18:3(n-3), but appropriate levels and ratios of 18:2(n-6) and 18:2(n-3) for formula are not well defined. The effect of formula with 1 or 4% fatty acids 18:3(n-3) and 16, 30 or 35% fatty acids 18:2(n-6) on synaptic plasma membrane and retina ethanolamine phospholipid fatty acids was therefore studied in piglets, with reference to piglets fed milk. Piglets fed 4% fatty acids 18:3(n-3), but not those fed 1% fatty acids 18:3(n-3), had similar central nervous system docosahexaenoic acid levels but had significantly lower brain weights than piglets fed sow milk. Synaptic plasma membrane and retina arachidonic acid were lower in piglets fed the formulas with 4% rather than 1% fatty acids 18:3(n-3). The dietary 18:3(n-3) content, rather than the 18:2(n-6) to 18: 3(n-3) ratio, seemed more important for deposition of docosahexaenoic acid in brain. However, synaptic plasma membrane and retina docosahexaenoic acid levels were further reduced in piglets fed 1% fatty acids 18:3(n-3) (0.4% energy) with 30% rather than with 16% fatty acids 18:2(n-6). The need for further study of upper limits of dietary 18:3(n-3) during development is suggested.

Addition of fish oils to infant formula provides (n-3) long-chain polyenoic fatty acids (LCP), specifically 22:6(n-3), to infants fed formula rather than human milk. Most fish oils, however, contain high levels of 20:5(n-3) and low (n-6) LCP. These studies determined the brain total, synaptic plasma membrane phosphatidylethanolamine and phosphatidylcholine, and plasma and liver phospholipid fatty acids of piglets fed from birth to 15 d with formula containing (percent fatty acids) 34% 18:2(n-6), 0.8% 18:3(n-3) and 0, 2 or 6 g/L menhaden oil, or sow milk. The brain 22:6(n-3) was higher and 22:4(n-6) lower in piglets fed 6 g/L menhaden oil compared with sow milk. Brain levels of 20:5(n-3) did not increase, or levels of 20:4(n-6) decrease, with increasing dietary (n-3) LCP. A diet concentration-dependent increase in 20:5(n-3) and decrease in 20:4(n-6) (P less than 0.0001) in liver phospholipid showed no evidence of maximum saturation or depletion, respectively, over the range of (n-3) LCP intake studied. The fish oil supplementation was effective in supplying 22:6(n-3) to the developing brain. The accompanying increase in 20:5(n-3) and decrease in 20:4(n-6), important eicosanoid precursors, in plasma and liver phospholipid show the need for caution in the use of fish oils low in (n-6) LCP as a source of (n-3) LCP for infant formula.

Previous studies have used relative (%) values of plasma 18:2n-6 (18:2 omega-6) and the ratio of 20:3n-9 to 20:4n-6 (triene/tetrene) to indicate the essential fatty acid (EFA: 18:2n-6 and 18:3n-3) status of preterm infants. The extent to which these indices reflect milligrams per liter quantities of n-6 and n-3 long-chain polyunsaturated derivatives of EFA (LCPs), required for cell membrane accretion, is unknown. Thus, 18:2n-6, the triene-tetrene ratio, and n-6 and n-3 LCPs were measured in plasma phospholipid of preterm infants' cord blood (n = 22) and of preterm infants fed formula (n = 12) or of preterm infants who received fat-free parenteral nutrition (n = 15) on postnatal day 3. Whether expressed as percent or milligrams per liter, 18:2n-6 was markedly higher and the triene-tetrene ratio lower in infants fed formula than in infants who had received no lipid. However, concentrations of n-6 and n-3 LCPs were similar in the two groups of infants and significantly higher than cord values. In the absence of an exogenous lipid source, it is suggested that tissue stores of LCPs are released in response to birth.

The effects of a vegetable-oil-based formula containing 30% 18:2n-6 (18:2 omega-6), 0.8% 18:3n-3, and no n-6 or n-3 long-chain polyunsaturated fatty acids (LCPs) on retina total lipid, ethanolamine phosphoglyceride (EPG), and phosphatidylcholine (PC) fatty acid composition were studied in neonatal piglets. Term-gestation piglets were fed sow milk (SMF) or the formula (FF) from birth for 5, 10, 15, or 25 d. After 25 d feeding, the 22:6n-3 was reduced by 24% in total lipid, 20% in EPG, and 28% in PC of retinas of FF relative to SMF piglets. A compensatory increase in 22:4n-6 and 22:5n-6 concentrations occurred in retina total lipid, EPG, and PC of FF animals. The data suggest that the exclusive feeding of formulas devoid of LCPs and high in 18:2n-6 and/or 18:2n-6 and 18:3n-3 compromises normal accretion of 22:6n-3 in neonatal piglet retina. The potential reversibility of these changes or their effects on vision are not known.

The fatty acid composition of plasma phospholipids, red blood cell (RBC) phosphatidylcholine (PC), and phosphatidylethanolamine (PE) was determined for low-birth-weight (LBW) infants when full oral feeding commenced (day 0) and after a further 28 d (day 28). They were fed their mother's expressed breast milk (PTM, n = 9), formula (SCF, n = 16) with 2% 18:3n-3 fatty acids, 20% 18:2n-6 fatty acids, or a combination of SCF and PTM (n = 11). Concentrations of all 20- and 22-carbon n-6 and n-3 fatty acids were similar among the infant groups on days 0 and 28 (mean postnatal age 42 +/- 1.3 d). The results suggest that formula with greater than or equal to 2% 18:3n-3 and a ratio of 18:2n-6 to 18:3n-3 similar to that of human milk may permit incorporation of n-3 fatty acids in LBW infant tissues equivalent to that from human milk.

Clinical studies showed that a decrease in red blood cell 22:6n-3 caused by feeding infants formula (F) can be prevented by supplementation with fish oil (F + O). It is not known whether fish-oil supplementation is able to support normal accretion of fatty acids with greater than or equal to 20 carbons (LCPs) in the brain. Therefore piglets were fed exclusively F + O, F, or sow milk (SM) for 15 d and their liver and brain synaptosomal fatty acids were determined. Feeding F + O corrected the low n-3 LCP in the liver phospholipid (PL) and synaptosomal phosphatidylethanolamine (PE) of piglets fed F compared with SM. An apparent compensatory increase in n-6 LCPs in liver PL and synaptosomal PE of piglets fed F compared with SM was suppressed by feeding F + O. F + O also reduced the ratio of plasma PL 20:4n-6 to 20:5n-3, important for eicosanoid metabolism. Supplementation of F with n-3 LCPs as fish oil, without n-6 LCPs, at levels giving normal brain n-3 LCP, may alter n-6 LCP accretion.

The effect of feeding sow-milk formula (SMF) or a vegetable-oil infant formula (FF) with minimal n-6 and n-3 long-chain polyenoic fatty acids (LCPs) but high linoleic acid (18:2n-6) and a high ratio of 18:2n-6 to linolenic acid (18:3n-3) on the fatty acids of brain lipid and liver, plasma, and red cell phospholipids was studied in piglets fed from birth for 5, 10, 15, or 25 d. Compared with SMF, FF reduced the concentrations of 18:1 and n-3 LCPs, especially 22:6n-3, in all tissues and increased 22:4n-6 in brain, liver, plasma, and red cell phosphatidylethanolamine. FF also increased 22:5n-6 in brain lipid, liver, and plasma but not in red cell phospholipids. Thus, changes in tissues capable of in situ desaturation were not completely reflected in the red cell phospholipids. The increased liver and brain n-6 LCP accretion in the FF piglets may suggest competent desaturation and possible inhibition of n-3 desaturation and/or acylation by dietary n-6 fatty acids.

Natural infestations of the cattle tick Boophilus microplus, levels of the buffalo fly Haematobia irritants exigua and faecal nematode egg concentrations (Bunostomum phlebotomum, Cooperia spp., Haemonchus placei, Oesophagostomum radiatum and Trichostrongylus axei) were assessed in 221 Belmont Red calves during the post-weaning period, when the animals were between 9 and 18 months of age. In addition, the 98 males of this group were challenged with B. microplus larvae on two separate occasions. There were strong positive correlations among replicate assessments of the same parasite. Field tick counts and tick counts following deliberate challenge were strongly correlated, and both showed negative correlations with post-weaning weight gain. There was a weak positive correlation between buffalo fly counts and post-weaning weight gain. There was a negative correlation between total worm egg count and weight gain. Among worm species, only the effect of O. radiatum on weight gain was significant. Cattle with bovine major histocompatibility (BoLA) antigens W6.1 and W7 had significantly fewer ticks than cattle lacking these antigens. Cattle with BoLA antigens W7 and CA36 had lower concentrations of nematode eggs in their faeces than cattle lacking these BoLA antigens.

The effect of ethinyl estradiol, a steroid commonly used in birth control pills and possibly associated with impaired drug metabolism in humans, on the activity of and turnover of components of the hepatic microsomal mixed-function oxidase system was studied in male rats. After 5 days of ethinyl estradiol, 5 mg/kg/day, there was a significant decrease in the activity of ethylmorphine-N-demethylase and in cytochrome P-450, cytochrome b2, and NADPH cytochrome c reductase. Cytochrome P-450 apoproteins were identified within an SDS-polyacrylamide gel system, and the rate of turnover of cytochrome P-450 apoproteins was studied by double-isotope labeling techniques. After 5 days of ethinyl estradiol administration, the rate of degradation of cytochrome P-450 apoprotein was reduced (half-life of 50 hr compared to 24 hr in control), and their relative rate of synthesis was likewise reduced, indicating that a new steady state of protein turnover associated with reduced synthesis rate had been reached. This was confirmed by studies of the effect of ethinyl estradiol on the level of microsomal cytochrome P-450 over a 10-day period.

Phenol sulfate esters have been analyzed by paired-ion reversed-phase high-performance liquid chromatography. The method provided direct, rapid chromatography of phenol sulfates in crude extracts of the red alga (Polysiphonia lanosa (2,3-dibromo-4,5-dihydroxybenzyl alcohol 1',4-disulfate), of the brown alga Ascophyllum nodosum (1,2,3,5-tetrahydroxybenzene 2,5-disulfate), and in rat urine (resorcinol mono- and disulfates). Detector response (254 nm) was linear within the approximate range from 30--125 ng to 5--10 microgram. Semipreparative scale chromatography provided sufficient amounts of purified phenol sulfates for further analysis by paper electrophoresis.

Sural nerve biopsy specimens from affected and non-affected limbs of stroke patients were examined morphometrically. Two principle abnormalities of peripheral nerve were found in hemiparetic and hemiplegic limbs. First, the frequency of abnormal teased nerve fibers was significantly increased with abnormal internodes frequently "clustered" and showing a 50% or more reduction in myelin thickness. Second, the mean diameter of myelinated nerve fibers was reduced. These results suggest a primary atrophy of peripheral nerve fibers in the affected limbs of stroke patients with secondary demyelination. Possible aetiological factors include disuse, transynaptic degeneration, ischemia, pressure effect, and decreased axoplasmic flow. It would seem that the structural integrity of peripheral nerve is frequently compromised following a cerebral lesion.

Since diabetes mellitus is a frequent manifestation of haemochromatosis the prevalence of the disease was investigated in 418 patients attending a diabetic clinic. 21 (5%) patients had a persistently high serum ferritin (men, over 400 micrograms/l; women, over 300 micrograms/l) and 5 of these had transferrin saturations consistently over 55%. Idiopathic haemochromatosis was confirmed by liver biopsy in 4 patients, all of whom had a hepatic iron index greater than 2.0. The prevalence rate of previously unrecognised idiopathic haemochromatosis was thus 9.6 per 1000 (general population prevalence 1 in 250), suggesting that screening of diabetic patients for this genetic disease may be more cost-effective than screening in the general population.

The effects of a vegetable oil-based infant formula, virtually devoid of n-6 and n-3 long chain polyenoid fatty acids (LCP) and high in 18:2(n-6) and 18:2(n-6)/18:3(n-3) ratio, on brain synaptosome lipid composition and enzyme thermotropic behavior were studied in neonatal piglets. Term gestation piglets were fed either sow milk (SMF) or formula (FF) from birth for 5, 10, 15, or 25 days. Synaptosomal cholesterol, total lipid phosphorus, and phospholipid class composition did not differ between SMF and FF piglets. Synaptosomal fatty acid composition, however, was influenced by diet. The proportion of n-3 LCP, especially 22:6(n-3), was decreased, while the n-6 LCP, especially 22:4(n-6) and 22:5(n-6), were increased in FF compared to SMF piglets. These diet-related changes were most pronounced in the ethanolamine glycerophospholipid fraction and increased with the duration of feeding. FF thus reversed an apparent developmental increase in the synaptosomal n-3/n-6 LCP ratio. The monoene content, especially 18:1, was also reduced in the synaptosomes of FF compared to SMF pigs. FF had no effect on the activity of synaptosomal acetylcholinesterase. However, higher transition temperatures for this enzyme, indicating decreased membrane fluidity, were found in the FF compared to SMF piglets. The data suggest that exclusive feeding of proprietary formulae, devoid of LCP and high in 18:2(n-6) and/or the 18:2 (n-6)/18:3(n-3) ratio, may compromise normal fatty acid accretion and physical properties of brain synaptosomal membranes.