Insulin resistance in the liver: Deficiency or excess of insulin?

In insulin-resistant states (obesity, pre-diabetes, and type 2 diabetes), hepatic production of glucose and lipid synthesis are heightened in concert, implying that insulin deficiency and insulin excess coexists in this setting. The fact that insulin may be inadequate or excessive at any one point in differing organs and tissues has many biologic ramifications. In this context the concept of metabolic compartmentalization in the liver is offered herein as one perspective of this paradox. In particular, we focus on the hypothesis that insulin resistance accentuates differences in periportal and perivenous hepatocytes, namely periportal glucose production and perivenous lipid synthesis. Subsequently, excessive production of glucose and accumulation of lipids could be expected in the livers of patients with obesity and insulin resistance. Overall, in this review, we provide our integrative perspective regarding how excessive production of glucose in periportal hepatocytes and accumulation of lipids in perivenous hepatocytes interact in insulin resistant states.     

Sheep prions with molecular properties intermediate between classical scrapie,BSE and CH1641–scrapie

Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions that BSE, classical scrapie and CH1641–a rare scrapie variant–could occur as mixtures. In field samples including those from fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistant part of the disease‑associated form of prion protein (PrP^res) represents a powerful tool for quick discrimination purposes. In this study we examined 7 deviant ovine field cases of scrapie for some typical molecular aspects of PrP^res found in CH1641‑scrapie, classical scrapie and BSE. One case was most close to scrapie with respect to molecular mass of its non-glycosylated fraction and N-terminally located 12B2‑epitope content. Two cases were unlike classical scrapie but too weak to differentiate between BSE or CH1641. The other 4 cases appeared intermediate between scrapie and CH1641 with a reduced molecular mass and 12B2‑epitope content, together with the characteristic presence of a second PrP^res population. The existence of these 2 PrP^res populations was further confirmed through deglycosylation by PNGaseF. The findings indicate that discriminatory diagnosis between classical scrapie, CH1641 and BSE can remain inconclusive with current biochemical methods. Whether such intermediate cases represent mixtures of TSE strains should be further investigated e.g. in bioassays with rodent lines that are varying in their susceptibility or other techniques suitable for strain typing.     

Reactive species, antioxidants and cold tolerance during deacclimation of Picea abies populations

Seasonal changes in levels of reactive oxygen species (ROS), low-molecular weight antioxidants and activities of antioxidant enzymes were analyzed in relation to the freezing tolerance of 1-year-old needles from four populations of Norway spruce. Throughout the study period (from January until May), no significant changes were observed in the superoxide anion radical (O ₂ ^·? ) or hydrogen peroxide (H₂O₂) levels in the needles. By contrast, a marked reduction was observed in concentrations of low-molecular weight antioxidants, including flavonoids (FL), ascorbic acid (AsA) and slight glutathione (GSH), during deacclimation. The activities of superoxide dismutase (SOD) (EC. 1.15.1.1.) and guaiacol peroxidase (PO) (EC. 1.11.1.7.) also decreased significantly. The activity of catalase (CAT) (EC. 1.11.1.6.) did not change significantly. Levels of low-molecular weight antioxidants (AsA, FL and GSH) and SOD activity were correlated significantly with freezing tolerance in the studied populations. The reactions were similar in all populations. This suggests that the response of the antioxidant system depends more strongly on climatic conditions than on population origin. The ability of spruce trees to cope with active oxygen species is discussed as an aspect of defense and a factor associated with freezing tolerance.     

Modelling the effect of fishing on southern Buller's albatross using a 60-year dataset

Abstract

Many albatross populations are declining and a major cause is believed to be incidental mortality from fishing. We investigated the effect of fishing on southern Buller's albatross Thalassarche bulleri bulleri, using a new approach to seabird population modelling that allows estimation of demographic parameters from multiple data types. Three types of data were used: a 60-year set of mark–recapture observations, four censuses of the breeding population, and estimates of fishing effort and bycatch. The fisheries risk to the viability of this population over the last 60 years appears to have been small, since the adult population is estimated to have increased about five-fold over that time. There is some cause for concern in recent changes (population growth has slowed, and perhaps reversed, and adult survival rates are falling). The most common age at first breeding was 12 years, and about 80% of adults breed each year. Annual survival was estimated to be 0.91 for juveniles, and varied between this value and 1 for adults. Though this population is not in immediate danger from fishing, there is a need for continued monitoring to see whether the recent fall in survival rates persists and causes a decline in abundance. Our analysis showed that when, as is common, mark–recapture data do not provide good estimates of all demographic rates, the assessment of seabird population trends can be improved by the use of other types of data, particularly abundance.     

Biomechanical factors and physical examination findings in osteoarthritis of the knee: associations with tissue abnormalities assessed by conventional radiography and high-resolution 3.0 Tesla magnetic resonance imaging

Introduction

We aimed to explore the associations between knee osteoarthritis (OA)-related tissue abnormalities assessed by conventional radiography (CR) and by high-resolution 3.0 Tesla magnetic resonance imaging (MRI), as well as biomechanical factors and findings from physical examination in patients with knee OA.

Methods

This was an explorative cross-sectional study of 105 patients with knee OA. Index knees were imaged using CR and MRI. Multiple features from CR and MRI (cartilage, osteophytes, bone marrow lesions, effusion and synovitis) were related to biomechanical factors (quadriceps and hamstrings muscle strength, proprioceptive accuracy and varus-valgus laxity) and physical examination findings (bony tenderness, crepitus, bony enlargement and palpable warmth), using multivariable regression analyses.

Results

Quadriceps weakness was associated with cartilage integrity, effusion, synovitis (all detected by MRI) and CR-detected joint space narrowing. Knee joint laxity was associated with MRI-detected cartilage integrity, CR-detected joint space narrowing and osteophyte formation. Multiple tissue abnormalities including cartilage integrity, osteophytes and effusion, but only those detected by MRI, were found to be associated with physical examination findings such as crepitus.

Conclusion

We observed clinically relevant findings, including a significant association between quadriceps weakness and both effusion and synovitis, detected by MRI. Inflammation was detected in over one-third of the participants, emphasizing the inflammatory component of OA and a possible important role for anti-inflammatory therapies in knee OA. In general, OA-related tissue abnormalities of the knee, even those detected by MRI, were found to be discordant with biomechanical and physical examination features.     

Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register

Introduction  

Anti-TNF therapies represent a breakthrough in the treatment of severe psoriatic arthritis. However, little is known about long-term drug persistence with these treatments in patients with psoriatic arthritis in routine clinical practice. The aim of this study was to assess persistence with first-course and second-course treatment with anti-TNF agents in a prospective cohort of psoriatic arthritis patients and to identify factors associated with and reasons for drug discontinuation.     

Cold-regulated proteins with potent antifreeze and cryoprotective activities in spruces (Picea spp.)

Antifreeze proteins (AFPs) were obtained from intercellular spaces of spruce needles Picea abies (L.) Karst. and Picea pungens Engelm. by vacuum infiltration with ascorbic acid, followed by centrifugation to recover the infiltrate. As shown by sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE), apoplastic proteins are accumulated in these spruce species as a group of 5–9 polypeptide bands. These proteins have a molecular mass of 7–80 kDa. The spruce AFPs have the ability to modify the growth of ice and thermal hysteresis, TH, caused by these AFPs was close to 2.0 °C at a concentration of 400 μg/ml. The antifreeze activity of proteins from these winter-hardy coniferous species showed a positive correlation with the concentration of proteins after cold acclimation of needle tissues. Apoplastic proteins from winter spruce needles exhibited antifreeze activity, whereas no such activity was observed in extracts from summer needles. When we examined the possible role of spruce AFPs in cryoprotection, we found that lactate dehydrogenase, LDH, activity was higher after freezing in the presence of AFPs compared with bovine serum albumin. Amino-terminal sequence comparisons indicated that a 27-kDa protein from both P. abies and P. pungens was similar to some pathogenesis-related proteins namely chitinases, also from conifer species. These results show that spruces produce AFPs that are secreted into the apoplast of needles. The accumulation of AFPs in extracellular spaces caused by seasonal cold acclimation during winter indicates that these proteins may play a role in the acquisition of freezing tolerance of needle cells in coniferous species.     

Antioxidative defense system in lupin roots exposed to increasing concentrations of lead

Yellow lupin (Lupinus luteus) cv. Juno seedlings exposed to increasing concentrations of Pb²⁺ (50–350 mg l⁻¹) were analysed in respect to its effect on the degradation of lipids, the content of antioxidants (ascorbate, α-tocopherol) and the activity of the ascorbate glutathione cycle enzymes (dehydroascorbate reductase DAR; EC 1.8.5.1 and glutathione reductase GR; EC 1.6.4.2). Lipid peroxidation, expressed as the content of TBArm (thiobarbituric acid reactive metabolites), increased only at 50 and 100 mg l⁻¹ Pb²⁺, whereas at higher lead concentrations it decreased as compared with the control. The level of free fatty acids was not significantly affected as a result of Pb²⁺ exposure, except for 300 mg l⁻¹ Pb²⁺. The content of α-tocopherol increased significantly at the range of concentrations between 150 and 300 mg l⁻¹ and at these concentrations lipid peroxidation was inhibited. Ascorbic acid (AA) and dehydroascorbic acid (DHA) content increased considerably in roots treated with 100 and 150 mg l⁻¹ Pb²⁺. In general the activity of DHAR and GR was stimulated by lead, however at higher Pb²⁺ concentrations (300 and 350 mg l⁻¹) GR revealed lower enzymatic activity. Our results suggest that in lead-treated roots lipids might be protected against reactive oxygen species (ROS) by lipid-soluble molecules of α-tocopherol and this direct defense seems to be supported by AA as well as the enzymes: DHAR and GR.     

Forefoot disease activity in rheumatoid arthritis patients in remission: results of a cohort study

Introduction  

The aim of our study was to investigate the presence of disease activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid arthritis (RA) patients in remission according to the Disease Activity Score based on 28 joints (DAS28) remission criterion.     

Long-term implications of industrial pollution stress on lipids composition in Scots pine (Pinus sylvestris L.) roots

The influence of pollution stress (SO₂, Cu²⁺, Pb²⁺, Zn²⁺ and fluoride) on composition changes in cellular membranes of roots of three European of Scots pine (Pinus sylvestris L.) populations were examined. Plant material growing in three experimental areas: Kórnik relatively free of air pollution (control), Luboń: SO₂ and HF and Głogów: SO₂ and heavy metals. Analysis of total phospholipids and their composition indicates that the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were present in lower concentration in the root tissues from both polluted sites (Luboń and Głogów). The difference in PC:PE ratio between control and both polluted sites was greater in root of Scots pine population from Russia than in the population from Slovakia. Under pollution conditions the content of lipid soluble antioxidant α-tocopherol was lower about 220 %, in comparison to the control. The action of pollution stress also lead to lowering of unsaturated:saturated ratio of total fatty acid, and lower content of polyunsaturated fatty acids, linoleic acid (18:2) and eicosatrienoic acid (20:3). We concluded that the long-term pollution stress markedly inhibited lipid biosynthesis in root tissue of Scots pine and it is probably contribute to the reduction of productivity of forests. These results also suggest that lipid composition can be used as an indicator of changes in tissue roots of Scots pine caused by air and/or soil long-term pollution.