Interstitial fluid lipoproteins.

PURPOSE OF REVIEW: The interstitium represents the fluid, proteins, solutes, and extracellular matrix comprising the microenvironment of tissues. We here review attempts to characterize the levels and composition of lipoproteins in human interstitial fluid, and identify potentially important questions for future research. RECENT FINDINGS: Despite the high relevance of understanding how lipoproteins enter and exit the interstitial compartment, and how they interact with extracellular and cellular molecules, scientific progress in this field has been rather slow. This is partly due to methodological difficulties, both regarding how to obtain representative samples and how to perform appropriate measurements to compare patient cohorts and to evaluate responses to treatment. Predominant techniques include peripheral lymph cannulation and suction blister creation, both of which have inherent advantages and disadvantages. Detailed studies comparing the effects of long-term incubation of serum and lymph lipoproteins are compatible with the view that HDL in interstitial fluid takes up free cholesterol from cells and transfers it into the circulation. SUMMARY: Studies of the concentration, composition, functionality, and turnover of interstitial fluid lipoproteins will be of great future interest for understanding how tissue cholesterol metabolism is regulated, and how different diseases link to increased risk for development of atherosclerosis.

Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency.

OBJECTIVE: Pain is one of the most debilitating symptoms reported by rheumatoid arthritis (RA) patients. While the collagen antibody-induced arthritis (CAIA) model is used for studying the effector phase of RA pathologic progression, it has not been evaluated as a model for studies of pain. Thus, this study was undertaken to examine pain-like behavior induced by anticollagen antibodies and to assess the effect of currently prescribed analgesics for RA. In addition, the involvement of spinal glia in antibody-induced pain was explored. METHODS: CAIA was induced in mice by intravenous injection of a collagen antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Disease severity was assessed by visual and histologic examination. Pain-like behavior and the antinociceptive effect of diclofenac, buprenorphine, gabapentin, pentoxifylline, and JNK-interacting protein 1 were examined in mechanical stimulation experiments. Spinal astrocyte and microglia reactivity were investigated by real-time polymerase chain reaction and immunohistochemistry. RESULTS: Following the induction of CAIA, mice developed transient joint inflammation. In contrast, pain-like behavior was observed prior to, and outlasted, the visual signs of arthritis. Whereas gabapentin and buprenorphine attenuated mechanical hypersensitivity during both the inflammatory and postinflammatory phases of arthritis, diclofenac was antinociceptive only during the inflammatory phase. Spinal astrocytes and microglia displayed time-dependent signs of activation, and inhibition of glial activity reversed CAIA-induced mechanical hypersensitivity. CONCLUSION: CAIA represents a multifaceted model for studies exploring the mechanisms of pain induced by inflammation in the articular joint. Our findings of a time-dependent prostaglandin and spinal glial contribution to antibody-induced pain highlight the importance of using appropriate disease models to assess joint-related pain.

Socioeconomic differences in outpatient healthcare utilisation are mainly seen for musculoskeletal problems in groups with poor self-rated health.

AIM: To assess whether there are socioeconomic (SES) differences in outpatient visits within groups of comparable morbidity (medical disease and self-rated health) and whether psychosocial factors can explain these differences. METHODS: Baseline data for SES, presence of disease, self-rated health (SRH), and psychosocial factors were collected during 2003-04 from 923 men and women aged 45-69 years in southeast Sweden. Outcome data were all registered outpatient healthcare visits to physicians during 2004-08. Cumulative incidences and standardised rate ratios (SSR) were calculated for strata of comparable morbidity for all visits, for visits due to cardiovascular disorders (CVD)/diabetes and for musculoskeletal problems. RESULTS: Low SES was associated with more outpatient visits due to musculoskeletal problems (SRR for education 1.52, 95% CI 1.35-1.73; for occupation 1.40, 95% CI 1.26-1.56) and accentuated in groups with poor SRH. The SES effect was significant for visits to primary care and to hospitals, for men and women, and independent of present disease, SRH, and psychosocial factors. Low SES was significantly associated with more total outpatient visits at primary healthcare centres. In contrast, for outpatient visits due to CVD/diabetes, high SES was related to more visits to hospitals among people with good SRH at baseline. CONCLUSIONS: We found a consistent pattern for outpatient visits related to musculoskeletal problems where people with low SES counted more visits and this was most prominent in groups of poor SRH. The results demonstrate the need to apply different morbidity measures when studying inequalities in healthcare utilisation.

Status incongruence revisited: associations with shame and mental wellbeing.

Status incongruence has been related to poor health and all-cause mortality, and could be a growing public health problem due to changes in the labour market in later decades. Shaming experiences have been suggested as playing a part in the aetiology. The aim here was to study the risk for shaming experiences, pessimism, anxiety, depressive feelings, and poor mental wellbeing (as measured by the GHQ) with a special focus on shame, in four social status categories: negatively and positively incongruent individuals, and low-status and high-status congruent individuals. Data comprised 14,854 working men and women from a regional sample of randomly selected respondents, 18-79 years of age. Logistic regression was used to study differences in risk for negative emotional outcomes. Results showed that the negative incongruent category persisted as the group most at risk for all negative emotional outcomes (OR 1.5-1.9; p < 0.05-<0.001).When testing the risk for poor mental wellbeing among the status categories with and without shaming experiences, ORs for all groups with shaming experiences were elevated. Among groups without shame, only the negative incongruent category remained at risk (OR 2.7; p < 0.05) after adjustment. Negative incongruent status is associated with adverse emotional outcomes, among them shame, which is a previously unappreciated aspect of status incongruence.

Does two-year stability for scale scores of psychosocial factors differ by socioeconomic position?

Previous longitudinal studies have demonstrated the importance of measuring stability of risk factors over time to correct for attenuation bias. The present aim was to assess the stability of scores for eight psychometric scales over a 2-yr. period and whether stability differed by socioeconomic position. Baseline data were collected during 2003-2004 from 1,007 men and women ages 45 to 69 years. Follow-up data were collected in 2006 from a total of 795 men and women. Analysis showed that stability over 2 yr. was moderate and tended to be lower in groups of low socioeconomic position. It is suggested that correction of attenuation bias is relevant in longitudinal studies for psychosocial factors, especially for groups of low socioeconomic position.

Adverse health effects of low levels of perceived control in Swedish and Russian community samples.

BACKGROUND: This cross-sectional study of two middle-aged community samples from Sweden and Russia examined the distribution of perceived control scores in the two populations, investigated differences in individual control items between the populations, and assessed the association between perceived control and self-rated health. METHODS: The samples consisted of men and women aged 45-69 years, randomly selected from national and local population registers in southeast Sweden (n = 1007) and in Novosibirsk, Russia (n = 9231). Data were collected by structured questionnaires and clinical measures at a visit to a clinic. The questionnaire covered socioeconomic and lifestyle factors, societal circumstances, and psychosocial measures. Self-rated health was assessed by standard single question with five possible answers, with a cut-off point at the top two alternatives. RESULTS: 32.2 % of Swedish men and women reported good health, compared to 10.3 % of Russian men and women. Levels of perceived control were also significantly lower in Russia than in Sweden and varied by socio-demographic parameters in both populations. Sub-item analysis of the control questionnaire revealed substantial differences between the populations both in the perception of control over life and over health. Logistic regression analysis revealed that the odds ratios (OR) of poor self-rated health were significantly increased in men and women with low perceived control in both countries (OR between 2.61 and 4.26). CONCLUSION: Although the cross-sectional design does not allow causal inference, these results support the view that perceived control influences health, and that it may mediate the link between socioeconomic hardship and health.

Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice.

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.