Socio-Economic Differences in the Association between Self-Reported and Clinically Present Diabetes and Hypertension: Secondary Analysis of a Population-Based Cross-Sectional Study

Background

Diabetes and hypertension are key risk factors for coronary heart disease. Prevalence of both conditions is socio-economically patterned. Awareness of presence of the conditions may influence risk behaviour and use of preventative services. Our aim was to examine whether there were socio-economic differences in awareness of hypertension and diabetes in a UK population.

Method

Data from the Scottish Health Survey was used to compare self-reported awareness of hypertension and diabetes amongst those found on examination to have these conditions, by socioeconomic position (SEP) (measured by occupation, education and income). Odds ratios of self-reported awareness against presence, and the sensitivity, specificity and predictive value of self-reporting as a measure of the presence of the condition, were calculated.

Results

Presence and self-reported awareness of both conditions increased as SEP decreased, on most measures. There was only one significant difference in awareness by SEP once other factors had been taken into account. Sensitivity showed that those in the most disadvantaged groups were most likely to self-report awareness of their hypertension, and specificity showed that those in the least disadvantaged groups were most likely to self-report awareness of its absence. There were few differences of note for diabetes.

Conclusion

We found no consistent pattern in the associations between SEP and the presence and self-reported awareness of hypertension and diabetes amongst those with these conditions. Without evidence of differences, it is important that universal approaches continue to be applied to the identification and management of those at risk of these and other conditions that underpin cardiovascular disease.     

Detection of feline immunodeficiency virus in semen from seropositive domestic cats (Felis catus).

Electroejaculates from experimentally infected domestic cats were evaluated for the presence of feline immunodeficiency virus (FIV). Virus was isolated from cell-free seminal plasma and seminal cells by cocultivation with a feline interleukin-2-dependent CD4+ T-cell line, in which productive infection was demonstrated by syncytium formation and FIV gag p26 antigen secretion. In addition, an 868-bp segment of the FIV gag provirus gene was identified in cocultured cells by PCR and Southern analysis. A 582-bp fragment of the FIV gag provirus genome was detected by nested PCR and Southern analysis in nonfractionated seminal cells and in sperm purified by a swim-up procedure. This is the first report describing the detection of replication-competent FIV in cell-free and cell-associated forms in domestic cat semen.     

The role of luminal factors in the recovery of gastric function and behavioral changes after chronic Helicobacter pylori infection

The role of chronic infections, such as Helicobacter pylori (Hp), to produce sustained changes in host physiology remains controversial. In this study, we investigate whether the antigenic or bacterial content of the gut, after Hp eradication, influences the changes in gut function induced by chronic Hp infection. Mice were infected with Hp for 4 mo and then treated with antibiotics or placebo for 2 wk. Gastric emptying was measured using videofluoroscopy, feeding behavior using a 24-h feeding system, and intestinal permeability using an isolated jejunal segment arterially perfused with an artificial oxygen carrier, hemoglobin vesicles. Immune responses were assessed by CD3(+) cell counts and anti-Hp antibodies using ELISA. To determine the role of luminal factors in host physiology posteradication, groups of mice received the probiotics containing Lactobacillus rhamnosus R0011 and L. helveticus R0052 or placebo for 2 wk or crude Hp antigen weekly for 2 mo. Chronic Hp infection was associated with delayed gastric emptying, increased intestinal permeability, and increased gastric CD3(+) cell counts. Hp-induced altered feeding patterns did not reverse after eradication. Probiotics accelerated the recovery of paracellular permeability and delayed gastric emptying, improved the CD3(+) cell counts, and normalized altered feeding patterns posteradication. Hp antigen resulted in increased anti-Hp antibodies and increased CD3(+) cell counts in the stomach and delayed recovery of gastric function. Our results suggest that the bacterial content of the gut, as well as the presence of relevant antigens, influences the rate of recovery of host pathophysiology induced by chronic Hp infection. These changes do not seem to occur in association with modulation of intestinal permeability.     

Do different parasite species interact in their effects on host fitness? A case study on parasites of the amphipod Paracalliope fluviatilis

There is a gap in our understanding of the relative and interactive effects of different parasite species on the same host population. Here we examine the effects of the acanthocephalan Acanthocephalus galaxii, an unidentified cyclophyllidean cestode, and the trematodes Coitocaecum parvum and Microphallus sp. on several fitness components of the amphipod Paracalliope fluviatilis, using a combination of infection surveys and both survival and behavioural trials. In addition to significant relationships between specific parasites and measures of amphipod survival, maturity, mating success and behaviour, interactions between parasite species with respect to amphipod photophilia were also significant. While infection by either A. galaxii or C. parvum was associated with increased photophilia, such increases were negated by co-infection with Microphallus sp. We hypothesize that this is due to the more subtle manipulative effect of A. galaxii and C. parvum being impaired by Microphallus sp. We conclude that the low frequency at which such double infections occur in our sampled population means that such interactions are unlikely to be important beyond the scale of the host individual. Whether or not this is generally true, implying that parasitological models and theory based on single parasite species studies do generally hold, requires cross-species meta-analytical studies.     

Rpp25 is a major target of autoantibodies to the Th/To complex as measured by a novel chemiluminescent assay

Introduction

Autoantibodies to the Th/To antigen have been described in systemic sclerosis (SSc) and several proteins of the macromolecular Th/To complex have been reported to react with anti-Th/To antibodies. However, anti-Th/To has not been clinically utilized due to unavailability of commercial tests. The objective of the present study is to evaluate the newly developed ELISA and chemiluminescent immunoassay (CLIA) to measure autoantibodies to Rpp25 (a component of the Th/To complex) using immunoprecipitation (IP) as the reference method.

Methods

The first cohort consisted of 123 SSc patients including 7 anti-Th/To positive samples confirmed by IP. Additional seven anti-Th/To positive samples from non-SSc patients were also tested. For evaluation of the QUANTA Flash Rpp25 CLIA (research use only), 8 anti-Th/To IP positives, a cohort of 70 unselected SSc patients and sera from various disease controls (n = 357) and random healthy individuals (n = 10) were studied.

Results

Anti-Rpp25 antibodies determined by ELISA were found in 11/14 anti-Th/To IP positive but only in 1/156 (0.6%) negative samples resulting in a positive percent agreement of 78.6% (95% confidence interval [CI] 49.2, 95.3%) and a negative percent agreement of 99.4% (95% CI 96.4, 100.0%). To verify the results using a second method, 53 samples were tested by ELISA and CLIA for anti-Rpp25 reactivity and the results were highly correlated (rho = 0.71, 95% CI 0.56, 0.81; P < 0.0001). To define the cutoff of the CLIA, anti-Th/To IP positive and negative sera were tested using the anti-Rpp25 CLIA. At the cutoff selected by receiver operating characteristic (ROC) analysis 8/8 (100.0%) of the anti-Th/To positive sera but only 2/367 (0.5%) of the controls were positive for anti-Rpp25 antibodies. The positive and negative percent agreements were 100.0% (95% CI 63.1, 100.0%) and 99.5% (95% CI 98.0, 99.9%), respectively. In the disease cohorts 2/70 (2.9%) of the SSc patients were positive for anti-Rpp25 antibodies compared to 2/367 (0.5%) of the controls (P = 0.032). ROC analysis showed discrimination between SSc patients and controls with an area under the curve value of 0.732 (95% CI 0.655, 0.809).

Conclusion

Rpp25 is a major target of autoantibodies to the Th/To autoantigen complex. Further studies are needed to evaluate the clinical utility of the new assays.     

Role of Protein Farnesylation in Burn-Induced Metabolic Derangements and Insulin Resistance in Mouse Skeletal Muscle

Objective

Metabolic derangements, including insulin resistance and hyperlactatemia, are a major complication of major trauma (e.g., burn injury) and affect the prognosis of burn patients. Protein farnesylation, a posttranslational lipid modification of cysteine residues, has been emerging as a potential component of inflammatory response in sepsis. However, farnesylation has not yet been studied in major trauma. To study a role of farnesylation in burn-induced metabolic aberration, we examined the effects of farnesyltransferase (FTase) inhibitor, FTI-277, on burn-induced insulin resistance and metabolic alterations in mouse skeletal muscle.

Methods

A full thickness burn (30% total body surface area) was produced under anesthesia in male C57BL/6 mice at 8 weeks of age. After the mice were treated with FTI-277 (5 mg/kg/day, IP) or vehicle for 3 days, muscle insulin signaling, metabolic alterations and inflammatory gene expression were evaluated.

Results

Burn increased FTase expression and farnesylated proteins in mouse muscle compared with sham-burn at 3 days after burn. Simultaneously, insulin-stimulated phosphorylation of insulin receptor (IR), insulin receptor substrate (IRS)-1, Akt and GSK-3β was decreased. Protein expression of PTP-1B (a negative regulator of IR-IRS-1 signaling), PTEN (a negative regulator of Akt-mediated signaling), protein degradation and lactate release by muscle, and plasma lactate levels were increased by burn. Burn-induced impaired insulin signaling and metabolic dysfunction were associated with increased inflammatory gene expression. These burn-induced alterations were reversed or ameliorated by FTI-277.

Conclusions

Our data demonstrate that burn increased FTase expression and protein farnesylation along with insulin resistance, metabolic alterations and inflammatory response in mouse skeletal muscle, all of which were prevented by FTI-277 treatment. These results indicate that increased protein farnesylation plays a pivotal role in burn-induced metabolic dysfunction and inflammatory response. Our study identifies FTase as a novel potential molecular target to reverse or ameliorate metabolic derangements in burn patients.     

The effect of mercury on the growth rate of Fragilaria crotonensis kitton and Asterionella formosa Hass.

The effects of two mercury salts Hg(NO₃)₂ and HgCl₂ on the growth rate ofFragilaria crotonensis Kitton andAsterionella formosa Hass. were investigated.Fragilaria crotonensis showed total inhibition at 0.1 ppm and a 4 day increase in lag phase along with a 2–4 fold reduction in growth rate at 0.05 ppm.Asterionella formosa showed a gradual increase in lag phase and reduction in growth rate with increasing concentrations of mercury up to 0.25 ppm with total inhibition at 0.5 ppm. Mercury salts in cultures of both species with soil extract additives were significantly less toxic than in totally defined systems. Cultures ofA. formosa deviated from the typical 8–16 celled stellate colony at sublethal concentrations to form large cylindrical stacks composed of 25 to 30 colonies.This study was supported in part by funds provided by the Navajo and Kaiparowits project participants.This study was supported in part by funds provided by the Navajo and Kaiparowits project participants.     

Dynamics of photoinduced cell plasma membrane injury.

We have developed a video microscopy system designed for real-time measurement of single cell damage during photolysis under well defined physicochemical and photophysical conditions. Melanoma cells cultured in vitro were treated with the photosensitizer (PS), tin chlorin e6 (SnCe6) or immunoconjugate (SnCe6 conjugated to a anti-ICAM monoclonal antibody), and illuminated with a 10 mW He/Ne laser at a 630 nm wavelength. Cell membrane integrity was assessed using the vital dye calcein-AM. In experiments in which the laser power density and PS concentration were varied, it was determined that the time lag before cell rupture was inversely proportional to the estimated singlet oxygen flux to the cell surface. Microscopic examination of the lytic event indicated that photo-induced lysis was caused by a point rupture of the plasma membrane. The on-line nature of this microscopy system offers an opportunity to monitor the dynamics of the cell damage process and to gain insights into the mechanism governing photolytic cell injury processes.