Low-dose radiation modifies the progression of chronic renal failure

Previous studies have indicated that the application of low dose radiation to an arterial ligation has the potential to subsequently reduce or eliminate restenosis caused by smooth muscle cell proliferation. Sufficient kidney irradiation causes a radiation nephropathy and often leads to renal failure. In order to evaluate the effect of low-dose irradiation on the kidney we hypothesized that this particular therapy modifies renal injury in rats with renal ablation and subsequently slows the rate of the progression. For further clarification of the effect of irradiation at low doses, we determined proliferating cell nuclear antigen (PCNA) and monocyte chemoattractant protein-1 (MCP-1) expression in remnant kidneys after low-dose radiation. Adult Wistar rats (n = 10) were studied during the two weeks after renal ablation. The left kidney was irradiated 24 hours after an operation in anaesthetised animals with 3 Grey in a single dose. Ablated rats without irradiation (n = 9) served as nephrectomized animals group. Rats without surgery and without radiation (n = 10) served as healthy controls. Renal damage was assessed using the following parameters: urine protein excretion rate (UprotV, mg/day), awake systolic blood pressure (SBP, mm Hg), serum creatinine (SCr, micromol/l). The indirect immunofluorescence method was used for the detection of PCNA and MCP-1 expression. Glomerular and tubular immunostaining was scored semiquantitatively. Numerous PCNA positive cells and MCP-1 expression were present in the glomerulus and tubulointerstitium in nephrectomized rat kidneys. Low-dose radiation application was associated with a significant reduction in PCNA and low MCP-1 expression. This study shows that the application of low-dose irradiation has the potential to modify the progression of chronic renal failure in rats.     

Phylogenetic analysis of porcine circovirus type 2 (PCV2) pre- and post-epizootic postweaning multisystemic wasting syndrome (PMWS)

The porcine circovirus type 2 (PCV2) genome encodes three major open reading frames (ORFs) encoding the replicase proteins (ORF1), the viral capsid protein (ORF2), and a protein with suggested apoptotic activity (ORF3). Previous phylogenetic analyses of complete genome sequences of PCV2 from GenBank have demonstrated 95–100% intra-group nucleotide sequence identity. However, although these isolates were readily grouped into clusters and clades, there was no correlation between the occurrence of specific PCV2 genotypes and the geographic origin or health status of the pig. In the present study, a unique dataset from a field study spanning the years pre and post the recognition of postweaning multisystemic wasting syndrome (PMWS) in Sweden was utilized. Using this dataset it was possible to discriminate three Swedish genogroups (SG1-3) of PCV2, of which SG1 was recovered from a pig on a healthy farm ten years before the first diagnosis of PMWS in Sweden. The SG1 PCV2/ORF2 gene sequence has been demonstrated to exhibit a high genetic stability over time and has subsequently only been demonstrated in samples from pigs on nondiseased farms. In contrast, SG2 was almost exclusively found on farms that had only recently broken down with PMWS whereas the SG3 genogroup predominated in pigs from PMWS-affected farms. These results further support the results obtained from earlier in vitro and in vivo experimental models and suggest the association of specific PCV2 genogroups with diseased and nondiseased pigs in the field. The GenBank accession numbers of the 37 sequences reported in this paper are: Sw64-EF184228; SwN2-EF184227; SwN1-EF184226; Sw3(03)-EF184225; Sw20-EF184224; Sw19-EF184223; Sw52-EF184222; Sw51-EF184221; Sw93(ab)-EF184220; Sw93′(bb)-EF371551; Sw4(04)-EF371518; Sw2(02)-EF371519; Sw71-EF371520; Sw79-EF371521; Sw81-EF371522; Sw78-EF371523; No4-EF371524; No2-EF371525; No3-EF371526; No5-EF371527; Sw5-EF371528; Sw40-EF371529; Sw42-EF371530; Sw24-EF371531; Sw29-EF371532; Sw32-EF371533; Sw35-EF371534; Sw68-EF371535; Sw73-EF371536; Sw74-EF371537; Sw75-EF371538; Sw82-EF371539; Sw31-EF371540; It1-EF371547; It5-EF371548; It16-EF371549; It18-EF371550.     

The Effect of a Home Delivery Meal Service of Energy- and Protein-Rich Meals on Quality of Life in Malnourished Outpatients Suffering from Lung Cancer: A Randomized Controlled Trial

Undernutrition is prevalent in cancer patients and associated with increased incidence of complications and mortality. We investigated the effects of a home delivery meal service, providing a selection of energy-dense, protein-rich meals, on quality of life (QoL) in malnourished lung cancer patients. Forty lung cancer patients with nutritional risk score ≥3 (NRS-2002) were randomized to control or intervention. The intervention group was offered energy- and protein-rich main meals and snacks, delivered 3 times per week. The control group continued their habitual diet. Primary endpoint, QoL, and secondary endpoints were assessed at baseline, and after 6 and 12 wk. Data on unplanned readmissions, length of hospital stay, and mortality were collected 3 and 6 mo post-intervention. Intervention group improved standard Chair Stand Test (30-s CST) after 6 and 12 wk (P < 0.01) compared to control. Intervention exerted a significant positive effect on performance score after 12 wk (P  = 0.047). Increased energy and protein intakes were strongly associated with improved QoL, functional score, hand grip strength, symptom and performance scores. Food delivery service with energy- and protein-rich main meals and snacks can improve lower body strength and performance status in malnourished lung cancer patients.     

Serum methylglyoxal level and its association with oxidative stress and disease severity in patients with psoriasis

Psoriasis vulgaris (PV), a chronic inflammatory skin disease, is a condition of increased oxidative stress (OxS). However, interest related to oxidative and carbonyl stress damages to proteins, such as the formation of advanced glycation end products (AGEs) and their precursor molecule methylglyoxal (MG) has been modest. The objective of this study was to compare the systemic levels of OxS markers in patients with PV and healthy controls (Co) and to investigate their correlation with the serum level of MG. Total peroxide concentration (TPX) and total antioxidant capacity (TAC) were estimated by means of spectrophotometry. The TPX and TAC ratio was regarded as OxS index (OSI). MG level was determined using ELISA. Compared to Co, patients with PV had significantly increased blood levels of TPX (P < 0.0001), OSI (P < 0.0001), and MG (P = 0.01), and lower TAC levels (P < 0.0001). Increase in body mass index (BMI) appeared to contribute to this imbalance as TAC levels decreased with increasing BMI (r = ?0.252, P < 0.01). Increased TPX concentration was associated with higher serum level of MG (r = 0.610, P = 0.004), the latter being positively correlated with psoriasis area and severity index (r = 0.577, P = 0.008). In performed multivariate regression analysis, TPX, TAC, and OSI were all significant predictors of MG level. Our study gave further proof of increased systemic psoriasis-related OxS. MG serum level, reflecting simultaneously OxS as well as carbonyl stress status, could be used as a marker of disease activity in clinical trials while looking for new systemic therapies for psoriasis.     

Seroprevalence of IgG antibodies to pertussis toxin in children and adolescents in Estonia

Background and aims

Despite high immunisation coverage and frequent booster doses, the national notification rates of pertussis in Estonia have been increasing. The peak of 97/100,000 was reached in 2010 which is the highest incidence rate since 1962 (210/100,000).We aimed to measure the prevalence of pertussis toxin (PT) IgG type antibodies in subjects of <18 years and to estimate the pertussis infection activity in a recently non-immunised cohort.

Methods

In a cross-sectional serosurvey, all consecutive leftover sera were collected in the Tartu University Hospital during April–August 2012. Anti-PT IgG concentration was measured by commercial ELISA and analysed in yearly cohorts. The antibody concentrations ≥62.5 IU/mL was considered suggestive to pertussis in the last year among 9- to 14-year-olds.

Results

The GMC of the anti-PT-IgG was 7.4 IU/mL (95% CI 6.9–8.0). In the total of 1053 serum samples, the highest proportion of sera with high antibody titres ≥125 IU/mL and ≥62.5 IU/mL were at the ages when pertussis vaccine boosters were given: 7 years 10.9% (95% CI 4.1–22.3) and 2 years 36.9% (95% CI 25.3–49.8), respectively. Approximately half of all sera had undetectable anti-PT IgG levels. The estimated incidence of Bordetella pertussis infection among 9- to 14-year-olds in the year before serum sampling was 6.3% (95% CI 3.3–10.8), which is at least 60 times higher than the officially reported incidence of pertussis disease in respective years.

Conclusions

The serologic method is not suitable for diagnosing pertussis in instances when the last pertussis immunisation was less than one year ago. The relatively high proportion of subjects with undetectable anti-PT IgG levels and the relatively low rate of officially reported pertussis cases suggest that low antibody levels do not necessarily indicate the absence of protection. The estimated incidence rate of pertussis is much higher than officially reported figures, which suggests that asymptomatic/mild B. pertussis infection remains unrecognised and unreported.     

The reference limits and cut-off value for serum soluble transferrin receptors for diagnosing iron deficiency in infants

Serum soluble transferrin receptors (sTfR) concentration is a useful test in the diagnosis of childhood iron deficiency (ID). The aims of this study were to establish reference limits and to evaluate the diagnostic characteristics of sTfR in the diagnosis of ID in infants aged 9-12 months. In addition to mean erythrocyte cell volume, haemoglobin and ferritin measurements, sTfR concentration was measured in 179 healthy children in Estonia using the IDeA and Tina-quant methods. Using the ID criteria of ferritin <10 microg/l, subjects were divided into healthy (n = 146) and ID (n = 33) groups. The reference limits (5th and 95th percentile) were calculated in the study group. We used receiver operating characteristic curves to find out the cut-off values for the best diagnostic characteristics. The reference limits for sTfR were 1.5-2.7 mg/l in the IDeA method and 4.1-7.8 mg/l in the Tina-quant) method. The methods had poor agreement, the mean ratio with 95% limits of agreement was 2.9 (2.4-3.6). The best cut-off value in order to identify ID by hypoferritinaemia in this population is an sTfR level > 2.4 mg/l in the IDeA (sensitivity 84%, specificity 94%) and an sTfR level > 7.4 mg/l in the Tina-quant (sensitivity 80%, specificity 92%). We conclude that sTfR concentration is an efficient tool in the diagnosis of ID, but that every method needs its own cut-off value.     

Leukocyte Migration Inhibition in Chorioretinitis

Leukocyte migration inhibition (LMI) by choroid, retina, and uveal tract antigens was studied in patients with active and quiescent chorioretinal disease. LMI by retina was more frequent in both groups of patients, occurring in 9 of 16 patients with active disease and in 8 to 15 patients with disease in remission. Choroid was tested in 15 patients with active inflammation and led to LMI in 7 of them when they were off steroid therapy; it produced LMI in 3 of 13 patients whose disease appeared healed. Significant LMI was detected in three of six patients with active chorioretinitis and in one of five patients with evidence of past chorioretinopathy when their cells were tested with antigen made from pooled uveal tract tissue. The LMI test, regarded as an indicator of cell-mediated immunity, is briefly discussed. LMI by retina in over one-half of patients with chorioretinopathies appears to be a secondary event, and cellular immunity to retina may be of pathophysiological importance in the chronicity of the disorder.     

Mucin5B expression by lung alveolar macrophages is increased in long-term smokers

This study investigated the expression of MUC5B by AMs in the lungs of cigarette smokers and nonsmokers. We analyzed MUC5B expression by measuring the levels of apomucin and mRNA in human BALF cells from 50 subjects (20 nonsmokers, 17 patients with CB, and 13 patients with COPD). apoMUC5B was observed in BALF mononuclear cells in 60% of all subjects, but a significantly higher frequency of apoMUC5B(+) cells was found in subjects with CB (95% CI, 4.5-24.9) or COPD (95% CI, 6.2-39.6) than in nonsmokers (95% CI, 0.5-2.5). apoMUC5B(+) mononuclear cells showed strong expression of CD163, confirming their identity as AMs. MUC5B mRNA expression was detected by ISH in AMs of subjects investigated, and real-time qPCR analysis confirmed MUC5B mRNA expression. In conclusion, MUC5B is expressed in a subset of lung AMs and long-term cigarette smoking may increase the level of MUC5B produced by these cells.