Comparison of Internal Transcribed Spacers and Intergenic Spacer Regions of Five Common Iranian Sheep Bursate Nematodes

Background

Accurate identification of sheep nematodes is a critical point in epidemiological studies and monitoring of drug resistance in flocks. However, due to a close morphological similarity between the eggs and larval stages of many of these nematodes, such identification is not a trivial task. There are a number of studies showing that molecular targets in ribosomal DNA (Internal transcribed spacer 1, 2 and Intergenic spacer) are suitable for accurate identification of sheep bursate nematodes. The objective of present study was to compare the ITS1, ITS2 and IGS regions of Iranian common bursate nematodes in order to choose best target for specific identification methods.

Methods

The first and second internal transcribed spacers (ITS1and ITS2) and intergenic spacer (IGS) of the ribosomal DNA (rDNA) of 5 common Iranian bursate nematodes of sheep were sequenced. The sequences of some non–Iranian isolates were used for comparison in order to evaluate the variation in sequence homology between geographically different nematode populations.

Results

Comparison of the ITS1 and ITS2 sequences of Iranian nematodes showed greatest similarity among Teladorsagia circumcincta and Marshallagia marshalli of 94% and 88%, respectively. While Trichostrongylus colubriformis and M. marshalli showed the highest homology (99%) in the IGS sequences. Comparison of the spacer sequences of Iranian with non-Iranian isolates showed significantly higher variation in Haemonchus contortus compared to the other species.

Conclusion

Both the ITS1 and ITS2 sequences are convenient targets to have species-specific identification of Iranian bursate nematodes. On the other hand the IGS region may be a less suitable molecular target.     

Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients

Critical illness is often associated with reduced TSH and thyroid hormone secretion as well as marked changes in peripheral thyroid hormone metabolism, resulting in low serum T(3) and high rT(3) levels. To study the mechanism(s) of the latter changes, we determined serum thyroid hormone levels and the expression of the type 1, 2, and 3 iodothyronine deiodinases (D1, D2, and D3) in liver and skeletal muscle from deceased intensive care patients. To study mechanisms underlying these changes, 65 blood samples, 65 liver, and 66 skeletal muscle biopsies were obtained within minutes after death from 80 intensive care unit patients randomized for intensive or conventional insulin treatment. Serum thyroid parameters and the expression of tissue D1-D3 were determined. Serum TSH, T(4), T(3), and the T(3)/rT(3) ratio were lower, whereas serum rT(3) was higher than in normal subjects (P < 0.0001). Liver D1 activity was down-regulated and D3 activity was induced in liver and skeletal muscle. Serum T(3)/rT(3) ratio correlated positively with liver D1 activity (P < 0.001) and negatively with liver D3 activity (ns). These parameters were independent of the type of insulin treatment. Liver D1 and serum T(3)/rT(3) were highest in patients who died from severe brain damage, intermediate in those who died from sepsis or excessive inflammation, and lowest in patients who died from cardiovascular collapse (P < 0.01). Liver D3 showed an opposite relationship. Acute renal failure requiring dialysis and need of inotropes were associated with low liver D1 activity (P < 0.01 and P = 0.06) and high liver D3 (P < 0.01) and skeletal muscle D3 (P < 0.05) activity. Liver D1 activity was negatively correlated with plasma urea (P = 0.002), creatinine (P = 0.06), and bilirubin (P < 0.0001). D1 and D3 mRNA levels corresponded with enzyme activities (both P < 0.001), suggesting regulation of the expression of both deiodinases at the pretranslational level. This is the first study relating tissue deiodinase activities with serum thyroid hormone levels and clinical parameters in a large group of critically ill patients. Liver D1 is down-regulated and D3 (which is not present in liver and skeletal muscle of healthy individuals) is induced, particularly in disease states associated with poor tissue perfusion. These observed changes, in correlation with a low T(3)/rT(3) ratio, may represent tissue-specific ways to reduce thyroid hormone bioactivity during cellular hypoxia and contribute to the low T(3) syndrome of severe illness.     

Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: relationship to histological improvement.

BACKGROUND & AIMS: Thiazolidinedione (TZD) therapy improves liver histology in nonalcoholic steatohepatitis (NASH) through a mechanism possibly related to its insulin-sensitizing or anti-inflammatory activity. This study was conducted to assess changes in serum levels of selected adipokines and proinflammatory cytokines and to relate these changes to the improved liver histology resulting from pioglitazone therapy for NASH. METHODS: Serum samples from 18 patients with NASH obtained at day 0 and week 48 of therapy during an open-label study of pioglitazone were tested for adiponectin, leptin, interleukin (IL)-1a, IL-6, and tumor necrosis factor (TNF)-alpha levels. Paired liver biopsy specimens were scored (0-4) for steatosis, parenchymal inflammation, cell injury, and fibrosis. RESULTS: Adiponectin levels increased from 3.7 to 10.3 mug/mL at week 48 (P < .01); the levels of the other cytokines were unchanged: TNF-alpha, 9.1 vs 8.8 pg/mL; IL-1a, 3.9 vs 3.4 pg/mL; IL-6, 19.4 vs 13.4 pg/mL; and leptin, 24.8 vs 29.6 ng/mL (P > .05 for all). Pioglitazone therapy was associated with improvements in steatosis (2.5 vs 1.0), parenchymal inflammation (3.3 vs 2.1), cell injury (2.2 vs 0.9), and fibrosis (2.0 vs 1.4). The change in adiponectin level was associated with the improvement in steatosis (P = .03) as well as in a summary NASH activity index score (P = .01). Changes in IL-1, IL-6, TNF-alpha, and leptin levels did not correlate with improvements in the histological features. CONCLUSIONS: Improvements in liver histology during TZD therapy may be modulated by an adiponectin-mediated effect on insulin sensitivity and hepatic fatty acid metabolism rather than by changes in proinflammatory cytokines.     

A model for undertaking effectiveness and cost-effectiveness analyses of primary preventive strategies in cardiovascular disease.

BACKGROUND: Clinical trials generally provide strong evidence of the efficacy of cardiovascular preventive strategies, but poor evidence of their 'real-life' utility, in terms of effectiveness and cost-effectiveness. DESIGN AND METHODS: The Cardiovascular Disease Prevention Model is presented, which represents a means of extrapolating the results of clinical trials to a broader, more relevant context. The model is configured as a decision-analysis tree, and underpinned by life-course analysis and Markov processes. Uncertainty and sensitivity analyses are undertaken by Monte Carlo simulation. RESULTS: The results of effectiveness and cost-effectiveness analyses of a hypothetical preventive intervention are presented to demonstrate the outputs of the model. The potential impact and efficiency of the intervention are made obvious. CONCLUSIONS: The Cardiovascular Disease Prevention Model offers a means to translate the results of trials of cardiovascular preventive interventions, in order to inform clinical and public health practice, as well as health policy.     

Do severity and duration of depressive symptoms predict cognitive decline in older persons? Results of the Longitudinal Aging Study Amsterdam

BACKGROUND AND AIMS: Some prospective studies show that depression is a risk factor for cognitive decline. So far, the explanation for the background of this association has remained unclear. The present study investigated 1) whether depression is etiologically linked to cognitive decline; 2) whether depression and cognitive decline may be the consequence of the same underlying subcortical pathology, or 3) whether depression is a reaction to global cognitive deterioration. METHODS: A cohort of 133 depressed and 144 non-depressed older persons was followed at eight successive observations over 3 years. All subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). Depression symptoms were measured by means of the CES-D at eight successive waves. Cognitive function (memory function, information processing speed, global cognitive functioning) was assessed at baseline and at the last CES-D measurement. RESULTS: The severity and duration of depressive symptoms were not associated with subsequent decline in memory functioning or global cognitive decline. There was an association between both chronic mild depression and chronic depression, and decline in speed of information processing. CONCLUSIONS: These results support the hypothesis that, in older persons, chronic depression as well as cognitive decline may be the consequence of the same underlying subcortical pathology.     

Predictors of Having Paid Work in Older Workers With and Without Chronic Disease: A 3-Year Prospective Cohort Study

Background As the prevalence of chronic disease amongst older workers is high and increasing, it is important to know if the large subgroup of older workers with chronic disease has specific needs when it comes to prolonging participation in paid work. Objectives To investigate differences and similarities in predictors of having paid work in workers aged 55+ with and without chronic disease. Methods Workers aged 55–62 years were selected from the 2002–2003 cohort of the Longitudinal Aging Study Amsterdam (n = 333). Potential predictors were: health, personality, work characteristics, and demographics. Per potential predictor, a logistic regression coefficient for ‘having paid work in 2005–2006’ was calculated for workers with and without chronic disease. A pooled estimate was computed and differences between the pooled estimate and the coefficients were tested. Results Follow-up data were available for 95 %, of whom 67 % still had paid work. Predictors of having paid work were similar for workers with and without chronic diseases, except for physical workload (χ² = 5.37; DF = 1) and psychosocial resources at work (χ² = 5.94; DF = 1). Having more psychosocial resources (OR = 3.57; 95 %CI 1.33–10.0) was predictive for having paid work in workers with chronic disease and not in workers without chronic disease. Lower age, more weekly working hours, no functional limitations, fewer depressive symptoms, lower neuroticism scores, and more sense of mastery were significantly associated with having paid work in all workers. Conclusions Differences between predictors of having paid work between workers with and without chronic disease should be taken into account when aiming to prevent exit from the workforce. In particular the vulnerable subgroup of older workers with chronic disease and low psychosocial resources at work is more likely to quit working.     

Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma

In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, P<0.001; median overall survival 115.3 vs. 31.0 months, P=0.004). Clinicians should be aware of the benign nature of this phenomenon, and secondary monoclonal gammopathy of undetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.)