The functional -765G→C polymorphism of the COX-2 gene may reduce the risk of developing crohn's disease

Background

Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1α/β, interferon-γ and tumor necrosis factor-α produced by inflammatory cells.

Aim

The aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms −1195 A→G and −765G→C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population.

Methods

Genomic DNA of 525 patients with Crohn''s disease (CD), 211 patients with ulcerative colitis (UC) and 973 healthy controls was genotyped for the −1195 A→G (rs689466) and −765G→C (rs20417) polymorphisms. Distribution of genotypes in patients and controls were compared and genotype-phenotype interactions were investigated.

Results

The genotype distribution of the −1195A→G polymorphism was not different between the patients with CD or UC and the control group. The −765GG genotype was more prevalent in CD patients compared to controls with an OR of 1.33 (95%CI 1.04–1.69, p<0.05). The −765GC and −765CC genotype carriers showed a tendency to be less frequent in patients with CD compared to controls, with ORs of 0.78 (95%CI: 0.61–1.00) and 0.49 (95%CI 0.22–1.08), respectively. Combining homozygous and heterozygous patients with the −765C allele showed a reduced risk for developing CD, with an OR of 0.75 (95%CI: 0.59–0.96). In the context of this, the G₋₁₁₉₅G₋₇₆₅/A₋₁₁₉₅C₋₇₆₅ diplotype was significantly less common in patients with CD compared to controls, with an OR of 0.62 (95%CI: 0.39–0.98). For UC however, such an effect was not observed. No correlation was found between COX-2 diplotypes and clinical characteristics of IBD.

Conclusions

The −765G→C polymorphism was associated with a reduced risk for developing Crohn''s disease in a Dutch population.     

CD154: the atherosclerotic risk factor in rheumatoid arthritis?

Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.     

Can treadmill-slip perturbation training reduce immediate risk of over-ground-slip induced fall among community-dwelling older adults?

The purpose of this study was to determine any potential falls-resistance benefits that might arise from treadmill-slip-perturbation training. One hundred sixty-six healthy community-dwelling older adults were randomly assigned to either the treadmill-slip-training group (Tt) or the treadmill-control group (Tc). Tt received 40 slip-like perturbations during treadmill walking. Tc received unperturbed treadmill walking for 30 min. Following their treadmill session, both groups were exposed to a novel slip during over-ground walking. Their responses to this novel slip were also compared to previously collected data from participants who received either over-ground-slip training (Ot) with 24 slips or over-ground walking (Oc) with no training before experiencing their novel over-ground slip. Fall rates and both proactive (pre-slip) and reactive (post-slip) stability were assessed and compared for the novel over-ground slip in groups Tt, Tc, and Oc, as well as for the 24th slip in Ot. Results showed Tt had fewer falls than Tc (9.6% versus 43.8%, p < 0.001) but more falls than Ot (9.6% versus 0%, p < 0.001). Tt also had greater proactive and reactive stability than Tc (Tt > Tc, p < 0.01), however, Tt’s stabilities were lower than those of Ot (p < 0.01). There was no difference in fall-rate or reactive stability between Tc and Oc, though treadmill walking did improve the proactive stability control of the latter. While the treadmill-slip-training protocol could immediately reduce the numbers of falls from a novel laboratory-reproduced slip, such improvements were far less than that from the motor adaptation to the over-ground-slip-training protocol.     

Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?

Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = ?0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = ?0.32, p = 0.0076), and increasing body mass index (BMI) (r = ?0.31, p =  < 0.0001; r = 0.39, p =  < 0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.     

Small leucine-rich proteoglycans in atherosclerotic lesions: novel targets of chronic statin treatment?

Small leucine‐rich proteoglycans (SLRPs), such as decorin and biglycan, regulate the assembly and turnover of collagenous matrix. The aim of the study was to analyse the effect of chronic rosuvastatin treatment on decorin, biglycan and the collagen matrix in ApoE‐deficient mice. Twenty‐week‐old male ApoE‐deficient mice received normal chow or 20 mg rosuvastatin/kg × day for 32 weeks. Subsequently, matrix composition was analysed by histochemistry and immunostaining at the aortic root and in innominate arteries of ApoE deficient mice as well as in human carotid endarterectomy specimens. Immunoblotting of proteoglycans was performed from aortic extracts of ApoE‐deficient mice. Immunohistochemistry and immunoblotting revealed strongly increased decorin and biglycan deposition in atherosclerotic plaques at the aortic root and in innominate arteries. In contrast, versican and perlecan expression was not changed by rosu‐vastatin. Furthermore, matrix metalloproteinase 2 and gelatinolytic activity were decreased in response to rosuvastatin and a condensed collagen‐rich matrix was formed. In carotid endarterectomy specimens of statin‐treated patients increased decorin and biglycan accumulation was detected as well. Drug treatment did not change low‐density lipoprotein (LDL) plasma levels in ApoE‐deficient mice and did not significantly affect lipid retention at the aortic root level as demonstrated by oil‐red O staining and immunohistochemistry of LDL. Long‐term treatment with rosuvastatin caused pronounced remodelling of atherosclerotic plaque matrix characterized specifically by enrichment with SLRPs and formation of a condensed collagen matrix. Therefore, decorin and biglycan might represent novel targets of statin treatment that contribute to a stable plaque phenotype.     

Can statin therapy really reduce the risk of Alzheimer's disease and slow its progression?

PURPOSE OF REVIEW: Statins are the most used cholesterol-lowering agents worldwide. Earlier studies suggested that they may have preventive effects in Alzheimer's disease. However, prospective studies have questioned this hypothesis. RECENT FINDINGS: Statins regulate beta-amyloid metabolism and microglial activation. Pathologically, patients with Alzheimer's disease have more severe atherosclerosis in cerebral arteries than do controls. Such lesions may cause cerebral hypoperfusion, a risk factor for dementia and cognitive decline. Although most population-based studies have failed to show a beneficial effect of statins in Alzheimer's disease, two randomized controlled trials suggested that statins slow cognitive decline in mild to moderate Alzheimer's disease. SUMMARY: There is still some hope that statins reduce the incidence of Alzheimer's disease and slow its progression. Large-scale randomized controlled trials of simvastatin and atorvastatin for mild to moderate Alzheimer's disease are underway, which might provide more conclusive results than earlier studies.     

Plasticity of parental care under the risk of predation: how much should parents reduce care?

Predation can be an important agent of natural selection shaping parental care behaviours, and can also favour behavioural plasticity. Parent birds often decrease the rate that they visit the nest to provision offspring when perceived risk is high. Yet, the plasticity of such responses may differ among species as a function of either their relative risk of predation, or the mean rate of provisioning. Here, we report parental provisioning responses to experimental increases in the perceived risk of predation. We tested responses of 10 species of bird in north temperate Arizona and subtropical Argentina that differed in their ambient risk of predation. All species decreased provisioning rates in response to the nest predator but not to a control. However, provisioning rates decreased more in species that had greater ambient risk of predation on natural nests. These results support theoretical predictions that the extent of plasticity of a trait that is sensitive to nest predation risk should vary among species in accordance with predation risk.     

Distribution of CC-chemokine receptor-5-?32 allele among the tribal and caste population of Vidarbha region of Maharashtra state

BACKGROUND:

Genetic relationships among the ethnic groups are not uniform across the geographical region. Considering this assumption, we analyzed the frequency of the CC-chemokine receptor-5 (CCR5)-∆32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in Bhil tribal and Brahmin caste sample sets from the population.

MATERIALS AND METHODS:

108 blood samples were collected from 6 tribe''s populations and a caste population from the district of Vidarbha region.

RESULTS AND DISCUSSION:

The presence of low frequencies of CCR5-Δ32 in an individual of Bhil tribe (0.034, χ² value 0.017) in the present study implies that these communities may have a better resistance toward human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) than the other studied tribe sample, as non-show such mutation.

CONCLUSION:

The marginal presence of the allele seen in the studied tribal population could be due to gene flow from the people of European descent. However, lack of the homozygous CCR5-Δ32 mutation and the low prevalence of heterozygous CCR5-Δ32 mutations suggest that the Indians are highly susceptible to HIV/AIDS, and this correlates with the highest number of HIV/AIDS infected individuals in India.     

Influence of the ABCG2 gout risk 141?K allele on urate metabolism during a fructose challenge

Introduction

Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.

Methods

Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution. Data were analyzed based on the presence or absence of the ABCG2 141 K gout risk allele.

Results

The 141 K risk allele was present in 23 participants (31%). Overall, serum urate (SU) concentrations during the fructose load were similar in those with and without the 141 K allele (P_SNP = 0.15). However, the 141 K allele was associated with a smaller increase in SU following fructose intake (P_SNP <0.0001). Those with the 141 K allele also had a smaller increase in serum glucose following the fructose load (P_SNP = 0.002). Higher fractional excretion of uric acid (FEUA) at baseline and throughout the fructose load was observed in those with the 141 K risk allele (P_SNP <0.0001). However, the change in FEUA in response to fructose was not different in those with and without the 141 K risk allele (P_SNP = 0.39). The 141 K allele effects on serum urate and glucose were more pronounced in Polynesian participants and in those with a body mass index ≥25 kg/m².

Conclusions

In contrast to the predicted responses for a hyperuricemia/gout risk allele, the 141 K allele is associated with smaller increases in SU and higher FEUA following a fructose load. The results suggest that ABCG2 interacts with extra-renal metabolic pathways in a complex manner to regulate SU and gout risk.

Clinical Trials Registration

The study was registered by the Australian Clinical Trials Registry (ACTRN12610001036000).     

Anthropometric data in middle-aged women. The population study of women in G?teborg 1968-1969.

Body weight, body height, skinfolds, circumferences and weight indices in a population sample of 1462 women in ages between 38 and 60 years are presented. Significant age differences were noted. High correlations (r) were found between body weight and triceps and subscapular skinfolds (0.62 and 0.72 respectively) and between body weight and arm, waist and buttock circumferences (0.75-0.88). Age differences were mostly noted between 46 and 50 years of age. After that age there was a comparatively greater increase of the waist circumference than of the buttock circumference, while triceps skinfold seemed to decrease after the age of 50 indicating an altered adipose tissue distribution from the extremities to the trunk with increasing age. When taking data from a previous study of body weight in the same population of women into consideration it seems that the age differences in body weight found in cross-sectional study like the present one may to a large extent depend on differences between different cohorts studied.     

Ectopic pregnancy among early abortion patients: does prostaglandin reduce the incidence?

The availability and efficacy of prostaglandin (PG) F2 alpha and E series analogues has prompted their frequent use for pregnancy interruption. In the course of evaluating our experience with PGs for interrupting early first trimester gestations, we became increasingly impressed by the absence of any with extrauterine pregnancy. A review of 63 reports encompassing 2,965 patients whose pregnancies were less than 8 weeks' gestational age dating from the last menstrual period and who were similarly treated yielded only 2 cases of ectopic pregnancy. When compared with the generally accepted ectopic gestation rates of the order of 1 in 200 pregnancies, this frequency of 1 in 1,483 is unexpectedly low. Preselection does not appear to explain this impressive discrepancy. If the observation proves correct, it implies that PGs have some form of therapeutic effect in eradicating extrauterine pregnancy by nonoperative means. The implications are obvious in terms of its potential therapeutic benefits.     

Does pollen competition reduce the cost of inbreeding?

We hypothesize that floral features promoting pollen competition in angiosperms may have evolved, in some cases, in response to selection generated by the negative effects of inbreeding, at least in plants with mixed-mating systems. Screening of haploid genotypes through pollen competition may purge recessive (or additive) deleterious alleles that are expressed in haploid pollen and hence may reduce the fitness cost of self-pollination, geitonogamy, or biparental inbreeding. We tested one prediction of this hypothesis, that offspring produced by more intense competition among self-pollen have higher fitness than offspring produced by less intense competition. Dalechampia scandens (Euphorbiaceae) flowers were pollinated with pollen from other flowers on the same plant (geitonogamous self-fertilization). Those flowers experiencing more intense pollen competition as a result of low pollen dispersion (positional variance) on the stigma produced heavier seeds and seedlings with faster-growing radicles than flowers experiencing less intense pollen competition (high pollen dispersion), as predicted by our hypothesis.     

Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations

The allelic frequencies of apolipoprotein E (apoE) vary substantially around the world. There is a conspicuous south-to-north gradient of e4 frequencies in Europe, with the proportion of e4 carriers from only 10–15% in the south to 40–50% in the north. The mechanism may be related to the possibility that e4 carriers are less likely to develop vitamin D deficiency. In addition, Asian populations traditionally have lower e4 frequency than Europeans, which may be attributed in part to the scarce or irregular food supplies in Western world in the recent past. However, whether these geographical distribution gradients exist in China is yet unknown. ApoE genotypes of 200 children from Nanning City were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. Allele frequency data of 18 other populations were collected from published sources and correlated with latitude and longitude information from different geographic resources. In our subjects, the frequencies of apoE genotypes were E3/E3: 73.0%, E3/E2: 15.0%, E4/E3: 5.0%, E4/E4: 5.0%, and E4/E2: 2.0%; the frequencies of apoE alleles were e2: 8.5%, e3: 83.0%, and e4: 8.5%, respectively. The total sample consisted of 3,679 individuals from 19 Chinese populations; the allelic frequencies were e2: 7.6%, e3: 85.5%, and e4: 6.9%, respectively; the proportion of e4 carriers was from 4.9% in Kunming to 17.5% in Harbin. Systemic comparison among multiple Chinese populations revealed that positive correlation existed between the e4 allele frequency distribution and latitude north (r = 0.586, P = 0.008), but no correlation of the e4 allele frequency distribution with longitude east was found (r = −0.018, P = 0.942). We conclude that there is a south-to-north, but not an east-to-west gradient for the apoE4 allele in China.     

Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?

End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.     

Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for readmission and mortality – a systematic review

Background

Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems. Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity. To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses.

Methods

Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings. We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation. Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality. We pooled the results using fixed effects models where statistically significant heterogeneity (p ≤ 0.1) was absent.

Results

We identified six trials including 230 patients. Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12–0.54]) and mortality (0.45 [0.22–0.91]). Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13–1.61) for the fatigue domain, 1.36 (0.94–1.77) for emotional function and 1.88 (1.67–2.09) for mastery. Weighted mean differences for the St. Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials, rehabilitation improved exercise capacity (64–215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48–115).

Conclusion

Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation. Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD.     

What may be the markers of the male equivalent of polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women (with a prevalence of 5-10 %), is characterized by hormonal and metabolic imbalance. Complexity of symptoms of close relatives of women with PCOS and genetic autosomal trait initiated a hypothesis about the existence of a male equivalent of PCOS. Premature alopecia was suggested as one of the signs of a male phenotype of this syndrome. The present study investigated a group of 30 men, in which premature hair loss started before 30 years of age. In all patients, their hormonal profile was determined. It was possible to form two subgroups. The first one showed similar hormonal changes as women with PCOS, the other had either no anomalies in steroid spectrum or just only lower level of sexual hormones binding globulin (SHBG). Both subgroups did not differ in either BMI or age. In all men with premature alopecia insulin tolerance test was also carried out and the occurrence of allele 3 INS VNTR was investigated, which is one of the candidate genes for PCOS. The subgroup with hormonal changes resembling those of women with PCOS showed a significantly higher insulin resistance than the group without these changes. About one third of the premature balding men showed the combination of hormonal shifts and higher insulin resistance. This frequency corresponds to the prevalence of PCOS in women. There was no significant difference between the two subgroups in the occurrence of allele 3 INS VNTR.     

Does copulation increase the risk of predation?

Studies of mating behaviour have assumed that individuals are at greater risk when paired than when engaged in other activities. Recently, four experimental studies of insects and crustaceans have tested this assumption using predators from divergent taxa. Three of these studies indicate that mating carries no additional risk to the participants. Indeed, the findings suggest decreased vulnerability, relative to other activities, due to decreased predation on one or the other of the mating pair.