Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients

Osteoprotegerin (OPG) gene polymorphisms (T245G, T950C and G1181C) have been associated with osteoporosis and early predictors of cardiovascular disease. The aim of this study was to evaluate whether these polymorphisms contribute to cardiovascular disease (CVD) in type 2 diabetic patients. We performed a case-control study with 178 CVD subjects with diabetes and 312 diabetic patients without CVD to assess the impact of variants of the OPG gene on the risk of CVD. The OPG gene polymorphisms were analyzed by using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). There was no significant association between the T245G and G1181C polymorphisms and CVD in the additive genetic model (OR = 0.96, 95% CI 0.64–1.45, p = 0.79; OR = 1.06, 95% CI 0.81–1.39, p = 0.65, respectively). However, the C allele of the T950C polymorphism was independently associated with a risk of CVD in type 2 diabetic patients in this genetic model (OR = 1.38, 95% CI 1.07–1.80, p = 0.01). This study provides evidence that the C allele of the T950C polymorphism is associated with increased risk of CVD in diabetic patients. However, well-designed prospective studies with a larger sample size are needed to validate these results.     

Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis

Context: Chemerin has been implicated to be correlated with inflammation.

Objective: This study aims to determine the association of chemerin levels in serum and synovial fluid (SF) with the disease severity of patients with knee Osteoarthritis (OA).

Methods: 124 patients with knee OA and 76 healthy controls were enrolled in this study.

Results: Chemerin levels in serum were significant higher with regard to paired SF. Chemerin levles in SF of knee OA patients were correlated with disease severity evaluated by KL grading criteria.

Conclusion: Chemerin levels may be involved in the pathophysiology of the development and progression of OA.     

Serum levels of heat shock protein 27 in patients with acute ischemic stroke

Expression of intracellular heat shock protein 27 (Hsp27) rises in the brain of animal models of cerebral ischemia and stroke. Hsp27 is also released into the circulation and the aim of the present study was to investigated if serum Hsp27 (sHsp27) levels are altered in patients with acute ischemic stroke. sHsp27 was measured in 15 patients with acute ischemic stroke and in 14 control subjects comparable for age, sex, and cardiovascular risk factors. In patients, measurements were performed at admission and 1, 2, and 30 days thereafter. At admission, mean sHsp27 values were threefold higher in patients than in controls. In patients, sHsp27 values dropped after 24 h, rose again at 48 h, and markedly declined at 30 days, indicating the presence of a temporal trend of sHsp27 values following acute ischemic stroke.     

Acute phase proteins and oxidised low-density lipoprotein in association with ischemic stroke subtype, severity and outcome

Objectives: The goal of our study was to investigate the associations of oxidized LDL (apoB100 aldehyde-modified form) and acute phase proteins (fibrinogen, CRP) with acute ischemic stroke severity and outcome.

Materials and Methods: The study included 61 ischemic stroke patients and 64 controls. Strokes were subtyped according to TOAST criteria, the severity and outcome of stroke (at 1 year) were measured.

Results: The mean triglyceride, fibrinogen, CRP and glucose values were significantly higher among cases. The median oxLDL value for patients with large artery atherosclerosis (LAA) type of stroke was significantly higher than for other subtypes. The oxLDL values did not correlate with age, stroke severity and outcome.

Conclusions: Inflammatory markers (fibrinogen and CRP) predicted the stroke severity and outcome whereas elevation of oxLDL levels did not. Our data refer to possibility that there may exist some links between the LAA subtype of stroke and elevated oxLDL (apoB100 aldehyde-modified form).     

Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians

Background  

Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke.     

Copeptin is associated with one-year mortality and functional outcome in patients with acute spontaneous basal ganglia hemorrhage

High plasma copeptin levels have been found to be associated with short-term poor outcome after intracerebral hemorrhage (ICH). We furthermore evaluate the relation of plasma copeptin levels to long-term outcome and early neurological deterioration after ICH. Fifty healthy controls and 89 patients with acute spontaneous basal ganglia hemorrhage were recruited in this study. Plasma copeptin concentrations on admission measured by enzyme-linked immunosorbent assay were considerably high in patients than healthy controls. A multivariate analysis identified plasma copeptin level as an independent predictor for 1-year mortality, 1-year unfavorable outcome (modified Rankin Scale score>2) and early neurological deterioration. A receiver operating characteristic curve showed that the predictive value of plasma copeptin concentration was similar to that of National Institutes of Health Stroke Scale scores for long-term poor outcome and early neurological deterioration. However, copeptin did not obviously improve the predictive values of National Institutes of Health Stroke Scale scores. Thus, increased plasma copeptin level is an independent prognostic marker of 1-year mortality, 1-year unfavorable outcome and early neurological deterioration after ICH.     

Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome

Background

Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome.

Methods

Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume.

Results

Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures.

Conclusions

These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.     

Influence of transoesophageal echocardiography on therapy and prognosis in young patients with TIA or ischaemic stroke

Objective. To determine the influence of transoesophageal echocardiography (TEE) on therapy and prognosis in patients with cryptogenic transient ischaemic attack (TIA) or ischaemic stroke under the age of 50 years. Methods and results. We evaluated all patients aged 50 and under who were referred to our university hospital for cryptogenic TIA or ischaemic stroke during the period 1 January 1996 to 31 December 2004. All patients underwent both transthoracic echocardiography (TTE) and TEE. Patients with known pre-existent heart disease, such as atrial fibrillation, were excluded. Eighty-three patients with TIA (22) and ischaemic stroke (61) were enrolled. Mean age was 39±8 years (range 18 to 50). In 30% of the patients TEE detected one or more potential cardioembolic source, compared with 10% for TTE (p=0.003). Standard treatment (aspirin 38 mg daily) was changed in 7% of the patients due to the TEE findings. Complete followup was obtained in 93% with an average of 5±3 years. Twelve recurrences occurred; two out of six patients (33%) with therapy change and ten out of 71 (14%) of the patients without therapy change had a recurrent TIA or ischaemic Stroke. Conclusion. In patients with cryptogenic TIA or ischaemic stroke, TEE is superior to TTE in the detection of a potential cardiac source of embolism. However, findings obtained by TEE only influence the already initiated treatment in a small percentage of patients. The recurrence rate both in the group with and without therapy change is high. (Neth Heart J 2009;17:373–7.)     

Functional outcome of pannexin-deficient mice after cerebral ischemia

Pannexin (Px, Panx) channels have been implicated in several physiological and pathological processes. We recently studied the potential contribution of pannexins in ischemic brain damage using Px1^-/- Px2^-/- mice and provided evidence that (1) the release of IL-1β and hemichannel function in astrocytes are, in contrast to published data, not affected by the absence of Px1 and Px2, (2) channel function in neurons lacking Px1 and Px2 is impaired and (3) Px1^-/- Px2^-/- mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. Here, we further investigate the neurological outcome of wild-type and pannexin double-knockout mice 48 h after permanent occlusion of the distal middle cerebral artery (MCAO). Pannexin double-knockout mice (Px1^-/- Px2^-/-) were less impaired in parameters such as exploration, anxiety, sensorimotor function and behavioral symmetry.     

Functional outcome of pannexin-deficient mice after cerebral ischemia

Pannexin (Px, Panx) channels have been implicated in several physiological and pathological processes. We recently studied the potential contribution of pannexins in ischemic brain damage using Px1^-/- Px2^-/- mice and provided evidence that (1) the release of IL-1β and hemichannel function in astrocytes are, in contrast to published data, not affected by the absence of Px1 and Px2, (2) channel function in neurons lacking Px1 and Px2 is impaired and (3) Px1^-/- Px2^-/- mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. Here, we further investigate the neurological outcome of wild-type and pannexin double-knockout mice 48 h after permanent occlusion of the distal middle cerebral artery (MCAO). Pannexin double-knockout mice (Px1^-/- Px2^-/-) were less impaired in parameters such as exploration, anxiety, sensorimotor function and behavioral symmetry.     

急性脑卒中患者医院感染分析

目的为探明急性脑卒中患者医院感染的特点及危险因素,以便采取有效控制措施。方法对温州医学院附属第一医院1997年1月1日～2002年12月31日6年间收治的4730例急性脑卒中患者进行监测。结果医院感染率为1252%。女性高于男性(P<005),感染率随年龄增大而升高(P<001)。医院感染多发生在入院2周内,感染部位以呼吸道为主(4796%),其次为泌尿道(3481%)。病原菌以G-菌为主(4309%),其次为G+菌(3091%)和真菌(2600%)。耐药菌株不断增加。结论免疫功能低下、侵袭性操作、滥用抗生素和激素是急性脑卒中患者医院感染的主要危险因素。加强对细菌耐药性的监测,合理选用抗生素,是减少或延缓耐药菌株产生的关键措施。     

Circadian rhythms may not influence the outcomes of thrombolysis in patients with ischemic stroke: A study from China

ABSTRACT

Circadian rhythms can affect physical or mental activities as well as the time of stroke onset. The impact of circadian rhythms on acute ischemic stroke (AIS) patients treated by recombinant alteplase (rt-PA) is still incongruent. This study aims to consider whether the outcomes of thrombolysis differ depending on stroke onset time and rt-PA infusion time in patients with AIS. A total of 447 AIS patients, who underwent rt-PA intravenous infusion within 4.5 hours after stroke onset, were enrolled in this study consecutively from June 2010 through December 2016. All of the patients were grouped based on the stroke onset time and rt-PA infusion time into two exact 12-hour intervals as daytime (06:01–18:00) and nighttime (18:01–06:00) and further divided into four subgroups at 6-hour time intervals (00:01–06:00, 06:01–12:00, 12:01–18:00 and 18:01–24:00). Major neurological improvement at 1 hour, 24 hours and 7 days, 7-day mortality rate and 24-hour hemorrhage transformation was recorded. The results showed that a total of 295 patients (66.4%) appeared with AIS and 252 (56.4%) were treated during daytime. Higher NIHSS at admission was observed when stroke occurred in nighttime, especially during 00:01–06:00. Patients with stroke onset in nighttime especially during 18:01–24:00 had a significant shorter onset-door time and onset-needle time. No differences of the major neurological improvement at 1 hour, 24 hours and 7 days, 24-hour hemorrhagic transformation and 7-day fatality rate were found among either 12-hour time frames or 6-hour time frames according to the time of stroke onset or rt-PA infusion. In conclusion, there was no evidence to predict that circadian rhythms could influence the outcomes of AIS patients treated with rt-PA in China, although stroke onset during nighttime might aggravate neurological impairment before treatment. Further, multicenter and prospective clinical trials with larger number of subjects are still needed to draw more reliable conclusions.     

Comparative evaluation of treatment with low-dose aspirin plus dipyridamol versus aspirin only in patients with acute ischaemic stroke

ABSTRACT: BACKGROUND: Previous studies have suggested that pre-stroke treatment with low-dose aspirin (A) couldreduce the severity of acute ischaemic stroke, but less is known on the effect of pre-stroketreatment with a combination of aspirin and dipyridamole (A + D) and post-stroke effects ofthese drugs. The aim of the present study was to evaluate the effect of this drug combinationon acute and long-term prognosis of ischaemic stroke. METHODS: Patients without atrial fibrillation admitted to the stroke unit with acute ischaemic stroke (n =554) or TIA (n = 108) were studied during acute hospital care and up to 12 months afterdischarge from hospital. RESULTS: Prior to acute stroke 62 patients were treated with A + D while 247 patients were treated withA only. No beneficial effects of the combination A + D compared to A only were noted onstroke severity and/or acute in-hospital mortality. However, survival analysis by Coxproportionalhazard model demonstrated lower 12-months all-cause mortality in patientsdischarged with A + D (n = 275) compared with patients on A only (HR, 0.52; CI, 0.32-0.86;p = 0.011; n = 262) after adjusting for age, baseline NIHSS, previous stroke, previousmyocardial infarction and type 2 diabetes. We also noted a tendency towards lower all-causemortality at 3 months with use of A + D, but this was not statistically significant (p = 0.12). CONCLUSIONS: Pre-stroke treatment with a combination of low-dose A + D does not reduce the severity ofacute stroke, nor does it reduce the acute in-hospital mortality. However, treatment with A +D at discharge from hospital is seemingly associated with lower long-term mortalitycompared with A only, contrary to the results from previous randomised studies. However,our results must be interpreted with extreme caution considering the non-randomised studydesign.     

Values of vanillylmandelic acid and homovanillic acid in the urine as potential prognostic biomarkers in ischaemic stroke patients

Background: Suitable biomarkers that have prognostic values are one of the key points of interest in ischaemic stroke. Increased sympathetic nervous system activity in ischaemic stroke causes multiple local and systemic effects that can be detrimental to the outcome. The mechanism of action is increased secretion and activity of catecholamines, whose end metabolic products are vanillylmandelic acid and homovanilic acid. Aim of our study was to determine whether these compounds can be used as potential prognostic biomarkers in ischaemic stroke, as a unique insight into the activity of the sympathetic nervous system.

Methods: Urine samples of 96 patients with ischaemic stroke and transitory ischaemic attacks were analysed. Values of vanillylmandelic and homovanillic acids in urine were tested using liquid chromatography on the first and third day post-stroke. Severity of stroke was determined using the NIHSS scale, while functional outcome was determined using the Modified Rankin Scale.

Results: Values of vanillylmandelic and homovanillic acids positively correlated with functional outcome of ischaemic stroke. Favorable outcomes correlated with decreased values, on contrary to increased values, which were associated with unfavourable outcomes.

Conclusion: Determining the values of these compounds in the urine is an easily available prognostic tool for the ischaemic stroke outcome, while also influencing potential therapeutic changes.     

Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome

Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.     

Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients

Damage-associated molecular pattern molecules such as high-mobility group box 1 protein (HMGB1) and heat shock protein 70 (HSP70) have been implicated in the pathogenesis of asthma. The aim of our study was to examine the induced sputum and plasma concentrations of HSP70 in asthmatic patients to determine their relationship with airway obstruction. Thirty-four healthy controls and 56 patients with persistent bronchial asthma matched for gender and age were enrolled in this study. Spirometry measurements were performed before sputum induction. HSP70 levels in induced sputum and plasma were measured using the ELISA Kit. Sputum and plasma concentrations of HSP70 in asthmatics patients were significantly higher than that in control subjects (sputum, (0.88 ng/ml (0.27–1.88 ng/ml) versus 0.42 ng/ml (0.18–0.85 ng/ml), p < 0.001); plasma, (0.46 ng/ml (0.20–0.98 ng/ml) versus 0.14 ng/ml (0.11–0.37 ng/ml), p < 0.001) and were significantly negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1 (percent predicted), and FEV1/FVC in all 90 participants and 56 patients with asthma. There were no significant differences in HSP70 levels between patients with eosinophilic and non-eosinophilic asthma. HSP70 levels in plasma were positively correlated with neutrophil count, and HSP70 levels in induced sputum were positively correlated with lymphocyte count. In multivariate analysis, independent predictors of sputum HSP70 were diseases and disease severity but not smoking, age, or gender, and independent predictors of plasma HSP70 were also diseases and disease severity. In conclusion, this study indicates that induced sputum and plasma HSP70 could serve as a useful marker for assessing the degree of airway obstruction in patients with asthma. However, further investigation is needed to establish the role of circulating and sputum HSP70 in the pathogenesis of asthma.     

Skeletal and functional status in patients with long-standing stroke

Introduction: Skeletal and functional status can be affected after stroke, mainly due to subjects' immobilisation. The aim of our study was to assess the functional and bone status in post-stroke patients with hemiplegia. Quantitative ultrasound at hand phalanges and bone mineral density (BMD) in the wrist and the calcaneal bone were compared between the paralysed and the non-paralysed side. The study was performed at the Department of Rehabilitation in Nowa Sol. Material and methods: The study included a group of 71 subjects (29 females and 42 males) who had suffered a stroke. Skeletal status was assessed by densitometry (Pixi, Lunar Corp., USA, forearm, calcaneus) and ultrasound (DBM Sonic 1200, IGEA, Italy, hand phalanges). Functional status was evaluated by the Barthel index. Results: The mean values of forearm BMD and ultrasound measurements were significantly lower in the affected limbs versus the opposite site. The mean Barthel index value was 73 ± 21.5. Reduction of the time interval between stroke and standing up positively influenced the difference between wrist BMD in the affected versus the opposite limb, both in the whole group of patients (r = 0.3, p 〈 0.05) and females (r = 0.41, p 〈 0.05). Forearm BMD in males in the affected limb correlated with the Barthel index (r = 0.35, p 〈 0.05). Conclusion: Fracture risk in post-stroke subjects may be increased due to disturbed skeletal and functional status. Reduction of the time interval between stroke and standing up improved wrist densitometric results. (Pol J Endocrinol 2011; 62 (1): 2-7).     

Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis

Fatigue is a common debilitating complication of primary biliary cirrhosis (PBC), the pathophysiologic mechanism of which is poorly understood. Recently, the neuroactive steroid dehydroepinadrosterone sulfate (DHEAS) was reported to be implicated in Chronic Fatigue Syndrome in the absence of liver disease. The present study was undertaken to analyse fatigue scores and their relationship with disease severity and circulating levels of DHEAS as well as its precursors DHEA and pregnenolone in PBC patients with (n=15) or without fatigue (n=10) compared to control subjects (n=11). Fatigue was assessed using the fatigue impact scale (FIS) including cognitive, physical and psychosocial subclasses. Steroids were measured by radioimmunoassay or gas chromatography/mass spectrometry. Plasma concentrations of DHEAS were significantly reduced in PBC patients with fatigue as compared to controls, while those of its precursors DHEA and pregnenolone remained within the control range. Plasma levels of DHEAS in PBC patients were significantly correlated with fatigue severity as reflected by total FIS scores including total (rp=-0.42; p=0.018), as well as the cognitive (rp=-0.37; p=0.03), physical (rp=-0.48; p=0.006) and psychosocial (rp=-0.35; p=0.04) subclasses of fatigue scores. No correlation of fatigue scores was observed with indices of liver function. These findings suggest that reduced levels of the neurosteroid DHEAS may contribute to fatigue in patients with PBC; substitutive therapy using DHEAS or its precursor DHEA could be beneficial in the management of fatigue in patients with low levels of DHEAS.     

Plasma carotenoid and malondialdehyde levels in ischemic stroke patients: relationship to early outcome

An association between ischemic stroke and increased oxidative stress has been suggested from animal studies. However, there is a lack of evidence with respect to this association in humans. Here, the time course of plasma levels of six carotenoids, which are lipophilic micronutrients with antioxidant properties, as well as of malondialdehyde (MDA), a marker of lipid peroxidation, was followed in ischemic stroke patients. Plasma levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, as well as MDA were measured by high-performance liquid chromatography in 28 subjects (19 men and nine women aged 76.9+/-8.7 years) with an acute ischemic stroke of recent onset (<24h) on admission, after 6 and 24 h, and on days 3, 5, and 7. Carotenoid and MDA levels in patients on admission were compared with those of age- and sex-matched controls. Plasma levels of lutein, lycopene, alpha- and beta-carotene were significantly lower and levels of MDA were significantly higher in patients in comparison with controls. Significantly higher levels of MDA and lower levels of lutein were found in patients with a poor early-outcome (functional decline) after ischemic stroke as compared to patients who remained functionally stable. These findings suggest that the majority of plasma carotenoids are lowered immediately after an ischemic stroke, perhaps as a result of increased oxidative stress, as indicated by a concomitant rise in MDA concentrations. Among the carotenoids, only lutein plasma changes are associated with a poor early-outcome.