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1.

Background

The aim of this study was to investigate the individual or combined effects of PPARA-L162V, PPARG-C161T and APOE polymorphisms on hyperlipidemia in coronary heart disease (CHD) patients.

Methods

Our study included 223 patients with CHD (103 with type 2 diabetes (T2DM), 120 without diabetes) and 101 controls. All genotypes were determined by PCR–RFLP technique.

Results

Genotypic and allelic distributions of PPARA-L162V polymorphism were similar between study and control groups (p > 0.05). The serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels were higher in PPARA-V162 allele carriers in non-diabetic CHD patients (p = 0.007 and p = 0.038, respectively). The increasing effect of the PPARA-V162 allele on serum TC and LDL-C levels was weakened with the presence of PPARG-161T allele in the non-diabetic CHD patients. The ApoE4–PPARA-V162 allelic combination of the ApoE/PPARA genes was found to be more frequent in diabetic CHD patients independent of serum lipids (p = 0.035).

Conclusions

The PPARA V162 allele has an increasing effect on TC and LDL-C levels and this effect was reduced by carrying PPARG T161 allele in non-diabetic CHD patients. On the other hand, the V162 allele may be associated with an increased risk of CHD in diabetic CHD patients due to the presence of ApoE4 allele independent of serum lipids. We suggest that the PPARA L162V polymorphism may have diverse effects on serum lipids and CHD risk depends on the presence of T2DM.  相似文献   

2.

Objective

Observe anti-inflammatory effect and the effect on acute pharyngitis rats model induced by ammonia water of compound Lobelia oral liquid, providing experimental basis for its clinical use.

Methods

Use egg white establish foot swelling rats model and use carboxymethyl cellulose establish white blood cell migration rats model. Then observe the anti-inflammatory effect of compound Lobelia oral liquid. Use 15% ammonia spray at pharyngeal establish acute pharyngitis rats model, Visual observation and conduct grading of pharyngeal tissue stimulation in rats, measure the levels of TNF-α and IL-6 in serum. Pharyngeal tissue was taken to observe the morphological changes.

Result

All dose groups of compound Lobelia oral liquid can reduce the rate of foot swelling of rats at all time points (P?<?0.01 or P?<?0.05), and significantly reduce the number of white blood cells of rats (P?<?0.01); And improve the local hyperemia degree, reduce secretion, reduce local swelling of pharyngeal tissue, reduce the serum TNF-α and IL-6 levels of acute pharyngitis rats with different degrees (P?<?0.01 or P?<?0.05).

Conclusion

Compound Lobelia oral liquid has a good anti-inflammatory effect on foot swelling and white blood cell migration rats model, as well as significant improvement effect on acute pharyngitis rats model.  相似文献   

3.

Objectives

Female reproductive dysfunction occurs in patients with pathological loss of adipose tissue, i.e. lipodystrophy (LD). However, mechanisms remain largely unclear and treatment effects of adipocyte-derived leptin have not been assessed in LD animals.

Methods

In the current study, C57Bl/6 LD mice on a low-density lipoprotein receptor knockout background were treated with leptin or saline for 8?weeks and compared to non-LD controls.

Results

The number of pups born was 37% lower in breeding pairs consisting of LD female mice x non-LD male mice (n?=?3.3) compared to LD male mice x non-LD female mice (n?=?5.2) (p?<?0.05). Mean uterus weight was significantly lower in the saline-treated LD group (18.8?mg) compared to non-LD controls (52.9?mg; p?<?0.0001) and increased significantly upon leptin treatment (46.5?mg; p?<?0.001). The mean number of corpora lutea per ovary was significantly lower in saline-treated LD animals compared to non-LD controls (p?<?0.01) and was restored to non-LD control levels by leptin (p?<?0.05). Mechanistically, mRNA expression of ovarian follicle-stimulating hormone receptor (p?<?0.01) and estrogen receptor β (p?<?0.05), as well as of pituitary luteinizing hormone β subunit (p?<?0.001) and follicle-stimulating hormone β subunit (p?<?0.05), was significantly upregulated in LD mice compared to non-LD controls. In addition, mean time to vaginal opening as a marker of puberty onset was delayed by 12.5?days in LD mice (50.9?days) compared to non-LD controls (38.4?days; p?<?0.001).

Conclusions

Female LD animals show impaired fertility which is restored by leptin. Future studies should assess leptin as a subfertility treatment in human leptin-deficiency disorders.  相似文献   

4.

Objective

Study the effect of the 3:7 ratio of Astragalus total saponins and Curcumin on the model of diabetic nephropathy rats, and explore its mechanisms.

Methods

Diabetic nephropathy rats model was established by high-fat and high-sugar feed feeding combined with streptozotocin (STZ) injection in sublingual vein. Measured fasting blood glucose of rats on the 10, 20 and 30th day, and measured urine protein content in urine of rats on 30th days. Two hours after the last administration, measured glycated serum protein (GSP), insulin antibody (IA), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), malondialdehyde (MDA), insulin, superoxide dismutase (SOD), glutathione (GSH), urea nitrogen (BUN), creatinine (Cr) in the serum and calculated the renal index of rat. Take the viscera of pancreas and kidney, and HE staining, so as to observe pathological changes.

Result

Astragalus total saponins and Curcumin 3:7 compatibility each dose group can significantly reduce the diabetic nephropathy rats blood glucose of 30th days, significantly reduce the level of GSP, IA, TG, TC, LDL (P?<?0.01), and reduce MDA levels with different degrees (P?<?0.01 or P?<?0.05), and significantly increase the level of insulin (P?<?0.01), increase the level of HDL, SOD and GSH with different degrees (P?<?0.01 or P?<?0.05 or P?>?0.05); Astragalus total saponins and Curcumin 3:7 compatibility each dose group also can decrease renal index, UN, and Cr levels with different degrees and improve the pathological changes of pancreatic tissue and kidney tissue in diabetic nephropathy rats with different degrees (P?<?0.01 or P?<?0.05 or P?>?0.05).

Conclusion

The 3:7 ratio of Astragalus total saponins and Curcumin can achieve the treatment and protection effects on diabetic nephropathy rats by improve the glycometableolism, insulin resistance, lipid metableolism, oxidative stress levels, and pathological changes.  相似文献   

5.

Objective

To determine the effect of laser needle-knife on PI-3K, AKT and VEGF mRNA expression of vertebral arteries in a rabbit model of cervical spondylotic arteriopathy (CSA) and the mechanism of action involved.

Methods

Forty healthy general-grade rabbits were divided into a normal control group, model group, acupuncture group, and laser needle-knife group (n?=?10 rabbits per group), and the CSA rabbit model was established in all but groups but the normal control group. CSA model rabbits in the acupuncture group were treated by acupuncture at the Fengchi (GB 20) and Cervical Jiaji (EX-B 2) points, whereas rabbits in the laser needle-knife group were treated with laser needle-knife targeting the Jiaji points near the C5 spinous process. Rabbits in the normal control and model groups were fixed using similar methods. Behavioral characteristics of all rabbits were evaluated before and after treatment. Peak systolic velocity (PSV) of the right carotid and vertebral arteries in each group were examined using beside B ultrasound, and PI-3K, AKT, VEGF mRNA expression in vertebral arteries were determined by real-time PCR.

Results

The behavioral signs of rabbits were improved after treatment in both the acupuncture and laser needle-knife groups. In comparison with control group, PSV of right carotid arteries in acupuncture group and laser needle-knife group were enhanced significantly (P?<?0.05 and P?<?0.01), PSV of right vertebral arteries in acupuncture group and laser needle-knife group were enhanced significantly too (P?<?0.01 and P?<?0.05). PI-3K mRNA expression in laser needle-knife and acupuncture group was significantly higher than that in control group (P?<?0.01, P?<?0.05). AKT mRNA expression in laser needle-knife and acupuncture group was significantly higher than that in control group (P?<?0.01). VEGF mRNA expression in laser needle-knife and acupuncture group was significantly higher than that in control group too (P?<?0.01, P?<?0.05). No significant differences were found in PI-3K, AKT and VEGF mRNA expression levels among acupuncture and laser needle-knife groups (P?>?0.05).

Conclusion

Laser needle-knife could effectively intervene the mRNA expression of PI-3K, AKT and VEGF, this may be one of the mechanisms of the effect of laser needle-knife in treating CSA in rabbits.  相似文献   

6.

Background

In a previous randomized controlled trial, we found that sitting isometric yoga improves fatigue in patients with chronic fatigue syndrome (CFS) who are resistant to conventional therapy. The aim of this study was to investigate possible mechanisms behind this finding, focusing on the short-term fatigue-relieving effect, by comparing autonomic nervous function and blood biomarkers before and after a session of isometric yoga.

Methods

Fifteen patients with CFS who remained symptomatic despite at least 6 months of conventional therapy practiced sitting isometric yoga (biweekly 20 min practice with a yoga instructor and daily home practice) for eight weeks. Acute effects of sitting isometric yoga on fatigue, autonomic function, and blood biomarkers were investigated after the final session with an instructor. The effect of a single session of sitting isometric yoga on fatigue was assessed by the Profile of Mood Status (POMS) questionnaire immediately before and after the session. Autonomic nervous function (heart rate (HR) variability) and blood biomarkers (cortisol, DHEA-S, TNF-α, IL-6, IFN-γ, IFN-α, prolactin, carnitine, TGF-β1, BDNF, MHPG, and HVA) were compared before and after the session.

Results

Sitting isometric yoga significantly reduced the POMS fatigue score (p?<?0.01) and increased the vigor score (p?<?0.01). It also reduced HR (p?<?0.05) and increased the high frequency power (p?<?0.05) of HR variability. Sitting isometric yoga increased serum levels of DHEA-S (p?<?0.05), reduced levels of cortisol (p?<?0.05) and TNF-α (p?<?0.05), and had a tendency to reduce serum levels of prolactin (p?<?0.1). Decreases in fatigue scores correlated with changes in plasma levels of TGF-β1 and BDNF. In contrast, increased vigor positively correlated with HVA.

Conclusions

A single session of sitting isometric yoga reduced fatigue and increased vigor in patients with CFS. Yoga also increased vagal nerve function and changed blood biomarkers in a pattern that suggested anti-stress and anti-inflammatory effects. These changes appear to be related to the short-term fatigue-relieving effect of sitting isometric yoga in patients with CFS. Furthermore, dopaminergic nervous system activation might account for sitting isometric yoga-induced increases in energy in this patient population.

Trial registration

University Hospital Medical Information Network (UMIN CTR) UMIN000009646. Registered Dec 27, 2012.
  相似文献   

7.

Background

Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case–control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed.

Methods

The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR–RFLP assay. Anthropometric measurements were measured in all participants.

Results

There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p = 0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA + AA genotypes in male CHD patients (p = 0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age < 55 (OR = 2.837, p = 0.001) and TC ≥ 5.18 mmol/L (OR = 1.970, p = 0.027) in male subjects. However, this association was not observed in female patients (p > 0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age < 55 years.

Conclusion

These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.  相似文献   

8.

Background

Previous studies have indicated that inefficient energy utilization may play a pivotal role in hypertrophic cardiomyopathy (HCM). However, whether plasma free fatty acid (FFA), a main energy substrate of heart, has an effect on HCM remains unclear. Besides, several studies have suggested sex-related differences in HCM features and FFA metabolism. Here, we aimed to explore the association between plasma FFA levels and HCM and potential effects of sex on this relation.

Methods

A total of 412 patients (age 47.8?±?12.7 years, 243 males (59.0%)) with HCM were recruited. Complete medical history was collected. Echocardiography and cardiovascular magnetic resonance imaging (CMRI) were performed. Fasting plasma FFA was determined by clinical laboratory. Left ventricular mass (LVM), maximum wall thickness (MWT), and left atrium diameter (LAD) were assessed with CMRI.

Results

The median FFA levels were 0.38 (interquartile range (IQR) 0.27–0.52) mmol/L in men and 0.40 (IQR 0.30–0.59) mmol/L in women. The FFA levels were significantly lower in men compared with those in women (p?=?0.005). Compared with women, men had greater LVM index (LVMI) (96.8?±?37.6 vs. 78.6?±?31.5 g/m2, p?<?0.001). FFA levels in male patients correlated positively with LVM, LVMI, LAD, cholesterol levels, high-density lipoprotein-cholesterol (HDL-C) levels, heart rate, and systolic blood pressure (SBP). However, none of these variables were significantly associated with sqrt (FFA) in female patients except a borderline correlation of LAD (p?=?0.050). Multiple linear regression analysis was performed in male patients and revealed that HDL-C (β?=?0.191, p?=?0.002), heart rate (β?=?0.182, p?=?0.004), SBP (β?=?0.167, p?=?0.007), LVMI (β?=?0.132, p?=?0.032), and LAD (β?=?0.165, p?=?0.009) were independently associated with increasing FFA levels.

Conclusions

In patients with HCM, LVMI, LAD, HDL-C, SBP, and heart rate were independently associated with increasing plasma FFA levels in males, whereas not in females. These results suggest that sex may affect the pathogenesis of HCM through influencing FFA metabolism. And these sex-related differences should be taken into account in therapeutic approaches to influence myocardial FFA metabolism in HCM.
  相似文献   

9.

Objective

To investigate the correlation between the level of glucose in serum and the development of acute pancreatitis (AP).

Methods

Data of 153 AP cases were collected, in which there were 130 patients with mild AP (MAP), 4 with moderate-severe AP (MSAP) and 19 with severe AP (SAP). At the time of admission, following indexes of patients were recorded: glucose, APACHE II score, TNF-α and C-reaction protein (CRP).

Results

At the time of admission, the levels of glucose in serum and APACHE II scores in the MSAP and SAP groups were significantly higher than those in the MAP group, but after treatment, the level of glucose in serum was recovered in 95.8% of the patients in the MAP group, while this digit in the SAP group remained to be 68.4%; in the SAP group, the levels of TNF-α and CRP in patients with sustained hypertension were significantly higher than those with non-persistent hypertension; in terms of the length of stay in hospital, the SAP group was shorter than that in the non-treatment group, and the difference had statistical significance (p?<?0.05). Moreover, we found that the level of glucose in serum was positively correlated with the APACHE II scores, TNF-α and CRP.

Conclusion

Glucose level in serum can be used as one of the indicators for evaluating the severity and development of AP in clinical practice.  相似文献   

10.

Background

Non-occupational heavy metals are considered risk factors for coronary heart disease (CHD). Several recent epidemiologic studies have evaluated the relationship between non-occupational cadmium exposure and risk factors for cardiovascular disease (CVD). This study was designed to investigate the relationship between non-occupational cadmium exposure and risk factors for CHD using the Framingham estimate of 10 year CHD risk.

Methods

The heavy metal dataset of the Korean National Health and Nutrition Examination Survey for 2008 through 2010, a cross-sectional survey of a representative sample of 4,668 non-institutionalized Koreans, was analyzed. Subjects were stratified into seven age groups to minimize the effects of age. The log-transformed blood cadmium concentrations were compared with the Framingham estimate of 10 year CHD risk in each age stratum.

Results

The Framingham estimate of 10 year CHD risk was significantly associated with the log-transformed blood cadmium concentrations (p<0.05) in all age groups of Korean men, with the lowest regression coefficient (0.254) for men aged 20 to <35 years and the highest (3.354) for men aged 55 to <60 years; similar results, however, were not observed in Korean women. After adjusting for survey year, age, and urinary cotinine concentration, the log-transformed blood cadmium levels among men aged 20 to <35, 40 to <45, 50 to <55, and 60 to <65 years were significantly associated with systolic blood pressure (p<0.05), but not with total and high density lipoprotein (HDL) cholesterol concentrations.

Conclusions

Cadmium exposure, even at non-occupational levels, may be associated with CHD risk in men. Despite the declines in non-occupational cadmium exposure over the past several decades, more efforts are needed.  相似文献   

11.

Objective

Explore the possible protective effect of Sargentodoxa cuneata total phenolic acids on cerebral ischemia reperfusion injury rats.

Methods

Focal cerebral ischemia reperfusion rats model were established by linear thrombus. Nimodipine group, Naoluotong group, the high, middle and low dose of Sargentodoxa cuneata total phenolic acids groups were given related drugs via intragastric administration before operation for seven days, once a day. At the same time sham operation group, and ischemia reperfusion group were given the same volume of physiological saline. One hour after the last administration, establish focal cerebral ischemia- reperfusion model in rats by thread method, and the thread was taken out after 2?h ischemia to achieve cerebral ischemia reperfusion injury in rats. After reperfusion for 24?h, the rats were given neurologic deficit score. The brain tissue was taken to measure the levels of IL-6, IL-1β, TNF-α, Bcl-2, Bax, Casp-3 and ICAM-1; HE staining observed histopathological changes in the hippocampus and cortical areas of the brain; Immunohistochemistry was used to observe the expression of NGF and NF-KBp65.

Result

Focal cerebral ischemia reperfusion rats model was copyed successed. Compared with model group, each dose group of Sargentodoxa cuneata total phenolic acids could decreased the neurologic deficit score (P?<?0.05 or P?<?0.01), decreased the levels of IL-6, IL-1β, ICAM-1, TNF-α, Bax and Caspase-3 in brain tissue (P?<?0.05 or P?<?0.01), increased the levels of IL-10, Bcl-2, NGF in brain tissue (P?<?0.05 or P?<?0.01), decreased the express of NF-KBp65 in brain (P?<?0.05 or P?<?0.01).

Conclusion

Sargentodoxa cuneata total phenolic acids can improve focal cerebral ischemia reperfusion injury rats tissue inflammation, apoptosis pathway, increase nutrition factor to protect the neurons, reduce the apoptosis of nerve cells, activate brain cells self-protect, improve the histopathological changes in the hippocampus and cortical areas of the brain, reduce cerebral ischemia reperfusion injury.  相似文献   

12.

Background

Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang-(1–7), its receptor (Mas1) and the enzymes involved in Ang-(1–7) production (ACE2 and Membrane metallo-endopeptidase; MME) are down regulated in response to glucocorticoid administration contributing to IUGR.

Methods

Pregnant female Sprague–Dawley rats were injected with dexamethasone (DEX; 0.4 mg/kg/day) starting from 14 day gestation (dg) till sacrifice at 19 or 21 dg while control groups were injected with saline (n?=?6/group). The gene and protein expression of ACE2, MME, Ang-(1–7) and Mas1 receptor in the placental labyrinth (LZ) and basal zones (BZ) were studied.

Results

DEX administration caused a reduction in LZ weight at 19 and 21 dg (p?<?0.001). IUGR, as shown by decreased fetal weights, was evident in DEX treated rats at 21 dg (p?<?0.01). ACE2 gene expression was elevated in the LZ of control placentas at 21 dg (p?<?0.01) compared to 19 dg and DEX prevented this rise at both gene (p?<?0.01) and protein levels (p?<?0.05). In addition, Ang-(1–7) protein expression in LZ was significantly reduced in DEX treated rats at 21 dg (p?<?0.05). On the other hand, Mas1 and MME were upregulated in LZ at 21 dg in both groups (p?<?0.05 and p?<?0.001, respectively).

Conclusion

The results of this study indicate that a reduced expression of ACE2 and Ang-(1–7) in the placenta by DEX treatment may be responsible for IUGR and consequent disease programming later in life.
  相似文献   

13.

Background

Enhanced secondary preventive follow-up after stroke or transient ischemic attack (TIA) is necessary for improved adherence to recommendations regarding blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels. We investigated whether nurse-led, telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels at 12 months after hospital discharge.

Methods

We randomized 537 patients to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C measurements were performed at 1 month (baseline) and 12 months post-discharge. Intervention group patients who did not meet target values at baseline received additional follow-up, including titration of medication and lifestyle counselling, to reach treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L).

Results

At 12 months, mean systolic BP, diastolic BP and LDL-C was 3.3 (95% CI 0.3 to 6.3) mmHg, 2.3 mmHg (95% CI 0.5 to 4.2) and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group compared to controls. Among participants with values above the treatment goal at baseline, the difference in systolic BP and LDL-C was more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1, and 0.6 mmol/L, 95% CI 0.4 to 0.9). A larger proportion of the intervention group reached the treatment goal for systolic BP (68.5 vs. 56.8%, p = 0.008) and LDL-C (69.7% vs. 50.4%, p < 0.001).

Conclusions

Nurse-led, telephone-based secondary preventive follow-up, including medication adjustment, was significantly more efficient than usual care at improving BP and LDL-C levels by 12 months post-discharge.

Trial Registration

ISRCTN Registry ISRCTN23868518  相似文献   

14.

Background

Evidence has shown that endogenous H2S plays an important role in the physiological and pathophysiological processes of many organs. The study aimed to explore whether exogenous H2S has a potential therapeutic effect on a rat ovariectomy-induced model of osteoporosis.

Methods

The OVX osteoporosis model was established in female Sprague-Dawley rats by full bilateral ovariectomy. The rats were randomly divided into four groups, with the two experimental groups receiving an intraperitoneal injection of GYY4137 or sodium alendronate. The level of H2S in the plasma was determined and common laboratory indicators to diagnose osteoporosis, such as alkaline phosphatase (ALP) activity and the levels of osteocalcin (OCN), calcitonin, parathyroid hormone and leptin were measured. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae was measured using dual-energy X-ray absorptiometry. The maximum stress of femoral fracture was obtained through a three-point bending test of the femur.

Results

The OVX osteoporosis model was successfully established. GYY4137 was injected to increase the level of H2S in the plasma in one group, designated OVX-GYY during the observation period (p?<?0.05). At 12 weeks, the BMD value of the fourth lumbar vertebra in the OVX-GYY group had increased (p?<?0.05). The BMD femur value in the OVX-vehicle group had decreased (p?<?0.05). Bilateral ovariectomy leads to biochemical disorders related to bone metabolism and hormone levels in rat plasma (all p?<?0.05). Ovariectomy also reduced blood calcium, blood phosphate and calcitonin, and increased parathyroid hormone and leptin. The opposite results were obtained for the groups with alendronate sodium or GYY4137 treatment (all p?<?0.05).

Conclusions

Through the slow release of H2S, GYY4137 did an excellent job of simulating endogenous neuroendocrine gaseous signaling molecules. Exogenous H2S had a regulatory effect on osteoporosis in ovariectomized rats, showing potential value for the treatment of human postmenopausal osteoporosis.
  相似文献   

15.

Background

Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither.

Method

Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart–ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured.

Results

In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean?±?SD, 8.3?±?1.2 vs 7.5?±?1.1 and 7.4?±?1.1 units; p?<?0.05), PWVao (9.1?±?1.4 vs 8.7?±?1.9 and 8.1?±?0.9 m/s; p?<?0.05) and haPWV (8.5?±?1 vs 7.9?±?1 and 7.2?±?0.7 m/s; p?<?0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (β?=?0.49, 0.2, 0.17 and -0.2 units; p?<?0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (β?=?0.42, 0.27 and 0.22; p?<?0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (β?=?0.46, 0.32, -0.2, 0.2 and 0.11; p?<?0.01).

Conclusion

In this sub-Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention.
  相似文献   

16.

Objective

The visceral sensitivity index (VSI) is a useful self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS). Previous research has shown that worsening GSA in IBS patients is related to the severity of GI symptoms, suggesting that GSA is an important endpoint for intervention. However, there is currently no Japanese version of the VSI. We therefore translated the VSI into Japanese (VSI-J) and verified its reliability and validity.

Material and methods

Participants were 349 university students aged 18 and 19 years and recruited from an academic class. We analyzed data from the VSI-J, Anxiety Sensitivity Index (ASI), Hospital Anxiety and Depression scale (HAD), and Irritable Bowel Syndrome Severity Index (IBS-SI). The internal consistency, stability, and factor structure of the VSI-J and its associations with anxiety, depression and severity measures were investigated.

Results

The factor structure of the VSI-J is unidimensional and similar to that of the original VSI (Cronbach’s α?=?0.93). Construct validity was demonstrated by significant correlations with ASI (r?=?0.43, p?<?0.0001), HAD-ANX (r?=?0.19, p?=?0.0003), and IBS-SI scores (r?=?0.45, p?<?0.0001). Furthermore, the VSI-J was a significant predictor of severity scores on the IBS-SI and demonstrated good discriminant (p?<?0.0001) and incremental (p?<?0.0001) validity.

Conclusion

These findings suggest that the VSI-J is a reliable and valid measure of visceral sensitivity.
  相似文献   

17.

Background

In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly.

Results

IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n?=?3496 individuals, p?<?0.001 and CRP: n?=?3632, p?=?0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n?=?1258, p?<?0.001 and CRP: n?=?1312, p?<?0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n?=?2238, p?<?0.001 and CRP: n?=?2320, p?=?0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p?<?0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p?<?0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR?=?1.063 per each pg/mL, 95 % CI: 1.052-1.074, p?<?0.001 and HR?=?1.020 per each mg/L, 95 % CI: 1.015-1.025, p?<?0.001, respectively) but also in the successfully aging subgroup (HR?=?1.163 per each pg/mL, 95 % CI: 1.128-1.199, p?<?0.001 and HR?=?1.074 per each mg/L, 95 % CI: 1.047-1.100, p?<?0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p?<?0.001).

Conclusions

Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.
  相似文献   

18.

Background

Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients.

Method

Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia.

Result

The blood ammonia level was positively correlated with the serum glutamate concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r = ?0.41, p = 0.01), citrulline (r = ?0.42, p = 0.01), and glycine concentrations (r = ?0.54, p < 0.01). It was also revealed that the concomitant administration of the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01) was positively associated with the elevation of the blood ammonia level.

Conclusion

We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.
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19.

Background

Increasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy.

Methods

In 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells.

Results

Patients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p?<?0.001). p62 MFI levels in lymphocytes and granulocytes from patients with RA (17.1 and 8.6, respectively) were significantly lower than those in the corresponding cells from HC (20.2, p?<?0.05; and 13.1, p?<?0.001, respectively). Significantly higher levels of LC3-II protein expression in contrast to lower p62 protein levels were observed in patients with RA than in HC. The autophagosome levels in immune cells were significantly correlated with inflammatory parameters in patients with RA, and they were significantly decreased with disease remission after treatment with tumor necrosis factor-α inhibitors or interleukin-6 receptor inhibitor.

Conclusions

Elevated autophagy with significant correlation to inflammation suggests the involvement of autophagy in RA pathogenesis. The effectiveness of biologic therapy might be partly related to the downregulation of autophagy expression.
  相似文献   

20.

Background

Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality.

Methods and Findings

Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09–1.28) in the 72 smaller ones (total 15,498 cases).

Conclusions

The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems. Please see later in the article for the Editors'' Summary  相似文献   

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