Pretreatment with probucol attenuates cardiomyocyte apoptosis in a rabbit model of ischemia/reperfusion

OBJECTIVE: Apoptosis plays an important role in ischemic reperfusion injury. Probucol is a hypolipidemic agent and has antioxidant activity, which may inhibit the oxidative modification of low-density lipoprotein cholesterol. Studies have demonstrated that probucol improves left ventricular function, prevents left ventricular dilatation, and reduces cardiac fibrosis. However, the exact mechanism of probucol on the cardioprotective effect is not known. The objective of the present study was to examine the effect of probucol on ischemia/reperfusion-induced cardiomyocyte apoptosis. MATERIAL AND METHODS: Thirty male New Zealand White rabbits were randomly divided into sham, control, and treated groups, each group comprising 10 rabbits. Before establishment of the ischemia/reperfusion model, animals in the treated group were additionally fed daily with probucol (1000 mg per day) for 4 weeks. In the sham group, the heart was exposed after the chest had been opened, but the coronary artery was not ligated. The animals were killed 150 min after the procedure. In the other two groups, the rabbits were subjected to 30-min of coronary occlusion followed by a 2-h reperfusion. A blood sample was drawn from the right atrium before the animal was killed. The apoptotic myocytes were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Expression of caspase-3 and mitochondrial cytochrome c release was detected by immunohistochemical analysis and Western blot analysis. The level of serum superoxide dismutase (SOD) was tested using the xanthine oxidase method, and the content of serum malondialdehyde (MDA) was measured by colorimetry. RESULTS: As compared with the sham group, the control group had a significantly higher apoptotic index ((32.48 +/- 4.56) % versus (0.56 +/- 0.18) %, p < 0.01) and serum MDA concentration (2.70 +/- 0.64 versus 1.06 +/- 0.46 micromol/L, p < 0.01), and a significantly lower serum SOD level (144.27 +/- 21.69 versus 204.64 +/- 16.67 microU/L, p < 0.01). Probucol pretreatment apparently caused a decrease in the apoptotic index ((21.64 +/- 3.08) %, p < 0.01 versus the sham or control group) and serum MDA concentration (1.95 +/- 0.51 micromol/L, p < 0.01 versus the sham or control group), and increased the levels of serum SOD (162.61 +/- 16.13 microU/L, p < 0.01 versus the sham group; p < 0.05 versus the control group). The caspase-3 activation and mitochondrial cytochrome c release in the control group were also higher than those in the treated group (p < 0.01). CONCLUSIONS: The present study shows that probucol attenuates ischemia/reperfusion-induced cardiomyocyte apoptosis. The protective effect of probucol on the myocardium may be partly due to its antioxidant activity.     

Updating biological variation databases and selecting reasonably correct published values

Objective. To investigate the effect of the mode of labour and delivery on total antioxidant status (TAS) and on the protein S100B serum concentrations in mothers and their newborns. Material and methods. Sixty women with normal pregnancies were divided into three groups: Group A (n = 20) with normal labour and vaginal delivery (VG), group B (n = 18) with prolonged labour+VG and group C (n = 22) with scheduled caesarean section (CS). Blood was obtained at the beginning of the labour process and immediately after delivery (pre‐ and post‐delivery) as well as from the umbilical cord (CB). TAS and creatine kinase (CK) were measured using commercial kits. Serum S100B levels were evaluated with the electrochemiluminescence immunoassay “ECLIA” on the ROCHE ELECSYS 2010 immunoassay analyser. Results. Post‐delivery, TAS levels were significantly decreased in group A and especially in group B. S100B levels were increased in group B (0.0712±0.02?µg/L) as compared with those of group A (0.0567±0.03?µg/L, p<0.01) and group C (0.038±0.03?µg/L, p<0.01), the levels in group C remaining practically unaltered (pre‐ versus post‐delivery). In the newborns, S100B levels were almost 2‐fold higher in group B (0.67±0.18?µg/L) than those in group A (0.40±0.05?µg/L p<0.001) and group C (0.31±0.04?µg/L p<0.001). A negative correlation was found between TAS and S100B protein (r = ?0.61, p<0.001), the latter positively correlated to CK (r = 0.48, p<0.01). Conclusions. The increased S100B serum levels in the mothers of group B, post‐delivery, may have been due to the long‐lasting, oxidative and/or psychogenic stress. The observed remarkably high levels of S100B in the group B newborns may have been due to compressive conditions on the foetus brain during this mode of delivery.     

Experimental hyperhomocysteinemia disturbs bone metabolism in rats

Objective. To investigate whether experimental hyperhomocysteinemia (HHCY) can induce adverse changes in bone metabolism. Methods. Blood and urine samples were collected from rats fed with a methionine‐enriched diet (HHCY, n = 18) or an isocaloric control diet (control, n = 10) for 12 weeks. Biochemical bone turnover markers (osteocalcin, hydroxyproline, N‐terminal collagen I telopeptides and homocysteine (HCY), folate and vitamin B12) were measured. Whole body bone mineral density (BMD) was assessed by dual energy X‐ray absorptiometry. Results. HCY was significantly higher in HHCY than in control rats (16.2 versus 3.2?µmol/L; p = 0.0006). Bone resorption parameters hydroxyproline (1.60±0.6 versus 0.85±0.4; p<0.05) and N‐terminal collagen I telopeptides (150.8±78 versus 48.1±26?nmol/L BCE; p<0.05) increased, whereas bone formation marker osteocalcin (9.01±3.8 versus 15.07±4.2?ng/mL; p<0.05) decreased in HHCY compared to control rats. The relation N‐terminal collagen I telopeptides/osteocalcin significantly increased in HHCY compared to control rats (13.14±3.1 versus 4.14±1.9). BMD measurement did not reveal any differences between groups. Conclusion. These findings demonstrate a significant modification of bone turnover in HHCY rats. The relation between bone resorption and formation indicates a shift toward bone resorption, which might be a plausible explanation for the relation between HHCY and fracture risk.     

Plasma homocysteine levels in patients with β‐thalassaemia major

Objective. We investigated the level of homocysteine (HCY) and its relation with vitamin B12, folate and oxidative stress in patients with β‐thalassaemia major. Material and methods. Plasma HCY, methionine, advanced oxidation protein products (AOPP) and serum vitamin B12, folate, ferritin and total antioxidant capacity (TAC) were determined in 32 thalassaemic patients and 27 control subjects. Results. HCY (6.44±0.44 versus 8.71±0.57?µmol/L), methionine (12.57±1.8 versus 22.2±3.8?µmol/L), folate (9.14±0.48 versus 15.38±0.71?nmol/L) and TAC (0.34±0.03 versus 0.56±0.03?mmol/L) significantly decreased in thalassaemic patients, whereas AOPP (20.26±1.8 versus 11.30±0.2 μmol/L) and ferritin (3481.0±512 versus 46.9±4.6?ng/mL) significantly increased. Vitamin B12 levels were similar in both groups (259.1±16.6 versus 228.9±7.4 pmol/L). Conclusions. These findings suggest that increased and uncompensated oxidative stress may lead to an increment in HCY catabolism in thalassaemic patients.     

普罗布考对缺血再灌注心肌细胞凋亡的作用

背景已发现细胞凋亡在缺血再灌注损伤中起重要作用.普罗布考除可降低血清低和高密度脂蛋白胆固醇浓度,有效治疗高胆固醇血症外,还有抗氧化活性,抑制低密度脂蛋白胆固醇的氧化修饰,减少其在血管壁沉积的作用.还有研究证明普罗布考可改善左心室功能、防止左心室扩张和减少心肌纤维化.但普罗布考保护心肌作用的确切机制尚未清楚.目的探讨普罗布考对新西兰白兔缺血再灌注心肌细胞凋亡的作用及其可能机制;并探讨其对血清超氧化物歧化酶(serum superoxide dismuase,SOD)和丙二醛水平的影响.设计随机对照的实验研究.地点、材料和干预本实验在广西医科大学医学科学实验中心完成.实验选用30只雄性新西兰白兔,白兔被随机分成3组假手术组、对照组和预治疗组,每组各10只.对照组(标准兔饲料饲养)和预治疗组(标准兔饲料饲养+普罗布考每日每只1 000 mg灌胃)各4周后建立缺血再灌注模型;假手术组(标准兔饲料饲养)4周后开胸用4-0号线穿过冠状动脉左前降支近端,但不予结扎.测定3组白兔心肌细胞凋亡指数、血清丙二醛、SOD水平.主要观察指标①普罗布考对心肌细胞凋亡的影响.②普罗布考对血清SOD和丙二醛水平的影响.结果对照组凋亡指数[(34.75±3.20)%]、血清丙二醛水平[(2.70±0.64)μmol/L]显著高于假手术组[(0.48±0.20)%,(1.06±0.46)μmol/L,q=18.42,6.29,P＜0.01].对照组血清SOD水平显著低于假手术组(q=8.78,P＜0.01).预治疗组凋亡指数和血清丙二醛水平明显低于对照组(q=9.17,4.68,P＜0.01),血清SOD水平高于与对照组(q=3.02,P＜0.05).结论普罗布考降低缺血再灌注心肌细胞凋亡,这一保护作用可能部分是通过减少血清丙二醛水平和提高血清SOD水平来实现的.     

Dramatic reduction of erythrocyte glucose‐6‐phosphate dehydrogenase activity in athletes participating in the ultradistance foot race “Spartathlon”

Objective. To investigate the effect of a long‐distance endurance exercise “Spartathlon” on erythrocyte glucose‐6‐phosphate dehydrogenase (G₆PD) activity. Material and methods. The study comprised 15 male runners, median age 36.5 years. Blood samples were obtained in the 15?min before the race and again within 15?min after the end of the race. Erythrocyte glutathione (GSH and GSSG) and plasma malonyldialdehyde were measured with HPLC methods, and total antioxidant capacity (TAC), total hyperoxides and G₆PD activity with commercial kits. Lipids, uric acid and total bilirubin were determined with a clinical chemistry analyser. Results. Total hyperoxides were found statistically reduced, whereas total bilirubin was measured elevated post‐race. Interestingly, GSSG levels were found increased (167.3±12.0 versus 219.5±20.3?µmol/L; p<0.005) as well as GSSG/GSH ratio (16.0±1.3 versus 20.60±1.65; p<0.05) post‐race. In contrast, G₆PD activity was found remarkably decreased (8.72±3.10 versus 3.8±2.5?U/g Hb; p<0.0001) pre versus post the event. Conclusion. Red blood cell G₆PD activity in athletes may be reduced post‐race as a consequence of the modulation of NADP/NADPH levels and elevation of the erythrocyte GSSG, and especially GSSG/GSH ratio, resulting in an impairment of the hexose monophosphate shunt.     

Leukotriene-mediated neuroinflammation,toxic brain damage,and neurodegeneration in acute methanol poisoning

Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied.

Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors.

Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88?±?20?h). In 36 survivors, control LT measurements were performed 2 years after discharge.

Results: The acute maximum (C_max) LT concentrations were higher than concentrations in survivors: C_max for LTC4 was 80.7?±?5.6 versus 47.9?±?4.5?pg/mL; for LTD4, 51.0?±?6.6 versus 23.1?±?2.1?pg/mL; for LTE4, 64.2?±?6.0 versus 26.2?±?3.9?pg/mL; for LTB4, 59.8?±?6.2 versus 27.2?±?1.4?pg/mL (all p?p?p?p?p?The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p?>?0.05). The mean decrease in LT concentration was 30.9?±?9.0?pg/mL for LTC4, 26.3?±?8.6?pg/mL for LTD4, 37.3?±?6.4?pg/mL for LTE4, and 32.0?±?8.8?pg/mL for LTB4.

Conclusions: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.     

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning

Context: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined.

Objective: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning.

Methods: The study was designed as observational cohort study. The mean time for an increase of 1?mmol/L HCO₃^–, 0.01 unit arterial blood pH, and the total time for correction of HCO₃^– were determined in IHD- and CRRT-treated patients.

Results: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79?±?0.10 versus 7.05?±?0.10; p?=?0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO₃^– correction correlated with arterial blood pH (r=??0.511; p?=?0.003) and creatinine (r?=?0.415; p?=?0.020). There was association between the time to HCO₃^– correction and dialysate/effluent and blood flow rates (r=??0.738; p?r=??0.602; p?The mean time for HCO₃^– to increase by 1?mmol/L was 12?±?2?min for IHD versus 34?±?8?min for CRRT (p?p?=?0.024). The mean increase in HCO₃^– was 5.67?±?0.90?mmol/L/h for IHD versus 2.17?±?0.74?mmol/L/h for CRRT (p?Conclusions: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.     

Elevated plasma glutathione peroxidase concentration in acute severe asthma: Comparison with plasma glutathione peroxidase activity,selenium and malondialdehyde

Objective. To investigate plasma glutathione peroxidase concentration, glutathione peroxidase activity, plasma selenium and oxidative stress in acute severe asthma. Material and methods. The study was case‐control in design, with cases presenting to the emergency department with acute severe asthma and controls randomly selected from a larger cross‐sectional study. Plasma malondialdehyde (MDA) was used as a measure of oxidative stress and plasma selenium was measured using ICP‐MS. Glutathione peroxidase (GPx) activity was analysed using a colorimetric GPx assay and plasma GPx level was measured by enzyme‐linked immunosorbent assay (ELISA). Results. Fifteen cases [mean (range) predicted peak expiratory flow rate (PEFR) of 43% (20–69)] and 15 matched controls were recruited. MDA levels (mean±SD) were higher in acute asthma subjects (1.30±0.56 µmol/L) than in controls (0.86±0.53 µmol/L; p<0.05). There were no differences between cases and controls for selenium (99±34 µg/L versus 109±17 µg/L) or for GPx activity (39±25 nmol min^?1 mL^?1 versus 38±24 nmol min^?1 mL^?1), however, GPx plasma levels measured by ELISA were higher in cases than controls (22.5±10.8 mg/L versus 13.8±7.3 mg/L; p<0.05). Conclusions. Patients with acute severe asthma demonstrated increased MDA levels but no differences in plasma selenium levels or GPx activity. GPx levels measured by ELISA were elevated in severe asthma. These results are consistent with an adaptive up‐regulation of GPx to protect against oxidative stress.     

Faecal and serum levels of eosinophil cationic protein in a healthy paediatric population

Background. Eosinophil cationic protein (ECP) has been regarded as an excellent marker of eosinophil activation in various diseases where eosinophil‐mediated inflammation plays a role. Recently, it has been suggested as a faecal marker of intestinal inflammation in several immune‐mediated diseases with gastrointestinal expression. Owing to the scarcity of information at paediatric age, the establishment of reference values is necessary before further clinical studies. Objective. To determine faecal and serum ECP levels in healthy children and their association with other biological parameters, thereby providing background additional validation data for this age group. Methods. Faecal and serum ECP levels were available from healthy Caucasian children recruited at a regular outpatient clinic. Exclusion criteria were: chronic illnesses, acute illness, mucosal bleeding and recent pharmacological medication. Faecal and serum ECP levels and faecal α1AT were determined by commercial radioimmunoassay and serum IgE by fluoroenzyme immunoassay Uni‐CAP. Results. Mean and median faecal ECP levels were 1.93?µg/g and 1.20?µg/g, respectively (range 0.41–22.20), while the corresponding serum ECP levels were 13.50?µg/L and 9.54?µg/L, respectively (range 0.20–74.8). The cut‐offs found were 2.80?µg/g and 16.89?µg/L for faecal and serum ECP, respectively. A significant (p = 0.001) increase in serum, but not in faecal, ECP levels was found among patients with high peripheral eosinophil blood count. Neither faecal nor serum ECP levels were influenced by serum IgE levels. Conclusions. Faecal and serum ECP levels, as determined in the present study, add background information concerning reference levels at paediatric age for further studies in different clinical settings.     

Serum level of interleukin-6 (IL-6) and N-terminal propeptide of procollagen type I (PINP) in patients with liver diseases

Introduction: The aim of this study was to evaluate the concentration of interleukin-6 and N-terminal propeptide of procollagen type I and their relationship in liver diseases of different etiologies.

Material and methods: Serum samples were obtained from 30 healthy volunteers and patients suffering from alcoholic cirrhosis (AC) – 31, non-alcoholic cirrhosis (NAC) – 28 and toxic hepatitis (HT) – 23 patients. Cirrhotic patients were classified according to Child–Pugh score. IL-6 and PINP concentrations were determined according to the electrochemiluminescence immunoassay.

Results: The mean serum IL-6 concentration was significantly higher in AC (mean?±?SD:21.52?± 15.01?pg/mL), NAC (20.07?±?32.12?pg/mL) and HT (15.14?±?17.18?pg/mL) when compared to the control group (C) (1.67?±?0.42?pg/mL) (Mann–Whitney U test: p?p?p?=?.020 and p?p?p?=?.022, respectively). IL-6 and PINP concentrations appeared to vary depending on the severity of liver damage (p?p?p?Conclusions: We conclude that serum concentrations of IL-6 and PINP change in liver diseases, and those changes reflect the severity of liver disease.     

Estrogen receptor‐1 genotype is related to coronary intima thickness in young to middle‐aged women

Objective. The incidence of coronary disease in premenopausal women is about one‐half that in men of similar age. The estrogen receptor‐1 (ESR1, c.454‐397T>C) CC variant genotype is associated with the severity of coronary artery disease (CAD) and an increased risk of myocardial infarction in men. The purpose of the present study was to investigate whether this ESR1 CC variant also disposes to atherosclerosis in women in terms of increased total coronary artery intima thickness. Material and methods. A total of 125 forensic autopsy cases of women aged 15 to 49 years were investigated. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The ESR1 c.454‐397T>C genotype was determined by polymerase chain reaction (PCR). Results. The mean intima thicknesses in the three genotype groups were 428±298?µm (TT), 494±371?µm (CT) and 636±436?µm (CC). We found that, on average, women with the CC genotype had a thicker coronary intima compared with that of women with the TT genotype, even after adjusting for age and body mass index (BMI) (p = 0.030). The intermediate group (TC) did not significantly differ from either the CC or the TT genotype group in this respect. Conclusion. Our results point to the importance of ESR1 genotype in relation to cardiovascular disease susceptibility.     

Arterial stiffness in fertile women with metabolic syndrome

Introduction: Although metabolic syndrome (MetS) is evidently associated with the risk of cardiovascular disease (CVD), recently its use has been questioned. We studied the utility of MetS diagnosis when estimating individual CVD risk.

Methods: We compared 27 fertile women with MetS and 27 counterparts without the syndrome, matched pairwise according to well-known risk factors of CVD. Pulse wave velocity (PWV) and central blood pressure (cBP) were determined noninvasively via a SphygmoCor device. Arterial compliance was measured noninvasively with an HDI/PulseWave^TMCR-2000 arterial tonometer.

Results: PWV (7.1?±?2.5 versus 6.5?±?1.1 m/s, p?=?.037), and both systolic (120.9?±?12.2 versus 111.5?±?16.0?mmHg, p?=?.031) and diastolic cBP (81.3?±?8.5 versus 74.1?±?11.2?mmHg, p?=?.035) were higher in the MetS group. Systemic arterial compliance values were lower in both large (15.1?±?8.0 versus 16.1?±?4.4?mL/mmHg?×?10, p?=?.034) and small arteries (7.1?±?2.5 versus 9.3?±?3.2?mL/mmHg?×100, p?=?.010) in women with MetS.

Conclusions: Fertile women with MetS had increased arterial stiffness, as measured by three different methods. Our results highlight the utility of MetS when revealing increased individual CVD risks in fertile-aged women.

• Key messages

• Women with MetS have increased arterial stiffness when measured by different methods.

• MetS is a useful clinical tool to assess increased cardiovascular risk, particularly among fertile-aged women.

     

Seemingly healthy 71‐year‐old men with minor elevations of cardiac troponin I and at risk of premature death in CVD have elevated levels of NT‐proBNP: Report from the ULSAM study

Background. Hypersensitive cardiac troponin I (cTnI) assays detect even minor elevations of cTnI. Previous findings identifying a group of seemingly healthy elderly men with very minor elevations of cTnI have shown that these men were at risk of premature cardiovascular death. Objectives. To study the association between cTnI concentrations and cardiovascular risk factors and subclinical cardiac and renal target organ damage in a community‐based sample of elderly men. Methods. Biomarkers reflecting glucose and lipid metabolism, renal function, cardiac function and inflammation were measured in the ULSAM study (n = 1205, mean age 71 years). The participants were placed in three subgroups based on the cTnI concentrations: a low group with cTnI <0.02?µg/L, an intermediate group with cTnI between 0.02 and 0.039?µg/L and a high group with cTnI >0.039?µg/L. Results. In the entire cohort of 71‐year‐old men, most markers of glucose and lipid metabolism, renal function, inflammation and NT‐proBNP were significantly related to the concentrations of cTnI, and most obviously in the high‐cTnI group. In subjects with no signs of CVD (cardiovascular disease), only levels of NT‐proBNP related to cTnI, and with the highest NT‐proBNP levels in the high‐cTnI group (p<0.01). A multiple regression analysis showed that NT‐proBNP was independently related to cTnI (p<0.001). Conclusions. Measurement of cardiac troponins with highly sensitive assays identifies those at risk of premature CVD death who have hitherto remained unrecognized. The associated elevations of NT‐proBNP in these participants support the fact that these elevations reflect ongoing pathological processes in the myocardium.     

Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure

Objective. The common C34T polymorphism in the AMP deaminase‐1 (AMPD1) gene results in an inactive enzyme in homozygotes for the mutated T allele. Some studies have shown an association of T allele with longer survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of this study was to assess genotype–phenotype correlations in such patients, with emphasis on components of the metabolic syndrome. Methods. Ninety‐seven patients with CAD without HF (CAD+ HF–) and 104 with HF (HF+) were genotyped by PCR‐RFLP. The genetic control group comprised 200 newborns. Results. No significant differences were found in the frequency of AMPD1 genotypes between the groups. In the CAD+ HF– group, the carriers of T allele compared to CC homozygotes had significantly lower values of waist circumference (89.5±8.5 versus 97.7±11.2?cm; p = 0.00029), waist/hip ratio (p = 0.0059) and BMI (p = 0.045). There was no diabetes or fasting glycaemia ?126?mg/dL in T carriers, while these features were present in 25?% of CC homozygotes (p = 0.0024). In the HF+ group, a tendency towards a lower prevalence of diabetes (20?% versus 41?%; p = 0.068) and significantly lower systolic blood pressure (p = 0.048) were observed in T allele carriers. Conclusions. C34T AMPD1 polymorphism may be associated with reduced frequency of obesity in CAD patients and of hyperglycaemia and diabetes in both CAD and HF patients. Morphometric parameters associated with adipose tissue distribution and parameters of glucose metabolism should be analysed as potential confounders in further studies on the role of polymorphisms of AMPD1 and other genes associated with AMP and adenosine metabolism in cardiovascular disease.     

D‐dimer as a predictor of the need for laparotomy in patients with unclear non‐traumatic acute abdomen. A preliminary study

Objective. The acute onset of intense abdominal pain requires rapid evaluation, and since D‐dimer level is reported to be useful in the diagnosis of patients with suspected acute superior mesenteric artery occlusion, our aim was to evaluate the value of D‐dimer testing in the diagnosis of acute surgical abdomen with no precise diagnosis. Material and methods. Between July 2004 and June 2006, 93 patients with acute abdomen who required surgical exploration without precise diagnosis were admitted to this prospective clinical study. After surgery, the patients were divided into two groups: group 1 (n = 52), patients who needed immediate laparotomy, and group 2 (n = 41), patients without the need for laparotomy. Blood samples were taken to analyse D‐dimer, white blood cell count and pH level. P‐values of <0.05 were considered statistically significant. Results. There was a positive correlation between the plasma D‐dimer level and leucocyte count. Leucocyte counts >16,800/mm³ (p<0.01) and D‐dimer levels >4.7?µg?FEU/mL were more sensitive (p<0.001). Sensitivity was 97.6?% and specificity 61.5?% for D‐dimer level, and 82.9?% and 42.3?%, respectively, for leucocyte count. Metabolic acidosis at admission was the most important factor for mortality (p<0.001). Conclusions. In a patient with acute abdomen without precise diagnosis, a D‐dimer level above the cut‐off value (4.7?µg fibrinogen equivalent units/mL) may be an indicator with high sensitivity for surgical pathology requiring laparotomy.     

Laparoendoscopic single-site nephrectomy for hemodialysis patients with dialysis-related renal tumors

Purpose: The purpose of this study is to assess the efficacy of laparoendoscopic single-site (LESS) nephrectomy in hemodialysis patients, we compared outcomes between LESS nephrectomy and conventional laparoendoscopic nephrectomy in hemodialysis patients with dialysis-related renal tumors.

Material and methods: A total of 16 hemodialysis patients who underwent LESS nephrectomy (LESS-N; n?=?8) or conventional laparoendoscopic nephrectomy (C-N; n?=?8) between November 2003 and July 2012 were retrospectively evaluated. Outcomes were compared between the two groups.

Results: Patient and tumor characteristics were similar between the LESS-N and C-N groups. The mean operative duration was longer in the LESS-N than in the C-N group (231.0?±?26.7?min versus 188.6?±?36.4?min; p?=?.025). The mean estimated blood loss was lower in the LESS-N compared with the C-N group (26.4?±?14.4?ml versus 65.6?±?45.2?ml; p?=?.047). Postoperative complications were observed in three cases, comprising one case of retroperitoneal hematoma in the LESS-N group and one case each of peritoneal hematoma and retroperitoneal abscess in the C-N group. Surgical scarring was minimal in the LESS-N group.

Conclusions: Although there is a little extension of the operating time, LESS nephrectomy in hemodialysis patients is a feasible procedure compared with the conventional method.     

Plasma beta-endorphin concentrations are increased in chronic obstructive pulmonary disease patients

Objective. Since fibroblast growth factor 19 (FGF‐19) is a potent metabolic regulator that influences glucose and lipid homeostasis, our aim was to develop an ELISA assay for measuring FGF‐19 in human serum and to investigate its concentrations in healthy volunteers and patients suffering from metabolic syndrome. Material and methods. A sandwich ELISA method was developed for quantitative determination of human FGF‐19 in serum samples. Blood pressure, waist circumference, FGF‐21 serum levels, serum cholesterol, triacylglycerols, HDL‐cholesterol, LDL‐cholesterol, insulin, glucose, adiponectin, uric acid, creatinine, hs‐CRP and calculated BMI and Quicki insulin sensitivity index were measured in 153 healthy volunteers and 66 persons with metabolic syndrome. Results. Neither sex nor age influenced FGF‐19 serum concentration in the healthy volunteers. Probands with metabolic syndrome had 65?% lower FGF‐19 serum values than the healthy ones (medians 158.6 versus 242.4?ng/L; p<0.01). FGF‐19 correlated with glucose (r = ?0.35, p<0.01), HDL (r = 0.24, p = 0.045), triacylglycerols (r = ?0.19, p = 0.05) and with a number of other risk facors for metabolic syndrome (r = ?0.28, p = 0.01). When adjusted to the concentrations of triacylglycerols, BMI and glucose, and finally to all data pertinent to FGF‐19 (according to correlation analysis), our data indicate that FGF‐19 is an independent marker of metabolic syndrome. Conclusions. The present study demonstrates the analytical properties of the ELISA FGF‐19 assay and its usefulness when studying the metabolic syndrome. Serum concentrations of FGF‐19 could be new key predictors of metabolic syndrome and thereby even a new negative risk factor of atherosclerosis.     

Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin II receptor

Objective. Little is known about the role of the renin–angiotensin–aldosterone system and the renal prostaglandins in modulating the renal vasoconstrictive and natriuretic effects of synthetic urodilatin (URO) in healthy humans. Material and methods. Twelve volunteers were pretreated in a randomized, single‐blind, crossover study with losartan 50?mg a day or placebo for 5 days. Another 12 healthy subjects received indomethacin 25?mg three times a day or placebo for 4 days and a single dose on day 5. All subjects received a URO infusion (15?ng kg^?1?min^?1) on day 5. Radioactive tracers and the lithium clearance technique were used. Results. The effective renal plasma flow (ERPF) decreased significantly during URO infusion: losartan pretreatment 573±63 to 461±76?mL/min versus placebo 540±89 to 432±90?mL/min. The urinary sodium excretion rate (UNa) increased significantly during URO infusion: losartan 335±115 to 502±134?umol/min (micromol/min) (UNa) versus placebo 386±142 to 476±137?umol/min (micromol/min) (UNa). In the indomethacin pretreated subjects, ERPF decreased significantly from 530±109 to 446±55?mL/min versus 533±89 to 449±69?mL/min in the placebo group. UNa increased significantly from 395±142 to 768±254?umol/min (micromol/min) (UNa) in the indomethacin group versus 282±117 to 552±242?umol/min (micromol/min) (UNa) in placebo. Conclusion. The renal vasoconstrictive and natriuretic effects of synthetic URO are not modified by sustained inhibition of the angiotensin II receptor or the cyclooxygenase in man in a sodium replete state.     

The influence of inspiratory muscle training on diaphragmatic mobility,pulmonary function and maximum respiratory pressures in morbidly obese individuals: a pilot study

Abstract

Purpose: To investigate whether 12 week inspiratory muscle training (IMT) has any impact on pulmonary function, maximum respiratory pressures and diaphragmatic mobility (DM) in morbidly obese subjects. Method: Thirty-one morbidly obese individuals were assessed. Volunteers were randomised into two groups. The IMT group (n?=?16) followed an IMT protocol for 12 weeks, with a training load of 30% of maximal inspiratory pressure (PImax). The control group (CG) (n?=?15) followed the same protocol but without inspiratory load. Results: A total of 14 subjects performed IMT for 12 weeks. Significant increases in PImax (?86.86?±??20.70?cmH₂O versus ?106.43?±??32.97?cmH₂O, p?<?0.05) and maximal voluntary ventilation (97.84?±?37.06?L/min versus 115.17?±?34.17?L/min, p?<?0.05) were observed in the IMT group when compared to baseline. However, only FIV₁ significantly differed between the IMT group and the CG after the 12 week protocol (3.35?±?0.96?L versus 2.22?±?1.07?L, respectively; p?<?0.05). No significant differences were found in DM after the IMT protocol was performed. Conclusion: IMT improved PImax and altered the FIV₁. These results suggest that the improvements in muscular respiratory efficiency were insufficient to mobilise the diaphragm and modify ventilation mechanics. Pre-operative IMT may be a valuable approach in obese patients for preventing post-operative pulmonary complications. http://clinicaltrials.org -- NCT01449643 -- The Influence of IMT on Diaphragmatic Mobility in Morbidly Obese.

• Implications for Rehabilitation Morbid Obesity

• Morbid obesity is a disabling condition that has a serious negative impact on lung function, respiratory muscle function and quality of life.

• Inspiratory Muscle Training (IMT) is a technique which aims to improve pulmonary expansion and to prevent post surgery complications on morbid obese individuals.

• This study shows significantly increased on maximal inspiratory pressure, maximal voluntary ventilation and promoted changes on spirometric variables after IMT.