PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients

Objectives

High-density lipoprotein (HDL) associated paraoxonase 1 (PON1) is an essential component of HDLs' capability to protect low-density lipoproteins (LDL) from oxidative modification and thus to limit the atherosclerotic process. The aim of the current study was to investigate the association between oxidative stress status, indices of inflammation and PON1 status parameters.

Design and methods

We determined the relationship between the oxidative stress status, inflammatory markers and PON1 status parameters in 261 middle-aged subjects: 156 coronary heart disease (CHD) patients and 105 CHD-free subjects (as the control group). The PON1 status involved PON1 activity measurements towards two substrates: paraoxon (POase activity) and diazoxon (DZOase activity) and subsequent PON1_Q192R activity phenotype determination.

Results

A statistically significant greater malondialdehyde (MDA) concentration in the RR phenotype subjects compared to QQ subjects within the CHD group was apparent (P < 0.05). Multiple linear regression analysis revealed an independent influence of plasmatic SOD activity (P < 0.05) on POase values and MDA (P < 0.01) and O₂⁻ (P < 0.05) on DZOase values. Involvement of inflammatory markers (fibrinogen and hsCRP) in the regression model did not hinder the influence of SOD and MDA on POase and DZOase activities, respectively.

Conclusions

Our CHD patients were in a state of oxidative stress, which was most evident in the RR phenotype group. The QQ phenotype group is associated with the lowest oxidative stress status level and also with a better capacity for anti-oxidative protection. Oxidative stress in CHD patients is maintained by systemic low-grade inflammation, which results in PON1 enzymatic activity exhaustion. Therefore, deeper investigation of an effective anti-oxidative and anti-inflammatory therapy should be necessary in order to increase anti-oxidative potency and improve PON1 status of CHD patients.     

Health-related quality of life in patients with coronary artery disease after coronary revascularization

The aim of this study was to investigate the quality of life (HRQoL) in coronary artery disease(CAD) patients, admitted for rehabilitation within 3 months after an acute coronary event, in relation to treatment strategy [conservative treatment without revascularization (WR), percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG)]. Methods: Overall 719 consecutive CAD patients were involved in the study: WR (n=170), PTCA (n=226), CABG (n=323). HRQoL was estimated using the SF-36 questionnaire for total QoL and its two dimensions for physical and mental health [physical and mental component scores (PCS, MCS)]. Sexual dysfunction was assessed using the ASEX scale. Results: Significantly higher PCS, MCS and total SF-36, but lower ASEX score, were found in men compared with women. The ASEX score was significantly affected by age. Significantly higher PCS was found in PTCA group compared with that of CABG group. In multivariate analysis a significant positive association was obtained between PCS/MCS and male sex, between regular exercise, hyperlipoproteinemia, and permanent stress. ASEX was significantly positively associated with the age, CHF and non smoking. Conclusion: The results of this study have demonstrated significantly better HRQoL in men, younger CAD patients, patients who underwent PTCA and in patients without self-reported exposition to stress.     

Severe cerebral aspergillosis after liver transplant

V. Leung, A. Stefanovic, D. Sheppard. Severe cerebral aspergillosis after liver transplant.
Transpl Infect Dis 2010: 12: 51–53. All rights reserved
Abstract: Cerebral aspergillosis is a rare complication of liver transplantation. We present the case of a 34-year-old woman with multiple brain lesions discovered 8 days after orthotopic liver transplant for autoimmune hepatitis. The epidemiology, differential diagnosis, diagnostic strategies, and management of cerebral aspergillosis are discussed.     

Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos

The development of effective antidotes against organophosphates such as dichlorvos has been a persistent challenge over the past decades. Therapy of organophosphate poisoning is based on the administration of atropine and oxime as standard antidotes. The present study was undertaken to evaluate the ability of sodium bicarbonate to improve protective effects of standard antidotes in rats poisoned with dichlorvos. The aim of this experiment was to establish the correlation between protective effects and biochemical parameters relevant for acid-base status. In order to examine the protective effect of both standard antidotes and their combinations, groups of experimental animals were poisoned subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These antidotes were administered either as single doses or in combinations. In the biochemical part of the experiments, rats were poisoned with dichlorvos 1.3 LD(50) (10.64 mg/kg) subcutaneously and immediately thereafter treated with atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as single doses or in combinations. Parameters relevant for acid-base status were measured 10 minutes after the administration of antidotes. The results of our study indicate that addition of sodium bicarbonate to standard antidotes significantly improves protective effects of atropine, obidoxime and trimedoxime. Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine.     

Anatomic analysis of the vascular network and vascular pedicle of the tensor fascia lata flap (angiographic and cadaver study)

Knowing the vascular network and properties of the vascular pedicle is of crucial importance for elevation of the tensor fascia lata (TFL) transpositional or free flap; therefore, the origin of the lateral circumflex femoral artery (LCFA), its diameter at the site of origin, the length of the vascular pedicle, the number of lateral branches, the number of terminal branches and the anastomosis of the LCFA ascending branch are of utmost importance for successful elevation and clinical application of this flap. The study was conducted on clinical (100 angiographic images of the femoral artery) and autopsy (48 preparations) material. The first part of the study comprised analysis of the angiographic images that were used to obtain the information on LCFA. The diameter of LCFA at its origin was measured to be 0.44 cm, while it was 0.33 cm at the origin of ascending branch. The mean value of the diameter at the bifurcation of the terminal branches of ascending branch (inside tensor fascia lata muscle) was 0.24 cm. It has been established that the vascular pedicle of the tensor fascia lata flap (ascending branch of LCFA) is anastomosed with the superior gluteal artery in all cases. Measurement of the tensor fascia lata muscle revealed an average length of 15.91 cm, width of 3.55 cm and thickness of 1.98 cm. Injection of colour-ink into the ascending branch LCFA that enters directly into the TFL muscle was used to measure the extent of the TFL flap vascularization and on the average, the TFL flap was 20.32 cm long and 16.57 cm wide while the surface was 17.52 cm³.     

Urinary creatinine excretion in children from families with Balkan endemic nephropathy: evidence for genetic predisposition to the disease

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease prevalent in Serbia, Bosnia, Croatia, Bulgaria and Romania. Genetic studies have supported the genetic predisposition to BEN, and some studies in Bulgaria and in the Kolubara region of Serbia have revealed abnormalities of the urinary tract in up to 46% of children from families with BEN. In the present study, urinary excretion of creatinine, an index of muscle mass, was studied in 703 healthy children from endemic and non-endemic areas around the South Morava River. The survey covered a three-year period, and the children were studied three times a year: in the spring, autumn and winter. A urine sample for the period corresponding to 7-10 a.m. was collected during each study period. Evidence has been presented that children from families with BEN excrete significantly less creatinine than those from families without BEN living in the same area, or than children living in villages outside the endemic region or in the city of Nis. This study supports the view that genetic predisposition to BEN is indicated by a smaller muscle mass, although the effect of living conditions and nutrition may also contribute to this.     

Balkan endemic nephropathy: a decreasing incidence of the disease

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease prevalent in Serbia, Bosnia, Croatia, Bulgaria and Romania. This study investigates the incidence of BEN patients on dialysis with end-stage kidney disease (ESKD), and BEN-associated mortality in endemic areas around the South Morava River in Serbia from 1978 to 1997. In the last 10 years a marked decrease in the incidence of ESRD and BEN-induced mortality has been documented in the region. This study shows a significantly decreased incidence of BEN in endemic areas in South Serbia. Since the effects of etiological agent(s) on renal function in children from families in endemic areas was demonstrated in the early nineties and the disease seems to have an endemic-epidemic profile, the possibility of another epidemic outbreak in the future cannot be excluded.     

The predictive value of 131I-hippurate clearance in the prognosis of acute renal failure

The aim of this investigation was to study the validity of the radionuclide methods in the estimation of kidney function, for prognosis and follow-up of acute renal failure (ARF). In thirty-one ARF patients, the evaluation of glomerular filtration rate (GFR) by 99mTc-DTPA clearance and effective renal plasma flow (ERPF) by 131 I-ortoiodohippurate (131I-OIH) clearance was performed within 7 days and after 6 months from ARF onset. All patients were divided in three groups according to 131I-OIH clearance values obtained within 7 days: group 1, under 150 mL/min; group 2, 150-250 mL/min; and group 3, over 250 mL/min. Seven days clearance values of both radiopharmaceuticals were found to be very low, however, GFR was found more severely impaired than ERPF. Clearance values obtained after 6 months demonstrated no recovery of renal function in the first group, partial recovery in the second and almost complete recovery in the third group. Patients with the lowest 131I-OIH clearance values at the ARF onset had no recovery of renal function, while in the other two groups recovery corresponded to initial 131I-OIH clearance values. In patients with ARF both, 99mTc-DTPA and 131I-OIH clearances were shown suitable for the follow up of renal function, however, only 131I-OIH clearance had a strong predictive prognostic value for renal function recovery in ARF.     

Planned Staged Reoperative Necrosectomy Using an Abdominal Zipper in the Treatment of Necrotizing Pancreatitis

Purpose The optimal operative treatment for severe necrotizing pancreatitis (SNP) still remains controversial. This article describes the operative approach with a planned staged necrosectomy using the “zipper” technique.Methods Between 1996 and 2000, 35 patients with SNP were treated with this approach. The patient demographics, etiology and severity of SNP, hospital course, and outcome were recorded and comparisons of several parameters were made between the patients who survived and those who died.Results Hospital mortality was 34%. A total of 16 fistulae developed in 11 patients (31%), recurrent intra-abdominal abscesses in 4 (11%), and hemorrhaging in 5 (14%). The patients who died compared with those who survived had a higher Acute Physiology and Chronic Health Evaluation (APACHE)-II score on admission (14.5 vs 9, P < 0.001), extrapancreatic extension of necrosis more often (100% vs 65%, P = 0.02), and developed postoperative hemorrhaging more often (33% vs 4%, P = 0.038). A multivariate logistic analysis revealed an APACHE-II score of >13 on admission (P = 0.018) and an extension of necrosis behind both paracolic gutters (P < 0.001) to both be prognostic factors for mortality.Conclusions Severe necrotizing pancreatitis still carries significant morbidity and mortality. This surgical approach facilitates the removal of all devitalized tissue and seems to decrease the incidence of recurrent intra-abdominal infection requiring reoperation. An APACHE-II score of ≥13 and an extension of necrosis behind both paracolic gutters was thus found to signify a worse outcome.