The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis

The one disease associated with the greatest morbidity and mortality in industrialized countries is coronary heart disease (CHD). High density lipoprotein (HDL) is one of the most important independent protective factors for the arteriosclerosis which underlies CHD. Paraoxonase 1 (PON1) is an enzyme that confers antioxidant properties to HDL. In vitro, PON1 hydrolyzes a large variety of endogenous or exogenous substrates, some of which are clearly involved in the progression of arteriosclerosis. A close relationship between PON1 deficiency and accelerated progression of arteriosclerosis has been found in animal models. Moreover, PON1 activity is reduced in high oxidative stress diseases such as CHD, dyslipoproteinemias, inflammatory processes, diabetes and certain neuropathies. Reduced PON1 enzyme activity is associated with several arteriosclerosis-related diseases. The most thoroughly studied genetic variant of PON1 is PON1-192, in which the R allele is associated with elevated paraoxonase activity. This allele, present in 24.8% of the Italian population, is found in up to 78.9% of the population of Ecuadorian Cayapa Indians. A metaanalysis of studies on the relationship between CHD and the R allele showed the latter to be an independent risk factor for this disease, with an odds ratio of 1.18 (95% confidence interval, 1.10-1.27). The PON1 enzyme is a potentially useful new qualitative indicator in addition to the well known reverse cholesterol transport capacity associated with high plasma levels of HDL.     

Transrectal ultrasonography: relationship with anorectal manometry, electromyography and sensitivity tests in irritable bowel syndrome

Irritable bowel syndrome is the most frequently diagnosed disorder in gastroenterology. It has been demonstrated with specialized motility studies that these patients compared to healthy subjects show changes in rectoanal electrical and mechanical activity and in rectoanal sensitivity. However, until now no report has been published on morphological alterations in the rectum or the internal anal sphincter. Twenty-five consecutive patients with irritable bowel syndrome (mean age 32, range 17–47 years; 24 females) were evaluated prospectively by transrectal ultrasonography, rectal sensitivity studies, and recordings of both electrical and mechanical activity of the distal rectum and internal anal sphincter during a 2-h interdigestive period. Ten healthy volunteers (mean age 34.5, range 19–50 years) served as a control group. Paired and non-paired Student's two-tailed t test and linear regression analysis were used. It was shown that muscle thickness of the rectum during rest (4.7±0.1 mm) was correlated neither with its rectal spike amplitude (0.73±0.1 mV) nor with rectal spike frequency (17.06±3.6 spike/2 h). In addition, the diameter of the internal anal sphincter (1.2±0.1 mm) was correlated neither with its resting pressure, nor with frequency (17.1±3.2/2 h), duration (14.9±1.5 s), or amplitude (14.1 ±1.9 mmHg), of inhibition of the spontaneous rectoanal inhibitory reflex. No correlation was found between ultrasonographic parameters and rectal distension variables (r=0.03). This study demonstrates for the first time morphological anorectal changes in patients with irritable bowel syndrome compared to healthy subjects, in addition to showing that morphological changes are independent of physiological ones. Therefore both transrectal ultrasonography to determine anorectal morphology and electromanometry to assess anorectal function are important measures in the evaluation of patients with irritable bowel syndrome. Accepted: 21 November 1997     

Hepatic hyper-vitaminosis A: importance of retinyl ester level determination

We report the case of a 32-year-old man with portal hypertension without cirrhosis due to chronic vitamin A intoxication. Portal hypertension revealed by oesophageal varice rupture progressively worsened and ascites occurred 5 years after the patient stopped vitamin A intake. Initially, serum retinyl palmitate concentration was increased whereas serum retinol concentration was normal. There was no hepatic fibrosis on light microscopic examination of liver biopsy specimens. Five years after the patient stopped excessive vitamin A intake, serum retinol and retinol-binding protein concentrations were below the normal range even though there was an increased hepatic retinyl ester content. This was attributed to the late development of peri-sinusoidal fibrosis. This case mainly shows the importance of retinyl ester level determination: serum retinyl palmitate should be measured immediately after intoxication and hepatic retinyl esters should be measured initially and particularly later. Indeed, later serum and hepatic retinol levels in chronic hyper-vitaminosis A may be normal and lead to under-estimation of liver vitamin A overload.     

Dynamic Left Ventricular Outflow Tract Obstruction During Myocardial Ischemia in Mitral Valve Prolapse Syndrome

Systolic anterior motion of the mitral valve (MV) with dynamic left ventricular (LV) outflow tract obstruction is a well known phenomenon in hypertrophic cardiomyopathy, or other forms of hyper-dynamic LV function associated with hypovolemic states, or LV hypertrophy. We report three patients with MV prolapse in the absence of the above predisposing factors, who developed an LV outflow dynamic gradient during acute transient myocardial ischemia. An interaction between structural abnormalities of the mitral apparatus and ischemia-dependent LV shape deformity most likely accounted for the outflow gradient.     

Overview of emerging pharmacologic agents for acute heart failure syndromes

BACKGROUND: Several therapies commonly used for the treatment of acute heart failure syndromes (AHFS) present some well-known limitations and have been associated with an early increase in the risk of death. There is, therefore, an unmet need for new pharmacologic agents for the early management of AHFS that may improve both short- and long-term outcomes. AIM: To review the recent evidence on emerging pharmacologic therapies in AHFS. METHODS: A systematic search of peer-reviewed publications was performed on MEDLINE, EMBASE and Clinical Trials.gov from January 1990 to August 2007. The results of unpublished or ongoing trials were obtained from presentations at national and international meetings and pharmaceutical industry releases. Bibliographies from these references were also reviewed, as were additional articles identified by content experts. RESULTS: Cumulative data from large studies and randomised trials suggest that therapies with innovative mechanisms of action may safely and effectively reduce pulmonary congestion or improve cardiac performance in AHFS patients. CONCLUSION: Some investigational agents for the management of AHFS are able to improve haemodynamics and/or clinical status. In spite of these promising findings, no new agent has demonstrated a clear benefit in terms of long-term clinical outcomes compared to placebo or conventional therapies.     

Toxigenic V. cholerae,V. parahaemolyticus,and V. vulnificus in oysters from the Gulf of Mexico and sold in Mexico City

Oysters can accumulate potentially pathogenic bacteria, such as Vibrio cholerae, V. parahaemolyticus, and V. vulnificus. The aim of this study was to detect the presence of these Vibrio species and their toxigenic variants in oysters from the Gulf of Mexico sold in Mexico City. Oyster samples were studied using traditional culture and molecular polymerase chain reaction analysis. V. cholerae was present in 30.4% of the samples and its toxigenic variant chxA+ in 26.1%. It was isolated only in deshelled oysters, mainly in the dry season. V. parahaemolyticus was present in 95.7% of the samples and the toxigenic variant was found in 17.4%. V. vulnificus was identified in 60.9% of the samples, 38% of which corresponded to the environmental genotype and 21.7% to the clinical genotype, mainly in the cold season. Consumption of the oysters analyzed poses health risks due to the presence of Vibrio species, especially in deshelled oysters.     

Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial

Introduction

Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study.

Methods

A case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes.

Results

In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB.

Conclusion

The use of TA attenuates the development of IR and VS after CPB.

Trial registration number

ISRCTN05718824.     

Increased urinary albumin excretion, insulin resistance, and related cardiovascular risk factors in patients with type 2 diabetes: evidence of a sex-specific association

OBJECTIVE: While the relevant role of insulin resistance in the pathogenesis of increased urinary albumin excretion (UAE) is well established in type 1 diabetes, its contribution in type 2 diabetes is controversial. Our aim was to investigate whether insulin resistance was associated with increased UAE in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 363 men and 349 women, aged 61 +/- 9 years, with a disease duration of 11 +/- 9 years and HbA(1c) levels of 8.6 +/- 2.0% were included. Insulin resistance was derived from the homeostasis model assessment of insulin resistance (HOMA(IR)), and UAE was derived from the albumin-to-creatinine ratio (ACR) defined as increased if the value was > or =2.5 mg/mmol in men and > or =3.5 mg/mmol in women. ACR was correlated with HOMA(IR) (r = 0.15, P = 0.0001), independently of age, disease duration, blood pressure, HbA(1c), triglycerides, waist circumference, and smoking. RESULTS: When the two sexes were investigated separately, a significant correlation between ACR and HOMA(IR) was reached in men (n = 363; r = 0.21, P = 0.0001) but not women (n = 349; r = 0.08, P = 0.14), suggesting that insulin resistance and sex may interact (P for interaction = 0.04) in determining UAE. When men were subgrouped into quartiles of HOMA(IR), those of the third and fourth quartile (i.e., the most insulin resistant) were at higher risk to have increased ACR than patients of the first quartile (third quartile: odds ratio 2.2 [95% CI 1.2-4.2], P = 0.01) (fourth quartile: 4.1 [2.2-7.9], P = 0.00002). Finally, ACR was significantly higher in men with two or more insulin resistance-related cardiovascular risk factors (i.e., abdominal obesity, dyslipidemia, and arterial hypertension) than in men with fewer than two insulin resistance-related cardiovascular risk factors (0.90 [0.2-115.1] vs. 1.56 [0.1-1367.6], respectively, P = 0.005). CONCLUSIONS: In type 2 diabetic patients, increased UAE is strongly associated with insulin resistance and related cardiovascular risk factors. This association seems to be stronger in men than in women.