Cu/Zn ratios are associated with nutritional status, oxidative stress, inflammation, and immune abnormalities in patients on peritoneal dialysis

Objectives

We evaluated the relationship of the plasma copper/zinc (Cu/Zn) ratio with nutritional status, inflammation, oxidative stress, and immune function in peritoneal dialysis patients.

Design and methods

Clinical and laboratory parameters were measured in patients (n = 45) and age- and sex-matched healthy individuals (n = 30).

Results

There were significant negative correlations of the Cu/Zn ratio with nutrition-related parameters (body mass index [BMI], creatinine, hemoglobin, and albumin) and antioxidant (vitamin C and E) levels and positive correlations of the Cu/Zn ratio with the levels of high sensitivity C-reactive protein (hs-CRP) and oxidation products (malondialdehyde [MDA] and protein carbonyl). The Cu/Zn ratio was negatively correlated with the percentages of B- and T-lymphocyte subsets and the ratio of CD4/CD8 antigens.

Conclusions

In peritoneal dialysis patients, elevated Cu/Zn ratios are associated with malnutrition, increased oxidative stress, inflammation, and disrupted immune status.     

Heavy metal levels in patients with ineffective erythropoiesis

Objectives

Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis.

Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis

Introduction

Circulating lipopolysaccharides released from bacteria may activate both neutrophils and monocytes. The activated neutrophils release myeloperoxidase (MPO), a specific enzyme with strong oxidative activity. The aim of this study was to evaluate MPO enzyme activity in plasma of critically ill patients and to check the hypothesis that these concentrations in plasma would be higher in sepsis and systemic inflammatory conditions, as neutrophils release their contents before proliferating in response to stress.

Material and Methods

Blood samples were collected from 105 critically ill patients admitted to the intensive care unit, consisting of those with systemic inflammatory response syndrome (n = 42), sepsis (n = 37), and septic shock (n = 26). Plasma MPO enzyme activity was determined by o-dianisidine-H₂O₂ method, modified for 96-well plates.

Results

The plasma MPO enzyme activity in sepsis patients was significantly higher than that in the control group (mean, 2.4 ± 1.8 in sepsis and 1.86 ± 1.2 nmol per milligram protein per 10 minutes in systemic inflammatory response syndrome vs 0.32 ± 0.11 nmol per milligram protein per 10 minutes in healthy controls). Mean plasma lactate levels in sepsis (7.8 ± 1.2 mmol/L) and shock patients (9.5 ± 1.2 mmol/L) and cytokines like tumor necrosis factor–α, interleukin-8, and interleukin-1β were simultaneously evaluated to establish onset of inflammation and sepsis. These results show that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO concentration.

Conclusion

The plasma MPO concentrations may be a marker of the neutrophil proliferation and severity of inflammation.     

Vitamin C Further Improves the Protective Effect of Glucagon-Like Peptide-1 on Acute Hypoglycemia-Induced Oxidative Stress,Inflammation, and Endothelial Dysfunction in Type 1 Diabetes

OBJECTIVE

To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1diabetes.

RESEARCH DESIGN AND METHODS

A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.

RESULTS

At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.

CONCLUSIONS

This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.Recent evidence suggests that hypoglycemia can be considered a new risk factor in favoring diabetes vascular complications (1). It has been reported that hypoglycemia produces endothelial dysfunction and inflammation (2,3), which are well-recognized pathogenic factors for vascular disease, particularly in diabetes (4). Oxidative stress is considered the key player in the pathogenesis of diabetes complications (5), and it has been suggested that hypoglycemia produces endothelial dysfunction and inflammation through oxidative stress generation both in vitro and in humans (2,3). However, clear evidence in humans is still lacking (6): particularly, what is still missed is the evidence that by using an antioxidant, the elevation of the markers of oxidative stress induced by hypoglycemia can be reversed.Recently, a possible beneficial effect of glucagon-like peptide 1 (GLP-1) analogs in the management of type 1 diabetes has been suggested (7,8). GLP-1 and its analogs, in addition to their insulin-tropic action in alleviating hyperglycemia, have beneficial effects in protecting progressive impairment of pancreatic β-cell function, preservation of β-cell mass, and suppression of glucagon secretion, gastric emptying, and appetite, all characteristics that could be beneficial for the management of type 1 diabetes (7,8).Apart from the well-documented incretin effect of GLP-1, its role in the cardiovascular system also arouses interest. GLP-1 effects on the cardiovascular system may include a direct action on the endothelium, where the presence of specific receptors for GLP-1 has been demonstrated (9). Consistently, GLP-1 has been demonstrated to improve endothelial function in diabetes (10,11), possibly increasing the antioxidant defenses of the endothelium (12) and decreasing oxidative stress generation (11). Recently, we have reported that in type 1 diabetes, during induced-hypoglycemia, GLP-1 can partially protect endothelial function and partially decrease the appearance of inflammation, reducing, concomitantly, the level of several markers of oxidative stress (13). However, it is worthy of interest that in type 2 diabetes, hyperglycemia induces an endothelial resistance to the action of GLP-1, oxidative stress being the mediator of such a phenomenon (11).The aim of this study was to test, in patients with type 1 diabetes, whether 1) the concomitant infusion of an antioxidant, vitamin C, can protect endothelial function and reduce the generation of oxidative stress and inflammation during acute induced-hypoglycemia and 2) the effects of GLP-1 and vitamin C on both endothelial dysfunction and oxidative stress induced by acute hypoglycemia were additive.     

Impact of residual renal function and HCV seropositivity on plasma CD40/CD40L system and oxidative status in haemodialysis patients

Objectives

We evaluated the impact of residual renal function (RRF) on oxidative stress (SOX) and CD40/CD40L system in haemodialysis (HD) patients.

Design and methods

We determined sCD40, sCD40L and SOX marker—Cu/Zn superoxide dismutase (Cu/Zn SOD) levels in HD patients with RRF, with anuria (A) and in healthy controls.

Results

sCD40 and Cu/Zn SOD plasma levels were higher in both groups of dialyzed patients compared to controls (all p < 0.001), and they were higher in A than in RRF patients (all p < 0.01). In RRF group, sCD40/sCD40L and Cu/Zn SOD were significantly higher in anti-HCV-seropositive (anti-HCV[+]) patients than in their anti-HCV[−] counterparts. This phenomenon was not observed in A group. Multiple regression analysis showed that Cu/Zn SOD, kt/V and low fibrinogen were the independent factors affecting sCD40 levels in the whole HD group.

Conclusions

The loss of RRF and HCV seropositivity increased plasma levels of sCD40/sCD40L and oxidative status in HD patients.     

Effect of laparoscopic sleeve gastrectomy on elevated C-reactive protein and atherogenic dyslipidemia in morbidly obese patients

Objectives

To examine the effect of weight loss by laparoscopic sleeve gastrectomy (LSG) on plasma hs-CRP and lipid profiles in morbidly obese patients.

Design and methods

A mean follow-up of 9 months in 37 patients.

Results

A mean weight loss of 35 kg decreased plasma hs-CRP, glucose, HbA1c, triglycerides, cholesterol, non-HDL-cholesterol, and increased HDL-cholesterol. The percentage reduction of BMI was significantly associated with changes in plasma hs-CRP.

Conclusions

Weight loss by LSG improves inflammation and dyslipidemia.     

Nutritional supplements and plasma antioxidants in childhood asthma

Objective

This study investigated the relationship of plasma antioxidants to airway inflammation and systemic oxidative stress in children suffering from atopic asthma with consideration of the intake of nutritional supplements.

Subjects and research methods

A total of 35 asthmatic children (AG) and 21 healthy controls (CG) participated in this study. Plasma levels of vitamins A and E, β-carotene, coenzyme Q10 and malondialdehyde (MDA) were analyzed with high-performance liquid chromatography (HPLC); the total antioxidant capacity (TAC) was measured photometrically, and selenium was determined by atomic absorption spectroscopy (AAS). The volume of fractionated exhaled nitric oxide (FeNO) was measured with the NIOX nitric oxide monitoring system.

Results

The plasma antioxidants vitamins A and E, selenium, and coenzyme Q10 but not β-carotene were significantly (p < 0.05) lower in asthmatics than in controls. Further, asthmatic children had significantly reduced plasma concentrations of TAC (p < 0.01), significantly enhanced levels of MDA (p < 0.001), and exhaled a significantly (p < 0.001) higher mean volume of FeNO than healthy children. Regular intake of supplements had a significant positive influence on plasma vitamin E (p < 0.01), selenium (p < 0.01), TAC (p < 0.05), MDA (p < 0.01), and FeNO (p < 0.01) in asthmatics but not in controls. Additionally, significant negative associations of vitamin E and MDA (AG: p < 0.01; CG: p < 0.05), and vitamin E and FeNO (AG: p < 0.05; CG: p > 0.05) were identified.

Conclusion

These results indicate that nutritional supplements beneficially modulate plasma antioxidants and thus might have a positive influence on systemic redox balance and subsequently, pulmonary inflammation in asthmatic children.     

Erythropoiesis versus inflammation in Hereditary Spherocytosis clinical outcome

Objectives

This study aimed to evaluate the relationship between erythropoiesis and inflammation, in Hereditary Spherocytosis (HS) clinical outcome.

Design and methods

We studied 26 controls and 82 HS patients presenting mild (n = 49) and severer (n = 33) HS forms. We evaluated plasma levels of EPO, sTfR, ferritin, iron, folic acid, vitamin B12, TNF-α, IFN-γ, elastase and lactoferrin; leukocyte and reticulocyte counts and RPI were determined.

Results

All HS patients showed significantly higher EPO, sTfR, reticulocytes and RPI but only mild HS presented normal hemoglobin levels; the positive significant correlations between EPO and sTfR, reticulocytes and RPI observed in mild HS were not observed in severer HS patients. HS patients presented with higher levels of neutrophils, TNF-α, IFN-γ, elastase, lactoferrin and ferritin.

Conclusions

Our data show HS as a disease linked to enhanced erythropoiesis that is disturbed in the more severe forms, to which inflammation may contribute, at least in part.     

Salsalate attenuates free fatty acid-induced microvascular and metabolic insulin resistance in humans

OBJECTIVE

Insulin recruits muscle microvasculature, thereby increasing endothelial exchange surface area. Free fatty acids (FFAs) cause insulin resistance by activating inhibitor of κB kinase β. Elevating plasma FFAs impairs insulin’s microvascular and metabolic actions in vivo. Whether salsalate, an anti-inflammatory agent, prevents FFA-induced microvascular and/or metabolic insulin resistance in humans is unknown.

RESEARCH DESIGN AND METHODS

Eleven healthy, young adults were studied three times in random order. After an overnight fast, on two occasions each subject received a 5-h systemic infusion of Intralipid ± salsalate pretreatment (50 mg/kg/day for 4 days). On the third occasion, saline replaced Intralipid. A 1 mU/kg/min euglycemic insulin clamp was superimposed over the last 2-h of each study. Skeletal and cardiac muscle microvascular blood volume (MBV), microvascular flow velocity (MFV), and microvascular blood flow (MBF) were determined before and after insulin infusion. Whole body glucose disposal rates were calculated from glucose infusion rates.

RESULTS

Insulin significantly increased skeletal and cardiac muscle MBV and MBF without affecting MFV. Lipid infusion abolished insulin-mediated microvascular recruitment in both skeletal and cardiac muscle and lowered insulin-stimulated whole body glucose disposal (P < 0.001). Salsalate treatment rescued insulin’s actions to recruit muscle microvasculature and improved insulin-stimulated whole body glucose disposal in the presence of high plasma FFAs.

CONCLUSIONS

High plasma concentrations of FFAs cause both microvascular and metabolic insulin resistance, which can be prevented or attenuated by salsalate treatment. Our data suggest that treatments aimed at inhibition of inflammatory response might help alleviate vascular insulin resistance and improve metabolic control in patients with diabetes.Insulin resistance and vascular dysfunction play key roles in the development of cardiovascular complications in patients with type 2 diabetes. Among many contributing factors, free fatty acids (FFAs) have been implicated as the key culprit. As major oxidative fuels for heart and resting muscle, plasma levels of FFAs are elevated in patients with diabetes and they induce insulin resistance, inflammation, and vascular dysfunction.In cultured endothelial cells (ECs), the inhibitor of κB kinase β (IKKβ) appears to be the common effector in FFA-mediated vascular insulin resistance and inflammation, as transfection of the ECs with a dominant negative IKKβ abrogates FFA-mediated insulin resistance, whereas overexpression of wild-type IKKβ recapitulates the effect of FFAs (1). IKKβ is a serine kinase that controls the activation of nuclear factor-κB and is a critical link between inflammation and insulin resistance (2–4). To date, evidence strongly suggests that FFAs induce inflammation, which contributes to the pathogenesis of insulin resistance and endothelial dysfunction in diabetes.We have previously shown that insulin at physiological concentrations potently increases microvascular recruitment in both cardiac (5,6) and skeletal muscle (6,7) in humans. Insulin’s vasodilatory effect appears to be mediated through the phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B/endothelial nitric oxide (NO) synthase (eNOS) pathway (8). This insulin-mediated microvascular recruitment is impaired in the presence of high plasma concentrations of FFAs (6,7,9). Whether inflammation is involved in this FFA-induced microvascular insulin resistance is not clear.In the current study, we examined the effect of salsalate, an anti-inflammatory agent that inhibits IKKβ, on lipid-induced microvascular and metabolic insulin resistance in healthy humans. Our results suggest that lipid likely induces microvascular and metabolic insulin resistance in humans via an inflammation-mediated mechanism, as salsalate treatment restored muscle microvascular insulin response, which was associated with decreased metabolic insulin resistance in the presence of high plasma concentrations of FFAs.     

Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients

Introduction

Cardio-renal syndromes are characterized by the impairment of cardiac and renal functions. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL), and plasma B-type natriuretic peptide (BNP) are markers of acute kidney injury (AKI) and heart failure (HF), respectively.The aim of this study was to assess the effect of the reduction of glomerular filtration rate (GFR) on plasma BNP and on plasma and urinary NGAL concentrations in stable chronic kidney disease (CKD) patients at different functional stages.

Methods

GFR (^99mTc-DTPA), plasma BNP, and plasma and urinary concentrations of NGAL were measured in 310 clinically stable CKD patients, at functional stages from 1 to 5. Serum and urinary low-molecular-weight proteins cystatin C and β2-microglobulin, and urinary tubular enzymes were measured for comparison. Plasma BNP, NGAL, cystatin C and β2-microglobulin were measured also in 31 maintenance hemodialysis patients.

Results

Plasma NGAL increased with the reduction of GFR in CKD patients from stage 2. In the different CKD stages modest differences were found for BNP values. Urinary NGAL increased slightly but significantly in patients at CKD stages 4 and 5, similarly to urinary cystatin C and β2-microglobulin. In maintenance hemodialysis patients, plasma NGAL and BNP were markedly increased, and high-flux hemodialysis significantly decreased their plasma concentrations.

Conclusions

Plasma NGAL increases markedly with the reduction in GFR, generating a very high number of false positive diagnoses of AKI in stable CKD patients. The grade of GFR impairment and the cause of kidney disease have a lower effect on urinary NGAL and on plasma BNP. In any case, specific reference values of NGAL and BNP should be used in chronic kidney disease patients, according to their functional stage, when assessing acute kidney injury, heart failure, and cardio-renal syndromes in patients with impaired GFR.     

Vitamin D Levels in Subjects With and Without Type 1 Diabetes Residing in a Solar Rich Environment

OBJECTIVE

Previous studies, largely in northern Europe, have suggested an association between type 1 diabetes and reduced serum 25-hydroxy(OH) vitamin D levels, a concept we tested in individuals residing in a solar-rich region (Florida).

RESEARCH DESIGN AND METHODS

Serum samples from 415 individuals residing in Florida were cross-sectionally analyzed: 153 control subjects, 46 new-onset type 1 diabetic patients, 110 established type 1 diabetic patients (samples ≥5 months from diagnosis), and 106 first-degree relatives of the diabetic patients.

RESULTS

In this study, 25-OH vitamin D levels (median, range, interquartile range [IQR]) were similar among control subjects (20.1, below detection [bd]–163.5, 13.0–37.4 ng/ml), new-onset type 1 diabetic patients (21.2, bd–48.6, 12.2–30.2 ng/ml), established type 1 diabetic patients (23.2, bd–263.8, 13.8–33.9 ng/ml), and first-degree relatives (22.2, bd–59.9, 12.7–33.1 ng/ml) (P = 0.87). Mean 25-OH vitamin D levels were less than the optimal World Health Organization level of 30 ng/ml in all study groups.

CONCLUSIONS

Reduced serum 25-OH vitamin D levels were not specifically associated with type 1 diabetes. The uniform suboptimal 225-OH vitamin D levels, despite residence in a zone with abundant sunshine, support additional dietary vitamin D fortification practices.The role for environment in the development of type 1 diabetes has remained elusive, with multiple factors purported to modulate risk for this disease (e.g., viruses, breast-feeding, age for cereal introduction, and childhood immunizations) (1,2). Further to this list is vitamin D levels (3), with previous studies suggesting type 1 diabetic patients had lower serum concentrations of this metabolite than healthy control subjects (4–6) as well as disease-associated polymorphisms in a vitamin D metabolism gene (7). Although certainly intriguing, we note the aforementioned studies were largely undertaken in northern European countries (4,5), whereas the one study performed in the U.S. failed to provide values among healthy control subjects and, hence, did not identify disease specificity (6). Therefore, we measured serum 25-hydroxy (OH) vitamin D levels from type 1 diabetic patients, their first-degree relatives, and healthy control subjects all residing in a solar-rich region (Florida).     

Prooxidant-anti-oxidant balance is not associated with extent of coronary artery disease

Objective

We have measured the pro-oxidant–antioxidant-balance (PAB) levels in patients with defined coronary artery disease (CAD) and compared them with concentrations in healthy subjects.

Design and methods

Based on angiography results, 400 patients with stable CAD were divided into CAD− and CAD+, this being further subcategorized into groups with single-, double- and triple-vessel disease (VD).

Results

The mean PAB values in the healthy subjects, was significantly lower than for other groups (P < 0.001). In CAD− patients, PAB levels were 123.2 ± 43.9, which was not statistically different compared to groups with SVD, 2VD and 3VD (P > 0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD were not significantly different among patients with SVD, 2VD and 3VD (P > 0.05).

Conclusions

In conclusion, we found higher levels of oxidative stress in CAD+ patients compared to healthy subjects. The oxidation level was not related to measures of the extent of CAD such as number of stenosed vessels.     

Elevated plasma matrix metalloproteinases and their tissue inhibitors in patients with severe sepsis

Purpose

Matrix metalloproteinases (MMPs) are essential for tissue remodeling. Our objectives were to determine (1) the concentrations of MMPs and their tissue inhibitors (TIMPs) in plasma obtained from patients with severe sepsis, (2) to correlate changes in MMP and TIMP levels with disease severity, and (3) to investigate recombinant activated protein C (rAPC) actions on plasma MMP2, 9 activities from severe sepsis patients.

Materials and methods

Matrix metalloproteinase and TIMP levels were quantified in plasma from patients with severe sepsis using antibody microarrays and gelatin zymography.

Results

Plasma MMPs (3, 7, 8, 9) and TIMPs (1, 2, 4) on microarray were increased in severe sepsis on intensive care unit (ICU) day 1, with more than 3-fold increases in MMP3, MMP7, MMP8, MMP9, and TIMP4. Latent forms of MMP2, 9 on zymography were increased in plasma from patients with severe sepsis, whereas only half of severe sepsis patients showed active MMP9. Elevated MMP7 and MMP9 on ICU days 1 and 3 negatively correlated with multiple organ dysfunctions. The temporal activity patterns of MMP2, 9 during 21 ICU days were not altered in patients treated with rAPC or by the addition of exogenous rAPC to plasma.

Conclusion

Most plasma MMPs and TIMPS were elevated in patients with severe sepsis, but only a limited subset of MMPs (7, 9) negatively correlated with disease severity. Recombinant activated protein C does not appear to directly alter MMP2, 9 activities.     

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

Introduction

Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress.

Methods

We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 μg, zinc 30 mg, vitamin C 1.1 g, and vitamin B₁ 100 mg) with a double-loading dose on days 1 and 2 or placebo.

Results

Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 ± 3.2 versus -4.2 ± 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).

Conclusion

The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.

Trials Registration

Clinical Trials.gov RCT Register: NCT00515736.     

Luminal concentrations of L- and D-lactate in the rectum may relate to severity of disease and outcome in septic patients

Introduction

Little is known about the condition of the large bowel in patients with sepsis. We have previously demonstrated increased concentrations of L-lactate in the rectal lumen in patients with abdominal septic shock. The present study was undertaken to assess the concentrations of L- and D-lactate in rectal lumen and plasma in septic patients including the possible relation to site of infection, severity of disease, and outcome.

Methods

An intensive care unit observational study was conducted at two university hospitals, and 23 septic patients and 11 healthy subjects were enrolled. Participants were subjected to rectal equilibrium dialysis, and concentrations of L- and D-lactate in dialysates and plasma were analysed by spectrophotometry.

Results

Luminal concentrations of L-lactate in rectum were related to the sequential organ failure assessment scores (R ² = 0.27, P = 0.01) and were higher in non-survivors compared to survivors and healthy subjects (mean [range] 5.0 [0.9 to 11.8] versus 2.2 [0.4 to 4.9] and 0.5 [0 to 1.6] mmol/l, respectively, P < 0.0001), with a positive linear trend (R ² = 0.53, P < 0.0001). Also, luminal concentrations of D-lactate were increased in non-survivors compared to survivors and healthy subjects (1.1 [0.3 to 2.5] versus 0.3 [0 to 1.2] and 0.1 [0 to 0.8] mmol/l, respectively, P = 0.01), with a positive linear trend (R ² = 0.14, P = 0.04). Luminal concentrations of L- and D-lactate were unaffected by the site of infection. Plasma concentrations of L-lactate were also increased in non-survivors compared to survivors (3.8 [1.7 to 7.0] versus 1.5 [0 to 3.6] mmol/l, P < 0.01). In contrast, plasma concentrations of D-lactate were equally raised in non-survivors (0.4 [0.1 to 0.7] mmol/l) and survivors (0.3 [0.1 to 0.6] mmol/l) compared with healthy subjects (0.03 [0 to 0.13] mmol/l).

Conclusion

In patients with severe sepsis and septic shock, luminal concentrations of L- and D-lactate in the rectum were related to severity of disease and outcome.     

Intermittent pneumatic compression for prevention of pulmonary thromboembolism after gynecologic surgery

Background

Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue.

Methods

A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis.

Results

Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue.

Conclusion

These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.     

Prediabetes and prehypertension in healthy adults are associated with low vitamin D levels

OBJECTIVE

To determine whether modest elevations of fasting serum glucose (FSG) and resting blood pressure (BP) in healthy adults are associated with differential serum vitamin D concentrations.

RESEARCH DESIGN AND METHODS

Disease-free adults in the National Health and Nutrition Examination Survey 2001–2006 were assessed. Prediabetes (PreDM) and prehypertension (PreHTN) were diagnosed using American Diabetes Association and Seventh Report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure criteria: FSG 100–125 mg/dL and systolic BP 120–139 mmHg and/or diastolic BP 80–89 mmHg. Logistic regression was used to assess the effects of low vitamin D levels on the odds for PreDM and PreHTN in asymptomatic adults (n = 1,711).

RESULTS

The odds ratio for comorbid PreDM and PreHTN in Caucasian men (n = 898) and women (n = 813) was 2.41 (P < 0.0001) with vitamin D levels ≤76.3 versus >76.3 nmol/L after adjusting for age, sex, and BMI.

CONCLUSIONS

This study strengthens the plausibility that low serum vitamin D levels elevate the risk for early-stage diabetes (PreDM) and hypertension (PreHTN).The link between low serum vitamin D concentrations and abnormal bone and calcium metabolism has been known for many years. The adverse associations between low vitamin D concentrations and metabolic syndrome (1), diabetes mellitus (2), hypertension (3), cardiovascular health (4), cardiovascular, and all-cause mortality (5) have also been identified. Vitamin D concentrations have an inverse relationship with circulating renin and angiotensin II, suggesting a mechanism for elevation of blood pressure (BP) (6). Moreover, dietary supplementation with vitamin D seems to reduce blood glucose and BP. The relationship between serum vitamin D and fasting serum glucose (FSG) and resting BP, specifically prediabetes (PreDM) and prehypertension (PreHTN), in healthy disease-free adults, however, is unknown.     

Copeptin is a predictive biomarker of severity in acute pancreatitis

Background

Acute pancreatitis remains a common intraabdominal disease with a complex pathophysiology. The overall outcome has improved, but specific treatment remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of copeptin in the initial phase of predicted severe acute pancreatitis.

Methods

Between August 2008 and December 2011, 57 patients with acute pancreatitis and 30 healthy individuals were included in the study. Four blood samples, for serum copeptin measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent 3 samples were taken at 12, 24, and 48 hours after the onset of pain.

Results

Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.

Conclusions

Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.     

Increased plasma levels of CATS mRNA but not CATB mRNA in patients with coronary atherosclerosis

Background

We hypothesized that patients with coronary atherosclerosis have increased plasma levels of cathepsin S (CATS) and cathepsin B (CATB) mRNA, the genes that are involved in atherosclerotic plaque development and destabilization.

Methods

mRNAs were isolated from plasma of 67 patients with coronary atherosclerosis (29 with stable angina, 38 with acute coronary syndrome) and 33 healthy subjects as controls, transcribed to cDNA and quantified by real-time PCR.

Results

Plasma levels were successfully measured in all samples. Patients with coronary atherosclerosis had 2.75 times higher plasma levels of CATS mRNA than controls (median 6.10 vs. 2.22; p < 0.001). No difference was observed in CATB mRNA levels (median 5.62 vs. 6.19; p = 0.866). Patients on therapy with statins and aspirin tended to have higher plasma levels of CATS mRNA than patients without statins and aspirin (median 6.41 vs. 4.27; p = 0.028).

Conclusions

Further evaluation of plasma CATS mRNA levels in patients with coronary atherosclerosis is reasonable.