Body mass index is associated with interleukin-1, adiponectin, oxidative stress and ioduria levels in healthy adults.

BACKGROUND: iodine contributes to maintain the balance of the reduced and oxidized species and is also required for thyroid hormones synthesis as triiodothyronine (T3), which regulates energy metabolism in adults. Increased body mass index (BMI) is associated with inflammatory markers, oxidative stress, and abnormalities in adipocytokines secretions that are associated with obesity and chronic disease. OBJECTIVE: the aim of the study is to investigate the association between ioduria, oxidative stress, total antioxidant status, adiponectin and interleukin-1 (IL-1) with BMI in healthy adults. METHODS: a cross-sectional study was performed in 114 healthy adult volunteers, aged 25-44 years, divided according to their BMI in three groups: normal weight (BMI < 25), overweight (BMI ≤ 25 to < 30), obesity (BMI ≥ 30). Adiponectin and IL-1 were measured by immune-enzymatic assays; oxidative stress, by determination of malondialdehyde (MDA); and total antioxidant status (TAS) and ioduria were measured by colorimetric assays. Statistical association was done by Spearman's test. RESULTS: overweight and obese subjects have higher serum levels of MDA, TAS and IL-1 vs normal weight subjects. Moreover, overweight and obese subjects have lower levels of iodine and adiponectin vs normal weight subjects. MDA was positively related only with obese subjects (r = 0.787, p = 0.008) and TAS with overweight (r = 0.398, p = 0.049) and obese subjects (r = 0.448, p = 0.030). In contrast, a reverse correlation with ioduria was found in obese subjects (r = 0.463, p = 0.001). Adiponectin was negatively related only in obese subjects (r = -0.477, p = 0.001), while, IL-1 was positively related with the increase of BMI (overweight r = 0.287, p = 0.050; and obesity r = 0.515, p = 0.006). CONCLUSION: alteration in IL-1, adiponectin and oxidative stress levels were found to be related to overweight and obesity; also, iodine levels decreased when BMI increased, contributing to loss of redox equilibrium. All this data may play an important role in etiopathogenesis of chronic disease related to the increase of BMI.

Assessment of Serum Level of Interleukin-37 in Asthmatic Children at Benha University Hospital.

Asthma is a complex inflammatory disease, characterized by airway hyperresponsiveness, inflammation, and reversible airway obstruction. Interleukin-37 (IL-37), functions as a fundamental inhibitor of innate inflammatory and immune responses, and it is an important cytokine in the control of asthma by suppressing the production of inflammatory cytokines. This study aimed to reveal the possible role of IL-37 in asthma through assessment of its serum level in controlled and uncontrolled asthmatic children as compared to controls. Serum IL-37 level was measured by ELISA. The serum level of IL-37 was significantly lower in patients than controls and in uncontrolled than in controlled asthma (P < 0.001). It is concluded that there is negative relation between serum level of IL-37 and asthma, which is more evident in uncontrolled asthmatic group, this observation may support the protective role of IL-37 in immune pathogenesis of asthma.

[ASSESSMENT OF POSTOPERATIVE PAIN SYNDROME AT SINGLE-PORT TRANSUMBILICAL LAPAROSCOPIC CHOLECYSTECTOMY COMPARED TO TRADITIONAL LAPAROSCOPIC CHOLECYSTECTOMY].

The article analyzes the dynamics of postoperative pain at single-port transumbilical laparoscopic cholecystectomy compared to traditional laparoscopic cholecystectomy. It is shown that the intensity of pain in patients who have undergone laparoscopic procedures through a single transumbilical access was significantly less than in patients with traditional laparoscopic intervention. Furthermore, the use of a single-port transumbilical laparoscopic cholecystectomy accompanied by a smaller increase in the concentration of proinflammatory cytokines compared with patients who had laparoscopic procedures through four trocar accesses.

Development and assessment of a complete-detoxication strategy for Fuzi (lateral root of Aconitum carmichaeli) and its application in rheumatoid arthritis therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi (lateral root of Aconitum carmichaeli) is a popular traditional Chinese medicine well known for its both therapeutic and high-toxic activities. Its toxic alkaloid ingredients, mainly aconitine, mesaconitine, and hypaconitine, are responsible for the high toxicity. However, to date, no detoxication strategy is available to completely eliminate Fuzi's toxicity, and, whether Fuzi's efficacy could be kept after detoxication, remain unknown and debatable. MATERIALS AND METHODS: The purpose of this study was to establish and validate a complete-detoxication strategy for Fuzi via acute toxicity test, to clarify the detoxication mechanism by HPLC and titrimetric analyses, and to evaluate the therapeutic effect of detoxicated Fuzi on adjuvant arthritis (AA). Three processed Fuzi (Bai-fu-pian) with 30-min, 60-min, and 120-min decoctions, respectively, named dBfp-30, dBfp-60, and dBfp-120, were prepared for this study. For the acute toxicity test, their oral doses to male and female Kunming mice were up to 70-190g/kg body weight, and their toxicological profiles were evaluated by median lethal dose (LD50), maximal tolerance dose (MTD), minimal lethal dose (MLD), no-observed-adverse-effect-level (NOAEL), and time-concentration-mortality (TCM) modeling methods using a 14-day schedule with up to five doses. The HPLC analysis was performed to determine the detoxication-induced changes in composition and amount of aconitine, mesaconitine and hypaconitine in Fuzi, whilst the titrimetric method was adopted to estimate the amount changes of Fuzi's total alkaloids. AA model was established by incomplete Freund's adjuvant injection in Wistar rats, and the animal's physiological (body weight, food intake, etc.), clinical (hind paw volume), and immunological (IL-1 and TNF-α) parameters were assessed as markers of inflammation and arthritis. RESULTS: With increasing decoction time, the acute toxicity of detoxicated Fuzi became decreased in the following order: dBfp-30 (LD50 of 145.1g/kg; MTD of 70g/kg; MLD of 100g/kg; NOAEL of 70g/kg) >dBfp-60 (too large LD50; MTD of 160g/kg; MLD of 190g/kg; NOAEL of 100g/kg) >dBfp-120 (no LD50; unlimited MTD; unlimited MLD; NOAEL of 130g/kg). dBfp-30 and dBfp-60 displayed the toxicity at a dose-dependent manner with maximum mortalities reaching 100% and 50% respectively, whereas no mortality or signs of intoxication was induced by dBfp-120. The chemical analyses revealed a dramatic reduction of the toxic alkaloids as well as total alkaloids in Fuzi after the detoxication, from which no level of aconitine and only minimum residual of mesaconitine (0.56±0.02µg/g) and hypaconitine (8.73±0.13µg/g) were detected in dBfp-120. However, no significant difference of total alkaloid amount was found among dBfp-30, dBfp-60, and dBfp-120 (P>0.05), suggesting an equivalent conversion from toxic alkaloids to its non-toxic derivants in dBfp-120. Further, also no significant differences were seen among dBfp-30, dBfp-60, and dBfp-120 for the therapeutic effects on physiological, clinical, and immunological parameters in AA rat, indicating that dBfp-120 is of non-toxicity and efficacy. CONCLUSIONS: A complete-detoxication strategy has been developed successfully for ensuring the safe and effective use of Fuzi. The detoxication mechanism associated with elimination of toxic alkaloids has kept Fuzi's efficacy, indicating a non-interdependent relationship between its efficacy and toxicity. This is the first report on such an optimal detoxication strategy and on the application of detoxicated Fuzi in AA. It may provide in depth understanding to the toxicological and pharmacological profiles of Fuzi and further benefit the herbal drug development with safety and efficacy for disease especially RA therapy.

Peritonitis from perforated appendicitis: stress response after laparoscopic or open treatment.

Elevated intra-abdominal pressure during laparoscopy may promote systemic inflammatory response. In patients with generalized peritonitis from perforated appendicitis, we sought to compare acute phase response and immunologic status from laparoscopic and open approach. One hundred and forty-seven consecutive patients underwent appendectomy for perforated appendicitis (73 patients had laparoscopic appendectomy and 74 patients had open appendectomy. Bacteremia, endotoxemia, white blood cells, peripheral lymphocytes subpopulation, human leukocyte antigen-DR (HLA-DR), neutrophil-elastase, interleukin-1 and 6 (IL-1 and 6), and C-reactive protein were investigated. One hour after intervention, bacteremia was significantly higher in the open group compared with the laparoscopic group (P < 0.05). A significantly higher concentration of systemic endotoxin was detected intraoperatively in the open group of patients in comparison with the laparoscopic group (P < 0.05). Laparotomy caused a significant increase in neutrophil concentration, neutrophil-elastase, IL-1 and 6, and C-reactive protein and a decrease of HLA-DR. We recorded 6 cases (8.1%) of intra-abdominal abscess in the open group and one (1.3%) in the laparoscopic group (P < 0.05). Open appendectomy, in case of peritonitis, increased the incidence of bacteremia, endotoxemia, and systemic inflammation compared with laparoscopic appendectomy. Early enhanced postoperative systemic inflammation may cause lower transient immunologic defense after laparotomy (decrease of HLA-DR), leading to enhanced sepsis in these patients.

Assessment of serum IL-1, IL-2 and IFN-γ levels in untreated pulmonary tuberculosis patients: role in pathogenesis.

BACKGROUND AND AIMS: Tuberculosis (Tb) infection is controlled by cell-mediated immunity through mediation of IL-1, IL-2 and IFN-γ. In this study IL-1, IL-2 and IFN-γ were determined in serum samples of untreated pulmonary Tb and control group including apparently healthy individuals or contacts and normal healthy blood donors with an objective of understanding defect(s), if any, in synthesis of any of these cytokines that may lead to a diseased state of Tb. METHODS: IL-1, IL-2 and IFN-γ were measured in serum samples of untreated Tb patients (n=33), contacts (n=19) and healthy individuals (n=20) by commercially available monoclonal antibody-based ELISA. RESULTS: Statistically significant differences in IL-1 and IFN-γ concentrations between groups of pulmonary Tb and controls were observed, whereas no significant difference in IL-2 was seen. CONCLUSIONS: In the present study, increased levels of cytokines in patients with pulmonary Tb are indicative of Th1 response. An increased level of cytokine (IFN-γ) in patients with untreated pulmonary Tb appears to be functionally defective.

The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy.

BACKGROUND: Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability. METHODS: In a prospective randomized double-blinded factorially designed study of T3 and MP therapy, we measured serum levels of interleukin-1 and -6 (IL-1 and IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein, and procalcitonin (PCT) levels in 79 potential heart or lung donors. Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and +/-hormone treatment. Donors were assigned to receive T3, MP, both drugs, or placebo. RESULTS: Initial IL-1 was elevated in 16% donors, IL-6 in 100%, TNF-alpha in 28%, CRP in 98%, and PCT in 87%. Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change. Both PCT (P =0.02) and TNF-alpha (P =0.044) levels were higher in donor hearts with marginal hemodynamics at initial assessment. Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng x mL(-1) may attenuate any improvement in cardiac index gained by donor management. No differences were observed between initially marginal and nonmarginal donor lungs. A PCT level less than or equal to 2 ng x mL(-1) but not other biomarkers predicted transplant suitability following management. CONCLUSIONS: There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction.

[Cardiovascular assessment of non diabetic patients on hemodialysis]. / Evolución del compromiso cardiovascular de pacientes insuficientes renales, en hemodiálisis, sin bloqueo del eje renina-angiotensina.

BACKGROUND: Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. AIM: To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. PATIENTS AND METHODS: Seventy five non diabetic patients aged 55.6 +/- 17 years (48 males), receiving hemodialysis three times a week were evaluated with laboratory tests, echocardiogram anda carotid ultrasound. In 26 patients, interleukin 6, tumor necrosis factor alpha, and intercellular adhesión molecule (ICAM-1) were also measured. Patients were followed during two years. RESULTS: The mean lapse of dialysis therapy was 6.5 +/-5 years. The main cause of renal failure was hypertension. Sixty two percent had systolic hypertension, 86% had concentric left ventricular hypertrophy, 43% had atrial dilatation and 60% had calcifications in the thoracic aorta. Compared with normal controls, patients had higher levels of interleukin 6, tumor necrosis factor alpha and ICAM-1. Carotid media thickness was also higher and increased in the two years of follow up. No correlations were found between ventricular hypertrophy and dialysis lapse, packed red cell volume, calcium phosphorus product, parathormone levels or median arterial pressure. No cardiovascular events were recorded during the follow up period. CONCLUSIONS: Non diabetic patients on chronic hemodialysis have a high frequency of ventricular hypertrophy, carotid media thickening, aortic calcifications and an increase in proinflammatory cytokines.

Evolución del compromiso cardiovascular de pacientes insuficientes renales, en hemodiálisis, sin bloqueo del eje renina-angiotensina / Cardiovascular assessment of non diabetic patients on hemodialysis

Background: Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. Aim: To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and methods: Seventy five non diabetic patients aged 55.6 ± 17 years (48 males), receiving hemodialysis three times a week were evaluated with laboratory tests, echocardiogram anda carotid ultrasound. In 26 patients, interleukin 6, tumor necrosis factor alpha, and intercellular adhesión molecule (ICAM-1) were also measured. Patients were followed during two years. Results: The mean lapse of dialysis therapy was 6.5 ±5 years. The main cause of renal failure was hypertension. Sixty two percent had systolic hypertension, 86 percent had concentric left ventricular hypertrophy, 43 percent had atrial dilatation and 60 percent had calcifications in the thoracic aorta. Compared with normal controls, patients had higher levels of interleukin 6, tumor necrosis factor alpha and ICAM-1. Carotid media thickness was also higher and increased in the two years of follow up. No correlations were found between ventricular hypertrophy and dialysis lapse, packed red cell volume, calcium phosphorus product, parathormone levels or median arterial pressure. No cardiovascular events were recorded during the follow up period. Conclusions: Non diabetic patients on chronic hemodialysis have a high frequency of ventricular hypertrophy, carotid media thickening, aortic calcifications and an increase in proinflammatory cytokines.

Biomarkers and health-related quality of life in end-stage renal disease: a systematic review.

BACKGROUND AND OBJECTIVES: Health-related quality of life (HRQOL) predicts mortality in ESRD, yet adoption of HRQOL monitoring is not widespread, and regulatory authorities remain predominantly concerned with monitoring traditional biologic parameters. To assist with future efforts to adopt HRQOL monitoring while acknowledging the importance of biomarkers, this study sought to establish which domains of HRQOL are most affected by ESRD and to measure the strength of evidence linking common biomarkers to HRQOL in ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review was performed to identify studies that measured HRQOL in ESRD. Data were abstracted according to a conceptual model regarding the measurement of HRQOL differences, and HRQOL data were converted to weighted mean effect sizes and correlation coefficients. RESULTS: The impact of ESRD was largest in the Short Form 36 domains of physical functioning (e.g., role-physical, vitality) and smallest in mental functioning (e.g., mental health, role-emotional). Dialysis adequacy, as measured by Kt/V, was a poor correlate for Short Form 36 scores. Similarly, mineral metabolism (e.g., calcium x phosphorous, parathyroid hormone) and inflammatory (e.g., C-reactive protein, TNF) biomarkers had small effect sizes and correlations with HRQOL. In contrast, hematocrit demonstrated small to moderate relationships with mental and physical HRQOL, and nutritional biomarkers (e.g., albumin, creatinine, body mass index) demonstrated moderate to large relationships. CONCLUSIONS: HRQOL in ESRD is most affected in the physical domains, and nutritional biomarkers are most closely associated with these domains. In contrast, Kt/V, mineral metabolism indices, and inflammatory markers are poor HRQOL correlates.

A global assessment of the inflammatory response elicited upon open abdominal aortic aneurysm repair.

The inflammatory response during elective open infrarenal abdominal aortic aneurysm repair and its impact on outcome is investigated. Twenty high-risk patients were enrolled, and blood samples were obtained at 8 perioperative time points. Endotoxin, cytokines (tumor necrosis factor-alpha and interleukin-1beta, and interleukin-6), CD11b expression, and nitric oxide were measured. Peak endotoxin levels occurred within 30 minutes of reperfusion and were higher among patients developing complications. Interleukin-6 levels increased during reperfusion, reaching a peak on the first postoperative day. Interleukin-6 increase correlated with aortic clamp time and morbidity. CD11b expression increased 30 minutes after reperfusion, and this effect was greater among patients who developed complications. Endotoxin may be important in the pathogenesis of multiple organ dysfunction syndrome. Activated neutrophils may have a central role in tissue injury after reperfusion. Intraoperative CD11b upregulation may be an early marker for postoperative complications after infrarenal abdominal aortic aneurysm repair.

[Pharmacotherapeutic assessment of antiosteoporotic properties of alpha-calcidol in chronic obstructive pulmonary disease].

AIM: To evaluate antiresorptive properties of alphacalcidol in the treatment of osteopenic syndrome in patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: A total of 94 COPD patients with low densitometric indices were studied for bone densitometric parameters, calcium-phosphorus metabolism, markers of bone tissue metabolism (osteocalcine-OC, tartrate-resistent acid phosphatase--TRAP, beta CrossLaps - BCL), cytokine profile in the course of 6-month continuous therapy with alpha-calcidol (alpha-D3-TEVA) in a dose 0.75-1 mcg/day. RESULTS: Six-month treatment with alpha-calcidol relieved pain, increased bone densitometric parameters, normalized calcium-phosphorus metabolism. While 3-month therapy induced positive dynamics in markers of bone metabolism (OC level increased, concentrations of BCL, TRAP reduced), 6-month therapy resulted in these parameters normalization close to the level of healthy persons. Proinflammatory cytokines (IL-1beta, IL-6 TNF-alpha) in COPD lowered significantly. CONCLUSION: Alpha-calcidol have analgetic, antiresorptive and immunomodulating effects which make this drug effective in prevention and pathogenetic therapy of osteopenic syndrome in COPD.

Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on adipogenesis, food intake, and energy expenditure.

Interleukin (IL)-1 is a regulator of inflammation but is also implicated in the control of energy homeostasis. Because the soluble IL-1 receptor antagonist (IL-1Ra) is markedly increased in the serum of obese patients and is overexpressed in white adipose tissue in obesity, we studied the metabolic consequences of genetic IL-1Ra ablation in mice. We have shown that IL-1Ra-/- mice have a lean phenotype due to decreased fat mass, related to a defect in adipogenesis and increased energy expenditure. The adipocytes were smaller in these animals, and the expression of genes involved in adipogenesis was reduced. Energy expenditure as measured by indirect calorimetry was elevated, and weight loss in response to a 24-h fast was increased in IL-1Ra-/- animals compared with wild-type mice. Lipid oxidation of IL-1Ra-/- mice was higher during the light period, reflecting their reduction in diurnal food intake. Interestingly, IL-1Ra-/- and IL-1Ra+/- mice presented an attenuation in high-fat diet-induced caloric hyperphagia, indicating a better adaptation to hypercaloric alimentation, which is in line with the role of IL-1Ra as a mediator of leptin resistance. Taken together, we show that IL-1Ra is an important regulator of adipogenesis, food intake, and energy expenditure.

Degeneration of intervertebral discs due to smoking: experimental assessment in a rat-smoking model.

We have investigated the intervertebral discs of rat-smoking models to demonstrate that smoking is a cause of degenerative intervertebral disc disease. A smoking box was developed for this study. We exposed 8-week-old rats to indirect tobacco smoke inhalation. Each rat was forced to inhale the smoke from one cigarette per hour. The mean blood nicotine level of rodents exposed to cigarette smoke corresponds to about twice that of ordinary human smokers. Histological and immunological studies were then performed to assess the effects of smoking for varying periods of time. After 8 weeks, the chondrocytes in the disordered annulus fibrosus layer tended to grow larger and attain a rounder form than normal chondrocytes. The interleukin-1beta level in the 8-week smoking group was significantly higher than that of the control group. Tobacco smoke inhalation increased local production and release of inflammatory cytokines and resultant decomposition of chondrocyte activity.

Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men.

Although catastrophic weight loss is no longer common in HIV-infected men, we hypothesized that a more gradual process of cachexia [loss of lean body mass (LBM) without severe weight loss, often accompanied by elevated resting energy expenditure (REE)] is still common and is driven by excessive production of the catabolic cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). We performed a longitudinal analysis of an ongoing cohort study of nutritional status in 172 men with HIV infection. LBM loss of >1 kg occurred in 35% of the cohort, and LBM loss of >5% occurred in 12.2% over 8 mo of observation, but classical wasting (loss of approximately 10% of weight) was rare (2%). Both TNF-alpha (-150 g LBM. ng(-1) x ml(-1), P < 0.02) and IL-1 beta production (-130 g LBM x ng(-1) x ml(-1), P < 0.01) by peripheral blood mononuclear cells predicted loss of LBM. A rise in REE of >200 kcal/day was found in 17.7% of the subjects regardless of weight change. IL-1 beta (+9 kcal/day per ng/ml, P < 0.002) and TNF-alpha (+10 kcal/day per ng/ml, P < 0.02) production predicted Delta REE. Serum free testosterone was inversely associated with TNF-alpha production and was not an independent predictor of either Delta LBM or Delta REE after adjustment for cytokine production. Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism.

Novel online infusate-assisted dialysis system performs microbiologically safely.

Administration of adequate amounts of commercial infusion fluids renders modern convective dialysis modalities, such as hemodiafiltration, labor-intensive and costly. Preparation of infusate by cold sterilization of dialysis fluid, which is abundantly available, and its immediate (online) use, in contrast, enables a large volume fluid exchange in a cost-effective manner. Recent developments aimed at more hygienic and user-friendly online systems with increased operational flexibility. As a result the novel ONLINEplus system does not only provide online prepared infusate for convective dialysis therapy, but also for priming and rinsing of the extracorporeal blood circuit, for intradialytic bolus administration, and for re-infusion of patients' blood as well. Production of infusate from potentially impure dialysis fluid containing endotoxins and other pyrogens raises severe concerns of affecting the patients' well-being. To assess its safety, the online system was challenged with microbially contaminated dialysis fluid. Despite high levels of microbial counts (7.5 x 104 +/- 105 CFU/ml), endotoxin concentration (14.1 +/- 7.7 IU/ml and 9.265 +/- 3.000 IU/ml, as measured turbidimetrically and chromogenically, respectively) and cytokine-inducing activity (20,827 +/- 3,082 pg IL-1Ra/Mio WBC), we failed to detect contaminants in the final infusate during a 5 week laboratory testing period. In addition, infusate samples complied consistently with the European Pharmacopeia test for sterility. The present online system is comprehensive, operates user-friendly, and provides microbiologically safe infusate in large quantities. In this way, both patients and dialysis staff will benefit from improved dialysis therapy and reduced treatment-related labor burden, respectively. Moreover, convective dialysis modalities will become less expensive.

Increased resting energy expenditure is related to plasma TNF-alpha concentration in stable COPD patients.

UNLABELLED: The objective of this study was to test whether increased resting energy expenditure (REE) in chronic obstructive pulmonary disease (COPD) patients is related to increased cost of breathing and/or to increased cytokine production. In 36 non-inflammatory (CRP: 17.6 +/- 13.1 mg.l(-1), mean +/- SD; orosomucoid: 0.71 +/- 0.18 g.l(-1)), non-malnourished (BMI: 23.6 +/- 4.3 kg.m(-2)), clinically stable, non severely hypoxic COPD patients (60.5 +/- 8.9 years) we measured REE, pulmonary function and plasma cytokine concentrations (TNF-alpha, IL1 and IL6). REE was increased by 10 +/- 11% (P< 0.001) above predicted values. Plasma TNF-alpha concentration was increased in all patients (mean value 26.3 +/- 14.3 pg.ml(-1)). Excess REE (with respect to values predicted by Harris-Benedict equations) was correlated with plasma TNF-alpha concentration (P< 0.005), but not with the degree of airway obstruction, lung overinflation, or with oxygen cost of breathing. Theophylline treatment resulted in a significant increase in REE by 15%. IN CONCLUSION: non-malnourished, clinically stable, non-severely hypoxic COPD patients display an increased REE that is related with plasma TNF-alpha concentration (without apparent systemic inflammation) and to theophylline treatment, but that is independent of parameters of respiratory function.

Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis.

OBJECTIVE: Proinflammatory cytokines are involved in the pathogenesis of acute pancreatitis. The value of serum levels of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, and interleukin-8 in predicting the outcome of acute pancreatitis was evaluated. METHODS: In 50 patients with acute pancreatitis, the serum concentrations of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein were determined on days 1, 2, 3, 4, and 7 after admission. Acute Physiology and Chronic Health Evaluation (APACHE II) scores were recorded on days 1, 2, and 3. RESULTS: Serum concentrations of interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein on days 1-7 were significantly higher in patients with severe pancreatitis than in patients with mild pancreatitis. Patients with severe attacks had significantly elevated serum tumor necrosis factor-alpha concentrations on days 1-3 compared with those with mild attacks, but not on days 4 and 7. The median peak value of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, and interleukin-8 was reached on day 1, in contrast to the median peak of C-reactive protein, which was reached on day 2. Using cutoff levels of 12 pg/ml for tumor necrosis factor-alpha, 1 pg/ml for interleukin-1-beta, 400 pg/ml for interleukin-6, 100 pg/ml for interleukin-8, 12 mg/dl for C-reactive protein, and 10 for the Acute Physiology and Chronic Health Evaluation (APACHE II) score, the accuracy rates for detecting severe pancreatitis were 72%, 82%, 88%, 74%, 80%, and 72%, respectively, on day 1 and 78%, 74%, 80%, 76%, 80%, and 78%, respectively, on day 2. CONCLUSION: Among the proinflammatory cytokines, interleukin-6 is the most useful parameter for early prediction of the prognosis of acute pancreatitis.

Influence of socioeconomic status on behavioral, emotional and cognitive effects of rubella vaccination: a prospective, double blind study.

A double-blind prospective design was used to investigate the immediate and prolonged psychological effects of a specific viral infection, and the role of immune activation in mediating these effects. Subjects were 240 female teenager girls who were vaccinated with rubella vaccine. Based on analysis of levels of antibodies to rubella, subjects were divided into two groups. An experimental group (n = 60), which included subjects who were initially seronegative and were infected following vaccination, and a control group (n = 180), which included subjects who were already immune to rubella before vaccination. Compared with the control group and to their own baseline, low socioeconomic status (SES) subjects within the experimental group showed a significant increase in the severity of depressed mood, social and attention problems, and delinquent behavior. Ten weeks post-vaccination there were no differences between the experimental and control groups in serum levels of interleukin-1 beta, interferon-gamma, soluble interleukin-2 receptors (sIL-2r), and cortisol. However, a significant negative correlation was found between fatigue-related symptoms and sIL-2r levels in the experimental (r = -0.325), but not the control group (r = -0.046). These findings suggest that viral infection can produce prolonged behavioral, emotional and cognitive problems mainly in subjects belonging to the low SES.

Nutritional assessment of children on haemodialysis: value of IGF-I, TNF-alpha and IL-1beta.

BACKGROUND: Protein-energy malnutrition (PEM) is associated with increased morbidity and mortality in haemodialysis (HD) patients. Insulin-like growth factor I (IGF-I) has proved to be a sensitive marker of malnutrition, while interleukin-1 (IL-1beta) and tumour necrosis factor (TNF) have been found to be raised in catabolic states. METHODS: We have investigated the nutritional status of 17 chronic renal failure (CRF) paediatric patients (8 boys, 9 girls) on maintenance HD. Eight predialysis CRF children (5 boys and 3 girls; mean creatinine 5.1+/-3.2 mg/dl) and 10 healthy children served as control groups. PEM was defined according to anthropometric measurements (triceps skinfold thickness (TST), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC)). These were correlated with serum IGF-I, IL-1, TNF-alpha, transferrin, and albumin (all sampled before the HD session). RESULTS: In the HD group, TST was reduced in 41.2% of the patients, whereas MAC and MAMC were reduced in 82.4 and 76.5% respectively. TST was depleted in only one of the predialysis CRF children. The degree of reduction in MAC and MAMC were 62.5 and 62.5% respectively. Median serum IGF-I level was decreased in both HD and predialysis CRF patients (205.1 interquartile range (IQR) 194.4 microg/l and 258.8 IQR 155.0 microg/l respectively) compared to the healthy children (418.0 IQR 310.5 microg/l) (P=0.0009 and P=0.01 respectively). Within the HD group, IGF-I levels were lower in patients with malnutrition defined according to TST (145.0 IQR 125.5 microg/l) compared to children with normal TST (301.2 IQR 218.8 microg/l) (P=0.05). IGF-I levels of the HD patients with malnutrition according to TST was also lower than the predialysis CRF patients and healthy children (P=0.04 and P=0.002 respectively). Serum IL-1beta was undetectable in all groups. Median serum TNF-alpha levels were higher in HD and predialysis CRF patients compared to healthy children, albeit statistically insignificant. There was no correlation between TNF-alpha, transferrin or albumin and anthropometric parameters. CONCLUSIONS: Our results support the high prevalence of malnutrition in CRF children, which becomes more pronounced when treatment by HD is initiated. We suggest that determination of IGF-I levels in childhood HD patients in conjunction with anthropometric measurements is useful for identification of malnutrition. We have not been able to demonstrate the catabolic effects of cytokines on this state of protein energy malnutrition.