Fever and malnutrition: endogenous pyrogen/interleukin-1 in malnourished patients

The effect of protein-calorie malnutrition on the release of endogenous pyrogen/interleukin-1 (EP/IL-1), the protein responsible for the induction of fever, was investigated in 18 hospitalized patients with chronic malnutrition. Monocytes from the 18 patients and from 19 healthy controls were cultured overnight after stimulation with Staphylococcus epidermidis. The presence of EP/IL-1 was tested by injecting culture supernatants into rabbits and measuring the maximum febrile response (delta Tmax). Malnourished patients produced significantly less EP/IL-1 than controls (delta Tmax = 0.27 +/- 0.04 degrees C for patients vs 0.49 +/- 0.03 degrees C for controls, p less than 0.001). The poor febrile response in the malnourished patients was related to low serum albumin and retinol-binding protein, but not to thyroxine-binding albumin or lymphocyte number. This abnormality may help explain the poor febrile response often noted in hospitalized debilitated patients.     

Parenteral nutrition does not stimulate tumor proliferation in malnourished gastric cancer patients

BACKGROUND: The present study evaluated the effects of preoperative parenteral nutrition (PN) on tumor cell proliferation in malnourished gastric cancer patients. METHODS: Twenty malnourished patients affected by gastric cancer were randomized to receive the standard hospital oral diet (control group) or the standard hospital oral diet plus PN (PN group; 0.2 g/kg/d of nitrogen and 30 nonprotein kcal/kg/d). Samples of tumor tissue and surrounding health mucosa were taken by endoscopic biopsies and from the operative specimen, immediately after resection. Tissues were sent for histologic examination and prepared for flow cytometry and for the measurement of the uptake of bromodeoxyuridine (BduR) by cells after in vitro exposure to the agent. The BduR uptake is largely used to assess the proportion of cells actively synthesizing DNA and is one of the principle methods used to measure tumor proliferation. RESULTS: In the PN group, the mean percentage of tumor cells incorporating BduR was 2.51% +/- 1.7% in the endoscopic samples and 1.52% +/- 0.8% in the operative specimens (p = .2). In the normal mucosa, the mean percentage of cells incorporating BduR was 2.24% +/- 1.8% and 1.13% +/- 1.1%, respectively (p = .1). In the control group, the percentage of cells incorporating BduR in the normal mucosa was 1.26% +/- 1.1% at endoscopy and 0.41% +/- 0.3% at surgery (p = .2), whereas the percentage of cells incorporating BduR in the tumor tissue was 1.41% +/- 1.2% at endoscopy and 0.48% +/- 0.6% at surgery (p = .2). The percentage of S-phase cells documented by flow cytometry in the PN group was: in the tumor, 6.6% +/- 2.9% in the endoscopic samples and 5.7% +/- 2.5% in the operative specimens (p = .6); in the normal mucosa, 5.8% +/- 2.5% at endoscopy and 5.4% +/- 0.9% at surgery (p = .7). In the control group, the percentage of proliferating cells measured by flow cytometry was 4.9% +/- 3.2% in the normal mucosa taken by endoscopic biopsy and 5.3% +/- 1.4% in the normal mucosa taken from the operative specimens (p = .8), whereas it was 11.4% +/- 7.2% in the tumor taken with endoscopic biopsy and 9.7% +/- 4% in the tumor tissue taken from the surgical specimens (p = .7). CONCLUSIONS: The present study suggests that PN does not stimulate tumor proliferation in malnourished patients affected by gastric cancer.     

Resting energy expenditure is increased in stable, malnourished HIV-infected patients

Resting energy expenditure (REE) was measured by reference to body composition in 50 malnourished patients with human immunodeficiency virus (HIV) infection and compared with that of 14 healthy subjects. Among HIV patients, 40 had acquired immune deficiency syndrome (AIDS) and 10 had AIDS-related complex (ARC). All were in stable condition and had a previous history of progressive wasting, ie, a mean body weight loss of 14.2 +/- 8.1 kg over 16.6 mo (range 2-49 ms). The mean REE was 14% higher than estimated basal energy expenditure (EBEE), according to the Harris and Benedict formula. Thirty-four patients (68%) were classified as hypermetabolic (REE greater than 110% EBEE). The best predictable variable for REE was fat-free mass (FFM), as determined by an anthropometric method (r = 0.72; P less than 0.001). The mean REE was 12% higher in HIV patients than in the control group FFM (156 +/- 19 vs 124 +/- 17 kJ.kg FFM-1.d-1). We concluded that in stable and malnourished HIV patients, the progressive wasting may be partly related to an increase in REE. The mechanism of this hypermetabolic state remains to be established.     

Calcium and magnesium status is not impaired in pregnant women

Deficiencies in calcium (Ca) and magnesium (Mg) are associated with various complications during pregnancy. To test the hypothesis that the status of these minerals is inadequate in pregnancy, a cross-sectional study was conducted of the dietary intake and status of Ca and Mg in pregnant women (n = 50) attending a general public university hospital in Brazil. Dietary intake was assessed from 4-day food records; levels of plasma Mg, erythrocyte Mg, and urinary Ca and Mg excretion were determined by flame atomic absorption spectroscopy; and type I collagen C-telopeptides were evaluated by enzyme-linked immunosorbent assay. Probabilities of inadequate Ca and Mg intake were exhibited by 58 and 98% of the study population, respectively. The mean levels of urinary Ca and Mg excretion were 8.55 and 3.77 mmol/L, respectively. Plasma C-telopeptides, plasma Mg, and erythrocyte Mg were within normal levels. Multiple linear regression analysis revealed positive relationships among urinary Ca excretion, Ca intake (P = .002) and urinary Mg excretion (P < .001) and between erythrocyte Mg and Mg intake (P = .023). It is concluded that the Ca and Mg status of participants was adequate even though the intake of Ca and Mg was lower than the recommended level.     

Milk folate secretion is not impaired during iron deficiency in humans

The purpose of this study was to examine whether maternal iron and/or folate status influences human milk folate secretion and is responsible for growth faltering of Otomi infants in Capulhuac, Mexico. Breast-feeding mothers (n = 71) were randomized at 22 +/- 13 d (baseline) postpartum to receive a daily multivitamin supplement containing folic acid (400 microg) with and without iron (18 mg). Mothers provided blood and milk samples at baseline, and at 82 +/- 15 and 138 +/- 18 d postpartum. Iron supplementation significantly improved hematocrit and transferrin receptor concentrations but had no influence on maternal folate status or milk folate or iron concentrations. Forty-three percent of mothers (29/68) had low blood folate concentrations at baseline, whereas only 6% (4/66) had low blood folate concentrations at approximately 138 d postpartum. Milk folate concentrations did not differ between Fe-deficient and Fe-sufficient women and provided adequate levels of dietary folate by approximately 82 d postpartum. While milk iron concentrations were unrelated to maternal iron status, they decreased during lactation, and, by approximately 138 d, they provided only 55% of the current recommendation. In conclusion, milk folate concentrations appear to be well preserved during maternal iron deficiency; hence, faltering growth among infants in Capulhuac, Mexico is unlikely the result of reduced milk folate concentration secondary to maternal Fe deficiency. However, milk Fe concentrations showed a temporal decline. Whether the disjuncture between recommended and actual Fe intakes among infants born with low Fe reserves and weaned to foods low in bioavailable Fe has functional consequences is worthy of further investigation.     

Oxidative stress in fish cells:In vitro studies

Bluegill sunfish BF-2 fibroblasts were used in the neutral red (NR) cytotoxicity assay to discern the toxicities of hydrogen peroxide (H₂O₂) and paraquat as indicated by their abilities to induce oxidative stress. The toxicity of H₂O₂ was markedly enhanced in BF-2 cells treated with the glutathione depleting agents, buthionine sulfoximine (BSO), maleic acid, and chlorodinitrobenzene; similar treatments did not sensitize the BF-2 cells to paraquat, a redox cycling xenobiotic. BSO treated BF-2 cells, however, were sensitized to nitrofurantoin, also a redox cycling chemical. Diethyldithiocarbamate, an ihibitor of superoxide dismutase, only weakly enhanced the sensitivity of the BF-2 cells to H₂O₂ and paraquat. 1,10-Phenanthroline, a chelator of Fe²⁺, reduced the cytotoxicity of H₂O₂ and paraquat, presumably by preventing hydroxyl radical formation in the Fenton reaction. Quin 2 AM, an intracellular chelator of Ca²⁺, markedly lessened the toxicity of H₂O₂, but not of paraquat; EGTA, an extracellular chelator of Ca²⁺, had no effect on the toxicity of H₂O₂ or paraquat. Apparently, perturbation of intracellular Ca²⁺ homeostasis is involved in H₂O₂ toxicity. For comparative purposes, some studies were performed with fathead minnow FHM epithelioid cells, BALB/c mouse 3T3 fibroblasts, and human HepG2 hepatoma cells. The BF-2 fibroblast/NR cytotoxicity red assay was shown to be a suitable model to study oxidative stress in fish.     

Benzotriazole is antiestrogenic in vitro but not in vivo

Benzotriazole (BT) is an anticorrosive agent well known for its use in aircraft deicing and antifreeze fluids but also used in dishwasher detergents. It is highly persistent in the environment; therefore, BT is frequently found in runoff emanating from large airports as well as in the surrounding groundwater. In addition, BT has recently been found to be ubiquitous in Swiss wastewater treatment plant effluents and their receiving waters; however, very little chronic toxicity data is available on which to base a sound ecological risk assessment of this chemical. In vitro assays conducted using a recombinant yeast (anti-) estrogen assay indicated that BT possessed clear antiestrogenic properties. This chemical was approximately 100-fold less potent than Tamoxifen, which was used as a positive control. A subsequent in vivo study, however, involving analysis of vitellogenin induction and somatic indices in adult fathead minnows (Pimephales promelas) exposed to BT at concentrations of 10, 100, and 1,000 mug/L for two weeks showed no evidence of antiestrogenic activity by this compound. The possibility exists that higher concentrations of BT may yet induce the type of activity observed in vitro, although the concentrations used here already far exceed those reported in surface-water samples. Furthermore, adverse effects may be observed in fish or other organisms exposed to BT for a longer period than employed here, although such studies are costly and unlikely to be included in standard risk assessment procedures. A rigorous investigation of the chronic toxicity of BT is imperative.     

Urinary catecholamines in iron-deficient rats at rest and following surgical stress

The purpose of this study was to determine catecholamine concentrations both at rest and in response to a surgical stress in iron-deficient and control rats. Twenty-one-day-old rats were randomized to one of two groups which received a diet containing either 6 or 50 mg iron/kg. Three to five days later, when anemia was first detectable, urinary norepinephrine (NE) concentrations were already significantly elevated in the iron-deficient compared to control rats. In contrast, urinary dopamine (DA) became depressed after 10 days of the iron-deficient regimen. At 38 days of age, both groups were subjected to a surgical stress. NE and DA became elevated over baseline values in both diet groups during the 24-h period following surgery; NE remained significantly higher and DA significantly lower in the iron-deficient than in the control group. We conclude that changes in urine catecholamine concentration occur early in the development of iron deficiency and that they are characteristic of both baseline and stress conditions.     

PPD induced in vitro interferon gamma production is not a reliable correlate of protection against Mycobacterium tuberculosis

Correlates of protection against tuberculosis are crucial for the evaluation of new vaccine candidates and for the demonstration of their potential efficacy. Such correlates can be proposed on the basis of animal models. In this study, we hypothesized that protection against tuberculosis (TB) induced by bacillus Calmette-Guerin (BCG) correlates with in vitro TB antigen-specific IFN-gamma production. BCG vaccination, known to provide effective protection against TB in animals, was used to investigate the use of in vitro IFN-gamma production as a marker of BCG-induced protection against TB. Our results show that BCG vaccination does provide substantial protection against challenge with Mycobacterium tuberculosis. However, despite previous compelling evidence that Th1 type immune responses are essential for TB immunity, the magnitude of in vitro purified protein derivative (PPD)-specific IFN-gamma production assessed during the course of TB infection did not correlate with protection. This emphasizes the need to identify further correlates of protection, in addition to IFN-gamma, to be used as markers of protective immunity against M. tuberculosis and/or to identify M. tuberculosis antigens inducing IFN-gamma that correlate with protective immunity.     

Perioperative nutrition in malnourished surgical cancer patients - a prospective, randomized, controlled clinical trial

Background & aims

Malnourished surgical patients are supposed to benefit from perioperative nutrition. It is unclear, however, whether enteral intervention really surpasses the parenteral one, and whether the modification of standard formula matters. The aim of the study was to evaluate the clinical value of the route and type of perioperative nutritional support.

Methods

A group of 167 malnourished patients (91 M, 76 F, mean age 61.4 years) operated between June 2001 and December 2008 was randomly assigned during postoperative period to four groups according to nutritional intervention: enteral and parenteral, standard or immunomodulating. All patients received parenteral nutrition before surgery for 14 days, which provided homogenous groups for the postoperative evaluation. The trial was designed to test the hypothesis that enteral nutrition and/or immunonutrition can reduce the incidence of postoperative complications.

Results

The incidence of individual complications was comparable among all four groups (p > 0.05). Infectious complications occurred in 23 of 84 patients with standard diets and in 20 of 83 patients receiving immunomodulatory formula (odds ratio 0.84; 95% CI 0.42 to 1.69). There were no significant differences in infectious complications’ ratio in patients receiving enteral (24/84 patients) and parenteral formulas (19/83 patients). Neither immunomodulating formulas nor enteral feeding significantly affected the length of hospitalization, overall morbidity and mortality rates.

Conclusions

Results demonstrated that postoperative nutritional intervention generates comparable results regardless of the route and formula used and that preoperative intervention is of the utmost importance.The study was registered in the Clinical Trials Database – number: NCT 00558155.     

The antibody response to influenza vaccination is not impaired in type 2 diabetics

BackgroundDiabetics are considered to be at high risk for complications from influenza infection and type 2 diabetes is a significant comorbidity of obesity. Obesity is an independent risk factor for complications from infection with influenza. Annual vaccination is considered the best strategy for protecting against influenza infection and it's complications. Our previous study reported intact antibody responses 30 days post vaccination in an obese population. This study was designed to determine the antibody response to influenza vaccination in type 2 diabetics.MethodsSubjects enrolled were 18 or older without immunosuppressive diseases or taking immunosuppressive medications. A pre-vaccination blood draw was taken at time of enrollment, the subjects received the influenza vaccine and returned 28–32 days later for a post-vaccination blood draw. Height and weight were also obtained at the first visit and BMI was calculated. Antibody levels to the vaccine were determined by both ELISA and hemagglutination inhibition (HAI) assays.ResultsAs reported in our previous work, obesity positively correlates with the influenza antibody response (p = 0.02), while age was negatively correlated with antibody response (p < 0.001). In both year 1 and year 2 of our study there was no significant difference in the percentage of the type 2 diabetic subjects classified as seroprotected or a responder to the influenza vaccine compared to the non-diabetic subjects.ConclusionsThese data are important because they demonstrate that diabetics, considered a high risk group during influenza season, are able to mount an antibody response to influenza vaccination that may protect them from influenza infection.     

Impaired pancreatic secretion in severely malnourished patients is a consequence of primary pancreatic dysfunction

Severe undernutrition has been associated with reduced secretions of gastric acid and pancreatic enzymes. This may be the result of an impaired gut mucosal response to food and primary gastric parietal and pancreatic acinar cell secretory dysfunction as a consequence of the poor nutritional state. To investigate the relative contributions of these factors, severely undernourished patients underwent enteral-meal-stimulated (ES; n = 7) or intravenous hormone (pentagastrin and cholecystokinin-8)-stimulated (HS; n = 12) gastric acid and pancreatic enzyme secretion before and after a period of nutritional support. Results were evaluated in comparison with normal healthy control subjects (ES = 7, HS = 10). In the control subjects, enteral-meal and cholecystokinin-8 stimulation resulted in similar outputs of the pancreatic enzymes amylase (2213 versus 2305 U/h), lipase (84.93 versus 118.6 U/h), and trypsin (498.9 versus 341.4 U/h), whereas acid output was significantly lower in the ES group (10.90 versus 25.53 mEq/h; P < 0.01). Compared with controls, malnourished groups had significantly reduced secretions of amylase (ES = 870.1 U/h, HS = 686.5 U/h; P < 0.02), lipase (ES = 30.68 U/h, HS = 25.96 U/h; P < 0.02), and trypsin (ES = 175.6 U/h, HS = 109.3 U/h; P < 0.01). The response to enteral-meal or CCK-8 stimulation was comparable. Gastric acid was similarly reduced in the undernourished patients (ES = 4.39 mEq/h, HS = 5.04 mEq/h; P < 0.01). After refeeding, secretion of amylase (ES = 2351 U/h, HS = 2228 U/h) and lipase (ES = 58.83 U/h, HS = 84.91 U/h) improved to levels not significantly different from controls, whereas trypsin (ES = 226.4 U/h, HS = 213.1 U/h; P < 0.03) and acid secretion (ES = 3.52 mEq/h, HS = 11.85 mEq/h; P < 0.01) remained significantly impaired. Severe undernutrition was associated with primary gastric parietal and pancreatic acinar cell dysfunction, which, at least in the case of pancreatic enzymes, appeared to be the determining factor controlling secretion in these patients.