Transfer of perfluorooctane sulfonic acid (PFOS) from contaminated feed to dairy milk.

Dietary intake is the predominant route for human exposure to perfluorooctane sulfonic acid (PFOS). Single pollution events may thus affect human exposure if polluted ground and water is used to produce animal feed or food. In this study, a physiologically based pharmacokinetic (PBPK-) model is derived that describes the uptake of PFOS from contaminated feed by cows and its subsequent elimination through the cows' milk. Parameter values of the model were estimated by fitting to experimental data of a cow feeding trial. Model calculations showed that almost all PFOS ingested is excreted through the cows' milk. The elimination rate, however, was low as the estimated half-life in the cow was 56days and it may, thus, take a long time after an initial pollution event to produce PFOS-free milk. The derived model can be used to estimate the transfer of PFOS through the dairy food chain and can be used for comparison of various contamination routes.

Quick screening of priority ß-agonists in urine using automated TurboFlow™-LC/Exactive mass spectrometry.

This paper describes a method for the determination of priority ß-agonists in urine based on a fully automated sample preparation procedure using an online TurboFlow™ chromatography clean-up step and determination with Orbitrap™ mass analyser technology. The principle of the method was the enrichment of the ß-agonists after enzymatic hydrolysis overnight on a small column packed with a special stationary phase (TurboFlow™) while flushing away sample matrix and interfering compounds. Thereafter, the analytes were transferred onto an analytical column and detected by liquid chromatography/high-resolution mass spectrometry in full-scan mode at a resolution of R = 50,000 FWHM (full width at half maximum) and in higher energy collisional dissociation (HCD) scan mode at a resolving power of 10,000 FWHM. The optimisation of each step of the method, such as selection of the TurboFlow™ and analytical column as well as sample loading and elution parameters were performed using a standard solution containing salbutamol, clenbuterol and mabuterol at a concentration of 100 µg l(-1). The developed automated sample preparation significantly improved the throughput and efficiency of the previously used screening method and it resulted in a considerable reduction in analysis time. Validation experiments including 24 ß-agonists in urine gave decision limits (CCα) between 0.05 and 0.35 µg l(-1). The repeatability of analyses for urine samples spiked at 0.5 µg l(-1) was within the range of 5-26% and recoveries for all compounds were within 89-107%.

[Occurrence and relevance to health of persistent organic substances and phthalates in breast milk]. / Vorkommen und gesundheitliche Bedeutung von persistenten organischen Substanzen und Phthalaten in der Muttermilch.

The aim of this study is to give an overview of the concentrations of persistent organic pollutants like the polychlorinated dibenzo- P-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), polychlorinated biphenyls (PCB), polybrominated diphenyl ether (PBDE), perfluorinated compounds (PFC) and of phthalates in breast milk. On the basis of median and 95 (th) percentile values an "average" and a "high" intake were calculated for a 3-month-old infant exclusively breast-fed. Moreover, the actual daily intake was compared with tolerable daily intakes (TDI) recommended by scientific institutions. On this basis, we found an "average" ("high") daily intake of 70 (140) pg TEQ/kg body weight (b. w.) for PCDD/F and dioxin-like PCB (dl-PCB), 10 (20) ng/kg b. w. for PFOS (perfluorooctanesulfonate), 20 (50) ng/kg b. w. for PFOA (perfluorooctanoate), 1.7 (7.5) ng/kg b. w. for BDE 47, and 0.6 (2.1) ng/kg b. w. for BDE 99. For di-2-ethylhexyl phthalate (DEHP) and di- N-butyl phthalate (DnBP) an "average" and "high" intake of 400 ng/kg b. w. and 2,000 ng/kg b. w. and of 100 and 500 ng/kg b.w. were assumed, respectively. For all of these substances we found a daily intake via breast milk below the TDI, established on a livelong basis. On contrary, the daily intake for the sum of the PCDD/F and dl-PCB considerably exceeded the recommended TDI value. Even with regard to the "high" daily intake values the share of PBDE, PFC, and phthalates on the TDI was only in the lower percentage. Scientific organisations assume that an exceeding of the PCDD/F and dl-PCB intake in relation to the TDI value is acceptable only on the basis of the still declining levels in breast milk and the fact that this high exposure only occurs during some months of the entire life when breast milk is consumed. On the basis of the recent exposure situation mothers can exclusively breast-feed their infants for 6 months without any hesitation. The well established health benefits for mothers and infants when exclusively breast-feeding should be utilised. There is also no health concern if the mother decides to breast-feed the baby for longer than 6 months when the infant also receives additional food.

Evaluation of dioxin-like chemicals in pooled human milk samples collected in Australia.

DESIGN: Human milk samples were collected and analysed for the levels of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and selected dioxin-like polychlorinated biphenyls (PCBs). In total, 157 individual samples collected during 2002 and 2003 as well as 24 samples collected in 1993 were analysed as 20 pools. RESULTS: PCDDs, PCDFs and dioxin-like PCBs were detected in all pooled samples. For samples collected during 2002/2003, the TEQ(DFP) ranged from 6.0 to 15.2 pg TEQ g(-1) lipid with an average of 9.0 pg TEQ g(-1) lipid. The average lipid content was 3.7+/-0.5%. No systematic differences were observed in the levels of PCDDs, PCDFs and PCBs in human milk samples collected from different regions of Australia during 2002/2003. For samples collected in 1993 and analysed as pools, the mean level, expressed as TEQ(DFP) was 16+/-1.4 pg TEQ g(-1) lipid. The average lipid content was 3.9+/-0.7%. CONCLUSION: The levels of PCDDs, PCDFs and dioxin-like PCBs in the human milk of Australian women are both low compared to international levels and similar across all regions of Australia. Consistent with world-wide trends, the levels of PCDDs, PCDFs and dioxin-like PCBs have decreased over a 10 year period from 1993 to 2003 by approximately 40%.

Levels of dioxins and dibenzofurans in breast milk of women residing in two cities in the Irkutsk Region of Russian Siberia compared with American levels.

The presence of dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs) in human tissue, food, and environmental samples from Russia has been monitored since 1988 as part of a research collaboration between a number of countries including Finland, the United States, Germany, the former Soviet Union, and Canada. Although elevated TCDD and PnCDD levels have previously been found in blood of male and female Russian chemical manufacturing workers and in their children, dioxin levels in the general population have usually been found to be lower than in Americans and Europeans. This study continues earlier work in the Irkutsk region of Russian Siberia, where we report levels of dioxin, dibenzofurans, and PCBs in human milk samples taken from general population women living in the industrialized cities of Angarsk and Usolye-Sibirskoye, near Lake Baikal. Total polychlorinated dibenzo-p-dioxin (PCDD) toxic equivalents (TEQs) compared in this paper for the industrialized regions of Siberia, Ukraine, and the US are similar, ranging from 6.1 to 7 parts per trillion (ppt). Recent 1998 milk samples from Angarsk and Usolye-Sibirskoye have total mean polychlorinated dibenzofuran (PCDF) TEQs of 10 and 21.7 ppt, respectively, with the other industrialized countries ranging from 2.3 to 6.7 ppt. Although dioxin-like PCBs were not measured for the city of Usolye-Sibirskoye (1998), total mean PCDD/F TEQ from Angarsk and Usolye-Sibirskoye (1998) were the two highest levels in this study, with 26.9 and 28.5 ppt, respectively, followed by 1993-1994 Ukraine samples with 24 ppt, 1989 Siberian samples with 13.6 ppt, and 1996 USA with 11.4 ppt total TEQ. In this study, higher levels of dioxins are noted in milk from Angarsk and Usolye-Sibirskoye than found in earlier Russian studies, with mean levels also exceeding 1996 and 1999 US breast milk dioxin levels.

Dioxin in infants--an environmental hazard?

The concentrations of the most common dioxin and dibenzofuran congeners were measured in different tissues (e.g. liver, kidneys, subcutaneous fatty tissue and spleen) from 27 infants who died suddenly and unexpectedly. The cases could be subdivided into 2 groups consisting of 15 infants who died in 1991/1992 and in 12 infants who died in 1996/1997. The autopsies were carried out using a standardised protocol and additionally the parents were asked to supply details of the nutritional conditions. The age of the mother and the birth order of the infants were also recorded. From the results obtained by correlating these parameters with the dioxin concentrations three main factors could be established: 1) there was a significant decrease in the total dioxin concentration in infant tissues from 1991/1992 to 1996/1997 indicating a decrease in the environmental dioxin levels due to a decrease in dioxin emission, 2) the birth order was inversely and the duration of breast feeding directly proportional to the dioxin concentrations thus showing that the mothers can decontaminate themselves by breast feeding and 3) an accumulation of specific dioxin congeners was observed in the liver tissue but the pathophysiological significance of these observations is not yet fully understood. Because of the well-known beneficial effects of breast feeding and considering the results of the present study, this type of infant nutrition can be recommended without any restrictions.

Impact of parenteral n-3 fatty acids on experimental acute colitis.

The present study was undertaken to investigate the effects of parenteral lipid emulsions (LE) enriched with n-3 fatty acids (n-3 FA) in experimental acute colitis. Seventy-four adult male Wistar rats were randomized into six groups, five of which had acetic acid-induced colitis. The animals received a fat-free diet and water ad libitum in individual metabolic cages. By a central venous catheter, saline was infused (0.5 ml/h) into the control groups CS (without colitis) and CC (with colitis), while the test groups received specific LE for 7 days. The n-3/n-6 FA ratio and the lipidic compositions regarding long chain (LCT) and medium chain (MCT) triglycerides were: group L--1:7.7 (LCT, n = 12), M--1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus n-3 FA, n = 12) and MW-3--1:3.0 (MCT and LCT plus n-3 FA, n = 13). The frequency of diarrhea, oral intake/body weight ratio, intestinal alterations, macrophage cellularity were evaluated and colonic concentrations of leukotrienes (LTB4, LTC4), prostaglandins (PGE2) and thromboxanes (TXB2) were measured. Groups M, MW-3 and LW-3 had less diarrhea than the CC group (P<0.05). Average oral intake/body weight ratio in MW-3 animals was comparable to the CS and better than the CC group. n-3 FA treated rats (LW-3 and MW-3) presented less intestinal inflammatory alterations than CC rats. Mucosal ulcer formation in MW-3 group did not differ from CS rats. M and MW-3 rats had less macrophages in the colon than the CC group. Compared with CC group, lower concentrations of LTB4 in the CS, LW-3 and MW-3 groups; of PGE2 in the CS, M and MW-3 groups; and of TXB2 in the CS and MW-3 groups were found. Mean concentrations of LTC4 did not differ among the groups. Thus, a LCT-containing LE with a low n-3-n-6 ratio does not modify inflammatory colitis manifestations; LE with a high n-3-n-6 ratio reduces diarrhea, preserves oral intake-weight ratio, attenuates morphological consequences and decreases colonic concentrations of inflammatory mediators; MCT/LCT-containing LE with 1:3 n-3-n-6 ratio exerts the most profound beneficial impact on the inflammatory response.

Impact of sepsis, lung injury, and the role of lipid infusion on circulating prostacyclin and thromboxane A(2).

OBJECTIVE: To investigate whether plasma levels of prostacyclin (PGI2) and thromboxane A(2) (TxA2) are a function of the infusion rate of soybean-based fat emulsions, severity of systemic inflammation, and pulmonary organ failure. DESIGN: Prospective, randomized, crossover study. SETTING: Intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients, ten presenting with severe sepsis, eight with SIRS or sepsis complicated with ARDS. INTERVENTIONS: Patients were randomly assigned to receive rapid fat infusion over 6 h (rFI) or slow fat infusion over 24 h (sFI) along with parenteral nutrition. MEASUREMENTS AND RESULTS: The stable prostanoids 6-keto-PGF1alpha and TxB2 were measured in arterial and mixed venous blood samples, and at 6-h periods trans-pulmonary balances (TPB) were calculated. Free linoleic acid fraction was determined in arterial blood. rFI induced greater increase of linoleic acid than sFI in both groups. Enhanced prostanoid levels and correlations with linoleic acid availabilities were found, however, in ARDS patients only, revealing the highest sepsis- and lung injury scores. Averaged TPB per 24 h was positive in the sepsis group and negative in the ARDS group as rFI induced lowest TPB values for TxB2 at 6 h. CONCLUSION: The quantity of prostanoids formed and their subsequent utilization are dependent on the availability of precursor linoleic acid and are probably affected by the severity of SIRS or sepsis and the existence of pulmonary organ failure, respectively. Because TxA2 might be extracted by the injured lung, rapid infusion of soybean-based fat emulsions should be avoided in patients suffering from severe pulmonary organ failure.

Food and nutritional care in hospitals: how to prevent undernutrition--report and guidelines from the Council of Europe.

In 1999 the Council of Europe decided to collect information regarding Nutrition programmes in hospitals and for this purpose a network consisting of national experts from eight of the Partial Agreement member states was established. The aim was to review the current practice in Europe regarding hospital food provision, to highlight deficiencies and to issue guidelines to improve the nutritional care and support of hospitalized patients. Five major problems seemed to be common in this context: 1) lack of clearly defined responsibilities; 2) lack of sufficient education; 3) lack of influence of the patients; 4) lack of co-operation among all staff groups; and 5) lack of involvement from the hospital management. To solve the problems highlighted, a combined 'team-effort' is needed from national authorities and all staff involved in the nutritional care and support, including hospital managers.

New developments in glutamine delivery.

Numerous studies demonstrate that free glutamine can be added to commercially available crystalline amino acid-based preparations before their administration. Instability during heat sterilization and prolonged storage and limited solubility (35 g/L at 20 degrees C) hamper the use of free glutamine in the routine clinical setting. Indeed, there are many well-controlled and valuable trials with free glutamine, yet its use is restricted to clinical research. The obvious limitations of using free glutamine initiated an intensive search for alternative substrates. Synthetic glutamine dipeptides are stable under heat sterilization and highly soluble; these properties qualify the dipeptides as suitable constituents of nutritional preparations. Industrial production of these dipeptides at a reasonable price is an essential prerequisite for implications of dipeptide-containing solutions in clinical practice. Recent development of novel synthesis procedures allows increased capacity in industrial-scale production. Basic studies with synthetic glutamine-containing short-chain peptides provide convincing evidence that these new substrates are cleared rapidly from plasma after parenteral administration, without being accumulated in tissues and with negligible loss in urine. The presence of membrane-bound as well as tissue-free extracellular hydrolase activity facilitates a prompt and quantitative peptide hydrolysis, the liberated amino acids being available for protein synthesis and/or generation of energy. In the clinical setting, glutamine dipeptide nutrition beneficially influences outcome (nitrogen balance, immunity, gut integrity, hospital stay, morbidity and mortality). The provision of conditionally indispensable glutamine should be considered a necessary replacement of a deficiency rather than a supplementation. The beneficial effects observed with glutamine dipeptide nutrition should be seen simply as a correction of disadvantages produced by the inadequacy of conventional clinical nutrition. The availability of stable dipeptide preparations certainly facilitates, for the first time, adequate amino acid nutrition of critically ill, malnourished or stressed patients in the routine clinical setting and, thus, represents a new dimension in artificial nutrition.

Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis.

OBJECTIVE: To investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I2/thromboxane A2 in arterial blood, pulmonary hemodynamics, and gas exchange. DESIGN: Prospective, controlled, randomized, crossover study. SETTING: Operative intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS). INTERVENTIONS: Patients were assigned randomly to receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B2 and 6-keto-prostaglandin-F1alpha plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostaglandin-F1alpha/thromboxane B2 ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index increased as well, whereas pulmonary vascular resistance and Pao2/Fio2 declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin-F1alpha or thromboxane B2 and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(a-a)o2/Pao2 decreased after rapid fat infusion, whereas Pao2/Fio2 increased. CONCLUSION: Pulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin I2 and thromboxane A2 may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.

Intestinal absorption of rutin in free and conjugated forms.

Quercetin is one of the most common flavonoids in nature, occurring mainly in glycosidic forms such as rutin. Rutin has been reported to exert numerous biochemical and pharmacological activities, though information about its absorption and metabolism is scarce. The aim of this study was to investigate intestinal handling of luminally administered rutin in an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium, with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate-buffered sodium chloride solution spiked with rutin (40.5 +/- 1.8 micromol/L). Viability was maintained during the entire perfusion; no differences between rutin and control perfusions for perfusion pressure, lactate-pyruvate ratio, oxygen uptake, and acid-base homeostasis were observed. About 10% of the administered rutin appeared at the vascular side, chiefly as free rutin (5.6%), but some rutin sulfate (2.5%) and glucuronide (2.0%) were also detected. The conjugates were preferentially absorbed to the vascular side, while only traces of the glucuronide (0.2%) were found in the luminal perfusate. Minute amounts of the rutin administered were located in the intestinal tissue (1.1%) in the form of unchanged rutin and its glucuronide and sulfate conjugates. The model used serves as a valuable tool for understanding intestinal handling of the bioactive flavonol glycoside rutin, and the obtained results confirm uptake of rutin in the rat small intestine.

Evaluation of various rapid chloride tests for assessing urinary NaCl excretion.

BACKGROUND/AIMS: The evidence linking NaCl intake to high blood pressure and probably to other diseases has become stronger. Therefore, a population-wide reduction of NaCl intake is generally recommended. Measuring NaCl excretion in urine is the preferred method for estimating dietary NaCl intake. Rapid tests measuring urinary NaCl excretion might be useful for self-monitoring the individual NaCl consumption. METHODS: The accuracy of four rapid tests measuring chloride content in urine was assessed. Three tests were originally not designed for urine analysis, but for water and food analysis. Totally 204 urine samples were analysed both with the 4 different rapid tests and with quantitative routine laboratory procedures for chloride and sodium. RESULTS: Chloride and sodium were highly correlated (r = 0.96), indicating chloride determination as a reasonable method to assess sodium and NaCl contents in urine. Accuracy of the rapid tests was acceptable in three cases. The drawback of two tests was their narrow calibration range, so that most urine samples had to be diluted. Use of one test showed problems in interpreting its results because the decolouration of the test pads was difficult to recognize. CONCLUSION: It is concluded that rapid chloride tests designed for water analysis might be suitable to determine NaCl in urine samples.

A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.

We describe the identification and in vitro characterization of a series of 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the 20S proteasome. Our initial SAR data demonstrate that the 2-aminobenzylstatine core structure can effectively serve as the basis for designing potent, selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.

Modeling of the binding mode of a non-covalent inhibitor of the 20S proteasome. Application to structure-based analogue design.

The 2-aminobenzvlstatine derivative I is a 20S proteasome inhibitor of a novel chemical type identified by high throughput screening. The compound specifically inhibits the chymotrypsin-like catalytic activity of the human proteasome with an IC50 value in the micromolar range. Using the crystal structure of the yeast proteasome, we modeled the structure of the human proteasome in complex with 1. As one of the first applications of the model in our oncology programme targeting the proteasome, we designed an analogue of the inhibitor having enhanced stacking/hydrophobic interactions with the enzyme. One order of magnitude in inhibitory potency was gained.

Dioxin contamination in food. Bayreuth, Germany, from September 28 to October 1, 2000.

Dioxin and PCB monitoring programs for food and feeding stuff in most countries of the world, including many European Countries are currently inadequate. Better control of food production lines and food processing procedures is needed to minimize entry of dioxin to the food chain and will help to avoid dioxin contamination accidents. This would also improve the ability to trace back a possible contamination to its source. European guidelines for monitoring programs should be established to ensure comparable and meaningful results. These guidelines should define the minimum requirements for the design of monitoring programs, analytical methods, and quality assurance. Though data from Northern Europe shows that the general population exposure to dioxin and PCB has decreased during the last ten years these compounds continue to be a risk of accidental contamination of the food chain. The most prominent recent example is the Belgian dioxin contamination of feeding stuff in 1999. The Belgian dioxin contamination was not detected due to dioxin monitoring programs but by their direct biological effects seen in animals. Four other cases of dioxin contamination have been detected in Europe since 1997 due to local monitoring programs. One of them (citrus pulp pellets 1998) was in a much larger scale than the Belgian dioxin contamination. The general population's exposure to dioxins and PCBs is still in the same range (1-4 pg WHO-TEQ/kg body weight and day) as the recently revised WHO tolerable daily intake (TDI). There is concern that short-term high level exposure to dioxins, furans, and PCB may cause biological effects on the human fetal development and further research is required. Further actions to control sources building on considerable advances already made in many countries may need to be supplemented by measures to prevent direct contamination of feeding stuff or food to reduce general population exposure further.

Dietary intake and nutritional status of women and pre-school children in the Republic of the Maldives.

OBJECTIVE: Malnutrition and poor nutritional status among children are common problems in the Republic of Maldives, a small island nation in the Indian Ocean. The aim of this study was to determine possible macro- and micronutrient deficiencies in the traditional Maldivian diet. DESIGN: In five atolls, 333 women with children aged between 1 and 4 years who were no longer breast-fed were interviewed, using a 24-hour recall. Additionally, the weights and heights of both the women and children were measured, and blood samples from 15 women were collected for measurements of vitamins A and E, beta-carotene, homocysteine, cholesterol and haemoglobin. RESULTS: Of the women, 22% had a body mass index (BMI) below 18.5. Of the children, 41% were stunted, 14% were wasted and 51% were underweight. The women's and children's diets were sufficient in protein (14%) and carbohydrates (67%) but deficient in fat, which contributed only 19% to the total energy intake. Consumption of dietary substances that depend on vegetable and fruit intake (e.g. beta-carotene, vitamin C, dietary fibre and folic acid) was low. The low intake of beta-carotene was underlined by low plasma concentration. The estimated iron intake was low, although blood haemoglobin levels were normal. CONCLUSIONS: Marginal nutritional status and marginal malnutrition are due to low fat intake and selected micronutrient deficiency. Higher intakes of locally available vegetables and fruits and fat (especially for children) on a regular basis might reverse the deficits documented on the atolls.

Plasma free amino acid concentrations in healthy Guatemalan adults and in patients with classic dengue.

BACKGROUND: Plasma free amino acid patterns in health and disease have been reported. However, amino acid concentrations in adult populations in developing countries and in patients with dengue, as a model for an acute infectious viral disease endemic to the tropics, have not been reported. OBJECTIVE: The purpose of this study was to determine the amino acid profile in both healthy Guatemalan adults from different socioeconomic backgrounds and at 3 time points during the course of classic dengue. DESIGN: The study was carried out in Guatemala and included measurement of plasma free amino acids in 22 healthy control subjects (14 low income, 8 middle class) and 17 febrile patients. Measurements of amino acids were repeated within a 48-h interval in 20 of the healthy Guatemalans. In 9 patients with dengue, amino acids were assayed 3 times: on admission to a local hospital in the coastal plain of Guatemala, on hospital discharge, and 7 d after hospital discharge. RESULTS: Branched-chain amino acid concentrations in healthy adults and dengue patients in Guatemala were lower than normal values reported in the literature for healthy Swedish adults. With the exception of increased phenylalanine concentrations and an increased ratio of phenylalanine to tyrosine, all amino acids as well as the Fischer molar ratio were decreased in the acute phase of dengue. CONCLUSIONS: Healthy Guatemalans have different amino acid patterns than do Swedish subjects independent of socioeconomic status. The systemic viral disease dengue is associated with changes in the plasma free amino acid pattern, reflecting infection-related alterations in amino acid metabolism.