Longitudinal alterations in nutrient intake and food pattern in patients with non-small cell lung cancer during anti-neoplastic treatment: a cohort study.

BACKGROUND: Unintentional weight loss is frequently observed in cancer patients. Nutritional therapy is essential, and dietary counselling is the first step. The present study aimed to explore the nutrient intake and food patterns in weight-stable and weight-losing patients with non-small cell lung cancer (NSCLC) during anti-neoplastic treatment. METHODS: Patients with NSCLC (n = 62) were observed during first-line systemic anti-neoplastic treatment. Body weight and dietary intake were assessed on the first and second cycle, and after completing three cycles of treatment. Longitudinal changes were analysed in three groups: weight stable, weight losers and mixed weight. RESULTS: Nutrient intake did not change during treatment in weight stable, although weight losers significantly increased the relative protein intake. Weight stable maintained the food pattern during treatment apart from a decreased consumption of oral nutritional support (ONS). At baseline, weight losers were characterised by pretreatment weight loss, high consumption of ONS, as well as low consumption of grains and animal products. During treatment, weight losers increased the consumption of protein, fatty foods and ONS but decreased the consumption of sweets and alcohol. CONCLUSIONS: Large heterogeneity in nutrient and food intake was observed in NSCLC patients during anti-neoplastic treatment. Weight losers and weight stable had a similar nutrient intake although protein intake increased in weight losers. Grains and animal products were lower and ONS higher in weight losers compared to weight stable during treatment. Weight losers further increased the consumption of ONS and fatty foods, while the consumption of sweets and alcohol decreased during treatment.

Positive effect of protein-supplemented hospital food on protein intake in patients at nutritional risk: a randomised controlled trial.

BACKGROUND: New evidence indicates that increased dietary protein ingestion promotes health and recovery from illness, and also maintains functionality in older adults. The present study aimed to investigate whether a novel food service concept with protein-supplementation would increase protein and energy intake in hospitalised patients at nutritional risk. METHODS: A single-blinded randomised controlled trial was conducted. Eighty-four participants at nutritional risk, recruited from the departments of Oncology, Orthopaedics and Urology, were included. The intervention group (IG) received the protein-supplemented food service concept. The control group (CG) received the standard hospital menu. Primary outcome comprised the number of patients achieving ≥75% of energy and protein requirements. Secondary outcomes comprised mean energy and protein intake, body weight, handgrip strength and length of hospital stay. RESULTS: In IG, 76% versus 70% CG patients reached ≥75% of their energy requirements (P = 0.57); 66% IG versus 30% CG patients reached ≥75% of their protein requirements (P = 0.001). The risk ratio for achieving ≥75% of protein requirements: 2.2 (95% confidence interval = 1.3-3.7); number needed to treat = 3 (95% confidence interval = 2-6). IG had a higher mean intake of energy and protein when adjusted for body weight (CG: 82 kJ kg(-1) versus IG: 103 kJ kg(-1) , P = 0.013; CG: 0.7 g protein kg(-1) versus 0.9 g protein kg(-1) , P = 0.003). Body weight, handgrip strength and length of hospital stay did not differ between groups. CONCLUSIONS: The novel food service concept had a significant positive impact on overall protein intake and on weight-adjusted energy intake in hospitalised patients at nutritional risk.

Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery.

BACKGROUND: Omega-3 fatty acids (n-3 FAs) may have beneficial clinical effects, and n-3 FA supplements may improve outcome after surgery. METHODS: In a randomized double-blind placebo-controlled trial in single centre, patients referred for elective colorectal cancer surgery received either an n-3 FA-enriched oral nutritional supplement (ONS) (Supportan, 200 ml twice daily) providing 2.0 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA) per day, or a standard isocaloric and isonitrogenous ONS, for 7 days before and 7 days after surgery. The primary endpoint was infectious and non-infectious complications within 30 days of surgery. Secondary endpoints were length of hospital stay, intensive care unit admission, readmissions, and concentrations of marine n-3 FAs and arachidonic acid in granulocyte membranes. RESULTS: Some 148 consecutive patients (68 women, 80 men; mean age 71 (range 41-89) years) were randomized. There was no significant difference between groups in infectious or non-infectious postoperative complications (P = 1.000). Granulocyte levels of EPA, DHA and docosapentaenoic acid (DPA) were significantly higher in the n-3 FA-enriched supplement group compared with the control group (P < 0.001). The arachidonic acid level in granulocytes was significantly lower in the enriched group than in the control group (P < 0.001). CONCLUSION: EPA, DHA and DPA were incorporated into granulocytes in patients receiving n-3 FAs, but this was not associated with improved postoperative outcomes. REGISTRATION NUMBER: NCT00488904 (http://www.clinicaltrials.gov).

Pectic polysaccharides isolated from Malian medicinal plants protect against Streptococcus pneumoniae in a mouse pneumococcal infection model.

The aim of this study was to investigate whether the pectic polysaccharides BP-II, Oc50A1.I.A and CC1P1 isolated from the Malian medicinal plants Biophytum petersianum, Opilia celtidifolia and Cola cordifolia, respectively, were able to protect against Streptococcus pneumoniae infection in mice. The pectin preparations were administered intraperitoneally 3 h before challenge with S. pneumoniae serotype 6B. Blood samples were obtained from all animals before and at 3 h, 24 h and 72 h after challenge with the pneumococci. The number of bacteria in blood was recorded and the blood concentration of a range of cytokines measured. The pretreatment with BP-II, Oc50A1.I.A and CC1P1 demonstrated a protective activity against S. pneumoniae serotype 6B infection, albeit at different range of concentrations. The pectins showed no direct antibacterial effects towards S. pneumonia; however, they induced the production of a range of cytokines and chemokines. We have previously shown that BP-II, Oc50A1.I.A and CC1P1 exhibit complement fixation activity and also that BP-II and Oc50A1.I.A stimulate macrophages to produce NO. The observed clinical effect might therefore be linked to the ability of the pectic polysaccharides to stimulate the innate immune system.

Bioassay-guided isolation of apigenin with GABA-benzodiazepine activity from Tanacetum parthenium.

Extracts of Tanacetum parthenium are used in the prophylactic treatment of migraine and have also been used in Danish folk medicine for the treatment of epilepsy. An ethanol extract of T. parthenium showed high affinity for the GABA(A)-benzodiazepine site. An ethanol extract of T. parthenium was fractionated by VLC on silica and preparative C18 HPLC. Each step was monitored with the GABA(A)-benzodiazepine bioassay. The fractionation led to the isolation of apigenin, which may be responsible for CNS-effects of T. parthenium extracts.

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants.

UNLABELLED: In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. INTRODUCTION: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. METHODS: Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. RESULTS: Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). CONCLUSIONS: This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Identification and evaluation of Peruvian plants used to treat malaria and leishmaniasis.

Households in eleven geographically and ethnically distinct areas in Loreto, Peru, were interviewed about their knowledge and use of plants, for the treatment of malaria and leishmaniasis. The survey resulted in 988 use records representing 118 plant-taxa for malaria and 289 use-records representing 85 plant-taxa for leishmaniasis. In both cases the 10 most frequently reported taxa accounted for about half of all the use-records. Plant material was collected and extracts were screened for in vitro inhibition of Plasmodium and Leishmania parasites. In the case of Plasmodium, extracts of 11 of the 13 most frequently reported plants showed significant growth inhibitory activity, while only a few plant extracts inhibited the growth of Leishmania parasites.

The influence of a chiral amino acid on the helical handedness of PNA in solution and in crystals.

The X-ray structure of a self-complementary PNA hexamer (H-CGTACG-L-Lys-NH(2)) has been determined to 2.35 A resolution. The introduction of an L-lysine moiety has previously been shown to induce a preferred left-handedness of the PNA double helices in aqueous solution. However, in the crystal structure an equal amount of interchanging right- and left-handed helices is observed. The lysine moieties are pointing into large solvent channels and no significant interactions between this moiety and the remaining PNA molecule are observed. In contrast, molecular mechanics calculations show a preference for the left-handed helix of this hexameric PNA in aqueous solution as expected. The calculations indicate that the difference in the free energy of solvation between the left-handed and the right-handed helix is the determining factor for the preference of the left-handed helix in aqueous solution.

Etiology of cecal and hepatic lesions in mice after administration of gas-carrier contrast agents used in ultrasound imaging.

The aim of the study was to investigate the etiology of cecal and hepatic lesions in mice and rats after intravenous administration of gas-carrier contrast agents (GCAs). A modified fluorescein flowmetry technique and 24 h necropsy were used in mice (conventional and germ free), rats, and guinea pigs after GCA administration. Different diets and oral nonabsorbable antibiotics were used. Nonfluorescence, edema, congestion, hemorrhage, and mucosal erosion in cecum and colon and nonfluorescent areas in the liver were observed from 16 min after GCA administration in conventional mice on standard diet. Numerous gas bubbles (>50 microm) were observed in the vasculature around the nonfluorescent areas of cecum and colon and in mesenteric vessels draining to the portal vein. Acute inflammation, edema, hemorrhage, and ulceration of the cecum and colon and liver necrosis were seen 24 h after GCA administration in conventional mice on standard diet. When mice were maintained on either a diet with glucose as the only carbohydrate source or on a standard diet supplemented with antibiotics, uniform fluorescence and no organ lesions were observed after GCA administration. Uniform fluorescence and no organ lesions were observed in germ-free mice, rats, and guinea pigs dosed with GCAs and in control animals (mice, rats, and guinea pigs) dosed with sucrose. The results indicate that intravascular growth of GCA microbubbles occurs in the cecal and colonic wall of mice, leading to occlusive ischemia and necrosis in these intestinal segments and secondary gas embolisation in the liver. Transmural gas supersaturation in the cecal wall may explain the intravascular bubble growth in mice.

Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet.

Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.

The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant capacity and cytokine production in healthy older adults consuming a fortified diet.

BACKGROUND: Inadequate micronutrient intake among older adults is common despite the increased prevalence of fortified/enriched foods in the American diet. Although many older adults take multivitamin supplements in an effort to compensate, studies examining the benefits of this behavior are absent. OBJECTIVE: To determine whether a daily multivitamin/mineral supplement can improve micronutrient status, plasma antioxidant capacity and cytokine production in healthy, free-living older adults already consuming a fortified diet. METHODS: An eight-week double-blind, placebo-controlled clinical trial among 80 adults aged 50 to 87 years (mean = 66.5 +/- 8.6 years). RESULTS: Multivitamin treatment significantly increased (p<0.01, compared to placebo) plasma concentrations of vitamins D (77 to 100 nmol/L), E (27 to 32 micromol/L), pyridoxal phosphate (55.1 to 75.2 nmol/L), folate (23 to 33 nmol/L), B12 (286 to 326 pmol/L)), C (55 to 71 micromol/L), and improved the riboflavin activity coefficient (1.23 to 1.15), but not vitamins A and thiamin. The multivitamin reduced the prevalence of suboptimal plasma levels of vitamins E (p=0.003), B12 (p=0.004), and C (p=0.08). Neither glutathione peroxidase activity nor antioxidant capacity (ORAC) were affected. No changes were observed in interleukin-2, -6 or -10 and prostaglandin E2, proxy measures of immune responses. CONCLUSIONS: Supplementation with a multivitamin formulated at about 100% Daily Value can decrease the prevalence of suboptimal vitamin status in older adults and improve their micronutrient status to levels associated with reduced risk for several chronic diseases.

A simple and efficient separation of the curcumins, the antiprotozoal constituents of Curcuma longa.

A simple and efficient method for the separation of the three phenolic diketones, curcumin 1, demethoxycurcumin 2, and bis-demethoxycurcumin 3, isolated from the rhizomes of Curcuma longa has been developed. The method is of general applicability for the separation of compounds containing acidic and chelating groups and is amenable to large scale separations. The curcumins 1-3 show moderate activity against Plasmodium falciparum (IC50: 3.5, 4.2 and 3.0 micrograms/ml) and Leishmania major (IC50: 7.8, 14.1 and 21.5 micrograms/ml) respectively.

Molecular cloning of a cDNA encoding human calumenin, expression in Escherichia coli and analysis of its Ca2+-binding activity.

By microsequencing and cDNA cloning we have identified the transformation-sensitive protein No. IEF SSP 9302 as the human homologue of calumenin. The nucleotide sequence predicts a 315 amino acid protein with high identity to murine and rat calumenin. The deduced protein contains a 19 amino acid N-terminal signal sequence, 7 EF-hand domains and, at the C-terminus, a HDEF sequence which has been reported to function as retrieval signal to the ER. The calumenin transcript is ubiquitously expressed in human tissue, at high levels in heart, placenta and skeletal muscle, at lower levels in lung, kidney and pancreas and at very low levels in brain and liver. Calumenin belongs to a family of multiple EF-hand proteins that include the ER localized proteins reticulocalbin and ERC-55 and the Golgi localized Cab45. Since its Ca2+ binding may be important for the function of the protein we have used microdialysis experiments in order to analyse for the affinity and the capacity of recombinant human (rh) calumenin. All 7 EF-hands of the protein are functional and bind Ca2+, each with an affinity of 1.6x103 M-1. The relatively low affinity for the EF-hands may suggest a role for the protein in Ca2+-dependent processes in the ER.

The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins.

The present report shows the molecular characterization of the rat 460-kDa epithelial glycoprotein that functions as the receptor facilitating uptake of intrinsic factor-vitamin B12 complexes in the intestine and kidney. The same receptor represents also the yolk sac target for teratogenic antibodies causing fetal malformations in rats. Determination of its primary structure by cDNA cloning identified a novel type of peripheral membrane receptor characterized by a cluster of eight epidermal growth factor type domains followed by a cluster of 27 CUB domains. In accordance with the absence of a hydrophobic segment, the receptor could be released from renal cortex membranes by nonenzymatic and nonsolubilizing procedures. The primary structure has no similarity to known endocytic receptors but displays homology to epidermal growth factor and CUB domain proteins involved in fetal development, e.g. the bone morphogenic proteins. Electron microscopic immunogold double labeling of rat yolk sac and renal proximal tubules demonstrated subcellular colocalization with the endocytic receptor megalin, which is expressed in the same epithelia as the 460-kDa receptor. Furthermore, megalin affinity chromatography and surface plasmon resonance analysis revealed a calcium-dependent high affinity binding of the 460-kDa receptor to megalin, which thereby may mediate its vesicular trafficking. Due to the high number of CUB domains, accounting for 88% of the protein mass, we propose the name cubilin for the novel receptor.

Dietary cholesterol affects Na+-K+ pump function in rabbit cardiac myocytes.

Alterations in membrane cholesterol induced in vitro can alter Na+-K+ pump function. Because dietary cholesterol can influence membrane cholesterol in vivo, we examined if dietary cholesterol is a determinant of Na+-K+ pump function. Rabbits were fed cholesterol-supplemented diets for 1-4 wk. Cardiac myocytes were then isolated, and Na+-K+ pump currents (Ip) were measured using the whole cell patch-clamp technique. When the Na+ concentration in the patch pipettes ([Na]pip) was 10 mM, a modest diet-induced increase in serum cholesterol was associated with stimulation of Ip; large increases in serum cholesterol were associated with inhibition. There was no effect of modest or large increases in serum cholesterol on Ip when [Na]pip was 80 mM. The [Na]pip-Ip relationship determined using seven different levels of [Na]pip from 0 to 80 mM indicated that a modest increase in serum cholesterol increased the apparent affinity of the pump for cytoplasmic Na+. In contrast, dietary cholesterol had no effect on the apparent affinity of the pump for extracellular K+. We conclude that cholesterol intake influences the sarcolemmal Na+-K+ pump. This may have clinical implications for cardiovascular function.

Expression and divalent cation binding properties of the novel chemotactic inflammatory protein psoriasin.

Psoriasin is a novel chemotactic inflammatory protein that possesses weak similarity to the S100 family members of Ca(2+)-binding proteins, and that is highly up-regulated in hyperproliferative psoriatic keratinocytes. Here we have used the psoriasin cDNA to express recombinant human (rh) psoriasin in Escherichia coli as a fusion protein containing a hexa His tag and a factor Xa cleavage site in the NH2-terminus. The protein was purified by affinity chromatography on Ni(2+)-nitrilotriacetic acid agarose, digested with factor Xa, further purified by ion-exchange chromatography and characterized by two-dimensional (2-D) gel electrophoresis and NH2-terminal sequencing. The ability of rh psoriasin to bind Ca2+, Zn2+, and Mg2+ was determined by dialysis experiments. We found that rh psoriasin may bind at least seven molecules of Ca2+ in KCl and several molecules in NaCl, with an affinity for the first bound molecule of 1.3-1.6 x 10(4) M-1. This indicates that psoriasin may cooperatively bind several molecules of Ca2+ when present in the extracellular space, or putatively, if localized in subcellular compartments where the concentration of Ca2+ is relatively high. At least eight molecules of Zn2+ were bound in KCl and four in NaCl, with an affinity just below 1 x 10(4) M-1 for the first molecule. Thus psoriasin does not bind significant amounts of Zn2+ at physiological concentrations. Mg2+ and Ca2+ are bound anti-cooperatively and binding of each of the ions (Ca2+, Zn2+, or Mg2+), is accompanied by conformational changes that move tyrosine residues to more hydrophobic areas.

Effects of National Cholesterol Education Program Step 2 diets relatively high or relatively low in fish-derived fatty acids on plasma lipoproteins in middle-aged and elderly subjects.

The effects of two National Cholesterol Education Program (NCEP) Step 2 diets (< or = 30% of energy as total fat, < 7% of energy as saturated fat, and < 200 mg cholesterol/d), one relatively high and the other relatively low in fish-derived fatty acids, on plasma lipoprotein concentrations and blood pressure were compared in 22 men and women with a mean (+/- SD) age of 63 +/- 10 y. Subjects were placed on a baseline diet similar to the diet currently consumed in the United States (35% of energy as total fat, 14% of energy as saturated fat, 35 mg cholesterol/MJ) for 6 wk and then on either an NCEP Step 2 diet relatively high in fish (Step 2 high-fish, n = 11) or relatively low in fish (Step 2 low-fish, n = 11) for 24 wk. All food and drinks were provided. Compared with baseline values, consumption of both the Step 2 high-fish and the Step 2 low-fish diets under weight-stable conditions was associated with significant decreases in plasma concentrations of total cholesterol (-14% and -19%, respectively), low-density-lipoprotein (LDL) cholesterol (-15% and -20%, respectively), and high-density-lipoprotein (HDL) cholesterol (-11% and -17%, respectively). Postprandial, but not fasting, triacylglycerol concentrations were significantly reduced during consumption of the Step 2 high-fish diet. There were no significant changes in these indexes after consumption of the Step 2 low-fish diet compared with the baseline diet. LDL particle size decreased significantly (-12%) only in subjects on the Step 2 low-fish diet. Both Step 2 diets caused small but significant reductions in diastolic blood pressure. Our results indicate that NCEP Step 2 diets relatively high or relatively low in fish are both effective in significantly reducing total and LDL-cholesterol concentrations without changes in the ratio of total cholesterol to HDL cholesterol under controlled weight-stable conditions in middle-aged and elderly subjects. A beneficial effect on diastolic blood pressure was also observed.

Benefits and costs of medical nutrition therapy by registered dietitians for patients with hypercholesterolemia. Massachusetts Dietetic Association.

The Massachusetts Dietetic Association implemented a statewide retrospective quality assurance audit to determine the effectiveness and cost of medical nutrition therapy in patients with hypercholesterolemia (> 5.20 mmol/L). Hypercholesterolemia is a major risk factor for coronary artery disease (CAD). Data were collected at 23 sites from 285 outpatients seen by a registered dietitian for a minimum of two visits. Patients taking lipid-lowering medications were excluded. Of the 285 patients, 108 (38%) were men and 177 (62%) were women. The mean age was 51.4 years (range = 22 to 79 years). Results showed that the mean reduction in serum cholesterol level was 8.6%, which translates to a decrease of approximately 17.2% in risk of CAD. Forty-five percent of the total population showed an 11% or greater reduction in serum cholesterol levels. Reduction in serum cholesterol levels correlated with increased time spent with a dietitian (r = .188, P < .001). The mean cost for nutrition intervention with a dietitian was $163 (a mean of four visits). In contrast, the estimated annual cost of treatment for patients with hypercholesterolemia using drug therapy is $1,450. A 1993 report calculated the annual cost of treating heart disease in the United States to be $80 billion. Medical nutrition therapy should be considered the initial, effective, and low-cost approach in the management of patients with mild to moderate hypercholesterolemia.