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Does food cause or cure arthritis?

Rheumatoid arthritis and most other forms of inflammatory joint disease--systemic rheumatic diseases--remain illnesses of unknown cause for which current therapy often is inadequate. The possibility that food antigens induce or perpetuate symptoms in at least some patients is novel, rational, and exciting. Studies that relate diet with arthritis might offer the potential of identifying new therapeutic approaches for selected patients and of developing new insights into disease pathogenesis.

Arthritis↗

Regulatory factors in the development of fatty infiltration of the liver during gram-negative sepsis.

To further understand the development of fatty liver during gram-negative sepsis, we measured fatty acid uptake in addition to esterification and secretion of lipids by freshly isolated hepatocytes from fasted and fed control and Escherichia coli-treated rats. Rats were made septic by intravenous (IV) injection of 8 x 10(7) live E coli colonies per 100 g body weight. For the fasted groups, food was removed after E coli injection. Fed rats received a nutritionally adequate diet intragastrically for 5 days before and 24 hours after inducing sepsis. Twenty-four hours after E coli injection, the esterification of newly synthesized fatty acids, as measured by 3H2O incorporation, and the esterification of exogenous fatty acids, measured from 14C-palmitate incorporation, into triglyceride (TG), total cholesterol, and total phospholipid phosphorus were significantly greater in hepatocytes from fasted septic rats compared with their control rats. In fed septic rats, esterification of 14C-palmitate into TG was fourfold greater than in the fed control rats. The increased rates of esterification in hepatocytes from fasted and fed septic rats were not accompanied by an increase in the labeled TG in the medium. This inability to secrete the additional TG that the hepatocytes produce resulted in a higher concentration of cellular TG in fasted and fed septic rats than in their controls. The enzymes glycerol-3-phosphate acyltransferase (GPAT) and phosphatidate phosphohydrolase (PPH) do not appear to be factors contributing to the increased TG synthesis, since the increase in enzyme activity was not accompanied by a similar increase in TG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Direct coupling of supercritical fluid extraction to a gas phase atmospheric pressure chemical ionisation source ion trap mass spectrometer for fast extraction and analysis of food components.

Supercritical fluid extraction (SFE) was coupled to a custom-built atmospheric pressure chemical ionization (APCI) source of an ion trap mass spectrometer (ITMS). This method was developed for the monitoring of static or dynamic carbon dioxide extraction of volatile aroma compounds in real time. The gas phase APCI source resulted in simple spectra where the extraction of individual compounds could be monitored. A classical mint extraction was used to demonstrate the possibilities of the method. Influence of cell loading and standard injection possibilities are described. Limit of detection of the system was 0.5 nl or lower for a series of test compounds. Prospect for a fast method for extraction and quantification was raised and discussed.

Atmospheric Pressure↗

[Reduced waiting capacities as a possible mechanism of action of benzodiazepines. A hypothesis derived from their behavioral effects in animals].

In classical punishment procedures, suppression of responding which allows the animal to avoid electric foot-shock is attenuated by benzodiazepines (BZD). Such a release of responding is interpreted as a reflection of the anxiolytic activity of BZD. In these situations however, behavioral suppression also delays the obtention of the food-reward. Therefore, shock-mediated waiting could be as critical a target as shock-induced fear for BZD in punishment procedures. The present study was designed to investigate whether BZD are effective in reducing the capacity of animals to wait for an expected food reward. Fasted rats trained in a T-maze were allowed to choose between two magnitudes of reward: immediate but small (2 pellets) vs delayed but large (8 pellets). Diazepam (2-4 mg/kg), nitrazepam (2 mg/kg), chlordiazepoxide (16 mg/kg) or clobazam (16 mg/kg) decreased the number of times the large reward was chosen by rats subjected to a waiting period of 15 s before having access to the large reward. In conflict situations, rats trained to press a level for food reward were given both 1 pellet and 1 electric foot-shock for pressing during punished periods of fixed duration signalled by a warning stimulus. The diazepam (2 mg/kg)-induced increase in the number of punished presses (anti-punishment effect) was closely related to the percent punishment time within a session. The release of punished responding reached a statistically significant level only when the total punishment-time accounted for at least 40% of the total duration of the session.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dopamine and serotonin VMN release is related to feeding status in obese and lean Zucker rats.

Study of neurotransmitter role in food intake regulation in a leptin signaling deficient model, such as the Zucker rat, would benefit in the understanding of mechanisms of human obesity, in which leptin resistance is a common syndrome. We studied dopamine (DA) and serotonin (5-HT) concentrations in vivo in the ventromedial nucleus (VMN) of the hypothalamus, as they relate to eating after food deprivation in obese and lean 9-week-old male Zucker rats. DA and 5-HT concentrations were measured by HPLC via microdialysis before and during refeeding in 24-h food-deprived rats. Before food was provided, mean baseline DA and 5-HT levels were lower in obese than in lean rats (9.2 +/- 0.9 vs 15.1 +/- 1.9 pg/10 microl, p < 0.01, and 0.68 +/- 0.05 vs 1.17 +/- 0.02 pg/10 microl, p < 0.001, respectively). Food intake was accompanied by a decrease in DA levels in both obese and lean rats to 64% (p < 0.01) and 65% (p < 0.02) of their baseline levels respectively. 5-HT levels were significantly increased during eating by 41% in obese and 35% in lean rats (p < 0.01) from the baseline levels. Thus in obese rats with altered leptin signaling we found an unaltered pattern of DA and 5-HT release associated with food deprivation and refeeding, but with presence of their low levels. This points to an impaired postsynaptic monoaminergic action to produce an adequate metabolic response in obese Zucker rats in response to feeding state.

Animals↗

Down-regulation of corticotropin-releasing hormone receptor type 2beta mRNA expression in the rat cardiovascular system following food deprivation.

The present study was conducted to assess the effect of nutritional stress induced by food deprivation on expression of messenger ribonucleic acid (mRNA) for corticotropin-releasing hormone receptor type 2beta (CRH-R2beta) in the rat cardiovascular system in the presence or absence of changes in circulating corticosterone. Food deprivation for 96 h caused a robust increase in plasma corticosterone levels and a significant decrease in CRH-R2beta mRNA expression in the rat heart. Starvation for 48 and 96 h decreased CRH-R2beta mRNA expression in the atria, ventricle as well as aorta of sham-adrenalectomized (sham) rats. Surprisingly, clamping plasma glucocorticoids at low levels by adrenalectomy with corticosterone pellet replacement (ADX+B) did not completely prevent starvation-induced decreases of CRH-R2beta mRNA expression in the rat cardiovascular system. Urocortin (Ucn) mRNA expression was increased significantly by food deprivation in the heart of sham as well as ADX+B rats. We speculate that food deprivation may increase urocortin, which in turn down-regulates CRH-R2beta mRNA expression in cardiovascular system. These data indicate that food deprivation despite the presence or absence of changes in circulating corticosterone may have an inhibitory effect on CRH-R2beta mRNA expression in the rat cardiovascular system.

Adrenal Glands↗

Pharmacokinetics of single and multiple ascending doses of the antiallergic agent tiacrilast in man.

Five groups of six healthy subjects received single oral doses of 150, 300, 450, 600 or 750 mg tiacrilast 150 mg capsules, followed 24 h later by the same dose given every 6 h for 7 days, in a study designed to assess the pharmacokinetics of single and multiple doses of tiacrilast. Plasma samples were obtained at specified times after the initial dose, after 4 days of multiple dosing and after the last dose of tiacrilast. Samples were assayed for unchanged drug by a specific HPLC method. Wide variability was seen in the plasma concentration-time data. Plasma concentrations and pharmacokinetic parameters were nearly proportional to dose over the 150 to 750 mg dose range studied. Moreover, there was no evidence of unexpected accumulation of the drug in the plasma during multiple dosing and food did not appear to alter the bioavailability of tiacrilast to any clinically significant extent. The apparent elimination half-life was similar after single and multiple doses and ranged from 1 to 3 h.

Adult↗

Spatial patterns of fasting and fed antropyloric pressure waves in humans.

1. Gastric mechanics were investigated by categorizing the temporal and spatial patterning of pressure waves associated with individual gastric contractions. 2. In twelve healthy volunteers, intraluminal pressures were monitored from nine side hole recording points spaced at 1.5 cm intervals along the antrum, pylorus and duodenum. 3. Pressure wave sequences that occurred during phase II fasting contractions (n = 221) and after food (n = 778) were evaluated. 4. The most common pattern of pressure wave onset along the antrum was a variable combination of antegrade, synchronous and retrograde propagation between side hole pairs. This variable pattern accounted for 42% of sequences after food, and 34% during fasting (P < 0.05). Other common pressure wave sequence patterns were: purely antegrade-29% after food and 42% during fasting (P < 0.05); purely synchronous-23% fed and 17% fasting; and purely retrograde-6% fed and 8% fasting. The length of sequences was shorter after food (P < 0.05). Some sequences 'skipped' individual recording points. 5. The spatial patterning of gastric pressure wave sequences is diverse, and may explain the differing mechanical outcomes among individual gastric contractions. 6. Better understanding of gastric mechanics may be gained from temporally precise correlations of luminal flows and pressures and gastric wall motion during individual gastric contraction sequences.

Adult↗

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity.

AIMS/HYPOTHESIS: Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. METHODS: Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. RESULTS: Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy (-/-) mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo-pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. CONCLUSIONS/INTERPRETATION: PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding.

Adipose Tissue↗

Administration of indinavir and low-dose ritonavir (800/100 mg twice daily) with food reduces nephrotoxic peak plasma levels of indinavir.

BACKGROUND: The objective of this study was to compare indinavir peak plasma (Cmax) values after administration of indinavir/ritonavir 800/100 mg on an empty stomach or with food. High indinavir Cmax values have been associated with indinavir-related nephrotoxicity. METHODS: This was an open-label, randomized, two-treatment, two-period, cross-over pharmacokinetic study performed at steady state. HIV-infected patients who had been using indinavir/ritonavir 800/100 mg twice daily for at least 4 weeks were randomized to take this combination with a light breakfast (two filled rolls and 130 ml of fluid) on a first study day, and without food on a second day, or in the reverse order. The pharmacokinetics of indinavir and ritonavir were assessed after plasma and urine sampling during 12 h. RESULTS: Data for nine patients were evaluated. Administration of indinavir/ritonavir 800/100 mg on an empty stomach resulted in a higher indinavir Cmax [geometric mean (GM) ratio - fasting/fed and 95% confidence interval (CI): 1.28 (1.08-1.52), P=0.01] and a trend to a shorter indinavir tmax (P=0.07) compared to administration with food. The mode of administration of indinavir/ritonavir did not affect plasma indinavir Cmax and AUC values, parameters that have been associated with the antiviral efficacy of indinavir, nor the urinary excretion of indinavir. CONCLUSIONS: Administration of indinavir/ritonavir 800/100 mg on an empty stomach results in a higher indinavir Cmax compared to ingestion with a light meal. Stated the other way round, intake with a light meal reduces indinavir Cmax, which probably reflects a food-induced delay in the absorption of indinavir. It is recommended to administer indinavir/ritonavir 800/100 mg with food, as a possible means to prevent indinavir-related nephrotoxicity in patients who start or continue with this regimen.

Adult↗

Effect of food on the bioavailability and pattern of release of a sustained-release theophylline tablet.

The effect of food on the bioavailability, time to peak level, and pattern of release of a sustained-release theophylline preparation was examined in six normal volunteers. The average bioavailability for the 100- and 300-mg tablets was 98 +/- 0.03% (S.E.M.). This is consistent with previously published data. Food decreased measured theophylline concentration during the first 4 hours for the 100-mg tablets and at the fourth-hour sample following the 300-mg tablets. The decreased rate of absorption resulted in a shift of the absorption curve to the right with a delay in the time to peak level. Peak serum concentrations for tablets given with a meal occurred 6 hours after the 100-mg tablets and 8 hours after the 300-mg tablets, as opposed to 4 and 6 hours, respectively, for tablets in the fasting state. The release pattern of the theophylline preparation approximated zero-order kinetics for all fasting and food treatments.

Adult↗

Insulin pretreatment protects the liver from ischemic damage during Pringle's maneuver.

BACKGROUND: Although maintenance of adenosine triphosphate (ATP) levels is important to restore liver functions during anoxia, ATP production by oxidative phosphorylation is inhibited during Pringle's maneuver, and only a little ATP can be supplied by glycolysis. The glycolytic activity of the liver is controlled by the nutritional condition and hormones. Enhancement of glycolytic activity by insulin may increase ATP production and thus may protect the liver from ischemia. METHODS: Rats were divided into three groups: fasted group, food was withheld for 24 hours; fed group, food was provided ad libitum; and insulin group, fed rats were administered insulin (12 units/kg during a 30-minute period) before portal triad clamping (PTC) was performed. After laparotomy was performed, PTC was performed for 30 minutes. The fructose 2,6-bisphosphate (F-2,6-BP) level, the hepatic levels of lactate and ATP, the bile flow rate, the plasma levels of aspartate transaminase and lactate dehydrogenase, and the indocyanine green clearance were measured at appropriate times. RESULTS: The hepatic F-2,6-BP levels before PTC in the fasted, fed, and insulin groups were 6.2 +/- 3.8, 55.6 +/- 10.6, and 122.2 +/- 31.3 nmol/gm dry weight liver, respectively. The glycolytic activity of the insulin group before PTC was significantly enhanced compared with that of the other groups. Lactate was more rapidly accumulated in livers of the insulin group during PTC than in those of the other groups. The ATP level and energy charge during PTC of the insulin group were higher than those of the other groups. The bile flow rate and indocyanine green clearance after PTC were restored in the order of the insulin, fed, and fasted groups. CONCLUSIONS: Insulin administration before PTC increased the hepatic F-2,6-BP content and enhanced glycolytic activity. Insulin pretreatment combined with feeding improved the hepatic energy metabolism during PTC and restored the liver functions after PTC. Insulin has protective effects on the liver during PTC.

Adenine Nucleotides↗

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.

Animals↗

Application of single-drop microextraction to the determination of dialkyl phthalate esters in food simulants.

A fast and simple method, using static single-drop microextraction (SDME), has been developed to facilitate the identification and quantification of seven dialkyl phthalate esters in the three aqueous food simulants. The simulants were: A, distilled water; B, 3% (w/v) acetic acid/water; and C, 15% (v/v) ethanol/water. The extraction is performed by simply suspending a drop of organic solvent in the aqueous sample using a conventional gas chromatography (GC) microsyringe. Following extraction, the organic phase is withdrawn into the syringe and analyzed by gas chromatography and flame ionization detection (FID). The optimized method yields a linear calibration curve over three orders of magnitude for all the simulants, and method detection limits (MDLs) allowing detection of all the studied compounds at concentrations below migration limits established by the European Union. The accuracy of the SDME method was tested and compared to that of solid-phase microextraction (SPME) by recovery experiments using spiked samples, with results ranging from 85 to 115% in most cases.

Food Analysis↗

Ondansetron absorption in adults: effect of dosage form, food, and antacids.

Ondansetron is a competitive serotonin 5-HT3 receptor blocker that has proved useful in the prevention of emesis due to cisplatin and other cancer chemotherapeutic agents. In a randomized, open-label, crossover study in 24 healthy male subjects, the relative bioavailability of a single 8-mg tablet was compared with that of an 8-mg solution using the two one-sided t-tests. The tablet and solution formulations were bioequivalent, as confirmed by similarities in mean Cmax (26.3 vs 27.7 ng/mL), Tmax (1.79 vs 1.70 h), and AUC (166.0 vs 167.3 ng.h/mL) values. In another randomized, open-label, crossover study in 12 healthy male subjects, the bioavailability of an 8-mg ondansetron tablet administered 5 min after a standard meal was slightly but significantly greater than in fasted subjects, as indicated by comparative mean AUC values [201.4 ng.h/mL (fed) vs 172.5 ng.h/mL (fasted)]. Coadministration of a magnesium hydroxide/aluminum hydroxide antacid did not affect the bioavailability of the ondansetron tablet.

Absorption↗

Effects of hydration on blood rheology.

This study investigated the impact of oral fluid intake on blood rheology of 17 healthy adults following a 12-14 hour overnight fast from food and drink. An oral fluid load of 500 ml was consumed every 30 minutes for 2 hours. Blood viscosity values at shear rates of 1, 10 and 100 s(-1) were reduced (p<0.05 to p<0.01) at 30 and 120 minutes following hydration; however, these differences were not significant after hematocrit correction. With fluid intake, both uncorrected and corrected viscous component of blood viscoelasticity at oscillatory shear rate of 1 s(-1) and at a constant frequency of 2 Hz were reduced (p<0.05 to p<0.001) at all time points as compared to fasting values. The corrected elastic component of blood viscoelasticity increased 90 minutes after hydration (p<0.05). An overnight fast is accompanied by rheological abnormalities that are altered by fluid intake.

Adult↗

[The effect of almagel, gastrotsepin and food on the acidity and protease activity of the stomach and duodenum in peptic ulcer].

Patients with duodenal ulcers were examined for the degree and duration of the effect of almagel, gastrocepin and food on pH and protein digestion by various enzymes of the contents of the stomach and initial part of the duodenum. Acidity and protein digestion were determined in vitro with 3 values of the substrate pH. It was established that almagel and food efficiently reduced the acidity and protein digestion in the stomach and duodenum. Gastrocepin decreased those indicators to a lesser degree but throughout a longer period of time. The data obtained can be used for optimizing the treatment of patients suffering from duodenal ulcers.

Aluminum Hydroxide↗