Effect of maternal malnutrition on surface activity of fetal lungs in rats.

The effects of maternal malnutrition on fetal lung growth and surface forces were studied in albino rats. Pregnant albino rats were subjected to one of the following diets: rat chow ad lib. (controls), partial food deprivation (intake one-half that of the controls), complete food deprivation for 4 days (on gestation day 3-7, 9-13, or 17-21), low protein (8%), and fat free. The fetal lungs were studied on the 21st day of gestation (delivered by cesarean section) or at birth (gestation day 22). Fetuses and neonates after maternal food deprivation (FD) on the 17-21 day of pregnancy, and after a low-protein (LP) diet during pregnancy, had significantly smaller body weight and lung wet or dry weight/body weight ratio (hypocellular lungs). The minimum surface tension (gamma min) of fetal lung extracts was significantly increased with FD and LP. This was associated with a reduction of about 35% in lung lecithin content, expressed per lung DNA. The earlier in pregnancy the rat was subjected to 4-day food deprivation the less the effect on the fetus. At birth the gamma min and the lung lecithin content reached control values. This recovery occurred after birth (at age 4-10 h) and prior to first feeding. However, the lungs remained small and hypocellular. The results indicate that the nutritional status of the pregnant rat influences the surface activity and the growth of the fetal lung.     

Effects of premature weaning and diet on lung growth and appearance of adenylate cyclase activator in rat lung

Early weaning of rat pups on day 16 to semi-ground Purina chow food and drinking water, ad libitum, delayed growth of body and lungs, and the appearance of adenylate cyclase activator (ACA) in lung after day 22. However, early weaning of pups to either milk or a gel diet containing semi-ground Purina chow food, agarose gel, water (30:1:69, w/w), and drinking water, restored lung and body growth and the appearance of ACA to control values. Early weaning of pups to dry semi-ground Purina chow food and drinking water also induced a transient rise in ACA on day 19. This early rise in ACA was completely absent in pups weaned on day 16 to milk, whereas it persisted in pups weaned similarly to a gel diet. Interestingly, lung glycogen decreased on day 19 in pups weaned early to dry semi-ground Purina chow food without (group 2) or with triiodothyronin administration (group 3), and on day 25 after normal weaning on day 22 (Nijjar, M.S. Biochim. Biophys. Acta 586: 464–472,1979). These data indicate 1) that reduced food intake (starvation) in pups weaned on day 16 to dry semi-ground Purina chow food was responsible for the delayed growth of body and lung, and the delayed appearance of ACA in lung after day 22, and 2) that a change in diet from milk to Purina chow food and associated alterations in hormones, possibly cortisol and insulin, were responsible for the appearance of ACA in rat lung. It would appear that reduced intake of food (starvation) and associated changes in hormones in rat pups at weaning induce ACA in lungs, stimulating adenylate cyclase to produce more cyclic AMP. A rise in cyclic AMP may initiate a cascade of enzymic reactions resulting in enhanced metabolism of glycogen to intermediates which are utilized for the production of energy during the time that the exogenous source of energy i.e. food, is restricted.     

Pulmonary histopathology in an experimental model of chronic aspiration is independent of acidity

Gastroesophageal reflux has become a major health concern in industrialized countries, with drugs aimed at blocking acid production being more frequently prescribed than any other drug. Damage to lung tissue as a result of chronic aspiration of gastric fluid is a primary health risk associated with gastro-esophageal reflux, with such aspiration being suspected in the induction or exacerbation of asthma and other lung diseases. In this study, a rodent model of chronic aspiration was used to characterize the pulmonary histopathology produced by repetitive aspiration events and to investigate the pathologic roles of individual gastric fluid components such as acid and particulate food matter. Rats exposed to chronic aspiration of whole gastric fluid developed a pathology distinct from that of acute lung injury, characterized by granulomatous interstitial pneumonitis with prominent formation of multinucleated giant cells. This pattern of injury could be reproduced with chronic aspiration of particulate food matter and with chronic aspiration of pH-neutralized gastric fluid, but not with chronic aspiration of hydrochloric acid. Thus, since acid-neutralizing therapy is currently the mainstay of treatment for patients with reflux-associated respiratory symptoms, these results strongly suggest that alternative therapeutic approaches aimed at preventing chronic-aspiration induced lung injury may be warranted.     

Liquid chromatographic measurement of -ascorbic acid and -ascorbic acid in biological samples

- and -Ascorbic acids have been separated using liquid chromatography (LC) on a polymer-coated silica-based NH₂ column and the -isomer has been quantified in human serum, rat serum, rat lung, rat lung perfusate, infant formula (SRM 1846) and mixed food sample (SRM 2383). The -isomer was observed only in trace amounts in the mixed food sample. The results demonstrate that ascorbic acid was stable on the column and completely recovered from supplemented samples of human serum and that this method of analysis is accurate, precise and has broad application exhibiting no dependence on the nature of the matrices evaluated herein.     

Further evidence for the hypothesis that beta-endorphin mediates maternal deprivation effects

Lung DNA synthesis was examined in 9-day-old rat pups following a 2-hour separation from their mothers (maternal deprivation), and compared to that of pups placed with a nipple ligated dam (food deprivation) or a lactating dam (control). Maternally deprived pups consistently showed a significant reduction in lung DNA synthesis which was not attributable to food deprivation. Central administration of naloxone prevented the decrease in DNA synthesis observed after maternal deprivation but did not inhibit the reductions in lung DNA synthesis seen two hours after sc administration of isoproterenol, suggesting that DNA response to maternal deprivation is a specific opioid receptor mediated event. These results are consistent with previous reports from our laboratory indicating that CNS beta-endorphin may mediate many of the biological alterations observed following maternal deprivation in neonatal rats.     

Effects of food restriction and hyperoxia on rat survival and lung polyamine metabolism

We fed Sprague-Dawley rats either freely or by restricting them to 20% of their usual diet for 21 days. In one experiment, we refed half of the food-restricted rats for 12 h, then exposed the three groups to air or 85% O2 for 5 days. The mortalities in 85% O2 were 100, 33, and 0% for the food-restricted, restricted-refed, and freely fed groups, respectively. In air lung polyamine contents and glucose 6-phosphate dehydrogenase and NADP-dependent isocitrate dehydrogenase activities were significantly lower with food restriction. After hyperoxia, lung polyamine and protein contents and enzyme activities were increased in the two surviving groups, but spermine and DNA contents of refed rats did not increase. In a second experiment, we exposed rats to 60% O2 and found that DNA synthesis of food-restricted rats was lower than the freely fed rats in air and remained low after hyperoxia. We conclude that food restriction increases the mortality from 85% O2 and is associated with lower DNA synthesis and polyamine content. We speculate that food-restricted animals may accumulate greater lung injury partly because of a compromised repair process.     

Effects of repeated cycles of starvation and refeeding on lungs of growing rats.

Adult male rats were subjected to four cycles of mild starvation (2 wk) and refeeding (1 wk) and were compared with a fed group. Starvation was induced by giving rats one-third of their measured daily food consumption. During each starvation cycle, rats lost approximately 20% of their body weight. Despite catch-up growth and overall weight gain, starved rats had lower final body weight than fed rats. Lung dry weight and lung volumes were also reduced in the starved group. The mechanical properties of air- and saline-filled lungs did not change significantly with repeated cycles of starvation. Mean linear intercept was similar in the two groups, but alveolar surface area was reduced in the starved rats. Total content of crude connective tissue and concentration per lung dry weight of hydroxyproline and crude connective tissue were reduced in starved rats. We conclude that lung growth is retarded in growing rats subjected to repeated cycles of mild starvation and refeeding, as manifested by smaller lung volume and reduced alveolar surface area. Because alveolar size is unchanged, a reduced number of alveoli is most likely responsible for decreased lung volumes.     

Metabolic activation of food mutagens by liver and lung enzymes from rats, pigs and oxen

Mutagenic activation of the 3 cooked food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was compared in liver and lung enzyme preparations from oxen, pigs and rats. Liver preparations from oxen were the most efficient in activating the mutagens, while the rat enzymes were more active than those from pigs. The different cooking mutagens showed different mutagenic potential. MeIQ was the most potent mutagen, followed by IQ and MeIQx in descending order. In oxen, MeIQx was as potent as IQ. The activation with the lung enzymes was 2-3 orders of magnitude lower than with liver. Furthermore, species differences in mutagenic activation with lung enzymes were small compared with liver enzymes. In lung preparations the differences between IQ and MeIQ were small, but in all 3 animal species the mutagenicity of MeIQx was 1 order of magnitude lower than that of the other 2 mutagens.     

Dietary Exposure Estimates of 14 Trace Elements in Xuanwei and Fuyuan,Two High Lung Cancer Incidence Areas in China

Xuanwei and Fuyuan, located in the Yunnan province in southwest of China, are known to have a strikingly high incidence of lung cancer. Among the many factors that have been explored, the association between lung cancer and trace elements has not received enough attention. In this study, dietary samples were collected from 60 families of the lung cancer and control groups and abundances of 14 trace elements were determined using inductively coupled–plasma mass spectroscopy. Accuracy and sensitivity of the method were demonstrated by analyzing national standard reference materials. The results showed that the dietary intake of the trace elements contributed 96.6% of total intake. Among the 14 elements tested, cadmium and titanium were found to be present at a significantly higher level in the food consumed by the cancer group than by the control group. The intake of selenium by the population living in the areas is much lower than what it should be, with the people in the cancer group experiencing even more severe selenium deficiency. In addition, in both groups, the intakes of several essential elements (iron, copper, and zinc) from food and the drinking water were found to be significantly lower than required according to the Chinese Dietary Reference Intakes. The present study of the relationship between trace element intakes of lung cancer cases and controls provides important information urgently needed for the assessment of lung cancer risk of healthy subjects. The study also gives rational dietary suggestions to local residents which is important to the early diagnosis and pretreatment of lung cancer.     

Reduction of paraquat-induced oxidative stress in rats by dietary soy peptide

The effect of a dietary soy protein isolate (SPI), soy peptide (PEP) and the amino acids in soy protein on paraquat (PQ)-induced oxidative stress was investigated in rats. In the first experiment, male Wistar rats were fed on experimental diets containing casein (CAS), SPI and PEP as nitrogen sources with or without 0.025% PQ. The reduced food intake and body weight gain of the rats fed with PQ was mitigated by either the SPI or PEP intake. Both SPI and PEP prevented the elevation of the serum TBARS concentration and tended to prevent the elevation of lung weight induced by PQ. In the second experiment, the rats were fed on diets containing an amino acid mixture resembling casein (CASAA) or soy protein (SPIAA) with or without PQ. The SPIAA intake did not affect the reduction of food intake and body weight gain, nor the elevation of lung weight and TBARS in the serum and liver induced by PQ. These results demonstrate that the intake of either dietary SPI or PEP, but not an amino acid mixture resembling soy protein, had the effect of reducing PQ-induced oxidative stress in rats.     

Expression of lung uncoupling protein-2 mRNA is modulated developmentally and by caloric intake

Lung expresses a high concentration of uncoupling protein-2 (UCP-2) mRNA, but neither its pulmonary regulation nor function is known. We measured lung UCP-2 mRNA expression in two animal models: in neonatal rats when both the metabolic rate, as measured by oxygen consumption, and levels of serum free fatty acids (FFAs) increase and in adult mice during decreased food intake, when levels of serum FFAs increase but the metabolic rate decreases. In rat lung, the concentration of UCP-2 mRNA was low and unchanged during late gestation, increased approximately twofold within 6 hrs after birth, and, compared with late gestation, remained approximately threefold higher from day 1 to adulthood. The early postnatal rise in the lung UCP-2 mRNA concentration was partially blocked by an antithyroid drug and was increased by treatment with triiodothyronine. Unlike lung, heart UCP-2 mRNA levels were lower during adulthood than at day 15. In adult mice, lung UCP-2 mRNA concentrations increased approximately fivefold within 12 hrs of 67% calorie restriction (CR), remained elevated during 2 weeks of CR, fell to control levels within 24 hrs of refeeding (CR-RF), and positively correlated with serum FFA concentrations. Heart UCP-2 expression during CR and CR-RF was similar to that of lung; liver UCP-2 mRNA levels were slightly lower during CR and returned to control levels during CR-RF. These data suggest that the regulation of UCP-2 is at least partly tissue-specific and that, in the adult mouse, lung UCP-2 is regulated not by oxygen consumption but by FFAs. Moreover, lung UCP-2 mRNA levels in mice fed ad libitum was increased by the intraperitoneal administration of Intralipid, a 20% fat emulsion. On the basis of these data in adult mice, together with the findings of others that levels of FFAs increase by 2 hrs after birth, we propose lung UCP-2 is regulated by FFA.     

Effects of undernutrition on respiratory mechanics and lung parenchyma remodeling.

Undernutrition thwarts lung structure and function, but there are disagreements about the behavior of lung mechanics in malnourished animals. To clarify this issue, lung and chest wall mechanical properties were subdivided into their resistive, elastic, and viscoelastic properties in nutritionally deprived (ND) rats and correlated with the data gathered from histology (light and electron microscopy and elastic fiber content), and bronchoalveolar lavage fluid analysis (lipid and protein content). Twenty-four Wistar rats were assigned into two groups. In the control (Ctrl) group the animals received food ad libitum. In the ND group, rats received one-third of their usual daily food consumption until they lost 40% of their initial body weight. Lung static elastance, viscoelastic and resistive pressures (normalized by functional residual capacity), and chest wall pressures were higher in the ND group than in the Ctrl group. The ND group exhibited patchy atelectasis, areas of emphysema, interstitial edema, and reduced elastic fiber content. The amount of lipid and protein in bronchoalveolar lavage fluid was significantly reduced in the ND group. Electron microscopy showed 1) type II pneumocytes with a reduction in lamellar body content, multilamellated structures, membrane vesicles, granular debris, and structurally aberrant mitochondria; and 2) diaphragm and intercostals with atrophy, disarrangement of the myofibrils, and deposition of collagen type I fibers. In conclusion, undernutrition led to lung and chest wall mechanical changes that were the result from a balance among the following modifications: 1) distorted structure of diaphragm and intercostals, 2) surfactant content reduction, and 3) decrease in elastic fiber content.     

Rapid onset of gene expression in lung, supportive of formation of alveolar septa, induced by refeeding mice after calorie restriction

Alveolar regenerative gene expression is unidentified partly because its onset, after a regenerative stimulus, is unknown. Toward addressing this void, we used a mouse model in which calorie restriction produces alveolar loss, and ad libitum access to food after calorie restriction induces alveolar regeneration. We selected four processes (cell replication, angiogenesis, extracellular matrix remodeling, and guided cell motion) that would be required to convert a flat segment of alveolar wall into a septum that increases gas-exchange surface area. Global gene expression supportive of processes required to form a septum was present within 3 h of allowing calorie-restricted mice food ad libitum. One hour after providing calorie-restricted mice food ad libitum, RNA-level expression supportive of cell replication was present with little evidence of expression supportive of angiogenesis, extracellular matrix remodeling, or guided cell motion. Cell replication was more directly assayed by measuring DNA synthesis in lung. This measurement was made 3 h after allowing calorie-restricted mice food ad libitum because translation may be delayed. Ad libitum food intake, following calorie restriction, elevated DNA synthesis. Thus RNA expression 1 h after allowing calorie-restricted mice food ad libitum supported increased cell replication; measurements at 3 h revealed increased DNA synthesis and RNA expression, supportive of the three other processes required to form a septum. These findings identify the first hour after providing calorie-restricted mice ad libitum access to food as the onset of gene expression in this model that supports processes needed for alveolar regeneration.     

Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD)

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.     

Establishment and evaluation of a mouse model of bronchial asthma with Yin deficiency syndrome

Objective: To establish and evaluate a mouse model of bronchial asthma with Yin deficiency syndrome. Methods: The mouse model of bronchial asthma with Yin deficiency syndrome was established by the treatment with injecting ovalbumin(OVA) two times to sensitize, inhaling OVA 14 times to stimulate, and using thyroxin through lavage during late stimulation. This model was evaluated through body weight, asthmatic behaviors, respiratory function, autonomous activity, lung pathology, and pulmonary fluid clearance. Results: OVA combined with thyroxin was an appropriate method to induce the mouse model with increased food and water intake, autonomous activity, asthmatic behaviors score, and respiratory rate, decreased body weight, tidal volume, and wet/dry ratio of lung, and changed with pathology of lung tissue. The changes of the above mentioned parameters indicated that the model was the bronchial asthma with Yin deficiency syndrome. Conclusion: The OVA combined with thyroxin is a good pattern to establish a mouse model of bronchial asthma with Yin deficiency syndrome successfully, which can highly simulate the clinical symptoms of this disease.     

Cell-mediated immunity in patients with cystic fibrosis.

Leucocytes from 26 patients with cystic fibrosis (CF) and 18 healthy controls were investigated by migration inhibition induced by a variety of antigens. In patients with CF cell-mediated immunity was found to human lung and pancreatic tissue extracts as well as to Aspergillus fumigatus, Pseudomonas aeruginosa, and food antigens but not to brain, heart, or kidney. Those patients with the severest form of the disease had the greatest impairment of cell-mediated immunity, but this impairment could be reversed by steroid treatment. Cell-mediated cytotoxicity may also be concerned in the pathogenesis of CF.     

Elevated choline concentration in neonatal plasma

Plasma choline concentrations were measured in humans, rats, and rabbits within the first few hours of life, before any food was ingested. Neonatal animals and humans had markedly elevated plasma choline levels compared to adult animals or humans. Possible mechanisms responsible for this elevation are discussed and possible consequences for brain function, lung function, and growth are presented.     

大鼠Walker-256移植性肺癌模型的建立

目的建立大鼠Walker-256移植性肺癌模型,探讨应用Walker-256癌细胞建立大鼠移植性肺癌模型的可行性。方法 SD大鼠经尾静脉注射高、中、低三种不同细胞浓度的大鼠Walker-256细胞悬液,观察大鼠的生存时间、体重变化、移植性肺癌模型的成模率,其他脏器转移情况及病理形态学变化情况。结果注射癌细胞后14 d,模型组大鼠均出现体重下降、摄食减少等体征,与正常对照组比较体重明显降低（P〈0.05）;注射癌细胞后21d,高浓度组大鼠开始出现死亡;高、中、低三组不同细胞浓度的移植性肺癌成模率分别为100%、80%、30%,模型组大鼠肝脏系数和肺脏系数均高于正常对照组。病理结果显示,模型组大鼠肺部可见明显的癌症病灶,而其他脏器未发现明显异常。结论注射高浓度Walker256癌细胞（3×105个细胞/只）能成功复制移植性肺癌模型,为移植性肺癌模型的建立和应用提供实验依据。     

The effect of intraperitoneally administered gold thioglucose on growth, food consumption and accumulation of gold in various organs of the chicken (Gallus domesticus)

1. Gold thioglucose (GTG) was intraperitoneally injected into 10-day-old male and female chickens in a dose of 0, 0.2, 0.4 or 0.8 mg per gram of body wt. 2. Mortality of the GTG-injected chickens was 100% and 25% for doses of 0.8 and 0.4 mg/gBW respectively, in both sexes and 25% for a dose of 0.2 mg in females, which were all found within 14.5 hr after the GTG treatment. 3. Body weight gain, food consumption and food efficiency of surviving chickens for 23 days after the GTG injection were not affected by GTG in spite of dose level. 4. Gold detected in blood, heart, liver, gallbladder, spleen, proventriculus, gizzard, duodenum, kidney, pectoral muscle, small intestine, lung and brain of the dead chickens accumulated most highly in heart and followed by spleen, but in the surviving chicken a little gold was only found in liver, spleen and kidney of some GTG-treated chickens.     

Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells

Silica (E551) is commonly used as an anti-caking agent in food products. The morphology and the dimension of the added silica particles are not, however, usually stated on the food product label. The food industry has adapted nanotechnology using engineered nanoparticles to improve the quality of their products. However, there has been increased debate regarding the health and safety concerns related to the use of engineered nanoparticles in consumer products. In this study, we investigated the morphology and dimensions of silica (E551) particles in food. The silica content of commercial food products was determined using inductively coupled plasma optical emission spectrometry. The result indicates that 2.74–14. 45 μg/g silica was found in commercial food products; however, the daily dietary intake in increase causes adverse effects on human health. E551 was isolated from food products and the morphology, particle size, crystalline nature, and purity of the silica particles were analyzed using XRD, FTIR, TEM, EDX and DLS. The results of these analyses confirmed the presence of spherical silica nanoparticles (of amorphous nature) in food, approximately 10–50 nm in size. The effects of E551 on human lung fibroblast cell viability, intracellular ROS levels, cell cycle phase, and the expression levels of metabolic stress-responsive genes (CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1) were studied. The results suggest that E551 induces a dose-dependent cytotoxicity and changes in ROS levels and alters the gene expression and cell cycle. Treatment with a high concentration of E551 caused significant cytotoxic effects on WI-38 cells. These findings have implications for the use of these nanoparticles in the food industry.