The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.

The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.     

The influence of maternal nicotine exposure on the interalveolar septal status of neonatal rat lung.

The aim of this study was to determine the effect of maternal nicotine exposure (1 mg nicotine/kg body mass/day, subcutaneously) on the status of the alveolar septa of the 1 to 21 day old offspring. The data obtained showed swelling of type II and interstitial cell mitochondria. The type I:type II cell ratio decreased as a result of type II cell proliferation. The number of capillaries per unit length of septum was also significantly lower than that of control lung. Ruptured blood-air barriers also occur in the nicotine exposed lungs of rats of all age groups. The results show that maternal nicotine exposure interfered with the morphometric and morphologic characteristics of the septa of lung tissue of the offspring.     

The influence of maternal nicotine exposure on neonatal lung alveolar epithelial status: an electron microscope study.

The aim of the present study was to investigate the effect of maternal nicotine exposure (1 mg nicotine/kg body mass/day) on neonatal lung alveolar epithelial cells. Rats (Wistar descendants) were used. The data illustrate that maternal nicotine exposure during pregnancy and lactation resulted in alveolar fenestrations, blebbing and rupturing of the blood-air barrier. The type I pneumocyte appears to be more sensitive to the effect of nicotine than the type II pneumocytes.     

Influence of maternal nicotine exposure on neonatal rat bone: protective effect of pentoxifylline

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. The aim of this study was to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on neonatal rat bone development, and to determine a protective effect of pentoxifylline (PTX). Gravid rats were assigned into four groups, one control (group I) and three experimental (groups II, III, and IV). In group II, pregnant rats received 3 mg/kg/day nicotine alone, subcutaneously, until 21 days postnatal. In group III, pregnant rats received nicotine (3 mg/kg/day) and PTX (60 mg/kg/day). In group IV, pregnant rats received PTX alone (60 mg/kg/day). Whole body mineral density (BMD), content (BMC), area (BA), and histopathologic and morphologic findings of the femur were determined at 21 days of age. The study revealed that nicotine exposure (group II) decreased birth weight, pregnancy weight gain, and length of femur compared with other groups (P < 0.01). Birth weight was higher in groups III (PTX + nicotine) and IV (PTX) than in group II (nicotine). Body weight at 21 days of age was higher (P = 0.009) in the PTX alone group (group IV) compared with the other groups. BMD was higher (P < 0.001) in the PTX-treated groups (group III and IV) compared with other groups. In addition, there were more apoptotic chondrocytes in the hypertrophic zone of rats exposed to nicotine alone (group II) compared with the other groups (P < 0.001). In conclusion, maternal nicotine exposure resulted in decreased birth weight, pregnancy weight gain, and bone lengthening, and increased apoptosis. Pentoxifylline supplementation was found to prevent the adverse effects of maternal nicotine exposure on BMD and birth weight.     

Influence of maternal diabetes on lipid metabolism in neonatal rat lung

The effect of maternal diabetes on tissue constituents, lipid metabolism and glucose utilization was examined in 1-day old rat lungs. Maternal diabetes was induced by intravenous injection of streptozotocin (50 mg/kg body weight) into pregnant Long-Evans hooded rats on the 10th day of gestation resulting in a maternal serum glucose concentration which was 3-fold higher than that of controls. Neonates from diabetic mothers showed a significant decrease in body weight (14%), lung weight (32%) and lung protein concentration (30%). Glycogen, DNA and lipid content of the lungs were significantly elevated in neonates from diabetic mothers. The percent of total phospholipid made up of phosphatidylcholine was not altered, but the percentage of disaturated phosphatidylcholine was decreased (25%). The activity of the CDPcholine pathway enzymes (choline kinase, cholinephosphate cytidylyltransferase and choline phosphotransferase) also showed a marked increase in lungs of neonates from diabetic mothers. Lung slices of neonates from diabetic mothers showed depressed in vitro incorporation of [U-¹⁴C]glucose into neutral lipids and decreased oxidation to CO₂. The results of these investigations show that maternal diabetes interferes with the structural and metabolic processes by which the undifferentiated lung becomes functional at birth.     

The influence of cytosolic phosphoglucomutase on photosynthetic carbohydrate metabolism

The aim of this work was to examine the role of cytosolic phosphoglucomutase (cPGM; EC 5.4.2.2) in photosynthetic carbon partitioning. We have previously described the generation and characterisation of the tuber metabolism of transgenic potato ( Solanum tuberosum cv. Desiree) lines expressing the StcPGM gene in the antisense orientation under the control of the 35S promoter. Here we extend the characterisation of leaf metabolism within these lines, examining properties of gas exchange, carbon partitioning, and the effect of the genetic manipulation on a wide range of metabolites including metabolites of the sucrose-starch transition, glycolysis, the Krebs cycle and amino acid metabolism. The data acquired in the present study surprisingly reveal that the photosynthetic sucrose synthetic capacity of the leaves is largely unaltered but that these plants display a reduced rate of photosynthesis, a dramatic reduction in nucleotide levels, and a general decline of biosynthesis. We conclude that these lines exhibit only moderate changes in sucrose synthesis but more complex changes on a range of diverse metabolic pathways.     

The influence of altered gravity on carbohydrate metabolism in excised wheat leaves

We developed a system to study the influence of altered gravity on carbohydrate metabolism in excised wheat leaves by means of clinorotation. The use of excised leaves in our clinostat studies offered a number of advantages over the use of whole plants, most important of which were minimization of exogenous mechanical stress and a greater amount of carbohydrate accumulation during the time of treatment. We found that horizontal clinorotation of excised wheat leaves resulted in significant reductions in the accumulation of fructose, sucrose, starch and fructan relative to control, vertically clinorotated leaves. Photosynthesis, dark respiration and the extractable activities of ADP glucose pyrophosphorylase (EC 2.7.7.27), sucrose phosphate synthase (EC 2.4.4.14), sucrose sucrose fructosyltransferase (EC 2.4.1.99), and fructan hydrolase (EC 3.2.1.80) were unchanged due to altered gravity treatment.     

The influence of carbohydrate dissimilation on the fatty acid metabolism of Monascus purpureus

The formation of methyl ketones from fatty acids is known as a detoxifying mechanism and takes place during the lag period of growth. Fermentations of fatty acid and saccharides mixture led to two-phase growth kinetics. It was found that first the fatty acid is oxidized before saccharide dissimilation and growth occurs. This principle can also be observed in fermentation processes with precursor mixtures. Precursor-induced breakdown happens due to the toxicity of fatty acids and methyl ketones. Thereby the fatty acid is metabolized prior to the methyl ketone. After this, saccharide dissimilation and growth take place. Correspondence to: N. Peters     

Maternal nicotine exposure: reponse of type II pneumocytes of neonatal rat pups.

The influence of maternal nicotine exposure during pregnancy and lactation on the Type II cells of lung tissue of one day old neonatal rat pups was investigated. The results clearly show that maternal nicotine exposure resulted in an increase in the type II cell count in the lungs of the offspring. In addition the lamellar body content of the type II cells of the nicotine exposed rat pups were significantly (P< 0.01) higher than that of the control animals. The type II cell mitochondria of lung tissue of nicotine exposed rat pups were swollen and no microvilli occurred on the alveolar surface. This clearly illustrates that nicotine interfered with type II cell integrity of tlte neonatal lung and may subsequently interfere with the normal development of the alveolar region of the lung.     

The carbohydrate metabolism of Brugia pahangi microfilariae.

Evidence is presented that the microfilariae of Litomosoides carinii, Dipetalonema viteae and Brugia pahangi have an aerobic requirement for motility, but possibly not for survival. In addition, the data suggest that in an in vitro anaerobic environment, B. pahangi microfilariae ferment glucose only as far as lactate. In an aerobic environment, however, the data are consistent with a portion of glucose being dissimilated via a one step oxidative decarboxylation of pyruvate formed from glycolysis to acetate and CO2. In addition, a low level of complete oxidation, possibly via a tricarboxylic acid cycle pathway, may be occurring. Finally, if B. pahangi microfilariae are immobilized with levamisole in an aerobic atmosphere, the drug appears to alter the aerobic glucose metabolism of the parasite both qualitatively and quantitatively. A decreased glucose utilization occurs, together with a shift to a more nearly homolactate fermentation. It is suggested that the effects of levamisole on the metabolism of the microfilariid are secondary to the observed paralysis.     

Acute exposure of rhesus monkeys to DDT: Effect on carbohydrate metabolism

Four furocoumarins, two having a linear molecule, psoralen and 8-methylpsoralen and two having an angular molecule, angelicin and 4,5′-dimethylangelicin were tested for mutagenesis in Escherichia coli B wild type and in various strains deficient in known repair systems. The results indicate that both monoadducts and crosslinks are mutagenic. The mutagenic efficiency of the furocourmarins ranks in the following order 8-methylpsoralen > psoralen > angelicin > 4,5′-dimethylangelicin.     

Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability.

Eight endurance-trained men cycled to volitional exhaustion at 69 +/- 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies (n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by approximately 30% when carbohydrate was ingested [199 +/- 21 vs. 152 +/- 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 +/- 0.08, Con: 0.23 +/- 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.     

The effect of sympathicomimetic agents on carbohydrate metabolism of planaria.

Epinephrine, ephedrine, dopamine and isoproterenol considerably influence carbohydrate utilization in planaria. Dopamine alone and in combination is the most potent, while ephedrine the least effective in this respect. The finding of increased responses to combined treatment supports the view of the existence of different receptor sites for the sympathicomimetic drugs. The results substantiate conclusions concerning the phylogenesis of hormone receptors.     

Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats

Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem‐spinal cord preparation in the split‐bath configuration, and applied drugs to the brainstem compartment while measuring the burst frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: (1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; (2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; (3) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; (4) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1138–1149, 2016     

In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism

We recently suggested that alveolar interstitial fibroblast-to-myofibroblast transdifferentiation may be a key mechanism underlying in utero nicotine-induced lung injury. However, the effects of in utero nicotine exposure on fetal alveolar type II (ATII) cells have not been fully determined. Placebo, nicotine (1 mg/kg), or nicotine (1 mg/kg) + the peroxisome proliferator-activated receptor (PPAR)-gamma agonist prostaglandin J(2) (PGJ(2), 0.3 mg/kg) was administered intraperitoneally once daily to time-mated pregnant Sprague-Dawley rats from embryonic day 6 until their death on embryonic day 20. Fetal ATII cells were isolated, and ATII cell proliferation, differentiation (surfactant synthesis), and metabolism (metabolic profiling with the stable isotope [1,2-(13)C(2)]-d-glucose) were determined after nicotine exposure in utero or in vitro. In utero nicotine exposure significantly stimulated ATII cell proliferation, differentiation, and metabolism. Although the effects on ATII cell proliferation and metabolism were almost completely prevented by concomitant treatment with PGJ(2), the effects on surfactant synthesis were not. On the basis of in utero and in vitro data, we conclude that surfactant synthesis is stimulated by nicotine's direct effect on ATII cells, whereas cell proliferation and metabolism are affected via a paracrine mechanism(s) secondary to its effects on the adepithelial fibroblasts. These data provide evidence for direct and indirect effects of in utero nicotine exposure on fetal ATII cells that could permanently alter the "developmental program" of the developing lung. More importantly, concomitant administration of PPAR-gamma agonists can effectively attenuate many of the effects of in utero exposure to nicotine on ATII cells.