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Biomedical subjects

T Barber

Publications and source records attributed to T Barber.

At least 19 recordsLinked to original sources

Role of GSH in the modulation of NOS-2 expression in the weaned mammary gland.

GSH delivery to the lactating mammary gland is essential for the maintenance of lactation as its decrease leads to apoptosis and involution of the mammary gland. In fact, it has already been demonstrated that some of the changes in gene expression found in the lactating mammary gland after forced weaning are reproduced in rats treated with buthionine sulphoximine to deplete GSH levels. An oligonucleotide microarray experiment would give us a better knowledge of the mRNA expression patterns during lactation and after weaning and the possible functions of GSH in the modulation of these events.

Animals↗

Tests of posterior pituitary function.

The posterior pituitary hormone vasopressin is one of the principal endocrine regulators of fluid and electrolyte balance. Tests of posterior pituitary function are based on the physiology and pathophysiology of vasopressin, and involve studies that aim at defining the production and action of the hormone in response to fixed stimuli with reference to standard normal ranges.

Arginine Vasopressin↗

Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys.

While the pathophysiological changes induced by the loss of dopamine innervation in the basal ganglia by Parkinson's disease (PD) are well studied, little is known about functional changes in the neural circuitry of this area during normal aging. Here we report the first survey of age-associated changes in the basal ganglia of behaviorally characterized, awake rhesus monkeys, using pharmacological MRI to map responses to dopaminergic stimulation. Apomorphine, a mixed D(1)/D(2) dopamine receptor agonist, evoked little change in the substantia nigra (SN) of aged animals while significantly reducing activation in young adult monkeys. Compared to young animals, both apomorphine and d-amphetamine (which increases synaptic dopamine levels) significantly increased activation of the aged rhesus globus pallidus externa (GPe). In addition, the aged animals showed decreased activity in the putamen in response to d-amphetamine administration. Although the responses in the SN and putamen of the aged monkeys differed from those in animal models of PD, the apomorphine-evoked activation of their GPe corresponded with apomorphine-induced increases in neuronal activity seen in Parkinson's patients and animal models. Given the major role of the GPe in regulating motor behavior, the altered responses in the aged GPe may contribute significantly to the motor slowing and movement dysfunctions characterizing advanced age.

Aging↗

Blood sulfur-amino acid concentration reflects an impairment of liver transsulfuration pathway in patients with acute abdominal inflammatory processes.

Whole-blood free amino acids were measured in a control group made up of eight healthy women fasted for 12 h and also in eight patients with acute pancreatitis, five patients with acute cholecystitis and seven patients with acute appendicitis. Blood was withdrawn immediately on admission to hospital and again 3 d later following a controlled peripheral parenteral nutrition diet; this is with the exception of the appendicitis group. l-Cystathionine and l-methionine concentrations were significantly higher in pancreatitis and appendicitis patients when compared with controls. In the pancreatitis and cholecystitis patients, l-serine concentration was also significantly higher when compared with controls. The l-homocysteine concentration was significantly higher only in the appendicitis group when compared with the control group. l-Cystine concentration was unchanged in all the patients studied when compared with control subjects. The l-methionine : l-cystine ratio was significantly higher and the l-glutamine : l-cystine ratio was significantly lower in all the patients when compared with controls. The blood S-amino acid pattern reflects an impairment in liver transsulfuration pathway during acute abdominal processes. This work supports the idea that the l-methionine : l-cystine and l-glutamine : l-cystine ratios can be taken as good markers to evaluate the S-amino acid metabolism and suggests the importance of using N-acetylcysteine as a required nutrient in these situations.

Acetylcysteine↗

Breastfeeding peer counseling: results from the National WIC Survey.

The objective of this study was to examine breastfeeding peer counseling within the context of the organizational structure of state and local Supplemental Nutrition Program for Women, Infants and Children (WIC) agencies. The National WIC Breastfeeding Peer Counselor Survey was distributed to a convenience sample of state WIC breastfeeding coordinators and breastfeeding project coordinators and to a sample of local agency WIC directors and staff, breastfeeding peer counselor coordinators, and peer counselors. The findings indicate that respondents in the WIC state and local organizations perceive peer counseling to be effective in promoting and sustaining breastfeeding among WIC mothers. There is, however, a lack of consistent policies and procedures concerning the recruitment, training, and counseling phases of peer counseling within and across state WIC agencies.

Adult↗

Breastfeeding peer counseling: rationale for the National WIC Survey.

Peer counseling has been recognized as an effective intervention in the promotion of breastfeeding among low-income women. This paper provides a literature review demonstrating the effectiveness of peer counseling in health care settings, especially those concerned with breastfeeding. In addition, barriers identified in the literature that limit the integration of peer counseling in medical settings are examined. The need for The National WIC Breastfeeding Peer Counselor Survey and background information on this survey are also discussed.

Adult↗

Vitamin A deficiency causes oxidative damage to liver mitochondria in rats.

Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was studied using three different groups of rats: (i) control rats, (ii) rats fed a vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re-fed a control diet for 30 d. No statistical difference in body weight and food intake was found between control and vitamin A-deficient rats. Liver GSH concentration was similar in both groups. However, in vitamin A-deficient rats, the mitochondrial GSH/GSSG ratio was significantly lower and the levels of malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were higher when compared to control rats. These values were partially restored in re-fed rats. The mitochondrial membrane potential of vitamin A-deficient rats was significantly lower than in control rats and returned to normal levels in restored vitamin A rats. Two populations of mitochondria were found in vitamin A-deficient rats according to the composition of membrane lipids. One population showed a similar pattern to the control mitochondria and the second population had a higher membrane lipid content. This report emphasizes the protective role of vitamin A in liver mitochondria under physiological circumstances.

8-Hydroxy-2'-Deoxyguanosine↗

Effects of vitamin A deficiency on mitochondrial function in rat liver and heart.

The aim of this study was to investigate comparative effects of vitamin A deficiency on respiratory activity and structural integrity in liver and heart mitochondria. Male rats were fed a liquid control diet (control rats) or a liquid vitamin A-deficient diet (vitamin A-deficient rats) for 50 days. One group of vitamin-A deficient rats was refed a control diet for 15 days (vitamin A-recovered rats). To assess the respiratory function of mitochondria the contents of coenzyme Q (ubiquinone, CoQ), cytochrome c and the activities of the whole electron transport chain and of each of its respiratory complexes were evaluated. Chronic vitamin A deficiency promoted a significant increase in the endogenous coenzyme Q content in liver and heart mitochondria when compared with control values. Vitamin A deficiency induced a decrease in the activity of complex I (NADH-CoQ reductase) and complex II (succinate-CoQ reductase) and in the levels of complex I and cytochrome c in heart mitochondria. However, NADH and succinate oxidation rates were maintained at the control levels due to an increase in the CoQ content in accordance with the kinetic behaviour of CoQ as an homogeneous pool. On the contrary, the high CoQ content did not affect the electron-transfer rate in liver mitochondria, whose integrity was preserved from the deleterious effects of the vitamin A deficiency. Ultrastructural assessment of liver and heart showed that vitamin A deficiency did not induce appreciable alterations in the morphology of their mitochondria. After refeeding the control diet, serum retinol, liver and heart CoQ content and the activity of complex I and complex II in heart mitochondria returned to normality. However, the activities of both whole electron transfer chain and complex I in liver were increased over the control values. The interrelationships between physiological antioxidants in biological membranes and the beneficial effects of their administration in mitochondrial diseases are discussed.

Animals↗

Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats.

Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver gamma-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver gamma-cystathionase were significantly greater in lactating rats and in high protein diet-fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet-fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet-fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 +/- 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks gamma-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver gamma-cystathionase during lactation.

Acetylcysteine↗

A deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats is counteracted by an increase in coenzyme Q.

Defects of NADH:coenzyme Q oxidoreductase (complex I) of mitochondria have been described in many congenital and acquired diseases. Administration of coenzyme Q (CoQ, ubiquinone) has been shown to benefit patients with some of these diseases. However, the mechanisms by which CoQ exerts the therapeutic effects are not clearly understood. A reason could be the lack of saturation of CoQ, in kinetic terms, for complex I activity. However, this hypothesis has not been proved in vivo because of the difficulty to incorporate CoQ into the mitochondrial membranes. We have found a deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats which was accompanied by high CoQ content. The defect in complex I activity was compensated by the increase in CoQ to maintain the mitochondrial electron transfer rate. This finding supports, for the first time in an in vivo experimental approach, the kinetic hypothesis to explain the short-term therapeutic effects of CoQ.

Animals↗

Post-translational regulation of perilipin expression. Stabilization by stored intracellular neutral lipids.

The perilipins are a family of polyphosphorylated proteins found exclusively surrounding neutral lipid storage droplets in adipocytes and steroidogenic cells. In steroidogenic cells, the cholesterol ester-rich lipid storage droplets are encoated with perilipins A and C. This study describes the dependence of perilipin levels on neutral lipid storage in cultured Y-1 adrenal cortical cells. The addition of fatty acids and cholesterol to the culture medium of Y-1 adrenal cortical cells greatly increased the storage of cholesterol esters and triacylglycerols concomitant with the formation of many new lipid storage droplets. The addition of fatty acids to the culture medium also produced a transient 6-fold increase in levels of perilipin A, but not C, mRNA, while much larger and stable increases in both perilipin A and C proteins were observed. The increases in perilipin protein levels were dependent upon the metabolism of fatty acids to triacylglycerol or cholesterol esters, since the incubation of cells with bromopalmitate, a poorly metabolized fatty acid, failed to yield large increases in lipid content or perilipin levels. Constitutive expression of epitope-tagged perilipins in transfected Y-1 adrenal cortical cells was regulated by lipid similarly to expression of the endogenous perilipins despite an absence of untranslated perilipin mRNA sequences in the expression constructs. Epitope-tagged perilipin A mRNAs were efficiently loaded with polyribosomes whether or not fatty acids were added to the culture medium; therefore, the increase in perilipin levels in the presence of fatty acids is likely due to factors other than increased translational efficiency. We suggest that the large increase in cellular perilipin levels upon lipid loading of cells is the result of post-translational stabilization of newly synthesized perilipins by stored neutral lipids.

3T3 Cells↗

Are backward words special for older adults?

Two experiments comparing older and young adults confirmed that Stroop interference from lists of incongruent color words was greater for older adults. Similar age effects were observed when the lists of words were presented in 2 unusual print orientations (upside-down; backward and upside-down). In contrast, no age effect was observed, when participants named colors on backward-word lists, as measured with a percentage interference score that corrected for individual differences in baseline (color patches) naming times. Reading speed failed to account for all the interference effects in these data.

Adolescent↗

Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats.

To study the fate of L-cysteine and amino acid homeostasis in liver after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC 4.4.1.1) activity was undetectable, L-cystathionine levels were significantly higher, L-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle, L-ornithine, L-citrulline and L-arginine and blood urea were significantly greater. Ura excretion was also higher in PPG-treated rats when compared with control rats. These data suggest a stimulation of ureagenesis in PPG-treated rats. The inhibition of gamma-cystathionase was reflected in the blood levels of amino acids, because the L-methionine: L-cyst(e)ine ratio was significantly higher in PPG-treated rats than in control rats; blood concentration of cystathionine was also greater. Histological examination of liver and kidney showed no changes in PPG-treated rats when compared with controls. The administration of N-acetylcysteine (NAC) to PPG-treated rats reversed the changes in blood urea and in liver GSH. These data suggest that when liver L-cysteine production was impaired by the blockage of the trans-sulfuration pathway, the concentration of this amino acid was maintained mainly by an increase in protein degradation and by a depletion in GSH concentration that may spare L-cysteine.

Acetylcysteine↗

Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein.

The adipose differentiation-related protein (ADRP) was first characterized as a mRNA induced early during adipocyte differentiation (Jiang, H. P., and G. Serrero. 1992. Proc. Natl. Acad. Sci. USA. 89:7856-7860). The present study demonstrates that ADRP mRNA is expressed in a variety of tissues and cultured cell lines. Immunocytochemical examination revealed that ADRP localizes to neutral lipid storage droplets in cultured murine 3T3-L1 adipocytes, murine MA-10 Leydig cells, Chinese hamster ovary (CHO) fibroblasts, and human HepG2 hepatoma cells; the association of ADRP with lipid droplets was confirmed by subcellular fractionation of MA-10 Leydig cells. In addition to ADRP, steroidogenic cells and adipocytes express the perilipins, a family of lipid droplet-associated proteins that share a highly related sequence domain with ADRP. ADRP and perilipins co-localize on lipid droplets in MA-10 Leydig cells. While ADRP was found on small lipid droplets in 3T3-L1 preadipocytes and early differentiated adipocytes, it was absent in maturing adipocytes. In contrast, perilipins were absent early during differentiation, but were found on small and large lipid droplets at later stages. The transition in surface protein composition of adipocyte lipid droplets from ADRP to perilipins occurred 3 days after the initiation of differentiation when cells displayed co-localizatioin of both proteins on the same lipid droplets. The specific localization of adipose differentiation-related protein to lipid droplets in a wide variety of cells suggests that ADRP plays a role in management of neutral lipid stores.

Adipocytes↗

Perilipin: possible roles in structure and metabolism of intracellular neutral lipids in adipocytes and steroidogenic cells.

Perilipins are a family of unique proteins intimately associated with the limiting surface of neutral lipid storage droplets in adipocytes and in steroidogenic cells. Lipid hydrolysis in these cells is initiated by cAMP, which leads to phosphorylation of hormone-sensitive lipase in adipocytes and cholesteryl esterase in steroidogenic cells by protein kinase A. Although the concurrent phosphorylation of perilipin by this kinase suggests a role for these proteins in lipid breakdown, a role for these proteins in lipid packaging or in maintaining the lipid droplet structure cannot be excluded.

Adipocytes↗

Protein synthesis is stimulated in nutritionally obese rats.

To investigate the tissue growth and the protein synthesis in vivo in nutritional obesity we used lipid-rich multichoice diet feeding. Young male rats of the Wistar strain were divided in two groups: control and obese. Control rats were fed pelleted nonpurified diet. Obese rats were fed a multichoice diet based on a variety of highly palatable energy-rich human foods for 30 d. Protein intake was kept equal in the groups to avoid its influence on protein turnover. The tissue growth pattern was evaluated by protein, DNA and RNA contents of liver, kidney, heart, skeletal muscles and small intestine. Protein synthesis in vivo was measured in these tissues by the phenylalanine flooding-dose technique. Rats fed the multichoice diet showed significantly greater body growth when compared with rats fed the nonpurified diet. Adipose and other tissue weights were significantly greater in the obese rats. The tissue growth pattern was characterized mainly by hyperplasia. In most tissues the net protein accretion found in obese rats resulted from an enhancement in the fractional rate of protein synthesis. The greater protein synthesis was due to an increase in the efficiency of ribosomes in kidney, heart and skeletal muscle and to an increase in the synthetic capacity in liver and small intestine. These data suggest that excess energy intake when protein intake is adequate stimulates tissue growth and protein synthesis in rats.

Adipose Tissue↗