Biomedical subjects

D K Rassin

Publications and source records attributed to D K Rassin.

At least 19 recordsLinked to original sources

PubMed1997

Hyperoxia and glutathione depletion in the isolated perfused rat liver.

BACKGROUND: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. METHODS: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargyglycine (PPG). Livers were then isolated and perfused. RESULTS: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. CONCLUSION: Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.

Alkynes↗

PubMed1996

Cysteine supplementation increases glutathione, but not polyamine, concentrations of the small intestine and colon of parenterally fed newborn rabbits.

The glutathione precursor cysteine is not contained in most total parenteral nutrition (TPN) formulations, and premature infants may not be capable of synthesizing cysteine because of a deficiency of cystathionase. Glutathione depletion may have negative effects on host defense against oxidative damage. Several studies have suggested that glutathione depletion induces ornithine decarboxylase activity and increases in polyamine concentrations. Since an inverse relationship between polyamine and glutathione concentrations has been suggested, the concentrations of both of these compounds may be altered in premature infants receiving TPN. We measured glutathione and polyamine concentrations of the small intestine and colon of prematurely delivered newborn rabbits administered TPN for 7 days after birth with or without added cysteine (75 or 150 mg kg-1 day-1). Maternally reared kits were also studied. Total glutathione concentrations in the gastrointestinal tract were significantly lower in kits administered cysteine-free TPN than in kits receiving cysteine or who were maternally reared. Polyamine concentrations did not differ among groups. Glutathione depletion of the small intestine and colon does occur during cysteine-free parenteral nutrition and may compromise intestinal defense against oxidant damage.

Animals↗

PubMed1996

Deficient quantitative expression of CD45 isoforms on CD4+ and CD8+ T cell subpopulations and subsets of CD45RA(low)CD45RO(low) T cells in newborn blood.

Deficiencies in the quantitative expression of CD45RA and CD45RO on CD4+ and CD8+ T cells and in a population of CD45RA(low)CD45RO(low) T cells in blood from term newborn infants were found by flow cytometry. The relative frequencies of CD45RO on CD4+ T cells from adults and newborn infants were 72 and 58%, respectively. However, in newborn infants greater than 70% of T cells expressing CD45RO also expressed CD45RA. In addition, the quantitative expression of CD45RA and CD45RO on newborn T cells was significantly less than that found on adult blood T cells.

Adolescent↗

PubMed1996

Decreased interleukin-10 production by neonatal monocytes and T cells: relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors.

The production of IL-10 by human neonatal blood mononuclear leukocytes (BML) stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), antibodies to CD3, or phorbol 12-myristate 13-acetate (PMA) was measured. The production of IL-10 by neonatal BML cultured with LPS or TNF-alpha was approximately 20 and approximately 15%, respectively, of adult BML. The combination of human recombinant TNF-alpha and LPS failed to augment IL-10 production in neonatal BML. The decreased production of IL-10 by neonatal leukocytes was not due to an autocrine feedback mechanism because only low concentrations of IL-10 were found in newborn sera. A connection with TNF-alpha could not be ruled out, because TNF-alpha production by LPS-stimulated newborn BML and the expression of TNF-alpha receptors on newborn monocytes were reduced. Mean +/- SD of concentrations of IL-10 in supernatants from adult and neonatal BML after stimulation with antibodies to human CD3 for 48 or 72 h were 914 +/- 386 and 178 +/- 176 pg/mL, respectively (p < 0.0001). In experiments with enriched populations of neonatal T cells, the addition of PMA failed to augment IL-10 production. This suggested that newborn T cells may be in a different state of activation than adult T cells Thus, IL-10 production in neonatal monocytes and T cells is reduced and this study suggests that the reduction may be secondary in part to regulatory processes involving TNF-alpha and its receptors.

Adolescent↗

PubMed1996

The acute effects of TNF-alpha on the isolated perfused rat liver.

BACKGROUND: TNF-alpha mediates the hepatic response to sepsis by mechanisms which are not well understood. TNF-alpha is known to stimulate the hepatocellular uptake of specific amino acids in vivo; however, little is known about the direct effects of TNF-alpha on hepatic amino acid or glutathione homeostasis, which is a potential factor in the acute hepatic response to sepsis. METHODS: Using the isolated perfused rat liver, we characterized the effects of TNF-alpha on the secretion of amino acids and glutathione into bile and perfusate. Livers taken from adult male Sprague-Dawley rats were perfused with TNF-alpha at a dose of 1 or 2 micrograms. Bile and perfusate were collected for the quantitation of amino acid and glutathione concentrations. RESULTS: Administration of 2 micrograms TNF-alpha resulted in significant increases in biliary and perfusate concentrations of branched chain, gluconeogenic, and total amino acids. TNF-alpha was also associated with dose-related increases in oxygen uptake, and greater biliary concentrations of glutathione. CONCLUSION: TNF-alpha has direct effects upon hepatic amino acid metabolism, which represent some of the early events involved in the mechanism of response to sepsis.

Amino Acids↗

PubMed1995

Brain large neutral amino acids and catecholamines in parenterally nourished preterm rabbits.

Total parenteral nutrition (TPN) has been adapted as a standard for providing nutrition to ill term and preterm infants. The availability of tyrosine in amino acid preparations utilized for TPN is limited and may potentiate a tyrosine-deficient state. Phenlyalanine hydroxylase activity, responsible for catalyzing tyrosine synthesis, has been suggested to be decreased in fetal and neonatal animals. Parenterally nourished premature rabbits (n = 16) and suckled rabbits (n = 19) were studied in order to compare growth parameters and amino acids in the plasma and brain, as well as whole brain catecholamine concentrations. Influx velocities into the brain of amino acids were also determined in these two groups. The preterm rabbit's average birth weight (42.6 +/- 6.0) was less than that of term rabbits (56.7 +/- 8.7, P < 0.005). Significantly lower concentrations of the catecholamine precursor tyrosine were found in both the plasma and brain of the parenterally nourished animals compared to the suckled animals. Tyrosine is reduced in the brain in TPN-supported animals reflecting both low tyrosine intake and increased plasma concentrations of large neutral amino acids that compete for uptake at the blood-brain barrier. However, no difference was observed between the two groups in their brain catecholamine concentrations. The seven-day parenterally nourished rabbit appears to be tyrosine-deficient but no evident effects on brain catecholamine concentrations were seen. The effects and impact of a tyrosine-deficient state might better be evaluated by regional evaluation of catecholaminergic areas of the brain or over a longer period of parenteral nutrition.

Amino Acids↗

PubMed1995

Interleukin-10 in human milk.

The concentrations of immunoreactive IL-10 in the aqueous fraction of 20 specimens of human milk obtained during the first 80 h of lactation and stored at -60 degrees C ranged from 66 to 9301 pg/mL (mean +/- SD, 3304 +/- 3127 pg/mL). IL-10 was present also in the lipid layer of milk. Gel filtration revealed that IL-10 was located in a high molecular weight fraction, where certain other cytokines in human milk have been found. In addition, immunoreactive IL-10 in milk increased after treatment with sodium taurocholate. Bioactive IL-10 was demonstrated by the finding that human milk inhibited [3H]thymidine uptake by human blood lymphocytes and that inhibition was partly overcome by concomitant incubation with antibodies to human IL-10. IL-10 mRNA but no protein product was found in cultured human mammary epithelial cells. Some IL-10 was associated with preparations of human milk leukocytes, but the data did not suggest that the cells were producing the cytokine. Bioactive IL-10 in a possible protected compartment suggests that IL-10 in human milk may have immunomodulating, antiinflammatory effects on the alimentary tract of the recipient infant.

Adult↗

PubMed1995

Use of C-reactive protein in differentiation between acute bacterial and viral otitis media.

OBJECTIVES: The objectives of this investigation were: (1) to determine degree of elevation of serum C-reactive protein (CRP) in uncomplicated acute otitis media (AOM); (2) to compare serum CRP levels in bacterial and viral otitis media; and (3) to determine whether a single serum CRP level, obtained early in the course of AOM, could be used to differentiate between viral and bacterial otitis media. DESIGN AND METHODS: Sera were obtained from otherwise healthy infants and children with AOM who were 3 months to 7 years of age between 1989 and 1991. Tympanocentesis, bacterial and viral studies of the middle ear fluids, virologic studies of nasal wash specimens, measurements of serum antibody titers to respiratory viruses, blood counts, and quantitation of serum CRP concentrations were performed. After the initial tympanocentesis, an oral antibiotic was given for the next 10 days. The patients were clinically reevaluated over next 4 weeks. OUTCOME MEASURES: Serum CRP concentrations were compared among subjects with AOM who were divided into four groups based on the results of bacteriologic and virologic studies: group I, Bacterial infection (n = 82); group II, bacterial and viral infections (n = 69); group III, viral infection (n = 12); and group IV, no identifiable pathogen (n = 22). RESULTS: There was no statistical difference in serum CRP values among the four groups. The ranges of CRP were less than 0.6 to 22.8, less than 0.6 to 17.8, less than 0.6 to 2.0, and less than 0.6 to 6.8 mg/dL in groups I through IV, respectively. However, when CRP values in bacteria-positive cases were compared with CRP concentrations in bacteria-negative cases (1.58 +/- 3.16 vs 0.64 +/- 1.24 mg/dL), the difference was statistically significant. Furthermore, a significantly higher proportion of bacteria-positive cases had serum CRP concentrations greater than 2 mg/dL, compared with those in bacteria-negative cases. There was no correlation between initial CRP values and clinical findings and/or the clearance of bacteria from the middle ear. After 10 days of antibiotic treatment, CRP values returned to normal (< 0.6 mg/dL) in all cases. CONCLUSION: In AOM, the range of serum CRP varied from less than 0.6 to 22.8 mg/dL. High CRP values (> 2.0 mg/dL) were associated with 22% of cases of bacterial AOM but only with 6% of nonbacterial AOM. High levels of serum CRP were found to be very specific in detecting bacterial AOM, and no cases of viral AOM without a concurrent bacterial infection were found to exhibit high serum levels of CRP.

Acute Disease↗

PubMed1994

Biliary glutathione and some amino acids are markedly diminished when biliary pressure is elevated.

We studied the effects of a transient elevation in biliary pressure on biliary glutathione and amino acids in rats. Other biliary solutes monitored were total bile salt, Pi, which is a putative marker of paracellular leakage, and glucose, which is reabsorbed from the biliary tract. Experiments were carried out on anesthetized rats intraduodenally infused with taurocholate to maintain bile flow during a 2-hr basal period, a 4-hr pressure period during which the bile duct cannula was elevated until bile flow decreased to 1/3 the basal rate, and a 2-hr period after release of hydrostatic biliary pressure. We found that pressure treatment caused biliary concentrations of glutathione to progressively decrease by 80%, while biliary Pi rapidly rose approximately 3- to 4-fold, bile salt gradually increased approximately 3-fold, and biliary glucose concentration progressively rose 15-fold. HPLC analysis of monobromobimane-derivatized biliary thiols indicated that the decline in biliary glutathione was not accompanied by an increase in its breakdown products, cysteine and cysteinylglycine. Pressure treatment led to four patterns of change in biliary amino acid concentrations: (1) increases of 29 to 76% for the basic amino acids lysine and arginine, which have very low bile/plasma ratios of about 0.1; (2) no change for the more water soluble amino acids with bile/plasma ratios close to 1.0, e.g., histidine and urea; (3) modest decreases of 16 to 48% for a variety of amino acids including serine, glutamate, and glycine; and (4) marked, progressive decreases of > 50% for aromatic and branched chain amino acids. By 2 hr after release of pressure, only the alterations in biliary glucose and some amino acids, particularly the branched chains, persisted. This is the first report of cholestasis-induced alterations in biliary amino acids.

Amino Acids↗

PubMed1994

Net taurine transport and its inhibition by a taurine antagonist.

P2-fractions were isolated from rat brain, and used to study net taurine transport. The fractions were incubated in increasing concentrations of [3H]taurine and the intraterminal concentration measured by liquid scintillation and amino acid analysis. The membrane potential of the isolated fractions was estimated using 86Rb+ as a marker for intracellular K+. Taurine was synthesized in the P2-fraction when incubated in taurine free medium. At external taurine concentrations below 370 microM a significant amount of the endogenous taurine was released to the incubation medium. Net taurine uptake into the P2-fraction was achieved at external taurine concentrations exceeding 370 microM. The taurine antagonist 6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide (TAG) competitively inhibited taurine and [3H]taurine transport into the P2-fraction. As the external concentration of taurine was increased, the accumulation of 86Rb+ into the P2-fraction was facilitated. This indicated an increasing hyperpolarization of the neuronal membrane as taurine transport shifted from release towards uptake. TAG reduced the hyperpolarization that paralleled taurine accumulation, in a dose dependent manner. Our results indicate that relatively low transmembranal gradients of taurine may be maintained by an electrogenic taurine transporter having a large transport capacity. Such a transporter may well serve the needs of osmotic regulation, i.e. to transport large amounts of taurine in any direction across the neuronal membrane.

Animals↗

PubMed1994

Acculturation and the initiation of breastfeeding.

Despite the fact that breastfeeding is the most appropriate form of nutrition for the healthy term infant, the rate of initiation in the U.S. is declining. One demographic factor associated with this low rate is ethnicity and so in this study we measured acculturation (one aspect of ethnicity) into the U.S. and its relationship to the successful initiation of breastfeeding in a sample of women recruited approximately 2 months prenatally in a U.S.-Mexico border city. Interviews were administered in English or Spanish by bilingual interviewers prenatally (n = 906), natally (n = 788), and postnatally (n = 715). Acculturation (measured with a 20 item instrument) was strongly related to the intent to (p < 0.001) or the successful initiation of breastfeeding (p < 0.001). Marital status (p = 0.014) and education (p = 0.002) were related to breastfeeding prenatally and natally. Initiation of breastfeeding was highest among those women least acculturated (52.9%) and lowest in those most acculturated (36.1%) indicating an inhibiting effect of acculturation. To improve the rate of initiation of breastfeeding in the U.S. (a national health goal) intervention programs must consider cultural factors.

Acculturation↗

PubMed1994

Facilitating faculty development and research through critical review of grant proposals and articles.

BACKGROUND: In 1983 the Department of Pediatrics at the University of Texas Medical Branch at Galveston established a faculty development program to address faculty needs for continuing education and improved resources for research. At first a part-time coordinator was hired; then, in 1985, a full-time, faculty-level science communicator provided help with strategic planning of projects and intensive review of grant proposals and journal articles. Faculty participation in the program was voluntary. METHOD: Pre- and post-intervention data for 1983-1992 included numbers of faculty using the program, faculty evaluations of the program, grant dollars awarded, counts of grant submissions and awards, and numbers of published articles. RESULTS: The review services were used heavily for grant proposals (75% of the department's proposals), but were used lightly for research articles (18% of publications). Grant funding quadrupled from 1983 to 1988; although funding peaked in 1988, it thereafter remained at three to four times the 1983 level. In contrast, the mean number of publications per faculty per year dropped between 1983 and 1990. CONCLUSION: The program provided valuable assistance to the faculty in writing grant proposals, and it helped to generate critically needed resources. However, the program's failure to increase the publication productivity of the faculty suggests that despite financial pressures, similar programs should use their influence and resources to promote a balance between scholarly publication and grant acquisition.

Faculty, Medical↗

PubMed1993

Acculturation and breastfeeding on the United States-Mexico border.

Previous studies have demonstrated a strong association between breastfeeding incidence and ethnic background, indicating the presence of strong cultural influences on infant-feeding patterns within ethnic groups. This study analyzed the relationship of acculturation into the United States, one aspect of ethnicity, to the initiation of breastfeeding among a sample of 213 women recruited approximately 2 months prenatally in the United States-Mexico border city of Brownsville, Texas. An in-depth, structured interview was conducted at that time (n = 213), at the time of birth (n = 207), and 2 to 3 weeks postnatally (n = 206). In addition, male partners of the mothers were interviewed prenatally when available (n = 119). Acculturation scores and demographic characteristics were tested relative to breastfeeding initiation. The degree of acculturation, age, and marital status were associated significantly with breastfeeding initiation (with breastfeeding continued at 2 to 3 weeks postnatally), but occupational status, education, and income were not. Breastfeeding incidence was highest among older, married, or low-acculturated, Anglo mothers. These data suggest that women being assimilated into the United States are inhibited in the initiation of breastfeeding. These findings suggest that to be successful, intervention programs to increase breastfeeding incidence must consider the cultural adaptation of different groups as they meld with the larger population.

Acculturation↗

PubMed1993

Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration.

Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia.

Animals↗

PubMed1993

Total parenteral nutrition-associated alterations in hepatobiliary function and histology in rats: is light exposure a clue?

Light exposure of amino acids, especially in the presence of photosensitizers such as riboflavin, has been shown to result in photoproducts that are toxic both in vivo and in vitro. Provision of photooxidized single amino acids has been shown to result in hepatic dysfunction in both gerbils and rats. However, studies of the effects of light exposure of complete nutrient mixtures (glucose-amino acid-vitamins) on hepatobiliary responses are limited. These are important because, in clinical practice, total parenteral nutrition (TPN) solutions are continually exposed to light and because hepatic dysfunction is the most common metabolic aberration associated with TPN. Studies were conducted to compare the effects of TPN that had been exposed to light (+L) or protected from light (-L) on hepatobiliary function of rats. TPN solutions were either exposed to light or protected from light for 24 h and then infused into rats for 10 d. Data for enterally fed rats are also shown for comparison with parenterally fed animals. +L animals lost more weight and had lower bile flow, higher taurocholate output in bile, higher biliary osmolarity, and higher inorganic phosphate in bile. Hepatic histology demonstrated scattered foci of necrosis in eight of the eight +L animals and in only one of eight -L animals. These data demonstrate that protection of TPN solutions from light minimizes TPN-associated alterations in hepatobiliary function and histology. These histologic changes observed in the +L animals are in contrast to previous reports of TPN-induced histologic changes, suggesting a different mechanism. Our observations suggest that consideration be given to the implications of exposing TPN solutions to light.

Animals↗

PubMed1992

On the activity of gamma-aminobutyric acid and glutamate transporters in chick embryonic neurons and rat synaptosomes.

The uptake of radioactive gamma-aminobutyric acid (GABA) and D-aspartate and the effect of SKF 89976-A, a non-substrate inhibitor of the GABA transporter, on this uptake have been investigated. Neuronal cultures from eight-day-old chick embryos grown for three or six days in vitro, were used as a model. For comparison, we also used the P2-fraction from rat. Neuronal cultures grown for three and six days expressed high-affinity uptake systems for [3H]GABA and for D-[3H]aspartate with an increasing Vmax during this period. The lipophilic non-substrate GABA uptake inhibitor, SKF 89976-A, inhibited transporter mediated uptake of GABA both in cell cultures from chicken, and in P2-fractions from rat. The results also showed that SKF 89976-A was a poor inhibitor of the uptake of D-aspartate. We found no non-saturable uptake of D-aspartate.

Amino Acid Transport System X-AG↗

PubMed1992

Glutathione and tissue amino acid responses to light-exposed parenteral nutrients.

Effects of infusion of light-exposed (+L) or light-protected (-L) total parenteral nutrition solutions were investigated in rats. The parenteral infusions were carried out for 7 days through jugular cannulas in freely moving rats in metabolic cages. Plasma tyrosine and citrulline, hepatic methionine, valine, isoleucine, leucine and tyrosine, and biliary cystathionine were significantly greater in the -L than +L rats, whereas biliary arginine was significantly lower in the -L compared to +L rats. Bile flow, biliary inorganic phosphate and glucose were significantly lower, whereas biliary total glutathione (GSH+GSSG) was significantly greater in the -L compared to +L animals. These data suggest adverse effects on hepatobiliary function due to light exposure of parenteral nutrients. The endogenous markers used suggest that tight junction permeability, bile acid-independent flow, glutathione and amino acid homeostasis are altered by light exposure and that these changes can be minimized by light protection. The mechanisms involved in the induction of these changes need to be elucidated. The role of light exposure of parenteral nutrients during routine clinical use in the induction of hepatic dysfunction, a common metabolic complication of parenteral nutrition, needs to be considered.

Amino Acids↗

PubMed1992

Height, infant-feeding practices and cardiovascular functioning among 3 or 4 year old children in three ethnic groups.

Barker recently hypothesized that factors affecting prenatal and infant growth are related to adult blood pressure and CVD mortality. Predictions from Barker's hypothesis in regard to infant feeding were tested among a sample of 3 or 4 year old children. The relationship of infant-feeding characteristics (duration of breast-feeding, times of introduction of high fat, high carbohydrate, high potassium foods and table salt) to indicators of cardiovascular functioning (resting blood pressures and heart rates, and heart rate response to graded activity) while controlling for anthropometric (height, sum of seven skinfolds, BMI) and demographic (ethnicity, gender, social status) characteristics revealed that infant-feeding practices were not related to CV functioning in the predicted directions among this sample of 3 or 4 year old children. Furthermore, the positive relationship between height and systolic blood pressure was inconsistent with the Barker hypothesis.

Black or African American↗