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Biomedical subjects

G Santiago

Publications and source records attributed to G Santiago.

At least 19 recordsLinked to original sources
PubMed2001

Role of membrane charge and semiquinone structure on naphthosemiquinone derivatives and 1,4-benzosemiquinone disproportionation and membrane-buffer distribution coefficients.

Semiquinone membrane/buffer partition coefficients have been determined for 1,2-naphthosemiquinone (ONQ.-), 1,4-naphthosemiquinone (NQ.-) and two of its hydroxylated derivatives, 5,8-dihydroxy-1,4-naphthosemiquinone (NZQ.-) and 5-hydroxy-1,4-naphthosemiquinone (JQ.-) as a function of membrane charge in multilamellar vesicles of phosphatidylcholine (PC) and equimolar mixtures of this lipid and phosphatidic acid (PC:PA) and cetyltrimethylammonium bromide (PC:CTAB) at physiological pH with the exception of values corresponding to PC:PA mixtures which were obtained at pH 9. These coefficients follow the order PC:PA < PC < PC:CTAB in agreement with the negative charge of the semiquinones. The disproportionation equilibria of the naphthosemiquinone derivatives are shifted to the semiquinone in the presence of neutral and positive membranes, being more pronounced in the latter. However, very low partition coefficients as well as small shifts in the semiquinone disproportionation equilibrium were observed for ONQ.- as compared to the other semiquinones. No partition of 1,4-benzosemiquinone (BQ.-) into the lipid phase was detected for either charged or neutral lipid membranes. The presence of lipid membranes decreases the BQ.- equilibrium concentration in the presence of all the types of membranes considered here.

Benzoquinones↗
PubMed2001

In vivo inhibition of Fas ligand-mediated killing by TR6, a Fas ligand decoy receptor.

TR6, a member of the tumor necrosis factor (TNF) receptor superfamily, has recently been shown to bind to Fas ligand (FasL) and inhibit FasL-mediated cell killing in vitro. In the current study, we demonstrate that TR6 can block the lethal activity of FasL in multiple in vitro systems, and extend this finding to an in vivo model of hepatitis. The binding of human TR6 to human FasL was verified with BIAcore chip technology. Human primary hepatocytes, HT-29 cells and Jurkat cells were assayed for viability to demonstrate TR6 inhibition of FasL-mediated cytotoxicity in vitro. Human TR6 was also shown to cross-react with membrane-bound mouse FasL, since the in vitro cytotoxic activity of L929 cells transfected with murine FasL was inhibited in the presence of human TR6. In vivo, FasL-induced acute, lethal, fulminant hepatic apoptosis resulting in death within 2 h of intravenous injection into Fas+ mice, but not Fas- MRL/lpr mice. Pretreatment of mice with TR6 blocked FasL-induced mortality, presumably by attenuating FasL-induced hepatic apoptosis. Thus, in both in vitro and in vivo systems, TR6 acts as a functional FasL decoy receptor and may be clinically useful in the treatment of hepatitis and other diseases associated with FasL-mediated tissue injury.

Animals↗
PubMed2000

Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats.

Keratinocyte growth factor-2 (KGF-2, repifermin) is a homolog of KGF-1 with epithelial mitogenic activities. We investigated the therapeutic role of KGF-2 in intestinal ulceration and its mechanisms of protection. KGF-2 (0.3-5 mg/kg) was administered before or after induction of small intestinal ulceration by indomethacin (Indo) in prevention and treatment protocols. In acute studies, KGF-2 was injected for up to 7 days before or daily for 5 days after Indo. In a 15-day chronic study, KGF-2 was injected intravenously daily beginning before or 7 days after Indo. Injury was evaluated by blinded macroscopic and microscopic inflammatory scores, epithelial BrdU staining, tissue IL-1beta, PGE(2), and hydroxyproline concentrations, and collagen type I RNA expression. In vitro effects of KGF-2 were evaluated by epithelial cellular proliferation, restitution of wounded monolayers, PGE(2) secretion, and expression of COX-2 and collagen mRNA. Intravenous KGF-2 significantly decreased acute intestinal injury by all parameters and significantly decreased chronic ulceration. Pretreatment, daily infusion, and delayed treatment were effective. KGF-2 promoted in vitro epithelial restitution with only modest effects on epithelial cell proliferation, stimulated COX-2 expression in cultured epithelial cells, and upregulated in vitro and in vivo PGE(2) production. KGF-2 did not affect in vivo fibrosis, although it induced collagen expression in cultured intestinal myofibroblasts. These results suggest that KGF-2 inhibits intestinal inflammation by stimulating epithelial restitution and protective PGs.

Acute Disease↗
PubMed1999

Efficacy of keratinocyte growth factor-2 in dextran sulfate sodium-induced murine colitis.

The purpose of this study was to determine the efficacy of a novel human protein, keratinocyte growth factor-2 (KGF-2), in a model of murine colitis induced by ad libitum exposure to a 4% solution of dextran sulfate sodium (DSS) in the drinking water. Initial evaluation of KGF-2 was based on its ability to reduce weight loss, stool score, and histological score in mice exposed to DSS for 7 days. When KGF-2 (0.1-10.0 mg/kg i.p. or s.c.) was injected daily into DSS-treated mice from day 0 to 7, it significantly reduced all three parameters in a dose-response fashion, with a minimum effective dose of between 1 and 3 mg/kg. When KGF-2 was given therapeutically, starting 4 days after initiation of the 7-day DSS treatment, the 3- but not the 0.5-mg/kg dose significantly enhanced weight recovery after discontinuation of DSS treatment. When DSS treatment was prolonged beyond the normal 7 days, therapeutic intervention on day 2 or 4 also significantly reduced mortality, weight loss, and stool score at the 1- and 3-mg/kg dose. Therapeutic treatment also resulted in reduction of colon myloperoxidase levels by more than 50%. These experiments suggest that KGF-2 may be clinically useful in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.

Animals↗
PubMed1997

Adriamycin and daunomycin semiquinone membrane/buffer partition constants using the spin-broadening technique.

Membrane/buffer partition constants have been determined for the semiquinones of adriamycin, Adrsq, and daunomycin, Daunosq, as a function of ionic strength and cholesterol content in phosphatidylcholine multilamellar vesicles using the spin-broadening technique. The partition constants corresponding to Adrsq were essentially similar to those of Daunosq under any of the conditions studied. These constants increase with ionic strength increase and decrease with an increase in cholesterol concentration at the membrane. These observations could have implications in the Adr and Dauno cytotoxicities where their corresponding semiquinones are postulated as important intermediates and consequently their interactions with biological membranes should also be considered as important.

Antibiotics, Antineoplastic↗
PubMed1994

High affinity [3H]glutamate uptake systems in normal and audiogenic seizure-susceptible mice.

Two high affinity sodium-dependent and PDC-sensitive glutamate (GLU) uptake systems are present in a whole brain synaptosomal preparation from adult C57BL/10 SPS/SPS normal mice. System 1 has an apparent Km of 3.65 microM while that of System 2 is 46.8 microM. Glutamate uptake in the normal mice increases gradually during development, displaying a striking peak at postnatal day 15, and decreases rapidly between PN 16 and PN 20 until it reaches adult levels. The developmental pattern of GLU uptake System 1 and System 2 in audiogenic seizure susceptible mice is similar to that described in normal mice. However, there are differences between GLU uptake system 1 and 2 during ontogenesis: (1) System 1 could not be detected until PN 15 while being markedly diminished in adulthood; and (2) GLU uptake by System 2 is increased in adults. In addition, the Umax for System 2 is significantly greater than that of normal mice at PN 2 and PN 15.

Acoustic Stimulation↗
PubMed1991

Inhibition of high-affinity [3H]L-proline binding to rat brain membranes by 2-amino-7-phosphonoheptanoic acid.

L-Glutamate and 2-amino-7-phosphonoheptanoic acid [corrected] (AP-7) (10(-9) to 10(-6) M), a competitive NMDA (N-methyl-D-aspartate) antagonist, inhibit approximately 60% of [3H]L-proline binding to rat membranes from midbrain. In hippocampal membranes, AP-7 inhibits proline binding by 80%, while in cerebellar membranes AP-7 had little effect. These results are indicative of the possible neuromodulatory role of proline in the central nervous system, possibly through the NMDA receptor(s).

2-Amino-5-phosphonovalerate↗
PubMed1976

Measured intelligence in offspring of oral and nonoral contraceptive users.

A study has been made of measures of intelligence of 210 children (5 to 8 years of age) born to mothers who used oral and nonoral contraceptives pregestationally. Ninety-six of these children were born to mothers who used oral contraceptives, and one hundred and fourteen were born to mothers who used vaginal contraceptive methods. The intelligence of the children was measured in the form of the full-scale I.Q. score by the Wechsler Intelligence Scale for Children (WISC) adapted and normalized for Puerto Rico by the Puerto Rico Department of Education. A three-factor analysis of variance was performed on the data collected for comparison of the two groups. It was observed that there was no significant difference between the average I.Q. scores of children born to mothers using oral contraceptives and those born to the mothers using nonoral contraceptives. The average I.Q. in children of the oral contraceptive group was 85.04 and that in children of the nonoral contraceptive group was 85.54. Distributions for both groups were also found to be similar. No significant differences between means were observed for sex, age, and interacitons with the exception of the age and sex interaction, where, again, no specific, meaningful trend could be established. The average I.Q. in the sample fell very close to the center of the "normal" range of the WISC, Puerto Rican adaptation. The results of the study do not offer any evidence as to the effect of the use of oral contraceptives on the intelligence measure (by the WISC) of the offspring born to mothers using them pregestationally. The children under study, on an average, are of "normal" intelligence as measured by the Puerto Rican intelligence standards.

Adult↗
PubMedDate not supplied

Possible regulation of high-affinity glutamate uptake in synaptosomes of normal and epileptic mice.

Glutamate (Glu) uptake is the primary mechanism for its removal from the synapse. In genetic audiogenic seizures (AGS), Glu uptake is elevated prior to the appearance of seizures. Increased Glu uptake is also observed in synaptosomes from normal mice preincubated with lithium or nitroarginine, an NO synthase inhibitor. Pertussis and cholera toxins cause a marked reduction in Glu uptake. In contrast, neither lithium nor nitroarginine affected Glu uptake by synaptosomes from genetic epileptic mice. Arachidonic acid inhibits Glu uptake, whereas synaptosomes from epileptic mouse brain appear to be more sensitive to arachidonic acid as indicated by a shift of the inhibition curve to the left. These observations are indicative of the possible regulation of Glu uptake by second messengers and its alteration in genetic epilepsy.

Acoustic Stimulation↗