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Biomedical subjects

T V Nguyen

Publications and source records attributed to T V Nguyen.

At least 109 records · Page 6Linked to original sources

Clinical response to non-steroidal anti-inflammatory drugs in urate-crystal induced inflammation: a simultaneous study of intersubject and intrasubject variability.

1. It is well known that an individual subject often responds preferentially to a particular nonsteroidal anti-inflammatory drug (NSAID) and clinical response to these drugs is characterised by considerable variability between individuals. Variability in response has often been attributed to the episodic nature of musculoskeletal disease. Few studies have studied intrasubject variability in response to these drugs using a multiple crossover design. A major difficulty has been the lack of objective, validated measures of inflammation sensitive to NSAIDs. The primary aim of the present study was to test the utility of urate-crystal induced inflammation as a tool to predict NSAID response in humans. 2. An inflammatory reaction was established in twenty-five healthy subjects with intradermal injection of urate crystals on four separate occasions separated by 1 week. Each subject was randomly assigned to receive either ibuprofen on two of these occasions (800 mg four times over 36 h) or matched placebo on the other two occasions using a double-blind, cross-over design. Decrease in the area under the wheal size-time curve was used to indicate anti-inflammatory response. 3. Peak inflammatory response was observed at about 32 h and had dissipated by 56 h post-urate injection. The logarithmic mean wheal area was significantly lower after ibuprofen (mean +/- s.e. mean; 6.74 +/- 0.09) compared with placebo (6.96 +/- 0.07 mm h); a difference of 20% (95% confidence interval for difference: 1 to 35%; P < 0.05). 4. There was marked intra- and intersubject variability in response to ibuprofen over the four treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bleomycin-induced flagellate dermatitis: a clinical and histopathological review.

We report a case of bleomycin-induced flagellate dermatitis. Our patient developed pruritic linear lesions 4 days after her first dose of bleomycin. A closed patch test was performed, and was negative. However, on rechallenge, the linear eruption recurred in the previously involved sites, and in new sites, within 24 h. Flagellate dermatitis is a characteristic reaction to bleomycin use, but varying histological features and clinical presentations may be seen.

Adult↗

Arginine vasopressin and osmolality in the elderly.

OBJECTIVES: To evaluate the influence of age on plasma arginine vasopressin (AVP) concentrations and the relationship between plasma AVP and serum osmolality in younger and older subjects, and in the elderly, to assess the effect of gender on plasma AVP concentration and to determine the impact of prostaglandin blockade on renal responsiveness to AVP. DESIGN: Cross-sectional study; randomized, double-blind, crossover, placebo-controlled study. SETTING: The Renal Laboratory, Royal North Shore Hospital (younger adults) and Clinical Room, St Vincents Hospital (elderly subjects). PARTICIPANTS: 45 younger adults (35 +/- 9 years), and 41 elderly subjects (29 males, 12 females; 78 +/- 3 years). All subjects were healthy and non-institutionalized. The elderly subjects were screened to exclude significant pathology (clinical assessment, multiple investigations). INTERVENTION: Blood samples were drawn from all younger and elderly subjects. The elderly subjects were randomly allocated indomethacin or placebo for 1 month. Following a 1 to 2-week washout, the alternative was administered for a further 1 month. MAIN OUTCOME MEASURES: Plasma AVP and serum osmolality and plasma AVP, serum, and urine osmolality at baseline were measured on indomethacin and placebo. RESULTS: In the elderly subjects, baseline plasma AVP concentration was significantly higher than in the younger subjects studied (4.7 +/- 0.7 vs 2.1 +/- 0.2 pg/mL respectively; P = 0.0003). Plasma AVP was strongly correlated with serum osmolality in the younger subjects (r = 0.76, P = 0.0001) but not in the elderly cohort (r = -0.18, P = 0.26). No difference was found between the sexes in plasma AVP (P = 0.89), and indomethacin treatment did not alter the plasma AVP/urine osmolality ratio (P = 0.85) in the elderly subjects. In addition, changes in plasma AVP with indomethacin therapy did not correlate with changes in serum osmolality (r = 0.16, P = 0.09). CONCLUSIONS: Aging is accompanied by an increase in plasma AVP concentrations. In healthy, elderly subjects, plasma AVP is not dependent on serum osmolality and is not influenced by gender. Indomethacin has no effect on the renal responsiveness to plasma AVP.

Adult↗

Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover.

Circulating osteocalcin, a marker of bone formation, is under strong genetic influence, and this effect is related to the genetic influence on bone density. To examine genetic influences on bone turnover further, other markers of bone formation (serum carboxyterminal propeptide of type I procollagen, PICP), bone resorption (serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, ICTP), and nonosseous connective tissue synthesis (serum aminoterminal propeptide of type III procollagen, PIIINP) were studied in 82 female twin pairs: 42 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs (mean age, MZ; 48.4 yr; DZ; 45.6 yr). The intraclass correlation coefficients of MZ twin pairs, rMZ, for serum PICP (0.78) and serum ICTP (0.68) were significantly greater than the corresponding rDZ (0.31 and 0.36, respectively), but a genetic effect on serum PIIINP was not demonstrable. Within DZ twin pair differences in serum PICP predicted differences in lumbar spine bone density (r = -0.37); higher serum PICP levels indicating the twin with the lower lumbar spine bone density. Also within pair differences in serum ICTP and PICP predicted differences in bone density at the lumbar spine independent of serum osteocalcin. These data indicate that both synthesis and degradation of type I collagen are genetically determined and that this phenomenon is related to the genetic regulation of bone density.

Analysis of Variance↗

The cAMP-response-element-binding protein interacts, but Fos protein does not interact, with the proenkephalin enhancer in rat striatum.

The proenkephalin gene is a well-studied model of transcription factor-target gene interaction in the nervous system and has been proposed as a regulatory target of the protein product of the immediate-early gene c-fos. This regulatory mechanism has been proposed, in part, because the cAMP response element 2 (CRE-2) site, the key DNA regulatory element within the proenkephalin second-messenger-inducible enhancer, avidly binds AP-1 proteins, including Fos, in vitro. However, we observe a dissociation in the time course of activation of c-fos and proenkephalin mRNA in rat striatum after administration of the dopamine D2 receptor antagonist haloperidol. This result prompted us to investigate the composition of protein complexes in striatal nuclear extracts that bind to the CRE-2 site. Even though our striatal nuclear extracts had substantial basal and haloperidol-inducible AP-1-binding activities that contained Fos, we could not detect Fos in complexes bound to the CRE-2 element. Instead, as determined by antibody supershift analysis, we detect CRE-binding protein (CREB)-like proteins binding to CRE-2 in both basal and haloperidol-stimulated conditions. Finally, we show that haloperidol induces CREB protein phosphorylation in striatum.

Animals↗

In vivo induction of increased DNA ploidy of mouse cervicovaginal epithelium by neonatal estrogen treatment.

The purpose of this study was to test the hypothesis that exposure to natural estrogen early in the development of hormone-dependent tissue induces a change in nuclear DNA content. Female BALB/c mice were treated neonatally with daily s.c. injections of either 25 micrograms of 17 beta-estradiol (E2) in 0.02 ml of sesame oil (vehicle) or vehicle alone for 5 days. Treatment was begun either within 15 h of birth or 6 days after birth. One set each of 10-day-old E2-treated and control mice received s.c. pellet implants containing 15 mg of E2 and cholesterol (10% E2 and 90% cholesterol), a second set received implants containing 25 mg of cholesterol alone, and a third set did not receive implants. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 21, 40, 70, 180, or 240 days of age. The results obtained include several important findings: 1) neonatal E2 treatment in BALB/c mice causes an increase in nuclear DNA content in cervicovaginal epithelium; 2) short-term administration of secondary exogenous E2 reduces the latency period for the appearance of increased nuclear DNA content in neonatally E2-treated cervicovaginal epithelium; 3) increased nuclear DNA content can indicate abnormal cervicovaginal epithelium before histological abnormalities become evident; and 4) there is a sensitive period for neonatal E2 induction of increased nuclear DNA content in the cervicovaginal epithelium. These findings support other reports of the carcinogenic potential of estrogen in vivo. Therefore, increased DNA ploidy may be an important early detectable event in estrogen-induced carcinogenesis.

Aneuploidy↗

Hydroxyurea and lower leg ulcers.

We report four cases of cutaneous lower leg ulcers associated with hydroxyurea treatment for myeloproliferative disorders. This association has been reported in one other series of patients who had chronic myelogenous leukemia and were treated with hydroxyurea. A review of the literature and survey of possible pathogenetic mechanisms is presented.

Aged↗

Everything activates c-fos--how can it matter?

It is probably safe to say that the regulation of c-fos expression by drug treatment and other stimulus paradigms has biological specificity and mechanistic significance. However, as this brief essay makes clear, the immunohistochemical detection of c-fos is only the tip of the biological iceberg. IEGs deserve to be studied as critical components of the intracellular signaling machinery that may transduce intercellular signals, including those produced by drugs of abuse, into longer term changes in cellular function. However, the study of IEG expression must be related to biologically significant target genes and must be complemented by the study of phosphorylation of constitutively expressed transcription factors. Moreover, as illustrated by the proenkephalin gene, the regulation of genes that play important roles in differentiated cell function may differ depending on which cell types and stimulus conditions are investigated. Finally, attention must be paid to the complexities of gene regulation under conditions of repetitive and chronic stimulation if phenomena such as the neural substrates of drug dependence are to be understood.

Animals↗

Differential expression of c-fos and zif268 in rat striatum after haloperidol, clozapine, and amphetamine.

Antipsychotic drugs are monoamine receptor antagonists. However, the mechanisms by which these direct actions are translated into therapeutic effects are unknown. Candidate mechanisms include receptor-mediated regulation of gene expression in target neurons. Inducible transcription factors, including certain immediate early genes (IEGs), may mediate between receptor-activated second messenger systems and expression of genes involved in the differentiated functions of neurons. We examined the specificity of induction of the IEGs c-fos and zif268 after acute administration of several antipsychotic drugs and, for comparison, the stimulant amphetamine, which has pharmacologic effects relatively opposite to those of antipsychotics. Antipsychotic drugs with potent dopamine D2 receptor antagonist properties, such as haloperidol, induced both c-fos and zif268 mRNA in the caudate-putamen; however, the atypical antipsychotic drug clozapine induced zif268 but not c-fos mRNA in that region. Similarly, haloperidol, but not clozapine, induced c-Fos-like immunoreactivity in the caudate-putamen. In contrast, both drugs induced c-Fos-like immunoreactivity in the nucleus accumbens. Like haloperidol, amphetamine induced both c-fos and zif268 mRNA in the caudate-putamen, but the anatomic patterns of induction of c-Fos-like immunoreactivity by the two drugs were dramatically different. Haloperidol and amphetamine induced AP-1 binding activity in cell extracts from the caudate-putamen, indicating that drug-induced IEG expression results in protein products that may function in the regulation of target gene expression. Thus these data demonstrate that inductions of IEG expression by haloperidol, clozapine, and amphetamine are specific, may be biologically relevant, and suggest avenues for further investigation.

Amino Acid Isomerases↗

Vaginal birth after cesarean section at the University of Texas.

Vaginal delivery was successful in 76% of the 242 women who underwent a trial of labor after cesarean section in a prior pregnancy. Separation of the uterine scar occurred in four women (1.7%). Women whose prior cesarean section was for breech presentation had the highest rate of successful vaginal delivery (86%). The vaginal delivery rates were similar in women who delivered infants with birth weights > or = 4,000 g (73%) and < 4,000 g (76%). The use of epidural anesthesia and oxytocin may enhance the success of vaginal delivery in women undergoing a trial of labor following an earlier cesarean section.

Anesthesia, Epidural↗

Down-regulation of tryptamine binding sites following chronic molindone administration. A comparison with responses of dopamine and 5-hydroxytryptamine receptors.

The present study assessed changes of tryptamine, dopamine D2, 5-HT1 and 5-HT2 binding sites in rat brain following chronic treatment with low (5 mg/kg/day) and high (40 mg/kg/day) doses of molindone, a clinically effective psychotropic drug. The high-dose molindone treatment produced a decrease in the number of tryptamine binding sites while both high and low doses caused an increase in the number of dopamine D2 binding sites in the striatum. No significant changes were observed in either 5-HT1 or 5-HT2 binding sites in the cerebral cortex. Competition binding experiments showed that molindone was a potent inhibitor at dopamine D2 but less effective at tryptamine, 5-HT1 and 5-HT2 binding sites. The inhibition activity of molindone towards type A monoamine oxidase produced a significant increase in endogenous tryptamine accumulation rate which was much higher than that of dopamine and 5-HT. These findings suggest that the reduction in the number of tryptamine binding sites produced by chronic molindone administration is related to monoamine oxidase inhibition and that the increase in the number of dopamine D2 binding sites is correlated to receptor blocking activity of the drug.

Animals↗

Binding sites for brain trace amines.

1. Neurochemical, neuropharmacological, and neurophysiological studies suggest that some of the so-called trace amines may have a role in the modulation of neurotransmission. This review examines the possible existence and characterization of brain binding sites for the trace amines. 2. The results of radioligand binding studies carried out so far suggest the existence of tryptamine binding sites that possibly constitute a true functional receptor. This is supported by evidence obtained from the saturation studies, drug-mediated inhibition of binding, and the changes in the number of sites induced by pharmacological and lesion studies. In addition, the existence of a functional tryptamine binding site is supported by the increased neurophysiological responses of tryptamine obtained from the striatum of rat with unilateral substantia nigra lesions. 3. It has been shown that the brain contains saturable binding sites for rho-tyramine that appear to be related to the transport of dopamine into synaptic vesicles. There are, however, some questions with respect to the homogenization technique employed and some inconsistencies with respect to the number of binding sites estimated in neuronal membrane preparations. 4. The existence of rho-octopamine binding sites has been demonstrated in crude membranes obtained from fruitflies but not shown so far in vertebrates. 5. The presence of brain binding sites for beta-phenylethylamine are suggested but they are not so well defined and its physiological implication remains to be elucidated.

Animals↗

Lesion-induced reductions in trace amine accumulation: dependence on MAO inhibitor pretreatment.

Striatal amine levels were measured six weeks after unilateral injections of 6-OHDA (8 micrograms) into the substantia nigra in male Wistar rats pretreated with monoamine oxidase inhibitors. After (-) deprenyl.HCl pretreatment (2 mg.kg-1 SC 2hr), beta-phenylethylamine, m- and p-tyramine ipsilateral to the 6-OHDA lesion decreased to 50, 18 and 25% of contralateral levels. DA, DOPAC and HVA also decreased on the lesioned side. Ipsilateral concentrations of tryptamine, 5-HT, 5-HIAA, p-tyrosine and L-tryptophan concentrations were equivalent to contralateral values in this condition. In animals pretreated with pargyline.HCl (200 mg.kg-1 IP 2hr) m- and p-tyramine and tryptamine ipsilateral to the lesion decreased to 48, 59 and 57% of contralateral levels. Ipsilateral DA decreased to 26% of the contralateral value. Under these conditions no change in concentrations of beta-phenylethylamine or of the above acid metabolites or amino acids was observed. The masking of lesion-induced changes in beta-phenylethylamine by pargyline is attributed to the lipophilic nature of of this molecule and consequent diffusion of this amine from other areas after maximal monoamine oxidase inhibition. Conversely the failure to demonstrate lesion-induced changes in tryptamine with (-) deprenyl pretreatment is attributed to the nonselectivity of monoamine oxidase for tryptamine and activity of monoamine oxidase A under these conditions. These results indicate that for further assessment of lesion-induced changes in beta-phenylethylamie and of tryptamine the respective (-) deprenyl and pargyline pretreatments used in this study are appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Phytophotodermatitis: differentiation from jellyfish stings.

A patient with phytophotodermatitis secondary to topical application of lime juice for relief of pain from a recent marine sting is reported. The absence of pain over the entire lesion and the failure of the patient to develop immune specific antibodies to common local coelenterates aided in establishing the diagnosis.

Adult↗

Kinetics of intraventricularly injected trace amines and their deuterated isotopomers.

Intraventricular injection into the rat brain of four trace amines and a catecholamine resulted in rapid exponential loss of the amines in the first 30 minutes after injection. The half-lives were: phenylethylamine 3.8 min, para-tyramine 5.1 min, meta-tyramine 7.4 min and dopamine 8.0 min. Tryptamine showed a biphasic loss with half-lives of 4.7 min (over the 5 to 10 min period) and 14.1 min (10 to 30 min). The half-lives were substantially increased by deuterium labeling at the alpha carbon position: phenylethylamine 4.8 min, para-tyramine 8.8 min, meta-tyramine 14.1 min, dopamine 13.0 min and tryptamine 6.0 min (5 to 10 min period) and 28.7 min (10 to 20 min). The loss of the amines was reduced by monoamine oxidase inhibition by pargyline hydrochloride and the deuterium isotope effect was abolished. It is noteworthy that the half-life of dopamine was similar to those of the trace amines in this time period and that the trace amine half-lives after i.v. injection was longer than those obtained from measurements of increases of concentrations of endogenous amines after MAOI in vivo and that of dopamine shorter than values calculated from turnover measurements.

Animals↗

Local skin reaction caused by the plastic catheter tubing of the continuous subcutaneous insulin infusion system.

Since the first studies with the continuous subcutaneous insulin infusion portable pump were published in 1978, many associated complications have been reported. Cutaneous complications could be caused by infections or local reactions to insulin preparations, adhesive tapes, and needle material. This report identifies plastic tubing as another one of the triggering causes of cutaneous complications due to continuous subcutaneous insulin infusion.

Adult↗

Effect of intranigral administration of 6-hydroxydopamine and 5,7-dihydroxytryptamine on rat brain tryptamine.

Earlier experiments have shown that unilateral electrolytic lesions of the substantia nigra result in significant reductions in the rate of accumulation of rat striatal tryptamine. For elucidation of the type of neuronal degeneration that is associated with tryptamine depletion, the effects of intranigral injections of 6-hydroxydopamine or 5,7-dihydroxytryptamine, which would affect, respectively, dopamine- or indoleamine-containing neurons, have been assessed. Nigral 6-hydroxydopamine lesions resulted in an ipsilateral reduction in the rate of accumulation of striatal tryptamine, but no changes were observed after nigral injections of 5,7-dihydroxytryptamine. The present results suggest that decreases in the pargyline-induced accumulation of striatal tryptamine may be associated with lesions of the nigral dopamine-containing cell bodies. Alternatively, there may exist specific tryptamine-containing neurons that are damaged by 6-hydroxytryptamine and unaffected by 5,7-dihydroxytryptamine.

5,7-Dihydroxytryptamine↗