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Biomedical subjects

C Flores

Publications and source records attributed to C Flores.

At least 55 records · Page 3Linked to original sources
PubMed1998

Long-lasting induction of astrocytic basic fibroblast growth factor by repeated injections of amphetamine: blockade by concurrent treatment with a glutamate antagonist.

Repeated administration of stimulant drugs leads to lasting changes in their behavioral and neurochemical effects. These changes are initiated by drug actions in the somatodendritic regions of midbrain dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) and continue to develop for a period of time after termination of drug treatment. Here we show that repeated administration of amphetamine (3.0 mg/kg, i.p.; three injections, once every other day) results in sustained increases in basic fibroblast growth factor immunoreactivity (bFGF-IR) in both VTA and SNc, 200-500% over that seen in saline-treated animals. Increases were observed 24 hr, 72 hr, 1 week and 1 month after the last drug injection. Because glutamate participates in the development of sensitization to stimulant drugs, we assessed the effect of the glutamate antagonist, kynurenic acid (KYN), on amphetamine-induced bFGF-IR. Coadministration of KYN prevented the increases in bFGF-IR in both VTA and SNc assessed 1 week after the amphetamine treatment. No changes in bFGF-IR were observed in the nucleus accumbens or dorsal striatum. bFGF-IR was found to be associated with astrocytes and not with dopaminergic neurons. These findings suggest that sustained enhancement of astrocytic bFGF expression in DA somatodendritic regions is a mechanism whereby stimulant drugs exert enduring effects on midbrain DA function. We hypothesize that increased glutamatergic activity elicited by amphetamine and other stimulant drugs places excessive demands on the functioning of DA neurons recruiting regulatory and neuroprotective processes that lead to enduring changes in DA neuron functioning and connectivity.

Amphetamine↗
PubMed1998

Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro.

To determine whether adefovir is active against lamivudine-resistant hepatitis B virus (HBV), the inhibition constants of adefovir diphosphate and lamivudine triphosphate for wild-type and mutant human HBV DNA polymerases, which contain amino acid substitutions associated with lamivudine resistance, were compared. Recombinant wild-type and mutant human HBV DNA polymerases were expressed and substantially purified using a baculovirus expression system and immunoaffinity chromatography. HBV DNA polymerase mutants M552I, M552V, and L528M/M552V showed resistance to lamivudine triphosphate with inhibition constants (Ki) increased by 8.0-fold, 19.6-fold, and 25.2-fold compared with that of wild-type HBV DNA polymerase. However, these mutants remained sensitive to adefovir diphosphate with the inhibition constants increasing by 1.3-fold and 2.2-fold or decreasing by 0.79-fold. The L528M single mutation, identified in patients with increasing HBV DNA levels during therapy with famciclovir, also remained sensitive to adefovir diphosphate with the inhibition constant increased by only 2.3-fold.

Adenine↗
PubMed1997

In vitro characterization of the anti-human cytomegalovirus activity of PMEA (Adefovir).

PMEA [9-[2-(phosphonomethoxy)ethyl]adenine; adefovir] has shown anti-cytomegalovirus activity in animal models and in preliminary human trials. PMEA diphosphate (PMEApp), the active antiviral metabolite of PMEA, is a potent inhibitor of human cytomegalovirus (HCMV) DNA polymerase. PMEA is efficiently taken up and phosphorylated to PMEApp in numerous human cell lines. In vitro replication of wild type and drug resistant HCMV clinical isolates is effectively inhibited by PMEA. PMEA in combination with other anti-HCMV agents shows additive inhibition of HCMV replication.

Adenine↗
PubMed1997

Fos-like immunoreactivity in the caudal diencephalon and brainstem following lateral hypothalamic self-stimulation.

Fos immunohistochemistry was used to stain neurons in the caudal diencephalon, midbrain and hindbrain driven by rewarding stimulation of the lateral hypothalamus (LH). Increases in Fos-like immunoreactivity were most pronounced ipsilateral to the site of stimulation and tended to be confined within discrete structures such as the posterior LH, arcuate nucleus, ventral tegmental area (VTA), central gray, dorsal raphé, pedunculopontine area (PPTg), parabrachial nucleus, and locus coeruleus. At least two of these structures, the VTA and PPTg, have been implicated in medial forebrain bundle self-stimulation.

Animals↗
PubMed1997

Fos-like immunoreactivity in forebrain regions following self-stimulation of the lateral hypothalamus and the ventral tegmental area.

According to the descending-path hypothesis, the direct excitation of descending fibers linking the lateral hypothalamus (LH) and ventral tegmental area (VTA) contributes to the rewarding effect produced by electrical stimulation of the medial forebrain bundle (MFB). To visualize forebrain neurons activated by stimulation of both the LH and VTA, Fos-like immunoreactivity (FLIR) in forebrain regions was assessed following self-stimulation of these two sites in male rats. Among the regions where FLIR was greater in the stimulated hemisphere following either LH or VTA stimulation were the anterior LH, the substantia innominata, and the bed nucleus of the stria terminalis, and olfactory tubercle. These findings are analyzed with reference to the effects of forebrain lesions on self-stimulation of the MFB. Advantages and limitations of using FLIR to identify neurons activated by rewarding stimulation are discussed.

Animals↗
PubMed1997

AZT induces high frequency, rapid amplification of centromeric DNA.

The reverse transcriptase inhibitor 3'-azido-deoxythymidine (AZT) has previously been shown to be incorporated into specific regions near the telomeres and centromeres of Chinese hamster ovary cell chromosomes. Our investigation of the effects of AZT on chromosome stability has led to the discovery of a high frequency amplification of telomere-like centromeric DNA. The amplified structures, when analyzed cytogenetically, appear as tandem arrays of tightly clustered blocks of centromeric repeats containing telomeric sequences (TTAGGG)n. There were 5-13 blocks of amplified DNA per structure. These structures form rapidly within one or two cell cycles and can be observed with an incidence as high as 2%. Because the amplification was so rapid, we tested whether the amplification structures could be the result of aberrant overreplication by analyzing BrdU incorporation. Our results indicate that the amplified DNA does not undergo abnormal replication during its formation, but appears to form from existing centromeric regions. We propose a model that involves the excision of multiple centromeric DNA regions from other chromosomes and their relocalization to a new site.

Animals↗
PubMed1996

Increased ipsilateral expression of Fos following lateral hypothalamic self-stimulation.

Immunohistochemical labeling of Fos protein was used to visualize neurons activated by rewarding stimulation of the lateral hypothalamic level of the medial forebrain bundle (MFB). Following training and stabilization of performance, seven rats were allowed to self-stimulate for 1 h prior to anesthesia and perfusion. Brains were then processed for immunohistochemistry. Two control subjects were trained and tested in an identical manner except that the stimulator was disconnected during the final 1 h test. Among the structures showing a greater density of labeled neurons on the stimulated side of the brains of the experimental subjects were the septum, lateral preoptic area (LPO), medial preoptic area, bed nucleus of the stria terminalis, substantia innominata (SI), and the lateral hypothalamus (LH). Several of these structures, the LPO, SI, and LH, have been implicated in MFB self-stimulation by the results of psychophysical, electrophysiological, and lesion studies.

Animals↗
PubMed1996

Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein.

Tight junctions, the most apical of the intercellular junctions that connect individual cells in a epithelial sheet, are thought to form a seal that restricts paracellular and intramembrane diffusion. To analyze the functioning of tight junctions, we generated stable MDCK strain 2 cell lines expressing either full-length or COOH-terminally truncated chicken occludin, the only known transmembrane component of tight junctions. Confocal immunofluorescence and immunoelectron microscopy demonstrated that mutant occludin was incorporated into tight junctions but, in contrast to full-length chicken occludin, exhibited a discontinuous junctional staining pattern and also disrupted the continuous junctional ring formed by endogenous occludin. This rearrangement of occludin was not paralleled by apparent changes in the junctional morphology as seen by thin section electron microscopy nor apparent discontinuities of the junctional strands observed by freeze-fracture. Nevertheless, expression of both wild-type and mutant occludin induced increased transepithelial electrical resistance (TER). In contrast to TER, particularly the expression of COOH-terminally truncated occludin led to a severalfold increase in paracellular flux of small molecular weight tracers. Since the selectivity for size or different types of cations was unchanged, expression of wild-type and mutant occludin appears to have activated an existing mechanism that allows selective paracellular flux in the presence of electrically sealed tight junctions. Occludin is also involved in the formation of the apical/basolateral intramembrane diffusion barrier, since expression of the COOH-terminally truncated occludin was found to render MDCK cells incapable of maintaining a fluorescent lipid in a specifically labeled cell surface domain.

Amino Acid Sequence↗
PubMed1996

Pericardial effusion. Unusual complication in thyroid cancer.

A case in which a prolonged hypothyroid state resulted in development of a pericardial effusion is presented. The compensatory mechanism for protein homeostasis is lost in severe hypothyroidism. Iodine is transported to the pericardial space, which is filled with a high-protein content fluid and remains trapped. The mechanism for the accumulation of the fluid in the pericardial space is discussed. To prevent this unusual but dangerous complication, the authors recommend close monitoring of the patient's clinical status and serum thyroid stimulating hormone. The use of a short acting thyroxine substitute for at least 2 weeks can decrease occurrence of this complication and will shorten the time the patient needs to be hypothyroid.

Adult↗
PubMed1995

Is the course of neurocysticercosis modified by treatment with antihelminthic agents?

BACKGROUND: Neurocysticercosis, occasionally associated with long-term neurologic sequelae such as epilepsy or hydrocephalus, is more often a condition characterized by a benign course and spontaneous remission without permanent neurologic symptoms. This variability in outcome has led to difficulties in the interpretation of studies of the effectiveness of drugs used to treat this condition. OBJECTIVE: To evaluate the relative efficacy of two antihelminthic agents against each other and against symptomatic treatment alone. METHODS: Randomized clinical trial of treatment of patients with newly identified active neurocysticercosis with oral prednisolone alone (27 patients), praziquantel with prednisolone (54 patients), or albendazole with prednisolone (57 patients). RESULTS: At 6 months and at 1 year after treatment, there were no differences in the three treatment groups in terms of the proportion of patients who were free of cysts or the relative reduction of number of cysts. At 2 years, there was no difference in the proportion of patients free of seizures during the entire follow-up period. Early and late sequelae occurred in a higher proportion of patients treated with praziquantel and albendazole, compared with those receiving only prednisolone. CONCLUSIONS: Previous reports of favorable response to treatment of neurocysticercosis with either praziquantel or albendazole are by no means definitive and may be a reflection of the natural history of the condition. The present study, with randomized treatment assignment and including a control group, raises questions as to what extent and in whom treatment with these drugs is effective, and suggests that treatment with antihelminthic agents may be associated with an increased frequency of long-term sequelae.

Adult↗
PubMed1994

Effects of sialoadenectomy and epidermal growth factor on testicular function of sexually mature male mice.

The effect of sialoadenectomy (Sx) and epidermal growth factor (EGF) administration on testicular function was investigated in 8-week old C3H mice. Animals were divided initially into three groups: sham operated controls, Sx, and Sx + EGF treated (100 micrograms./kg./day subcutaneously for 28 days). Sialoadenectomy completely depleted the circulating levels of EGF and reduced body weight and reproductive organ weights. However, kidney weight was not affected. Quantitative analysis of spermatogenesis showed a decrease in preleptotene and pachytene spermatocytes and round spermatids, which resulted in a decrease in sperm counts. Sperm motility and fertility were also significantly decreased. Endocrinologic studies showed a 2- and 6-fold elevation in intratesticular and serum levels of testosterone and a decrease in luteinizing hormone (LH) levels. Follicle stimulating hormone levels were not altered. Administration of EGF to the Sx animals maintained reproductive organ weights, spermatogenesis and levels of LH and testosterone closer to control values; however, sperm motility was not maintained at control value. That sialoadenectomy resulted in a decline in androgen-dependent parameters, in spite of an elevation in testosterone levels, and EGF maintained them closer to the control value suggested that EGF may modulate androgen action. A comparison was therefore carried out between the effects of Sx and administration of flutamide (F), an androgen receptor blocker. Animals were subjected to Sx, F treatment (100 mg./kg./day subcutaneously for 28 days), Sx + F, or Sx + F + EGF. The effects of Sx and F treatment on organ weights, sperm counts and sperm motility were more or less similar. As expected, flutamide treatment increased LH and FSH levels, and testosterone levels were normal. The Sx + F animals showed no further decrease in organ weights, sperm count and motility. Treatment with Sx + F increased intratesticular and serum levels of testosterone by 2- and 10-fold. Circulating levels of LH and FSH were the same as in the flutamide-treated group. Administration of EGF to Sx + F maintained all these parameters, except sperm motility, closer to the control value. These results suggest that EGF either bypasses flutamide effects and acts directly or that EGF modulates androgen action at one or more steps in the signal transduction pathway in the male reproductive organs.

Animals↗
PubMed1994

[Bacterial infections in hepatic cirrhosis].

The aim of this work was to study the prevalence of bacterial infections in hospitalized patients with liver cirrhosis and to compare clinical, bacteriological and evolution features of patients with (group 1) and without bacterial infections (group 2). One hundred thirty two hospitalized patients with liver cirrhosis were prospectively studied and 61 episodes of bacterial infections were diagnosed in 52 (27 spontaneous bacterial peritonitis (44.3%), 16 urinary tract infections (26.2%), 10 pneumonias (16.4%), 3 spontaneous bacteremias (4.9%9, and 5 miscellaneous infections (8.2%)). Twenty six percent of infections were nosocomial. Child-Pugh score was 12 +/- 2 in group 1 vs 10 +/- 2 in group 2 (p = 0.047). Sixty five percent of identified microorganisms were gram negative and 61.5% of these were E. coli. Hospital mortality of group 1 was 29% and that of group 2 was 9% (p = 0.002). It is concluded that there is a high prevalence of bacterial infections in hospitalized cirrhotic patients, that is associated to a high mortality.

Adult↗
PubMed1992

Epidermal growth factor: receptor binding and effects on the sex accessory organs of sexually mature male mice.

The role of epidermal growth factor (EGF) in maintaining the integrity of the male sex accessory glands was investigated in the mouse. In the sexually mature male C3H mouse, EGF levels were highest in the submandibular gland, followed by the seminal vesicles and the prostate. Twenty eight days after sialoadenectomy (Sx), EGF fell below detectable limits in the serum and in the seminal vesicles. However, the prostate still retained 22% of its immunoreactive EGF. There was a seven-fold increase in serum testosterone after sialoadenectomy. Despite this drastic rise in testosterone, both prostatic and seminal vesicular weights were reduced, serum levels of LH were suppressed only by 37% and FSH levels were not altered. All these changes were abolished by the simultaneous administration of exogenous EGF at 100 micrograms./kg./day for 28 days. Both prostatic and seminal vesicular membranes contained binding sites for 125I-EGF. Binding was maximal after one hour of incubation at room temperature. Two classes of binding sites were shown for either organ (Kd = 1.2 nM, n = 56 fmol/mg. and Kd = 74 nM, n = 540 fmol/mg. for prostate; Kd = 0.9 nM, n = 29 fmol/mg. and Kd = 93 nM, n = 150 fmol/mg. for seminal vesicle). The binding of 125I-EGF was displaced by excess EGF and TGF-alpha but not by insulin, ILGF-2 and PDGF. These data suggest that EGF may have an important role in maintaining the integrity of the seminal vesicle and the prostate in the mouse. While the seminal vesicle appears to acquire EGF by uptake from the environment, the prostate may have the ability to synthesize EGF locally.

Animals↗
PubMed1992

Short term effects of cis-platinum on male reproduction, fertility and pregnancy outcome.

In order to find out the short term effects of cis-platinum treatment on reproductive function of the treated male rats and their progeny, sexually mature male Sprague-Dawley rats were given a single intra-peritoneal injection of either saline or cis-platinum (2, 4, 8 mg./kg.body wt.). One week following the treatment, the animals were mated with proestrus females of proven fertility. The females were scored positive or negative depending upon whether or not spermatozoa were seen in the vaginal smear after mating. However, all the females were watched until day 18, and on day 19, the females that became pregnant were subjected to laparotomy, and the number of corpora lutea, implantation sites and fetuses were counted. The fetuses were weighted and observed for the presence of any morphological abnormalities. Significant pre-implantation loss was seen in the treated groups. The weights of the fetuses were also significantly lower than those from the control group. Analysis of the effects of cis-platinum on the reproductive system of treated males revealed that cis-platinum reduced the reproductive organ weights, sperm counts, sperm motility, fertility and the levels of testosterone, LH and FSH. These results suggest that cis-platinum has a profound deleterious effect on the reproductive system and on the fertility potential of the treated male rats.

Animals↗
PubMed1992

The effects of an LHRH agonist on testicular function in the cryptorchid rat.

To assess the effects of an LHRH analog (LHRH-ethylamide des gly10 D-Leu6) on the function of the cryptorchid testis, an animal model was created, using prepubertal male Sprague-Dawley rats (21 days old). The animals were divided into six groups: 1) sham operated; 2) sham + LHRH treated; 3) cryptorchid; 4) cryptorchid + LHRH treated; 5) cryptorchid and orchidopexed; 6) cryptorchid, LHRH treated and orchidopexed. Two weeks post cryptorchidism, the animals were treated with either saline or LHRH-analog (one microgram./rat/day) subcutaneously for a total of twenty five days. Orchidopexy was performed following hormonal treatment. The effects of treatment were assessed in terms of body and reproductive organ weights, serum testosterone and LH levels, sperm counts and motility and fertility. The results demonstrated that experimental cryptorchidism impaired reproductive function, which was restored by orchidopexy, alone. Treatment of cryptorchid rats (groups 4 and 6) with LHRH did not produce any lasting improvement in spermatogenesis or fertility.

Animals↗
PubMed1992

The mechanism of cyclosporine's action in the inhibition of testosterone biosynthesis by rat Leydig cells in vitro.

We have previously demonstrated that cyclosporine inhibits testosterone (T) biosynthesis in vivo. To better understand the mechanism by which CsA inhibits T synthesis, interstitial cells were isolated from rat testes and incubated in the standard medium 199 with or without CsA (0-10 micrograms/ml) in the presence or absence of human chorionic gonadotropin (hCG, 10(-7) M) and 8-bromo cyclic AMP (cAMP, 0.5 mM) for 3 hr at 32 degrees C. The levels of cAMP and T were determined by RIA. CsA did not inhibit the basal secretion of T, but inhibited hCG-stimulated T production in a dose-dependent manner (4 ng/10(6) cells vs. 10 ng/10(6) cells at a CsA dose of 5 micrograms/ml, P less than 0.05). Radioligand binding of 125I-hLH to testicular membranes was not affected by CsA, as CsA did not compete with hCG/LH for binding sites (25-28% binding with or without CsA). Similarly, the MIX-stimulated cAMP production was not affected by CsA (24.03 +/- 1.09 vs. 20.60 +/- 0.38 pmol/10(6) cells), suggesting that CsA does not inhibit the accumulation of the second messenger. However, when interstitial cells were incubated with CsA in the presence of cAMP, a significant dose-dependent decline in T secretion was observed (7 ng/10(6) cells vs. 20 ng/10(6) cells at a CsA dose of 5 micrograms/ml). To determine whether CsA inhibits the steps beyond cAMP stimulation of T secretion, the kinetic parameters (Km and Vmax) of steroidogenic enzymes, delta 4-3 keto-17 alpha hydroxylase (17 alpha-hydroxylase), and delta 4-3 keto-17 beta hydroxy steroid dehydrogenase (17B-HSD) were determined by using Michaelis Menten analysis. Results are shown in the presence of CsA vs. no CsA: Km and Vmax values for 17 alpha-hydroxylase were (2.32 vs. 7.98 microM) and (27.96 vs. 100.97 pmol/mg protein/min), respectively. For 17B-HSD the Km and Vmax were (2.14 vs. 1.52 microM) and (15 vs. 15 pmol/mg protein/min), respectively. These results indicate that CsA inhibits the activity of 17 alpha-hydroxylase uncompetitively and 17B-HSD activity competitively. In conclusion the primary site for CsA inhibition is the cAMP stimulation and, CsA inhibits T synthesis at multiple sites.

Animals↗