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Biomedical subjects

L Hernandez

Publications and source records attributed to L Hernandez.

At least 109 records · Page 6Linked to original sources
PubMed1992

Demonstration of ryanodine-induced metabolic effects in rat liver.

The effects of ryanodine, a plant alkaloid which alters Ca2+ sequestration in the liver, on O2 uptake and gluconeogenesis were measured. Ryanodine administration to perfused rat liver resulted in the stimulation of O2 uptake and of gluconeogenesis. Because ryanodine does not affect directly mitochondrial respiration, its stimulatory effect on O2 uptake in the whole cell is likely to be secondary to the increased cytosolic free Ca2+ levels.

Animals↗
PubMed1992

Activation of a beta-hydroxyalkylnitrosamine to alkylating agents: evidence for the involvement of a sulfotransferase.

N-Nitrosomethyl(2-hydroxyethyl)amine (NMHEA), when administered by gavage, is a strong liver carcinogen in F344 female rats, but a weak liver carcinogen in male rats. After repeated exposure to NMHEA, either in drinking water or by gavage, female rats accumulated higher levels of DNA-guanine adducts than did their male counterparts, suggesting a correlation with the observed disparity in carcinogenicity. NMHEA has been shown to alkylate rat liver DNA in vivo in a dose-dependent manner. Chemical investigations of NMHEA suggest that it becomes a strong electrophile when a good leaving group is substituted on the hydroxyl. We have proposed that NMHEA is activated to its ultimate carcinogenic form by conjugation with sulfate. The sulfate ester was postulated to undergo rapid cyclization to 3-methyl-1,2,3-oxadizolinium ion, which has previously been found to be a potent methylating agent in vitro. The effect of sulfotransferase inhibitors on the DNA alkylation in rats by NMHEA was studied in vivo. Dichloronitrophenol, a powerful inhibitor of phenol sulfotransferase, had little effect on the methylation and O6-hydroxyethylation of DNA guanine in female rats, while depressing the hydroxyethylation of the N-7 position of guanine. Dichloronitrophenol, however, dramatically enhanced the methylation of DNA in male rats. It also slightly inhibited the N-nitrosodimethylamine-induced methylation of DNA. On the other hand, propylene glycol, an alcohol sulfotransferase inhibitor, had a profound inhibitory effect on DNA methylation induced by NMHEA, very little effect on the formation of N7-(2-hydroxyethyl)guanine, but a very strong effect on the O6-hydroxyethylguanine lesions. NMHEA-induced alkylation was also studied in male and female brachymorphic mice, which are deficient in the ability to synthesize the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate required for sulfotransferase activity, and their heterozygous siblings. No significant differences were seen between the heterozygous and brachymorphic mice in overall levels of alkylation, except in the case of 7-hydroxyethylation. In contrast to rats, male mice showed higher levels of formation of all DNA guanine adducts than did the females. However, propylene glycol was found to depress all the levels of alkylation in the brachymorphic mice, except for N7-(2-hydroxyethyl)guanine, as was observed in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylation↗
PubMed1992

Screening for antimicrobial activity of crude drug extracts and pure natural products from Mexican medicinal plants.

Preliminary antimicrobial screening against Candida albicans and selected Gram-positive and Gram-negative bacteria of methanol extracts prepared from eight Mexican medicinal plants, noted for their antiseptic properties, was conducted. The significant activity exhibited for extracts of Ratibida latipalearis, Teloxys graveolens, Dodonaea viscosa, Hyptis albida, H. pectinata, H. Suaveolens and H. verticillata tends to support their traditional use as anti-infective agents. Only the extract of Hintonia latiflora was inactive. The antimicrobial activities of 44 pure natural compounds and two derivatives were determined. Of these, only 23 compounds were effective in inhibiting the growth of the tested organisms (MIC less than or equal to 100 micrograms/ml).

Anti-Bacterial Agents↗
PubMed1992

In vivo evidence of hydroxyl radical formation after acute copper and ascorbic acid intake: electron spin resonance spin-trapping investigation.

Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the ESR spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl-N-t-butylnitrone (PBN). Because copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stabilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts were generated ex vivo and could be mistaken for radical adducts generated in vivo and excreted into the bile. Besides the PBN/.CH3 adduct, three other radical adducts were produced in vivo and excreted in bile.

Animals↗
PubMed1991

DNA methylation and oncogene expression in methapyrilene-induced rat liver tumors and in treated hepatocytes in culture.

Continued exposure of rats to carcinogenic doses of methapyrilene (MP) leads to elevated levels of 5-methyl-deoxycytidine (5MC) in liver DNA. Since gene expression often correlates with DNA methylation, we investigated these parameters in the MP-induced hepatocellular carcinomas of Fischer 344 rats. DNA was hypermethylated in liver tissue surrounding the tumors relative to liver tissue of untreated controls of the same age, while tumor DNA was not; DNA methylation declined to normal levels when MP treatment ceased. Gene expression analysis showed measurable levels of mRNA for c-Ki-ras, erb-B, erb-B2, hck, src, lyn, vav, trk, raf-1, l-myc, c-jun, c-yes, c-myc, c-abl, and p53. No significant differences in expression for these and other oncogenes were seen between tumors and surrounding livers, although erb-B2 and vav showed visible decreases compared with normal liver. Hypermethylation of DNA and expression of these oncogenes in MP-treated tissues were not correlated. Levels of mRNA for the same genes in MP-treated hepatocytes in culture were similar to in vivo levels; analysis of DNA synthesis levels showed that this gene expression pattern occurred in the absence of proliferation bursts or toxicity in these cells, thus suggesting that treatment in vivo may produce the same results.

Animals↗
PubMed1991

Bidirectional microdialysis in vivo shows differential dopaminergic potency of cocaine, procaine and lidocaine in the nucleus accumbens using capillary electrophoresis for calibration of drug outward diffusion.

Cocaine and two other local anesthetics were applied directly into the nucleus accumbens for 20 min by diffusion from a 4 mm microdialysis probe in freely moving rats. Cocaine (7.3 mM) increased the extracellular concentration of dopamine (DA). Equimolar procaine did also, but was not as potent as cocaine. Equimolar lidocaine had no effect. The concentration of these drugs outside the probe as measured by capillary electrophoresis in vitro was about 28% of that inside the probe, i.e. 72% remained inside. However, an in vivo test showed that about 53% cocaine and procaine, and 37% lidocaine remained in the perfusion fluid after passing through a probe inserted in the brain. This suggests that in vivo about 68 nmol cocaine diffused into the nucleus accumbens (NAC) during the 20 min. Five conclusions are drawn: (1) this confirms our earlier finding that local injection of cocaine increases extracellular DA, but in this case the cocaine was infused via the probe without disturbing the animal; (2) the action of cocaine on dopamine terminals in the accumbens is independent of local anesthesia; (3) procaine may enhance mood by a cocaine-like effect; (4) capillary electrophoresis has potential for measuring cocaine levels in small samples and (5) in vitro calibrations are of limited value to evaluate in vivo performance of microdialysis probes.

Animals↗
PubMed1991

A pilot study on the assessment of a progesterone/estradiol sustained release as once-a-month-injectable contraceptive.

A pilot study to assess the use of natural hormones in macrocrystalline sustained release system was undertaken in normal menstruating women. Progesterone at a dose of 100 mg in combination with 5 mg estradiol-17 beta aqueous macrocrystalline suspension (3ml) of defined particle size range (100-250 microns) were administered to five female volunteers of reproductive age, on day 5 of their normal menstrual cycles and then every 28 days consecutively for the next two months. Peripheral venous blood samples were obtained from the women three times a week for 60 days after the third injection for the measurement of serum progesterone, estradiol-17 beta, LH and FSH. The menstrual bleeding patterns were closely monitored during the study period. The results obtained indicate that the exogenous hormone administration produces blood levels similar to those observed during the luteal phase of the menstrual cycle. Follicular maturation as assessed by endogenous estradiol rise, above 150 pg/ml, occurred 29.7 days s.d. 6.4 after the injection. Ovulation as measured by progesterone levels above 5 ng/ml was documented 34.4 days s.d. 4.3 after the third injection. The bleeding patterns were regular though initially shorter but these increased progressively towards normal pattern during course of the study. The data suggest that progesterone/estradiol-17 beta combination administered as an aqueous macrocrystalline suspension is capable of producing sustained ovulation inhibition and could be applied in the design of new once-a-month injectable contraceptives.

Adult↗
PubMed1991

Ventromedial hypothalamus vs. lateral hypothalamic D2 satiety receptors in the body weight increase induced by systemic sulpiride.

Two experiments were conducted in order to see if dopamine satiety receptors in the lateral hypothalamus or satiety mechanisms in the ventromedial hypothalamus were involved in the hyperphagia and body weight increase induced by systemic sulpiride. In the first experiment, it was shown that systemic sulpiride (20 mg/kg) does not block the anorexia caused by intraperifornical injections of amphetamine. In the second experiment, sulpiride (20 mg/kg during 18 days) did not produce an additional increase in body weight in previously VMH-lesioned female rats. This last fact cannot be explained by a ceiling effect since insulin (5 U/day during 7 days) increased body weight in the same VMH rats in which sulpiride was not effective. These results do not support the hypothesis that systemic sulpiride reaches the perifornical dopamine D2 receptors to disinhibit feeding, but suggest instead an involvement of the ventromedial hypothalamus. This last suggestion is more in agreement with the hypothesis that sulpiride alters feeding and body weight gain through the induction of a functional gonadectomy.

Amphetamine↗
PubMed1991

Mechanism of the sex-dependent effect of lithium on body weight in rats.

Two experiments are reported here. First, the effect of lithium chloride (1, 2 and 4 mEq/kg IP for 21 days) on body weight was assessed in female and male rats. Food intake was measured in the rats treated with 2 mEq/kg. All the doses tested significantly increased body weight in female rats. A linear relationship between body weight gain and lithium dose was also observed. In contrast, in male rats, the low doses of lithium (1 and 2 mEq/kg) did not affect body weight, whereas the high dose (4 mEq/kg) decreased body weight. These results confirm previous reports on a sex-dependent effect of lithium on body weight in rats. In the second experiment, body weight and food intake were assessed in female rats treated with lithium alone, or in combination with insulin or sulpiride, a D2 dopamine receptor blocker. It was found that the effect of lithium on body weight and feeding was additive to the effects of sulpiride and insulin. These findings are indirect evidence that lithium enhances body weight in rats by a different mechanism than the one described for sulpiride or insulin.

Animals↗
PubMed1991

Hypothalamic sites affecting masticatory neurons in rats.

The effects of hypothalamic electrical stimulation and dl-sulpiride injections on the unit activity of masticatory trigeminal neurons were assessed in rats. Unilateral electrodes or bilateral cannulas were implanted in the perifornical hypothalamus. The animals which exhibited eating to electrical stimulation or to sulpiride injections were selected. Then, under urethane anesthesia, electrical stimuli or sulpiride injections were applied at sites which elicited eating while a passive jaw movement-related neuron was recorded. Electrical stimulation or sulpiride injections affected the basal firing rate of 15 out of 32 (53%), and 13 out of 17 (76%) jaw movement-related neurons, respectively. The basal firing rate of 3 out of 18 (16.6%) was affected by electrical stimulation of noneliciting feeding nearby places. Facilitation was observed in 7 out of those 13 jaw movement-related trigeminal neurons after intrahypothalamic sulpiride injections. When dopamine was injected in the hypothalamus 3 minutes before sulpiride, this drug could only affect the basal firing rate of 1 out of 12 (8%) jaw movement-related neurons. The electrical stimulation and sulpiride injections into the hypothalamus had the same inhibitory or excitatory effect on a given trigeminal neuron as the passive jaw movement did. A similar phenomenon was observed with the sulpiride-induced facilitation. These results suggest that hypothalamic D2 satiety receptors modulate brain stem feeding reflexes.

Animals↗
PubMed1991

A polymer carrier system for taste masking of macrolide antibiotics.

A polymer carrier system was developed to reduce the bitterness of erythromycin and its 6-O-methyl derivative, clarithromycin, by absorption to Carbopol. The mechanism involves ionic bonding of the amine macrolide to the high molecular weight polyacrylic acid, thereby removing the drug from the solution phase in an ion-free suspension. After ingestion, endogenous cations displace the drug from the polymer in the gastrointestinal tract to achieve bioavailability. The macrolide-Carbopol complexes were prepared by dissolving or slurrying predetermined ratios of drug and polymer in water or hydroalcoholic mixtures. A series of in vitro equilibrium studies, taste screening, and bioavailability studies in dogs established the characteristics for the various drug-polymer ratios. Taste protection was further improved by encapsulating the adsorbate particles with polymer coatings. Hydroxypropyl methylcellulose phthalate (HP-55) provided the best combination of suspension stability, taste protection and bioavailability. Human bioavailability studies demonstrated that the microencapsulated Carbopol absorbates of erythromycin and clarithromycin gave blood levels comparable to those obtained from conventional solid formulations.

Absorption↗
PubMed1991

Hypothalamic serotonin in treatments for feeding disorders and depression as studied by brain microdialysis.

Microdialysis was used to measure changes in extracellular serotonin in the hypothalamus of rats while they engaged in feeding behavior or received drug treatments used to treat feeding disorders and affective disorders in humans. Hypothalamic serotonin increased significantly relative to controls in response to (1) intraperitoneal tryptophan after food deprivation, (2) the smell of food and eating a meal, (3) a conditioned taste aversion, (4) d-fenfluramine and fluoxetine, and (5) an amphetamine challenge test after chronic low doses of lithium. In some cases, increases correlated with nonspecific behavioral arousal were seen in the hippocampus. The results suggest that diet, drug, and behavioral therapies, alone or combined, can be used to preferentially modify hypothalamic serotonin in the control of behavioral, emotional, and endocrine problems.

Animals↗
PubMed1990

Involvement of sulfhydryl metabolism in tolerance to cadmium in testicular cells.

Cadmium (Cd)-induced acute testicular toxicity and testicular interstitial cell (IC) tumors can be prevented by low-dose Cd pretreatment. The mechanism of this self-tolerance is unknown. In this regard glutathione (GSH) may play a role in protecting cells from damage by Cd. Therefore, possible mechanisms of self tolerance to Cd in ICs were investigated with emphasis on sulfhydryl metabolism. Rats were pretreated with low-dose Cd (3.0 mumol/kg, sc). Such low-dose Cd pretreatment prevented the necrotizing effects of normally testopathic doses of Cd (20.0 mumol/kg, sc) given 24 hr later. ICs were isolated by collagenase dispersion 24 hr after pretreatment and incubated with Cd (1.0 mM) for 1 hr. In vivo Cd-pretreatment alone increased GSH levels (as determined by HPLC) of whole cells (17%) and cytosol (17%) compared to nonpretreated control. When ICs from nonpretreated rats were exposed to Cd in vitro, GSH in whole cells declined 8% compared to nonpretreated control and 21% compared to cells from in vivo Cd-pretreated rats. In ICs isolated from pretreated rats and exposed to Cd in vitro, GSH levels were normal in whole cells and slightly increased in cytosol. In whole testes low-dose Cd reduced GSH overall, both in cytosol (34%) and in nuclei (14%). Changes in cysteine levels were also seen, similar to those of GSH in whole ICs and cytosol. Neither low-dose in vivo Cd-pretreatment nor in vitro Cd exposure greatly altered levels of the low Mr testicular Cd-binding proteins as assessed by electrophoresis. These results indicate that sulfhydryl metabolism, specifically increased GSH, may be a factor in self tolerance to Cd in ICs.

Animals↗
PubMed1990

Electrical hypothalamic stimulation in rats induces hyperthermia if and only if they learn to self-stimulate.

Handling and exposure to a novel environment has been shown to produce an emotional fever in rats. Electrical stimulation of lateral hypothalamus sites produced a rise of intracranial temperature not different from this emotional fever. Once the rats learned to self-stimulate, the same electrical stimulation produced a rise of the intracranial temperature significantly higher than the emotional fever. During the autoshaping for self-stimulation a significant relationship was found between the rise of the intracranial temperature and time expressed as successive days of self-stimulation training, or between the rise of intracranial temperature and the increasing frequency of operant responses. This seems to indicate that when the rats learned to self-stimulate, an initially nonsense signal, without specific thermal effect, was transformed into a neural or neurochemical code producing a new or modified effect which was a significantly higher fever.

Animals↗