Biomedical subjects

N Fajardo

Publications and source records attributed to N Fajardo.

10 recordsLinked to original sources

PubMed2000

Prolonged ambulatory colonic manometric studies using endoclips.

BACKGROUND: It is difficult to study human colonic motility under physiologic conditions. An important limitation associated with prolonged colonic recording is the failure of the sensors to resist normal expulsive forces. METHOD: In this article we describe a method of endoscopically positioning a manometric catheter by using clips in conjunction with a solid-state catheter. With the use of a rotatable clip-fixing device loaded on to a colonoscope, the manometric catheter was clipped to the colonic mucosa. RESULTS: Recordings for up to 120 hours were obtained from 6 subjects without apparent migration of the catheter assembly. No complications were noted, the catheter does not interfere with defecation, and defecation does not result in its expulsion. CONCLUSION: The current technique will allow reliable ambulatory measurements over prolonged periods of time in relatively comfortable and unrestrained subjects. This technique should increase our understanding of normal and abnormal colonic motility.

Colon↗

PubMed1998

Long-term alpha1-adrenergic blockade attenuates diet-induced dyslipidemia and hyperinsulinemia in the rat.

This study evaluated the ability of alpha1-adrenergic blockade to interfere with the development of diet-induced hyperlipidemia and deterioration of insulin action. Diets having extremely divergent effects on glucose and lipid metabolism were contrasted. Rats were fed for 4 weeks either a nonpurified diet (chow) or a hyperlipidemic (HL) purified diet containing 40% energy as sucrose, 40% as fat, and 20% as casein. Half of each dietary cohort was given the alpha1-adrenergic antagonist prazosin (3 mg/kg/day in the food). Blood was collected in the fasted state (10 h after food removal) and 2 h after the intake of a meal. In the fasted state, plasma triacylglycerols (TGs) were higher in rats fed the HL diet than in those given chow and were not affected by long-term treatment with prazosin. Postprandially, plasma TG increased twofold in the chow-fed group, with or without long-term prazosin. In contrast, prazosin reduced by more than half the eightfold increase in TG that followed intake of the high-fat meal (Diet x Blocker interaction; p < 0.002) in the HL cohort. The HL-fed animals also displayed fasting hypercholesterolemia (+30%; p < 0.0001), which was prevented by long-term treatment with prazosin. Likewise, the 50% increase in plasma cholesterol that followed meal ingestion only in the HL cohort was blunted by the alpha1-blocker (Diet x Blocker interaction; p < 0.001). Long-term prazosin also abolished fasting hyperinsulinemia in the HL cohort, whereas it did not alter fasting insulin in chow-fed animals (Diet x Blocker interaction; p < 0.005). Measurement of postprandial lipoprotein lipase activity in several tissues did not suggest the involvement of changes in the absolute availability of the enzyme as a determinant of the hypotriacylglycerolemic action of the alpha1-blocker. Thus long-term alpha1-adrenergic blockade, with minimal effects in rats fed a hypolipidemic diet, strongly attenuates several of the fasting and postprandial alterations in plasma variables of lipid and glucose metabolism induced by an extremely lipogenic diet.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1996

Gonadal steroid modulation of neuroendocrine transduction: a transynaptic view.

1. Steroid hormones act on neuronal communication through different mechanisms, ranging from transynaptic modulation of neurotransmitter synthesis and release to development and remodeling of synaptic circuitry. Due the wide distribution of putative brain targets for steroid hormones, acute or sustained elevations of their circulating levels may affect, simultaneously, a variety of neuronal elements. In an elementary mode of interaction, steroids are able to modulate both the synthesis and release of a neurotransmitter at a particular synapse, and the response of its target postsynaptic cells. Using two neuroendocrine transducing systems-the rat pineal gland and the GT1-7 cell line-we have examined these interactions and the following findings are discussed in this article. 2. In the rat, pineal melatonin production is partially controlled by gonadal hormones. In females, melatonin synthesis and secretion is reduced during the night of proestrus, apparently as a consequence of elevated estradiol and progesterone levels. In males, circulating testosterone seems to be necessary to maintain the amplitude of the nocturnal melatonin peak. 3. Some gonadal effects on pineal activity are exerted on its noradrenergic input, since changes in circulating steroid hormone levels are able to induce acute modifications of tyrosine hydroxylase activity in pineal sympathetic nerve terminals. 4. Gonadal steroids are also able to regulate the response of pineal cells to adrenergic stimulation, since in vivo treatment of both male and female rats with steroid hormone blockers induces profound modifications in adrenergically-induced accumulation of cyclic AMP (cAMP) in dispersed pinealocytes. 5. Direct exposure of pineal cells from gonadectomized female and male rats to estradiol (E2) or testosterone (T), respectively, potentiates pinealocyte response to adrenergic activation. In addition, short-term (15 min) exposure to either progesterone (Pg) or progesterone coupled to bovine serum albumin (P-3-BSA) suppresses the E2-dependent potentiation of adrenergic response in female rat pinealocytes. 6. Exposure of GT1-7 cells to E2 completely blocked the norepinephrine (NE)-induced elevation of cAMP content. In E2-treated GT1-7 cells, additional exposure (15 min) to either Pg or P-3-BSA abolished E2-dependent inhibition of NE responsiveness. In addition, P-3-BSA alone increased basal cAMP levels in GT1-7 cells, regardless previous exposure to E2. 7. In conclusion, there are evidences, both from the current literature and from the present results, supporting the view that in some neuroendocrine systems gonadal hormones modulate neurotransmission by acting, simultaneously, at pre- and postsynaptic sites. The models presented here constitute appropriate examples of this transynaptic mode of steroid and, therefore, may offer a useful approach to investigate steroid hormone actions on the brain.

Adrenergic Fibers↗

PubMed1996

Glucose tolerance and postprandial glucose and insulin kinetics in rats with short- and long-term alpha 1-adrenergic blockade.

The present study was designed to evaluate the acute and chronic effects of the alpha 1-adrenergic antagonist prazosin (Praz) on glucose tolerance and on postprandial plasma glucose and insulin kinetics. Rats were fed a high sucrose diet for 3 weeks, to which Praz (3 mg/kg/day) was added or not. They were then accustomed to ingest a meal 1 h after a single intraperitoneal (i.p.) injection of saline or Praz (1 mg/kg). Plasma levels of glucose and insulin were recorded at various times after meal intake. In addition, a fasting intravenous glucose tolerance test (IVGTT) was performed. In the chronic control cohort, pre-IVGTT plasma glucose and insulin levels were slightly but significantly higher after acute Praz than after acute saline administration. Factorial analysis of variance (ANOVA) showed that the increase in plasma glucose and insulin after intravenous (i.v.) glucose administration was also slightly greater in the animals that received acute Praz than in their saline counterparts. In contrast, after chronic treatment with Praz, pre- and post-IVGTT plasma glucose and insulin concentrations were identical in groups acutely injected with saline or Praz. In the chronic control cohort, preprandial plasma glucose and insulin measured in a sample collected before acute injection of saline or Praz were similar in both groups. The postprandial increase in plasma glucose and insulin was potentiated by the acute administration of Praz. Fasting plasma glucose and insulin concentrations were also similar in both groups chronically treated with Praz, and acute administration of the blocker still potentiated the increase in plasma glucose and insulin that followed meal intake. Chronic treatment alone did not affect postprandial glucose and insulin concentrations, and acute injection of Praz had comparable effects whether rats were chronically treated with the blocker or not. Therefore, potentiation of the glucose and insulin response to meal intake by Praz persisted after chronic treatment but required the acute presence of the blocker. However, repeated exposure to acute bouts of postprandial hyperinsulinemia induced by Praz did not lead to deterioration of insulin sensitivity or of the capacity of the pancreas to secrete insulin, as suggested by a normal response of glucose and insulin to IVGTT.

Adrenergic alpha-Antagonists↗

PubMed1995

Ovarian hormones regulate alpha 1- and beta-adrenoceptor interactions in female rat pinealocytes.

We have examined the effects of alpha 1- and beta-receptor activation on cyclic AMP (cAMP) accumulation in cultured pinealocytes from female ovariectomized rats, and from intact rats at proestrus treated with the antiestrogen Tamoxifen, the antiprogestagen RU486, or with both. Isoproterenol (a beta-agonist) significantly increased cAMP levels in pinealocytes from intact and ovariectomized rats. This response was considerably enhanced in pinealocytes from rats treated with RU486 or Tamoxifen alone, but not with both. Moreover, incubation of pinealocytes with isoproterenol together with phenylephrine (an alpha 1-agonist) produced a synergistic effect in animals that had been ovariectomized, or that had received RU486, either alone or in combination with Tamoxifen. These results suggest that, in female rats, ovarian steroids may regulate the interactions between alpha 1- and beta-adrenergic receptors, and thus modulate pineal melatonin synthesis during the oestrous cycle through these mechanisms.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1994

Tyrosine hydroxylase activity in peripherally denervated rat pineal gland.

The presence of tyrosine hydroxylase (TH) in the rat pineal gland was studied using a combination of immunochemical and biochemical methods. In superior cervical ganglionectomized (SCGx) animals and in isolated pineals incubated for 72 h, both TH immunoreactive (TH-IR) fibers and TH biochemical activity were still present but reduced. Conversely, in dispersed pinealocytes incubated for only 24 h we were unable to detect either TH activity or TH-positive cells. Since in the pineal gland of intact rats total 3-methoxy-4-hydroxy phenylglycol (MHPG) was undetectable, and only traces of norepinephrine (NE) were present in the pineal of ganglionectomized animals, the results suggest a central pinealopetal catecholaminergic pathway which could use dopamine as a neurotransmitter.

Animals↗

PubMed1994

Changes in tyrosine hydroxylase activity and melatonin synthesis in rat pineal glands throughout 72 hours of incubation.

Time-dependent modifications of N-acetyltransferase (NAT) activity, melatonin content, and tyrosine hydroxylase (TH) activity within the isolated rat pineal over a 72 h of incubation period were studied. Both pineal NAT activity and melatonin content displayed similar decreases after 12 h of incubation, and reached a maximal reduction of 82% or 93%, respectively, after 48 h. However, a maximal decrease of pineal TH activity was only 47% after 72 h of incubation. Neither the nuclear area of pinealocytes, nor lactate dehydrogenase (LDH) activity in the incubation medium showed any significant variation dependent on the incubation time. Treatment with isoproterenol caused an expected elevation of NAT activity and melatonin content but was unable to modify TH activity. Since a significant degree of pineal TH activity remained following 3 days of incubation, a non-sympathetic source of TH within the rat pineal gland is suggested.

Acetyltransferases↗

PubMed1993

Progesterone does not mediate the inhibition of pineal melatonin production during the rat proestrous night.

N-Acetyltransferase (NAT) activity and melatonin content were determined in pineal glands obtained during the proestrous stage of the rat estrous cycle. In control animals, both pineal NAT activity and melatonin levels were reduced during the first hours of proestrous night, as compared with day-time proestrous levels. The administration of antiprogestagen RU486, in a dose which blocked the preovulatory rise of serum luteinizing hormone and follicle-stimulating hormone levels, failed to prevent the reduction of pineal melatonin synthesis associated with the ovulatory events at proestrous night. These results suggest that estradiol, but not progesterone, might be the ovarian hormone responsible for the inhibition of pineal melatonin synthesis observed in the normal cycling female rat during proestrous night.

Acetyltransferases↗

PubMed1992

Determination of kinetic properties of serotonin-N-acetyltransferase in bovine pineal gland using HPLC with fluorimetric detection.

The determination of serotonin-N-acetyltransferase (NAT) activity in the bovine pineal gland and other rat tissues was based upon the separation and detection of N-acetyltryptamine formed from tryptamine and acetyl CoA by means of high performance liquid chromatography with fluorimetric detection. In the bovine pineal the enzyme exhibited a Km value of 31.45 +/- 4.98 microM and a Vmax value of 30.90 +/- 1.18 pmol N-acetyltryptamine/min/mg protein for tryptamine, and a Km value of 28.72 +/- 7.50 microM and a Vmax value of 25.90 +/- 1.50 pmol N-acetyltryptamine/min/mg protein for acetyl CoA. The present method is simple, allows the determination of NAT activity from a variety of enzyme sources, has application to pharmacological studies of NAT regulation in tissue cultures, and provides an alternative to current radioenzymatic assays.

Animals↗

PubMed1990

Immunoreactive somatostatin diurnal rhythms in rat pineal, retina and harderian gland: effects of sex, season, continuous darkness and estrous cycle.

Diurnal profiles of the content of immunoreactive somatostatin (IRS) in the male and female rat pineal, Harderian gland and retina have been studied. Supplementary experiments have been performed to elucidate a possible effect of infradian cycles, namely estrous and seasonal cycles, and continuous dark on IRS concentration. Results demonstrate that the IRS content in the rat pineal gland, Harderian gland and retina is submitted to diurnal variations, but not under all studied conditions. A sexual dimorphism exists between male and female animals: male rats showed higher IRS content in pineal (103.8 +/- 4.7 vs 32.3 +/- 1.8 pg IRS/gland), but lower in retina (1,362.1 +/- 82.7 vs 2,176 +/- 102.2 +/- pg IRS/mg of protein) and Harderian gland (10.3 +/- 0.8 vs 30.6 +/- 3.5 pg IRS/mg of protein). Additionally, seasonal differences appeared: in male and female animals pineal IRS content was lower in spring than in November. This decrease also appeared in female retina IRS concentration. Estrous cycle did not seem to change IRS content in the three studied tissues. Finally, pineal IRS rhythm persisted after continuous dark for a week. These results demonstrate, in the rat, sexual differences in the IRS content of the various tissues studied and suggest a physiological role for somatostatin, possibly related to seasonal adaptation.

Animals↗