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Biomedical subjects

Enrique Hong

Publications and source records attributed to Enrique Hong.

12 recordsLinked to original sources
PubMed2007

Indorenate improves motor function in rats with chronic spinal cord injury.

The effect of indorenate (5-methoxytryptamine, beta-methyl carboxylate hydrochloride), a 5-HT1A agonist, was investigated on the motor performance of rats with chronic spinal cord injury. Four months after a ninth thoracic vertebrae spinal cord contusion, 29 rats were randomly allocated into two groups: saline solution and indorenate-treated animals with daily doses incremented at weekly intervals. The locomotor performance of all rats was measured by the Basso, Beattie, and Bresnahan (BBB) rating scale. The results showed that at the end of the treatment, the motor activity of indorenate group was significantly better than that presented by saline solution group. The 80% of indorenate, (against 15% of saline solution) did not show detriment on motor activity. When we analysed the motor activity of rats with basal BBB lower than 10, a significant improvement of motor recovery in indorenate-treated animals was observed. The benefits observed in locomotor function at low doses followed by increasing doses could be associated with pharmacological treatment by indorenate, a well-known 5-HT1A receptor agonist. Our results suggest a potential mechanism by which serotonergic agents may improve motor function in rats with chronic spinal cord injury.

5-Methoxytryptamine↗
PubMed2006

Interval bisection in spontaneously hypertensive rats.

An interval bisection procedure was used to study time discrimination in spontaneously hypertensive rats (SHR), which have been proposed as an animal model for the attention deficit hyperactivity disorder (ADHD); Wistar Kyoto and Wistar rats were used as comparison groups. In this procedure, after subjects learn to make one response (S) following a short duration stimulus, and another (L) following a long duration stimulus, stimuli of intermediate durations are presented, and the percentage of L is calculated for each duration. A logistic function is fitted to these data, and different parameters that describe the time discrimination process are obtained. Four conditions, with different short and long durations (1-4, 2-8, 3-12, 4-16s) were used. The results indicate that time discrimination is not altered in SHR, given that no difference in any of the parameters obtained were significant. Given that temporal processing has been proposed as a fundamental factor in the development of the main symptoms of ADHD, and that deficits in time discrimination have been found in individuals with that disorder, the present results suggest the necessity of exploring time perception in SHR with other procedures and sensory modalities, in order to assess its validity as an animal model of ADHD.

Animals↗
PubMed2005

5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats.

The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1, 0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three type of seizures in male Wistar rats: clonic-tonic convulsions induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the mortality rate induced by PTZ. Indorenate increased the latency to the PTZ-induced seizures and decreased the percentage of rats showing tonic extension and death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished the occurrence and delayed the establishment of SE. Indorenate augmented the latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and Indorenate did not alter the expression of kindled seizures. However, Indorenate enhanced the refractoriness to subsequent seizures during the postictal depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures evaluated and postictal depression were fully or partially blocked by WAY100635. These results suggest that 5-HT1A receptor agonists modify epileptic activity depending on the type of seizure.

5-Methoxytryptamine↗
PubMed2004

Role of the sympathetic and renin angiotensin systems in the glucose-induced increase of blood pressure in rats.

The pressor effect induced by acute hyperglycemia is not well understood, therefore, it was of interest to study the effect of intravenous glucose infusion on the mean arterial pressure of anesthetized Wistar rats. Animals received glucose (100 mg/kg/min, i.v.), mannitol or saline during 30 min, but only glucose increased the mean arterial pressure (about 40 mm Hg), plasma glucose, insulin and nitric oxide (NO). Pretreatment with reserpine or indorenate (a central antihypertensive) inhibited completely the pressor effect of glucose. Reserpine also decreased the plasma NO levels. Pretreatment with ramipril or with streptozotocin decreased the late phase of the glucose-induced pressor response and the NO levels, the latter treatment also abolishes insulin plasma concentrations. The present results suggest that the pressor effect induced by glucose has an early phase due to an increase of efferent sympathetic discharges and a delayed phase produced by the activation of the renin angiotensin system.

Anesthesia↗
PubMed2004

Synthesis and cardiovascular activity of metoprolol analogues.

The synthesis of four novel analogues of metoprolol, a well-known beta1-blocker used to reduce arterial blood pressure, is described. The preparation of (2S,2'S)-7, (2R,2'S)-7, (2R,2'R)-8, and (2S,2'R)-8 was based on the reaction of racemic 2-[4-(2'-methoxyethyl)-phenoxymethyl]-oxirane (4) with (R)- or (S)-2-amino-1-butanol. Salient characteristics of analogues 7 and 8 relative to metoprolol are the incorporation of an additional stereogenic center, as well as a methyl group and a hydroxyl function on the nitrogen-containing chain. These novel derivatives present significant hypotensive and bradycardiac activity, although no blocking action toward beta1 and beta2 adrenergic receptor.

Animals↗
PubMed2004

Antispasmodic activity of extracts and compounds of Acalypha phleoides Cav.

The aerial parts of Acalypha phleoides are usually prescribed in the Mexican traditional medicine for a variety of gastrointestinal complaints. The MeOH-CHCl(3) (1:1) extract of the aerial part of A. phleoides showed an inhibitory effect on the gastrointestinal propulsion of a charcoal meal in mice. In isolated guinea-pig ileum, this extract produced a concentration dependent inhibition of the contractions induced by 5-hydroxytryptamine, but it was unable to inhibit the contractions elicited by acetylcholine, histamine, KCl and BaCl(2). This extract produced also a concentration dependent inhibition of the spontaneous pendular movement of the isolated rabbit jejunum. This inhibitory activity was partially blocked by propranolol. The essential oil, obtained from the aerial part of this plant, was more potent than the MeOH-CHCl(3) (1:1) extract in inhibiting the spontaneous pendular movement of the rabbit jejunum. Thymol, camphor and gamma-terpinene were identified from the essential oil by GC-MS. These monoterpenes showed antispasmodic activity in the rabbit jejunum preparation, thymol was the most active compound, followed by camphor and gamma-terpinene. Thymol and camphor in high concentrations also showed tracheal relaxant properties, but gamma-terpinene did not. These in vivo and in vitro results tend to support the traditional use of A. phleoides as an antispasmodic agent.

Animals↗
PubMed2004

Systemic microcirculation after complete high and low thoracic spinal cord section in rats.

Spinal cord injury (SCI) produces multiple systemic and metabolic alterations. Although some systemic alterations could be associated with ischemic organ damage, little is known about microvascular blood flow (MVBF) in organs other than the spinal cord after acute SCI. We used laser Doppler flowmetry in anesthetized rats to assess MVBF in several tissues before and after complete T-2 and T-9 SCI at 1 h and on days 1, 3, and 7 post-SCI. Mean arterial blood pressure (MAP), heart rate and hematologic variables also were recorded. MAP changes after T-2 injury were not significant, while MAP decreased significantly 1 h after T-9 injury. Statistically significant bradycardia occurred after T-2 injury at 7 days; statistically significant tachycardia occurred after T-9 injury at 1, 3, and 7 days. Hematocrit significantly increased at day 1 and decreased at days 3 and 7 after T-2 injury. SCI was associated with significant decreases in MVBF in liver, spleen, muscle and fore footpad skin. Changes in MVBF in hind footpad skin and kidney were not significant. Changes were more pronounced at 1 h and 1 day post-SCI. Significant differences between MVBF after T-2 and T-9 SCI occurred only in liver. MVBF significantly correlated with regional peripheral vascular resistances (assessed using the MAP/MVBF ratio), but not with MAP. In conclusion, organ-specific changes in systemic MVBF that are influenced by the level of SCI, could contribute to organ dysfunction.

Animals↗
PubMed2004

Platelet glycoprotein IIb/IIIa inhibition and its clinical use.

The activation of platelets and the resultant aggregation have been shown to play important role in the pathogenesis of cardiovascular, cerebrovascular and peripheral vascular diseases and in acute coronary syndromes. Hence platelet adhesion and aggregation have been identified as promising targets for the development of anti-thrombotic drugs. Glycoprotein (GP) IIb/IIIa antagonism exerts a strong anti-platelet effect, because this interference inhibits the final common pathway of platelet aggregation and is not dependent on a single activation pathway. Three GPIIb/IIIa antagonists have been approved by the US Food and Drug administration. They include abciximab (the chimeric monoclonal antibody 7E3 Fab fragment), eptifibatide (the cyclic heptapeptide based on the KGD amino acid sequence) and tirofiban (a nonpeptide tyrosine derivative). In addition, nonpeptide oral GPIIb/IIIa antagonists are also in various stages of clinical development. This paper reviews the molecular biology of the GPIIb/IIIa receptor, history of development of GPIIb/IIIa antagonists, some issues about GPIIb/IIIb antagonists including their affinity, reversibility and receptor specificity, adverse effects including bleeding and thrombocytopenia, clinical trials and costs. Future direction in the development of GPIIb/IIIa antagonists is also discussed.

Clinical Trials as Topic↗
PubMed2003

Role of central and sympathetic nervous systems in pressor effect of L-NAME.

The pressor effect of N -nitric-l-arginine methyl ester (l-NAME) in rats has been attributed to the inhibition of the endothelial nitric oxide synthase; however, recent findings suggest that the central and sympathetic nervous systems may be also involved. In the present work, the authors attempted to study the possible central and sympathetic mechanisms involved in the pressor effect of l-NAME. They compared mean arterial pressure response during 1 h of continuous infusion of normal saline or l-NAME (0.031 mg. kg. min ) in Wistar rats treated with reserpine, adrenal medullectomy, pithing, and pithing + medullectomy. After 15-20 min infusion, a significantly greater increase of mean arterial pressure was observed in anesthetized rats with l-NAME and l-NAME + medullectomy versus rats with l-NAME + reserpine and l-NAME + pithing, and the magnitude of the difference increased further during the continuous 1-h l-NAME infusion. Adrenal medullectomy totally abolished the pressor effect of l-NAME in pithed group. The present findings suggest that the central and sympathetic nervous systems play important roles in the maintenance of the pressor effect of l-NAME, while the adrenal medulla becomes important only when the sympathetic nervous system has been suppressed.

Adrenal Medulla↗
PubMed2002

Lipid peroxidation by nitric oxide supplements after spinal cord injury: effect of antioxidants in rats.

To determine the extent to which exogenous nitric oxide (NO) might affect hemodynamics and/or increase oxidative damage after acute spinal cord (SC) injury, rats were submitted to SC contusion, and given a NO donor or NO precursor. Intravenous isosorbide dinitrate (10 microg/kg per min) or L-arginine (300 mg/kg per 23 h) showed a tendency to increase lipid peroxidation (LP), although without reaching significance compared to non-treated injured rats 24 h post-injury, and without affecting mean arterial pressure and heart rate importantly. LP due to injury and exogenous NO was significantly inhibited by the co-administration of a cocktail of antioxidants (12 mg/kg superoxide dismutase mimetic, 27000 U/kg catalase, and 12 mg/kg glutathione), but less effectively for the injury-L-arginine condition. These results demonstrate that in order to further test the potential neuroprotective effect of NO enhancing reagents after SC injury, antioxidants must be included in the treatment scheme.

Animals↗
PubMed2002

Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.

Because shikimic acid is the key intermediate in the shikimate pathway in plants and microorganisms, shikimic acid and its derivatives have been described as herbicides and anti-microbial agents. Triacetylshikimic acid (TSA) is an acetylate derivative of shikimic acid. The possible anti-platelet activity and anti-thrombotic efficacy of TSA were evaluated and its effect on arachidonic acid (AA) metabolism and second messengers including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) was evaluated. After oral pretreatment with TSA, adenosine diphosphate (ADP)-, collagen-, and AA-induced rat platelet aggregation was inhibited ex vivo in a dose-dependent manner. In an arteriovenous-shunt thrombosis model, oral administration of TSA resulted in a dose-dependent inhibition of thrombus growth. TSA markedly increased the cAMP level and showed no effect on the cGMP level in rat platelets. Also, no significant changes in ADP-induced thromboxane B2 formation in rat platelets or 6-keto-prostaglandin F 1alpha production from the abdominal aorta were observed after oral administration of low and medium doses of TSA (12.5 and 50 mg/kg). Additionally, prothrombin time, activated partial thromboplastin time, and thrombin time were unchanged at effective anti-platelet doses of TSA. These results demonstrate that TSA exerts oral anti-platelet and anti-thrombotic efficacy without perturbation of systemic hemostasis in rats, which was partially concerned with the elevation of cAMP in platelets.

6-Ketoprostaglandin F1 alpha↗