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Biomedical subjects

E Hong

Publications and source records attributed to E Hong.

At least 19 recordsLinked to original sources
PubMed2004

Comparison of histologic grade between initial and follow-up biopsy in untreated, low to intermediate grade, localized prostate cancer.

OBJECTIVE: To examine the change of histologic grade of untreated, low to intermediate grade, clinically localized prostate cancer over time on repeat prostate biopsy. METHODS AND MATERIALS: In a prospective single-arm cohort study, patients were managed with observation alone unless they met pre-defined criteria of disease progression (PSA, clinical or histologic progression). Sixty-seven (54%) of a total of 123 eligible patients underwent follow-up prostate biopsy. Median time to the follow-up biopsy was 22 months (range: 7-60). RESULTS: On the follow-up biopsy, Gleason score was unchanged in 20 patients (30%), upgraded in 19 (28%), and downgraded in 27 (40%). Twenty-one (31%) had no malignancy on the follow-up biopsy. Sixteen (37%) of 43 patients with < or = 2 positive cores on the initial biopsy had negative follow-up biopsy, while only 2 (11%) out of 18 with > or = 3 positive cores on the initial biopsy did. Five (7%) patients were upgraded to Gleason score 8. There was no correlation between the extent of grade change and baseline variables (age, clinical stage, and initial PSA) as well as PSA doubling time. CONCLUSIONS: There was no consistent histologic upgrade on the follow-up biopsy at a median of 22 months in untreated, low to intermediate grade, clinically localized prostate cancer.

Aged↗
PubMed2003

Further evidence that the discriminative stimulus properties of indorenate are mediated by 5-HT 1A/1B/2C receptors.

Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors. Unlike other anxiolytics such as 5-HT receptor agonists, INDO may not share tolerance or dependency with the benzodiazepine anxiolytics. It has been reported that the discriminative stimulus properties of 5-HT(1A/1B/2C) agonists, but not those of 5-HT(3/4) agonists, generalize to INDO. Therefore, the aim of the present study was to obtain further evidence on the differential involvement of 5-HT(1A/1B/2C) receptors in the discriminative stimulus properties of INDO by evaluating its interactions with antagonists of the 5-HT(1A), 5-HT(1B), 5-HT(2C), and 5-HT(3/4) receptor subtypes. Rats were trained to discriminate INDO from saline in a conditioned taste aversion paradigm. For Group D(+)S(-), administration of INDO signalled that saccharin flavour was followed by LiCl, while injection of vehicle signalled safe consumption of saccharin solution. Group D(-)S(+) had the contingencies reversed. After this training, rats had generalization tests where INDO administration was preceded by different doses of the following antagonists: WAY100635 (5-HT(1A)), NAN190 (5-HT(1A)), methiothepin (5-HT(1A/1B/2C)), GR127935 (5-HT(1B/1D)), ketanserin (5-HT(2A/2C)), ritanserin (5-HT(2C/2A)), mesulergine (5-HT(2C/2A)), metergoline (5-HT(2C/2A)), SB206553 (5-HT(2B/2C)), and tropisetron (5-HT(3/4)). In Group D(+)S(-), the order of potency to block the discriminative stimulus properties of INDO was WAY100635>ketanserin>ritanserin>GR127935>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190, while in Group D(-)S(+), the order was WAY100635>GR127935>ketanserin>ritanserin>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190. Tropisetron did not produce any alteration of the discriminative control by INDO. These results suggest that the discriminative signal of INDO is mediated by 5-HT(1A/2C/1B) receptors and that blockade of any of its components produces a degradation of its discriminative effects.

5-Methoxytryptamine↗
PubMed2003

Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery?

OBJECTIVE: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. METHODS AND MATERIALS: A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. RESULTS: Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. CONCLUSION: There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.

Adenocarcinoma↗
PubMed2002

Sympathetic blockade significantly improves cardiovascular alterations immediately after spinal cord injury in rats.

Immediately after an experimental spinal cord injury (SCI) in rats, there is a large fall in mean arterial pressure (MAP) and heart rate (HR), followed by an abrupt increase in MAP. To better understand the mechanism involved in these early cardiovascular alterations, we tested the effect of treatment with ganglionic and sympathetic blockers in anesthetized rats subjected to T-5 SCI. Fall in MAP was partially diminished by propranolol and pentolinium, while increase in MAP was abolished by propranolol and pentolinium. Adrenalectomy did not diminish the fall in MAP and HR, however, the increase in MAP was significantly reduced. Likewise, propranolol and pentolinium completely abolished the effects in HR. These data suggest that the early cardiovascular alterations secondary to SCI results from an increased parasympathetic activity and a sympathetic withdrawal.

Adrenergic beta-Antagonists↗
PubMed2001

Mechanisms involved in the cardiovascular alterations immediately after spinal cord injury.

The early cardiovascular effects resulting from an acute spinal cord injury (SCI) produced by a contusion procedure at T5-T6 were evaluated in anaesthetized rats. The mean arterial pressure (MAP) and heart rate (HR) were measured during one hour after the injury. A marked decrease in MAP and HR was observed immediately after injury, followed by an abrupt increase in MAP. These changes were observed between 3 and 9 min and the basal values were recovered after 20 min. Fall in the MAP and HR and increase in MAP induced by SCI were abolished by atropine. The interruption of the parasympathetic outflow by vagotomy also significantly diminished the fall and increase in MAP and the fall in HR. Likewise, pre-treatment with nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) completely abolished the effects produced by SCI. These data suggest that after SCI the decrement in MAP and HR was probably due to acetylcholine release from parasympathetic fibers and NO from endothelial source probably by a cholinergic stimulation. Additionally, the MAP increase observed was probably due to a reflex compensatory vasoconstriction.

Acetylcholine↗
PubMed2001

Discriminative stimulus properties of indorenate in a conditioned taste aversion paradigm.

Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors. It possesses anxiolytic and antihypertensive actions mediated by 5-HT(1A) receptors and anorectic activity mediated by 5-HT(2C/1B) receptors. This study examined whether INDO may exert discriminative control using a conditioned taste aversion (CTA) paradigm, and whether differential participation of 5-HT receptor subtypes may be involved in its cue. Male Wistar rats trained to drink their daily water in a 30-min period were trained to discriminate INDO from saline. One group received the intraperitoneal administration of INDO (10.0 mg/kg) before saccharin-LiCl pairings; on alternate days, rats received saline before the saccharin-saline pairings (Group D(+)S(-)). The other group had the contingencies reversed (i.e., the administration of INDO preceded saccharin-saline pairings: Group D(-)S(+)). In two-bottle generalization tests (one bottle containing saccharin, the other plain water), the preference for saccharin was evaluated after different doses of INDO, [3H]-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (5-HT(1A)), buspirone (5-HT(1A)), RU24969 (5-HT(1A/1B)), TFMPP (5-HT(1B/2C)), MK212 (5-HT(2C)), alpha-Me-5-HT (5-HT(2C/2A)), 2-Me-5-HT (5-HT(3)) and cisapride (5-HT(4)). The results showed that INDO, RU24969, TFMPP, alpha-Me-5-HT and MK 212 produced a dose-dependent generalization; 8-OH-DPAT and buspirone produced only partial generalization, while 2-Me-5-HT and cisapride did not produce generalization. The results indicate that INDO administration may exert discriminative control over saccharin preference mediated mainly by 5-HT(1B/2C) receptors, but with an important contribution of 5-HT(1A) receptors.

5-Methoxytryptamine↗
PubMed2001

Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia.

The activity-guided fractionation of the ethanol extract of leaves of Annona diversifolia Saff., led to the isolation of palmitone (16-hentriacontanone) as the only anticonvulsant active compound. This aliphatic ketone was highly effective to diminish pentylenetetrazole (PTZ)-induced clonic-tonic seizures and toxicity. Also, it produced a prolongation of the latency for onset of seizures and a reduction of the death rate produced by 4-aminopyridine (4-AP) and bicuculline (BIC). However, it was inactive to inhibit the kainic acid (KA)- and strychnine (STC)-induced seizures. Palmitone did not produce motor incoordination and loss of righting reflex which are used as signs of neurological impairment. Palmitone (ED50 = 1.85 mg/kg) proved to be a more potent antiepileptic drug against the PTZ-induced seizures than etosuximide (ED50 = 59.6 mg/kg), sodium valproate (ED50 = 63 mg/kg), and carbamazepine (ED50 > 300 mg/kg) and it was only four-fold less potent than diazepam (ED50 = 0.48 mg/kg). The pharmacological profile of palmitone suggests that this compound could be acting on the GABAergic inhibitory system.

Animals↗
PubMed2001

Thiazide-sensitive cotransporter mRNA expression is not altered in three models of hypertension.

BACKGROUND/AIMS: Several lines of evidence support that the kidney is involved in the increase of arterial blood pressure, and some genetic studies suggest that the thiazide-sensitive Na+:Cl- cotransporter could be implicated in the development of hypertension. In the present study, we analyzed the Na+:Cl- cotransporter mRNA levels in the kidney during the development of hypertension in three experimental models. METHODS: The first model included 18 spontaneously hypertensive rats studied at 4, 10, and 16 weeks of age. The second model included 28 Wistar rats with two-kidney, one-clip Goldblatt hypertension studied at 7, 14, 21, and 28 days. The third model included 6 Wistar rats treated with N(G)-nitro-L-arginine methyl ester during 10 days. Respective controls were studied for all models. At the end of each experimental period, the systolic blood pressure was measured in the tail by plethysmography. Individual renal cortex total RNA was extracted, and the mRNA levels of the thiazide-sensitive Na+:Cl- cotransporter were assessed following a semiquantitative RT-PCR strategy. RESULTS: All experimental models developed systemic hypertension. However, the level of mRNA expression of the Na+:Cl- cotransporter did not change in any of the models studied as compared with their respective controls. CONCLUSION: Our results suggest that a change in mRNA levels of the thiazide-sensitive Na+:Cl- cotransporter is not associated with the development of hypertension in spontaneously hypertensive rats, in rats with renovascular hypertension, nor in rats with hypertension induced by nitric oxide synthesis inhibition.

Animals↗
PubMed2000

Solution structure of a designed amphipathic antimicrobial synthetic peptide, PGAa.

A designed peptide, PGAa showed an excellent antifungal activity as well as an efficient bactericidal activity toward gram-positive, especially in the pathogenic yeast Candida albicans 28838. The solution structures of PGAa have been determined both in 40% TFE/water solution and DPC micelle by CD and NMR spectroscopy. Based on NOEs, vicinal coupling constants, backbone amide exchange rates, and chemical shift indices, PGAa formed a long amphipathic alpha-helical conformation in both TFE and DPC micelle environments, spanning the residues Ile(2)-Ala(19) in TFE and Lys(5)-Ala(19) in DPC micelle, respectively. Solution structures suggested that the hydrophobic residues would interact with the fatty acyl chains of the lipid bilayer, while the positively charged side-chains exposed to aqueous environments. Therefore, we conclude that the alpha-helical structure as well as the highly amphiphatic nature of PGAa peptide may play a critical role in its antimicrobial activity as well as selectivities in different species.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Influence of admixed citric acid on the release profile of pelanserin hydrochloride from HPMC matrix tablets.

Pelanserin is a weakly basic experimental drug with a short half-life and a prolonged release formulation was developed using hydroxypropyl methylcellulose (HPMC) and citric acid to set up a system bringing about gradual release of this drug. For this purpose powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using 900 ml HCl 0.1 N, the first 3 h, and phosphate buffer pH 7.4, h 3-8. Dissolution curves were described by M(t)/M(inf)=kt(n), applied separately for each dissolution medium. The dissolution mechanism involved a coupled diffusion/relaxation with a trend favoring the diffusion mechanism with increasing citric acid concentrations. Increasing concentrations of citric acid produced increasing values of the kinetic constants, in a cubic relationship. Higher HPMC proportions produced slower dissolution rates but with a citric acid compensating more clearly a decreased solubility of pelanserin at pH 7.4. Individually calculated dissolution curves showed experimental 8 h pelanserin dissolution in a range of 65-99% for matrices with 100 mg HPMC/tab., while those with 200 mg HPMC/tab. were in the range 57-73%.

Antihypertensive Agents↗
PubMed2000

Inhibition of lipopolysaccharide-induced I-kappaB degradation and tumor necrosis factor-alpha expression by acriflavine, an antimicrobial agent.

Acriflavine neutral (ACF) has been used for treatment of microbial infections for humans and fishes. Effects of ACF on the nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS), an endotoxin, were examined in rat and RAW264.7 cells. Gel retardation analysis revealed that LPS (1 microg/kg) activated NF-kappaB in the liver, whereas pretreatment of rats with ACF (10 mg/kg) completely prevented the NF-kappaB activation. Selectivity of the NF-kappaB DNA binding was confirmed by immunodepletion with anti-p65 and anti-p50 antibodies. Translocation of NF-kappaB to the nucleus is preceded by phosphorylation and proteolytic degradation of inhibitor-kappaBalpha (I-kappaBalpha) subunit. Whereas the level of I-kappaBalpha protein was rapidly decreased after treatment of rats with LPS (1 microg/kg), ACF treatment prior to LPS attenuated the decrease in I-kappaBalpha protein level. LPS-induced increase in the production of TNF-alpha, the principal inflammatory mediator, was prevented by ACF pretreatment by 80%. Stimulation of RAW264.7 cells with 1 microg/ml of LPS caused an increase in DNA binding activity of NF-kappaB, which was 80% inhibited by 1 microg/ml of ACF. LPS reduced I-kappaBalpha level in RAW264.7 cells by 77%. ACF attenuated LPS-induced decrease in I-kappaBalpha protein in a concentration-dependent manner. Production of TNF-alpha by LPS from RAW264.7 cells was decreased by 84% in the presence of ACF. Data showed that ACF inhibited LPS-induced NF-kappaB activation through inhibition of I-kappaBalpha degradation and TNF-alpha production in both rat and RAW264.7 cells. Inhibition of NF-kappaB activation and TNF-alpha production may be associated with the anti-inflammatory activity of ACF.

Acriflavine↗
PubMed2000

The alpha-adrenoceptor antagonist, zolertine, inhibits alpha1D- and alpha1A-adrenoceptor-mediated vasoconstriction in vitro.

1. The antagonist effect of zolertine (4-phenyl-1-[2-(5-tetrazolyl)ethyl]piperazine trihydrochloride), on vascular contraction elicited by noradrenaline in aorta, carotid (alpha1D-adrenoceptors), mesenteric (alpha1A/D-adrenoceptors) and caudal arteries (alpha1A-adrenoceptors) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats and rabbit aorta (alpha1B-adrenoceptors), was investigated in endothelium-denuded arterial rings. 2. The selective alpha1D-adrenoceptor agonist, noradrenaline, elicited concentration-dependent contractions in all arterial rings from both species. Noradrenaline selectivity was: carotid = aorta >> mesenteric = rabbit aorta > caudal arteries. 3. The contractile responses induced by noradrenaline were competitively antagonized by zolertine in rat carotid and aorta arteries, yielding pA2 values of WKY, 7.48 +/- 0.18; SHR, 7.43 +/- 0.13 and WKY, 7.57 +/- 0.24; SHR, 7.40 +/- 0.08, respectively. Zolertine was a non-competitive antagonist in some blood vessels as Schild plot slopes were lower than unity. The pKb estimates for zolertine were WKY, 6.98 +/- 0.16; SHR, 6.81 +/- 0.18 in the mesenteric artery, WKY, 5.73 +/- 0.11; SHR, 5.87 +/- 0.25 in the caudal artery and 6.65 +/- 0.09 in rabbit aorta. 4. Competition binding experiments using the alpha1-adrenoceptor antagonist [3H]prazosin showed a zolertine pKi of 6.81 +/- 0.02 in rat liver (alpha1B-adrenoceptors) and 6.35 +/- 0.04 in rabbit liver (alpha1A-adrenoceptors) membranes. 5. Zolertine showed higher affinity for alpha1D-adrenoceptors compared to alpha1A-adrenoceptors, while it had an intermediate affinity for alpha1B-adrenoceptors. The ability of the alpha1-adrenoceptor antagonist zolertine to block alpha1D-adrenoceptor-mediated constriction in different vessels of WKY and SHR rats may explain its antihypertensive efficacy despite its low order of potency.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2000

Normative and validation studies of the Nine-hole Peg Test with children.

This study evaluated norms for fine motor dexterity skills on elementary school children of ages 5 through 10 and conducted reliability and validity stud ies utilizing the Nine-hole Peg Test. The sample included 826 students in 10 elementary schools. Moderately high test-retest reliability (rs = .81 and .79) and high interrater agreement (rs > .99) were obtained. Older students had shorter completion time that measured fine motor dexterity than younger students. Significant sex differences were found in completion time, but only for the dominant hand. Correlations of -.80 and -.74 between the scores on the Nine hole Peg Test and Purdue Pegboard Test at all tested ages indicated adequate concurrent validity of the measures and a significant difference in test scores between regular and special education groups provided further evidence of construct validity. The findings supported the Nine-hole Peg Test as an effective screening tool for fine motor dexterity of school-age children.

Child↗
PubMed1999

Early changes in nitric oxide synthase activity in atrial intramural arteries following experimental spinal cord injury in rats.

Previously, we have shown that immediately after an experimental spinal cord injury (SCI) in anaesthetized rats, there is a large fall in mean arterial pressure (MAP) and heart rate (HR), followed by an abrupt increase in MAP. To evaluate the participation of nitric oxide (NO), we evaluated the activity of nitric oxide synthase (NOS) using Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry in sections of atria at several post-injury time-intervals. Staining increased at 3 min, reached a maximum at 9 min and diminished 30 min after injury. Pretreatment with atropine prevented changes in MAP, HR and NADPH-d staining suggesting that such modifications result from an increased vagal stimulation. In conclusion, the NOS activity is transiently elevated in the atrial intramural arteries of rats subjected to an SCI.

Animals↗
PubMed1999

5-HT1A receptors modulate the consolidation of learning in normal and cognitively impaired rats.

Attempts were made to further analyze the role of 5-HT1A receptors in consolidation of learning by evaluating the role of these receptors in cognitively normal and impaired animals. The effects of post-training administration of 8-OH-DPAT and 5-HT1A receptor antagonists, WAY 100135, WAY 100635, and S-UH-301, plus the cholinergic and glutamatergic antagonists, scopolamine and dizolcipine, respectively, were determined using an autoshaping learning task. The results showed that 8-OH-DPAT increased the number of conditioned responses, whereas WAY100135, WAY100635, and S-UH-301, and the 5-HT depleter, p-chloroamphetamine (PCA), had no effect. PCA did not change the silent properties of the 5-HT1A receptor antagonists. PCA, WAY100635, and S-UH-301, but not GR127935 (a 5-HT1B/1D-receptor antagonist) or MDL100907 (a 5-HT2A receptor antagonist), reversed the effect to 8-OH-DPAT. Ketanserin (a 5-HT2A/2C receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist), at a dose that increased the conditioned responses by itself, reversed the effect of 8-OH-DPAT. Moreover, 8-OH-DPAT or S-UH-301 reversed the learning deficit induced by scopolamine and dizocilpine whereas WAY100635 reversed the effect of scopolamine only. These data confirm a role for presynaptic 5-HT1A receptors during the consolidation of learning and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Discriminative stimulus properties of indorenate, a serotonin agonist.

OBJECTIVE: To determine whether indorenate, a serotonin-receptor agonist, can exert discriminative control over operant responses, to establish the temporal course of discriminative control and to compare its stimulus properties to a (5-HT)IA receptor agonist. [3H]-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT). DESIGN: Prospective animal study. ANIMALS: Ten male Wistar rats. INTERVENTIONS: Rats were trained to press either of 2 levers for sucrose solution according to a fixed ratio schedule, which was gradually increased. Rats were given injections of either indorenate or saline solution during discrimination training. Once they had achieved an 83% accuracy rate, rats underwent generalization tests after having received a different dose of indorenate, the training dose of indorenate at various intervals before the test, various doses of 8-OH-DPT, or NAN-190 administered before indorenate or 8-OH-DPAT. OUTCOME MEASURES: Distribution of responses between the 2 levers before the first reinforcer of the session, response rate for all the responses in the session, and a discrimination index that expressed the drug-appropriate responses as a proportion of the total responses. RESULTS: Indorenate administration resulted in discriminative control over operant responses, maintained at fixed ratio 10, at a dose of 10.0 mg/kg (but not 3.0 mg/kg). When the interval between the administration of indorenate and the start of the session was varied, the time course of its cue properties followed that of its described effects on 5-HT turnover. In generalization tests, the discrimination index was a function of the dose of indorenate employed; moreover, administration of 8-OH-DPAT (from 0.1 to 1.0 mg/kg) fully mimicked the stimulus properties of indorenate in a dose-dependent way. The (5-HT)IA antagonist NAN-190 prevented the stimulus generalization from indorenate to 8-OH-DPAT. Also, NAN-190 antagonized the stimulus control of indorenate when administered 45 minutes before the session, but not when administered 105 minutes before the session (i.e., 15 minutes before the administration of indorenate). CONCLUSION: (5-HT)IA receptors are of relevance to the stimulus function of indorenate. However, other receptor subtypes may also be involved. Hence, other agonists and specific antagonists should be studied before definite conclusions are drawn.

5-Methoxytryptamine↗